.
Search for "inclusion body myositis" English only.
[There is always overlap in these lists but they should be inclusive as a result]
1: Curr Opin Rheumatol. 2005 Mar;17(2):164-71.
The role of exercise in the rehabilitation of idiopathic inflammatory
myopathies.
Alexanderson H, Lundberg IE.
Department of Physical Therapy, Rheumatology Unit, Karolinska University
Hospital, Solna, Stockholm, Sweden, and bRheumatology Unit, Department of
Medicine, Karolinska University Hospital, Solna, Karolinska Institutet,
Stockholm, Sweden.
PURPOSE OF REVIEW: The objective of this review is to provide an update on
exercise and clinical assessment in the idiopathic inflammatory myopathies.
RECENT FINDINGS: Polymyositis, dermatomyositis and inclusion body myositis are
rare conditions with muscle weakness as a common prominent feature. Earlier,
these patients were discouraged from active exercise due to a fear of increased
muscle inflammation with recommendations to rest, perform range of motion
exercises and in some cases, isometric exercises. However, beginning in the
1990s, studies reported reduced disability in patients with chronic
polymyositis/dermatomyositis following resistive mild/moderate to intensive
muscular training and aerobic endurance training, without signs of increased
muscle inflammation. Patients with active, recent onset disease seem to benefit
from mild/moderate muscular exercise without signs of increased muscle
inflammation. There is no evidence of increased muscle inflammation following
exercise in inclusion body myositis. However the beneficial effects are unclear
as one study report increased muscle strength, while the other could not achieve
impairment reduction. SUMMARY: Studies evaluating active exercise in IIM support
the notion of safety and benefits. However, large multi-center studies are
needed to fully establish the safety and benefits of different types of
exercise. Data indicate that active exercise, adapted to disease activity and
disability should be included in the rehabilitation of patients in all stages
of
IIM. The newly developed and validated outcome measures for patients with
polymyositis and dermatomyositis help assess the effects of interventions on
disease activity and disability in clinical trials and in clinical practice.
However, there are no sensitive and valid outcome measure for patients with
inclusion body myositis.
PMID: 15711230 [PubMed - in process]
2: Neurobiol Aging. 2005 May;26(5):645-54.
Age- and region-dependent alterations in Abeta-degrading enzymes: implications
for Abeta-induced disorders.
Caccamo A, Oddo S, Sugarman MC, Akbari Y, Laferla FM.
Department of Neurobiology and Behavior, University of California, Irvine,
1109
Gillespie Neuroscience Bldg., Irvine, CA 92697-4545, USA.
Accumulation of amyloid beta-protein (Abeta) is a fundamental feature of certain
human brain disorders such as Alzheimer's disease (AD) and Down syndrome and
also of the skeletal muscle disorder inclusion body myositis (IBM). Emerging
evidence suggests that the steady-state levels of Abeta are determined by the
balance between production and degradation. Although the proteolytic processes
leading to Abeta formation have been extensively studied, less is known about
the proteases that degrade Abeta, which include insulin-degrading enzyme (IDE)
and neprilysin (NEP). Here we measured the steady-state levels of these
proteases as a function of age and brain/muscle region in mice and humans. In
the hippocampus, which is vulnerable to AD pathology, IDE and NEP steady-state
levels diminish as function of age. By contrast, in the cerebellum, a brain
region not marked by significant Abeta accumulation, NEP and IDE levels either
increase or remain unaltered during aging. Moreover, the steady-state levels
of
IDE and NEP are significantly higher in the cerebellum compared to the cortex
and hippocampus. We further show that IDE is more oxidized in the hippocampus
compared to the cerebellum of AD patients. In muscle, we find differential
levels of IDE and NEP in fast versus slow twitch muscle fibers that varies with
aging. These findings suggest that age- and region-specific changes in the
proteolytic clearance of Abeta represent a critical pathogenic mechanism that
may account for the susceptibility of particular brain or muscle regions in
AD
and IBM.
PMID: 15708439 [PubMed - in process]
3: Clin Neuropathol. 2005 Jan-Feb;24(1):36-41.
Inclusion body myopathy associated with motor neuron syndrome: three case
reports.
Cafforio G, Pistolesi S, D'Avino C, Galluzzi F, Patricelli A, Solito B,
Fontanini G, Siciliano G.
Department of Neuroscience, University of Pisa, Italy.
BACKGROUND: Hereditary inclusion body myopathy (h-IBM) is an autosomal-recessive
or autosomal-dominant hereditary disease characterized by peculiar findings
in
muscle biopsies which resemble those occurring in inclusion body myositis (IBM).
The absence of an inflammatory infiltrate in myofibers in h-IBM is a relevant
differential criterion between the two pathologies. Motor neuron diseases (MND)
represent a group of disorders involving both upper and lower motor neurons,
characterized by fasciculations, progressive muscle weakness, and muscle
atrophy. The most common form and prototype of MND is the amyotrophic lateral
sclerosis (ALS) or Charcot's Disease, a progressive and fatal neurodegenerative
disorder occurring in late adulthood. The pathogenesis of ALS remains still
unknown, a variety of hypotheses having been proposed to account for the
disease. The association of both pathologies is not common and offers new
hypotheses about the pathogenic mechanisms in skeletal muscle and nervous system
degeneration. PATIENTS AND METHODS: Described are three case reports in which
we
observed the clinical, laboratory and histopathological association of IBM and
MND. In one case, dementia was also present. Muscle data was obtained by muscle
biopsies and immunohistochemistry, while diagnosis of MND was supported by
common neurophysiological techniques. RESULTS: The accumulation ofphosphorylated
neurofilaments with a hereditary IBM-like pattern in skeletal muscle fibers
without accumulation of amyloid-beta protein was observed. CONCLUSIONS: A better
knowledge of the mechanisms in cellular death cascade could explain the
pathogenesis of these different degenerative disorders.
PMID: 15696783 [PubMed - in process]
4: Neurology. 2005 Jan 25;64(2):389.
Finger flexor weakness in inclusion body myositis.
Takamure M, Murata KY, Kawahara M, Ueno S.
PMID: 15668452 [PubMed - in process]
5: Acta Clin Belg. 2004 Sep-Oct;59(5):290-9.
Inflammatory myopathies.
Cherin P.
Service de Medecine Interne I, CHU Pitie-Salpetriere, 47 Boulevard de l'Hopital,
75013, Paris, France. patrick.cherin@psl.ap-hop-paris.fr
Publication Types:
Review
Review, Tutorial
PMID: 15641400 [PubMed - indexed for MEDLINE]
6: Neuromuscul Disord. 2005 Jan;15(1):32-9.
Diaphragmatic dysfunction in patients with idiopathic inflammatory myopathies.
Teixeira A, Cherin P, Demoule A, Levy-Soussan M, Straus C, Verin E, Zelter
M,
Derenne JP, Herson S, Similowski T.
UPRES EA 2397, Universite Pierre et Marie Curie Paris VI, Paris, France.
Polymyositis, dermatopolymyositis, and inclusion body myositis imply chronic
inflammation of skeletal muscles. Pulmonary complications include aspiration
pneumonia, interstitial pneumonitis, or respiratory muscle myositis. This study
aims at better describing their impact on respiratory muscle. Twenty-three
consecutive patients (12 PM, 5 DM, 6 IBM) were studied (static inspiratory and
expiratory pressures; diaphragm function in terms of the mouth and
transdiaphragmatic pressure responses to bilateral phrenic stimulation).
Pulmonary parenchymatous abnormalities were mild (6 cases) or absent. The mouth
pressure produced by phrenic stimulation was 6.83+/-3.01 cm H2O, with 18
patients (78%) diagnosed with diaphragm weakness (<10 cm H2O) and lower values
in DM (4.35+/-1.48 cm H2O) than in IBM and in PM (P<0.05). Diaphragm weakness
is
frequent and probably overlooked in inflammatory myopathies. Further studies
are
needed to delineate the clinical relevance of these results.
PMID: 15639118 [PubMed - in process]
7: Neuropathol Appl Neurobiol. 2005 Feb;31(1):70-9.
Expression of the beta chemokines CCL3, CCL4, CCL5 and their receptors in
idiopathic inflammatory myopathies.
Civatte M, Bartoli C, Schleinitz N, Chetaille B, Pellissier JF,
Figarella-Branger D.
Laboratoire de Biopathologie Nerveuse et Musculaire (EA 3281), Faculte de
Medecine Timone, Universite de la Mediterranee, Institut de Physiopathologie
Humaine de Marseille (I.P.H.M), FR125 Marseille.
The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases
characterized by chronic lymphocytic and macrophagic infiltration in muscle.
Because the mechanism for recruitment of these cells probably involves
chemokines, we focused on the study of the expression pattern of some beta
chemokines and receptors because it may provide a basis for selective
immunotherapy. The expression of CCL3 (MIP-1alpha), CCL4 (MIP-1beta), CCL5
(RANTES) and their main receptors (CCR1 and CCR5) was studied by
semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and
immunohistochemistry in a series of 16 IIM and five controls (four normal
muscles and one tonsil). Except for CCL5, strong expression was observed by
RT-PCR with all molecules in all IIM subtypes in comparison to control muscle.
Immunohistochemistry revealed diffuse CCL4 expression in all vessels in
dermatomyositis. In both polymyositis and sporadic inclusion body myositis
(s-IBM) it was restricted to vessels in the vicinity of inflammatory exudates.
CCL5 expression was low, restricted to a few inflammatory cells in all IIM;
CCR1
expression was mainly restricted to macrophages and s-IBM endothelial cells,
whereas CCR5 was localized in inflammatory cells invading non-necrotic muscle
fibres. Expressions of both receptors were also recorded in few muscle fibres.
In conclusion, the upregulation of beta chemokines and receptors in IIM and
their differential expression by various cells may contribute to chronic
inflammation and to the peculiar distribution of inflammatory exudates in these
diseases.
PMID: 15634233 [PubMed - in process]
8: Neurology. 2004 Dec 28;63(12):2396-8.
Associations with autoimmune disorders and HLA class I and II antigens in
inclusion body myositis.
Badrising UA, Schreuder GM, Giphart MJ, Geleijns K, Verschuuren JJ, Wintzen
AR,
Maat-Schieman ML, van Doorn P, van Engelen BG, Faber CG, Hoogendijk JE, de Jager
AE, Koehler PJ, de Visser M, van Duinen SG; Dutch IBM Study Group.
Department of Neurology, K5Q, Leiden University Medical Center, PO Box 9600,
2300 RC Leiden, The Netherlands. ubadrising@lumc.nl
Whether autoimmune mechanisms play a role in the pathogenesis of inclusion
body
myositis (IBM) is unknown. Human leukocyte antigen (HLA) analysis in 52
patients, including 17 with autoimmune disorders (AIDs), showed that patients
were more likely to have antigens from the autoimmune-prone HLA-B8-DR3 ancestral
haplotype than healthy control subjects, irrespective of the presence of AIDs.
Patients lacked the apparently protective HLA-DR53 antigen. The results provide
further support for an autoimmune basis in IBM.
PMID: 15623710 [PubMed - in process]
9: Lancet Neurol. 2005 Jan;4(1):6-7.
Neuromuscular disorders: molecular and therapeutic insights.
Mastaglia FL.
Centre for Neuromuscular and Neurological Disorders, University of Western
Australia, Queen Elizabeth II Medical Centre, Perth, Western Australia,
Australia. flmast@cyllene.uwa.edu.au
Publication Types:
Review
Review, Tutorial
PMID: 15620848 [PubMed - indexed for MEDLINE]
10: Acta Myol. 2004 Sep;23(2):90-6.
Myopathies associated with myosin heavy chain mutations.
Oldfors A, Tajsharghi H, Darin N, Lindberg C.
Department of Pathology, Sahlgrenska University Hospital, Goteborg, Sweden.
anders.oldfors@pathology.gu.se
Myosin, a molecular motor, converts chemical energy into mechanical force.
The
motor domain of myosin heavy chain (MyHC) includes an ATP binding region with
ATPase activity and an actin-binding region. Motor function is achieved by
conformational changes, at hydrolysis, of ATP causing a shift in the angle
between the actin binding head and the rod region of the molecule. The elongated
alpha-helical coiled-coil rod region of MyHC molecules constitutes the major
part of the thick filaments of the sarcomere. Three major MyHC isoforms are
expressed in human skeletal muscle (type I, MYH7, expressed in type 1 fibres;
IIa, MYH2, expressed in 2A fibres; IIx, MYH1, expressed in 2B fibres). While
mutations in slow/beta cardiac MyHC (MYH7) are a common cause of familial
hypertrophic cardiomyopathy, no skeletal myopathies have, until recently, been
associated with mutations in MyHC. A heterozygous mutation, Glu706Lys, in the
core of the head of MyHC IIa is associated with a familial congenital myopathy,
which, in most instances, has shown mild phenotypic expression in children but
progressive course in some adults. There is a relationship between the level
of
expression of mutated MyHC IIa and muscle pathology. Some adults with a
progressive course show muscle fibres with rimmed vacuoles and filaments of
the
type seen in inclusion body myositis/myopathy (IBM). Endurance training in a
group of affected patients caused a shift in the expression of myosin from fast
(IIx) to slow (I) isoforms but no reduction in the expression of MyHC IIa. A
heterozygous mutation, Arg1845Trp, in the distal rod region of slow myosin (type
I, MYH7) is associated with familial congenital myopathy, with large deposits
of
MyHC I in the subsarcolemmal region of type 1 muscle fibres, "Myosin storage
myopathy". These patients showed slowly progressive muscle weakness but
no overt
cardiomyopathy. These two muscle diseases, which are caused by mutations in
MyHC, form the basis of a novel entity: "Myosin myopathies".
PMID: 15605950 [PubMed - in process]
11: Acta Myol. 2004 Sep;23(2):79-84.
Journey into muscular dystrophies caused by abnormal glycosylation.
Muntoni F.
Dubowitz Neuromuscular Centre, Department of Paediatrics, Imperial College
of
Medicine, Hammersmith Hospital, London, UK. f.muntoni@imperial.ac.uk
An increasing number of genes encoding for putative or demonstrated
glycosyltransferases are being associated with muscular dystrophies of variable
severity, ranging from severe congenital onset and associated structural eye
and
brain changes, to relatively mild forms with onset into adulthood. Five of these
genes (POMT1; POMGnT1; FXRP; Fukutin; LARGE) encode for proteins involved in
the
glycosylation of alpha-dystroglycan and, indeed, abnormal glycosylation of this
molecule is a common finding in all the respective conditions (Walker Warburg
syndrome; Muscle-Eye-Brain disease; congenital muscular dystrophy type 1C and
Limb girdle muscular dystrophy type 21; Fukuyama muscular dystrophy; congenital
muscular dystrophy type 1D). A 6th gene, GNE, responsible for the hereditary
form of inclusion body myositis, encodes for a glycosyltransferase the
substrate(s) of which is, however, still unclear. This article provides an
overview of the clinical, biochemical and genetic features of this group of
disorders.
PMID: 15605948 [PubMed - in process]
12: Neurology. 2004 Dec 14;63(11):2191-2.
Primary respiratory failure in inclusion body myositis.
Voermans NC, Vaneker M, Hengstman GJ, ter Laak HJ, Zimmerman C, Schelhaas HJ,
Zwarts MJ.
Neuromuscular Centre Nijmegen, Department of Neurology, University Medical
Centre Nijmegen, The Netherlands.
PMID: 15596785 [PubMed - in process]
13: Curr Opin Rheumatol. 2004 Nov;16(6):707-13.
Have recent immunogenetic investigations increased our understanding of disease
mechanisms in the idiopathic inflammatory myopathies?
Chinoy H, Ollier WE, Cooper RG.
Rheumatic Diseases Centre, Hope Hospital, Salford M6 8HD, UK.
PURPOSE OF REVIEW: The idiopathic inflammatory myopathies (IIM) continue to
provide a challenge given the variable effectiveness of the available
treatments, and immunogenetic studies are ongoing to further elucidate IIM
disease mechanisms. This review examines how recent research has improved our
understanding of the mechanisms that lead to IIM. RECENT FINDINGS: HLA-DRB1
studies in a large homogenous cohort of UK Caucasian patients have confirmed
that polymyositis (PM) and dermatomyositis (DM) are not genetically identical
diseases while other studies have shown that tumor necrosis factor alpha is
genetically implicated in disease susceptibility. Some remarkable results from
an international collaboration, correlating gene-environment interactions,
clearly suggest that ultraviolet light is capable of modulating both clinical
and immunologic features of IIMs. Studies on microchimerism are unraveling
interesting associations in juvenile DM patients, and bolstering the hypothesis
that myositis may be an 'allo-immune' disease. mRNA gene expression profiling
is
helping to increase our understanding of myositis pathogenesis, whilst animal
models have provided new information on the roles of Th1 responses and nitric
oxide synthase in muscle disease. New candidate genes have been examined in
inclusion body myositis (IBM), and a novel gene transfer experiment has been
conducted, which led to significant changes in expression of the IBM phenotype.
SUMMARY: Improving the understanding of the immunogenetics and
immunopathogenesis of the IIMs may in the future provide novel therapeutic
targets, and thus improve outcomes in these difficult diseases.
Publication Types:
Review
PMID: 15577608 [PubMed - indexed for MEDLINE]
14: Curr Opin Rheumatol. 2004 Nov;16(6):700-6.
Myositis: an update on pathogenesis.
Christopher-Stine L, Plotz PH.
Division of Rheumatology, Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA.
PURPOSE OF REVIEW: The etiology and much about the pathogenesis of the
inflammatory myopathies remain a mystery. In this review, we investigate recent
research efforts to understand the pathogenesis of the diverse entities of
polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM),
diseases that result from interactions between environmental risk factors and
genetic susceptibility. RECENT FINDINGS: Over the past year, there has been
considerable progress toward better understanding of IBM, with relatively few
developments toward understanding PM and DM. Although these diseases may share
some common clinical phenotypic and serologic components, they differ on a
molecular and cellular level. SUMMARY: The need for definitive, safer therapies
in these diseases makes vital the search for defining detailed pathogenesis
of
inflammation and muscle fiber damage at the molecular level.
Publication Types:
Review
PMID: 15577607 [PubMed - indexed for MEDLINE]
15: Curr Opin Rheumatol. 2004 Nov;16(6):684-91.
Is it really myositis? A consideration of the differential diagnosis.
Nirmalananthan N, Holton JL, Hanna MG.
Neurogenetics Group, National Hospital for Neurology and Neurosurgery, Queen
Square, London WC1N 3BG, UK.
PURPOSE OF REVIEW: The idiopathic inflammatory myopathies are an important
and
treatable group of disorders. However, the potential toxicity associated with
the immune therapeutic regimens used to treat these disorders may be
significant; therefore, accurate diagnosis before such treatment is essential.
The differential diagnosis is potentially large. Accurate diagnosis usually
depends on a combination of careful clinical assessment in conjunction with
detailed laboratory investigations. Muscle biopsy remains essential in achieving
an accurate diagnosis that will then guide treatment. This review describes
the
diagnostic approach used. RECENT FINDINGS: There has been debate over the
requirements for an accurate diagnosis of inflammatory myopathy (i.e.,
polymyositis and dermatomyositis). It is increasingly recognized that there
can
be clinical and muscle histopathologic overlap between the features of
inflammatory myopathies and those of other muscle disorders, in particular,
the
genetic muscular dystrophies. Pathologic findings of inflammation and major
histocompatibility complex upregulation, although typical of inflammatory
myopathies, have been shown to occur in some muscular dystrophies, complicating
the diagnostic process. Inclusion body myositis is much less responsive to
immunotherapy and is now recognized as the most common acquired muscle disease
in those older than 50 years of age. It is likely that genetic muscular
dystrophies and inclusion body myositis account for some cases of apparently
"treatment-resistant" myositis. SUMMARY: A thorough clinical assessment,
including a detailed family history, complemented by electromyography and
creatine kinase measurements, should be undertaken in any patient with presumed
idiopathic inflammatory myopathy. In addition, a muscle biopsy remains essential
in all cases. A precise tissue diagnosis confirming features of an active
inflammatory process should be achieved before immunosuppressive treatment is
commenced. An increasing array of immunocytochemical and histioenzymatic stains
now allows a full analysis and will help to confirm or exclude virtually all
the
differential diagnostic possibilities considered in this review. Electron
microscopy may also be valuable in selected cases. Close collaboration between
clinicians and muscle pathologists is essential in allowing the most accurate
interpretation of myopathologic findings in the clinical context.
Publication Types:
Review
PMID: 15577605 [PubMed - indexed for MEDLINE]
16: Neuropathol Appl Neurobiol. 2004 Dec;30(6):624-34.
Tau aggregates are abnormally phosphorylated in inclusion body myositis and
have
an immunoelectrophoretic profile distinct from other tauopathies.
Maurage CA, Bussiere T, Sergeant N, Ghesteem A, Figarella-Branger D, Ruchoux
MM,
Pellissier JF, Delacourte A.
INSERM U422, Faculte de Medecine, 1 place de Verdun, Lille cedex, France.
ca-maurage@chru-lille.fr
Sporadic inclusion body myositis (s-IBM) is the most frequent progressive
acquired inflammatory myopathy in people older than 50 years. Abnormal
aggregates of 'Alzheimer's proteins', including tau proteins, have been
previously demonstrated in s-IBM. In the present study, we have investigated
by
immunohistochemistry and immunoblotting analysis the presence of tau proteins
in
muscle biopsy samples from patients with s-IBM and other myopathies with rimmed
vacuoles, using newly developed antibodies raised against tau protein epitopes
found in Alzheimer's disease brain. Tau immunoreactivity was shown in rimmed
vacuoles or inclusions, preferentially with antibodies directed against
phosphorylated carboxy-terminal epitopes of tau proteins. Cytoplasmic reactivity
was also demonstrated in atrophic, nonvacuolated fibres, as well as in
non-necrotic fibres invaded by inflammatory cells. Abnormally phosphorylated
tau
aggregates were also found in other compartments of the muscle fibre in s-IBM
and other myopathies. Tau immunoblotting showed an electrophorectic profile
of a
doublet within the range of 60-62 kDa isovariants, which was different from
tauopathies of the central nervous system. Finally, the unique pattern of
immunoreactivity of s-IBM samples towards anti-tau antibodies is a new clue
to a
possible distinct subclass of peripheral tauopathy, different from the
tauopathies of the central nervous system.
PMID: 15541003 [PubMed - indexed for MEDLINE]
17: Tissue Antigens. 2004 Nov;64(5):575-80.
Two major histocompatibility complex haplotypes influence susceptibility to
sporadic inclusion body myositis: critical evaluation of an association with
HLA-DR3.
Price P, Santoso L, Mastaglia F, Garlepp M, Kok CC, Allcock R, Laing N.
School of Surgery and Pathology, University of Western Australia, Nedlands,
Australia. pprice@cyllene.uwa.edu.au
Previous studies of sporadic inclusion body myositis (sIBM) have shown a strong
association with HLA-DR3 and other components of the 8.1 ancestral haplotype
(AH) (HLA-A1, B8, DR3), where the susceptibility locus has been mapped to the
central major histocompatibility complex (MHC) region between HLA-DR and C4.
Here, the association with HLA-DR3 and other genes in the central MHC and class
II region was further investigated in a group of 42 sIBM patients and in an
ethnically similar control group (n = 214), using single-nucleotide
polymorphisms and microsatellite screening. HLA-DR3 (marking DRB1*0301 in
Caucasians) was associated with sIBM (Fisher's test). However, among
HLA-DR3-positive patients and controls, carriage of HLA-DR3 without
microsatellite and single-nucleotide polymorphism alleles of the 8.1AH (HLA-A1,
B8, DRB3*0101, DRB1*0301, DQB1*0201) was marginally less common in patients.
Patients showed no increase in carriage of the 18.2AH (HLA-A30, B18, DRB3*0202,
DRB1*0301, DQB1*0201) or HLA-DR3 without the central MHC of the 8.1AH, further
arguing against HLA-DRB1 as the direct cause of susceptibility. Genes between
HLA-DRB1 and HOX12 require further investigation. BTL-II lies in this region
and
is expressed in muscle. Carriage of allele 2 (exon 6) was more common in
patients. BTL-II(E6)*2 is characteristic of the 35.2AH (HLA-A3, B35, DRB1*01)
in
Caucasians and HLA-DR1, BTL-II(E6)*2, HOX12*2, RAGE*2 was carried by several
patients. The 8.1AH and 35.2AH may confer susceptibility to sIBM independently
or share a critical allele.
PMID: 15496200 [PubMed - in process]
18: J Pathol. 2004 Nov;204(3):241-7.
The prion protein in human neuromuscular diseases.
Kovacs GG, Kalev O, Gelpi E, Haberler C, Wanschitz J, Strohschneider M, Molnar
MJ, Laszlo L, Budka H.
National Institute of Psychiatry and Neurology, Budapest, Hungary.
The basis of human prion diseases affecting the nervous system is accumulation
of a disease-associated conformer (PrPSc) of the normal cellular prion protein
(PrPC). Earlier studies demonstrated increased expression of PrPC in inclusion
body myositis (IBM), dermato-, and polymyositis, as well as neurogenic muscle
atrophy. To define the spectrum and reliability of PrPC immunoreactivity, its
expression was examined systematically in a series of pathologically
characterized muscular disorders by means of immunohistochemistry, confocal
laser microscopy, and immunogold electron microscopy. Anti-PrPC immunolabelling
of rimmed vacuoles was observed in IBM, inclusions of myofibrillary myopathy,
targets, regenerating, and atrophic fibres, mononuclear cells, in addition to
ragged red fibres in mitochondrial myopathies, and focal sarcolemmal
immunostaining in non-diseased controls. Quantitative analysis demonstrated
that, in neurogenic muscle lesions, anti-PrPC staining detects a significantly
broader spectrum of fibres than anti-vimentin or anti-NCAM. In dystrophic
muscle, PrPC expression was mainly restricted to regenerating fibres. In IBM,
PrPC expression was not confined to rimmed vacuoles or vacuolated fibres and
only a small percentage (7.1%) of rimmed vacuoles were PrPC positive.
Ultrastructurally, PrPC was observed in the cytoplasm of lymphocytes, in the
myofibrillar network of targets, and in rimmed vacuoles. Knowledge of disease
circumstances with altered expression of PrPC is important in the setting of
a
potentially increased chance for extraneural PrPC-PrPSc conversion. In addition,
our observations suggest that PrPC may have a general stress-response effect
in
various neuromuscular disorders. Copyright (c) 2004 Pathological Society of
Great Britain and Ireland.
PMID: 15476279 [PubMed - indexed for MEDLINE]
19: FEBS Lett. 2004 Oct 8;576(1-2):57-62.
Transglutaminase catalyzes differential crosslinking of small heat shock
proteins and amyloid-beta.
Boros S, Kamps B, Wunderink L, de Bruijn W, de Jong WW, Boelens WC.
Department of Biochemistry 161, Nijmegen Center for Molecular Life Sciences,
University of Nijmegen, P.O. Box 9101, 6500HB Nijmegen, The Netherlands.
Crosslinking of proteins by tissue transglutaminase (tTG) is enhanced in amyloid
(Abeta) deposits characteristic of Alzheimer's disease and sporadic inclusion
body myositis. Small heat shock proteins (sHsps) also occur in amyloid deposits.
We here report the substrate characteristics for tTG of six sHsps. Hsp27, Hsp20
and HspB8 are both lysine- and glutamine-donors, alphaB-crystallin only is a
lysine-donor, HspB2 a glutamine-donor, and HspB3 no substrate at all. Close
interaction of proteins stimulates crosslinking efficiency as crosslinking
between different sHsps only takes place within the same heteromeric complex.
We
also observed that alphaB-crystallin, Hsp27 and Hsp20 associate with Abeta in
vitro, and can be readily crosslinked by tTG. Copyright 2004 Federation of
European Biochemical Societies
PMID: 15474010 [PubMed - indexed for MEDLINE]
20: Neurology. 2004 Sep 28;63(6):1114-7.
Mutant ubiquitin UBB+1 is accumulated in sporadic inclusion-body myositis muscle
fibers.
Fratta P, Engel WK, Van Leeuwen FW, Hol EM, Vattemi G, Askanas V.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA
90017-1912, USA.
Mutant ubiquitin (UBB+1), a product of "molecular misreading," is
toxic to cells
because its ubiquitinated form inhibits the proteasome, contributing to
accumulation of misfolded proteins and their ensuing toxicity. The authors
demonstrate in 10 sporadic inclusion body myositis (s-IBM) muscle biopsies that
UBB+1 is accumulated in aggregates containing amyloid-beta and
phosphorylated-tau. In s-IBM, UBB+1 may be pathogenic by inhibiting proteasome,
thereby promoting accumulation of cytotoxic misfolded amyloid-beta and
phosphorylated-tau.
PMID: 15452314 [PubMed - in process]
21: Folia Neuropathol. 2004;42 Suppl A:69-76.
Contribution of neuropathology to the understanding of human prion disease.
Kovacs GG, Kalev O, Budka H.
National Institute of Psychiatry and Neurology, Department of Neuropathology,
and Hungarian Reference Centre for Human Prion Diseases, Huvosvolgyi ut 116,
H-1021 Budapest, Hungary. kovacsgg@opni.hu
Neuropathology is an important tool for definitive diagnosis of sporadic,
genetic, and acquired prion disease. Classical neuropathological hallmark is
the
highly disease-specific spongiform change accompanied by neuronal loss, astro-
and microgliosis. Spongiform change of the neuropil consists of either
microcystic or confluent vacuoles and varies greatly within the same brain.
In
addition, the most important aspect of confirmatory diagnosis is the
demonstration of disease-associated prion protein (PrP(d)) by
immunohistochemistry or Western blotting. Different PrP(d) immunostaining
patterns include patchy/perivacuolar surrounding spongiform change,
diffuse/synaptic, perineuronal, or plaque type. The latter includes unicentric
kuru-type plaques or multicentric plaques as in the peculiar genetic prion
disorder, Gerstmann-Straussler-Scheinker disease. PrP(d) immunostaining patterns
correlate well with phenotypes defined by the polymorphic codon 129 and the
type
of protease resistant PrP(d) seen on Western blots. PrP(d) immunoreactivity
in
the cerebellum may be highly informative about disease subtypes. Although the
central nervous system is the major site of PrP(d) accumulation, it may also
be
observed in peripheral nerves as adaxonal deposits; in skeletal muscle as
granular immunoreactivity in particular in abundance in a unique instance of
concomitant Creutzfeldt-Jakob disease and inclusion body myositis; as well as
associated with dendritic cells and macrophages in vessel walls. A subset of
inhibitory GABAergic neurons is selectively affected in experimental and human
prion disease. The central pathogenetic cascade includes oxidative stress and
apoptosis. Deposition of terminal complement components on neurons accompanies
tissue damage.
Publication Types:
Review
Review, Tutorial
PMID: 15449461 [PubMed - indexed for MEDLINE]
22: Muscle Nerve. 2004 Aug 18;31(2):260-265 [Epub ahead of print]
Reversible inflammatory and vacuolar myopathy with vitamin E deficiency in
celiac disease.
Kleopa KA, Kyriacou K, Zamba-Papanicolaou E, Kyriakides T.
Department of Clinical Neurosciences, Cyprus Institute of Neurology and
Genetics, P.O. Box 23462, Nicosia, Cyprus.
We report a patient with late-onset celiac disease and neurological
manifestations including myopathy, polyneuropathy, and ataxia. Laboratory
investigations showed anti-gliadin antibodies and severe vitamin E deficiency.
Muscle biopsy revealed inflammatory infiltrates and rimmed vacuoles, similar
to
those found in inclusion-body myositis. A gluten-free diet and vitamin E
supplementation reversed both the clinical neurological manifestations and the
abnormalities in the muscle biopsy. Anti-gliadin antibodies were no longer
present. This case illustrates the spectrum of neurological complications of
celiac disease and documents the occurrence of reversible pathology resembling
inclusion-body myopathy in the muscle. Muscle Nerve 2004.
PMID: 15389648 [PubMed - as supplied by publisher]
23: J Biol Chem. 2004 Dec 17;279(51):53524-32. Epub 2004 Sep 22.
Calcium dyshomeostasis in beta-amyloid and tau-bearing skeletal myotubes.
Christensen RA, Shtifman A, Allen PD, Lopez JR, Querfurth HW.
Department of Neurology, Caritas St. Elizabeth's Medical Center, Tufts
University School of Medicine, 736 Cambridge St., Boston, MA 02135, USA.
The relative scarcity of inclusion-affected muscle cells or markers of cell
death in inclusion body myositis (IBM) is in distinction to the specific and
early intracellular deposition of several Alzheimer's Disease (AD)-related
proteins. The current study examined the possible correlation between myotube
beta-amyloid and/or Tau accumulations and a widespread mishandling of
intracellular muscle calcium concentration that could potentially account for
the unrelenting weakness in affected patients. Cultured myogenic cells
(C(2)C(12)) expressed beta-amyloid-42 (Abeta(42)) and fetal Tau peptides, as
human transgenes encoded by herpes simplex virus, either individually or
concurrently. Co-expression of Abeta(42) in C(2)C(12) myotubes resulted in
hyperphosphorylation of Tau protein that was not observed when Tau was expressed
alone. Resting calcium concentration and agonist-induced RyR-mediated Ca(2+)
release were examined using calcium-specific microelectrodes and Fluo-4
epifluorescence, respectively. Co-expression of Abeta(42) and Tau cooperatively
elevated basal levels of myoplasmic-free calcium, an effect that was accompanied
by depolarization of the plasma membrane. Sarcoplasmic reticulum (SR) calcium
release, induced by KCl depolarization, was not affected by Abeta(42) or Tau.
In
contrast, expression of Abeta(42), Tau, or Abeta(42) together with Tau resulted
in enhanced sensitivity of ryanodine receptors to activation by caffeine.
Notably, expression of beta-amyloid, alone, was sufficient to result in an
increased sensitivity to direct activation by caffeine. Current results indicate
that amyloid proteins cooperate to raise resting calcium levels and that these
effects are associated with a passive SR Ca(2+) leak and Tau
hyperphosphorylation in skeletal muscle.
PMID: 15385569 [PubMed - indexed for MEDLINE]
24: Curr Opin Neurol. 2004 Oct;17(5):561-7.
Inflammatory disorders of muscle: progress in polymyositis, dermatomyositis
and
inclusion body myositis.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, Maryland 20892-1382, USA.
dalakasm@ninds.nih.gov
PURPOSE OF REVIEW: To provide an update on the major advances in inflammatory
myopathies. RECENT FINDINGS: Polymyositis is an uncommon disorder that can be
misdiagnosed when the old, and never validated, criteria of Bohan and Peter
are
used. New diagnostic criteria were recently introduced, in which the MHC/CD8
complex is considered a specific immunopathological marker because it
distinguishes the antigen-driven inflammatory cells that characterize
polymyositis and sporadic inclusion-body myositis from the non-specific,
secondary inflammation seen in other disorders, such as dystrophies. In sporadic
inclusion-body myositis the inflammatory cells invade non-vacuolated fibers,
whereas the vacuolated fibers are not invaded by T cells, implying two
independent processes, a primary immune process with antigen-driven T cells
identical to polymyositis, and a degenerative process in which beta-amyloid
and
amyloid-related proteins participate in vacuolar degeneration. In polymyositis
and sporadic inclusion-body myositis, antigen-specific and clonally expanded
autoinvasive T cells persist for years, even in different muscles, as
reconfirmed by proof-of-principle techniques involving CDR3 spectratyping
combined with laser microdissected single-cell polymerase chain reaction of
the
T-cell receptor genes. The formation of immunological synapse between
autoinvasive T cells and muscle fibers was recently strengthened by the
upregulation of co-stimulatory molecules ICOS/ICOS-L and PD-L1. A new, distinct
myopathy characterized by T-cell-triggered macrophage hyperactivation has now
been recognized in patients with dermatomyositis-like disease. SUMMARY: Despite
recent progress, the antigen(s) responsible for T-cell activation in
polymyositis and sporadic inclusion-body myositis and the cause of vacuolar
degeneration in sporadic inclusion-body myositis remain unclear. Newer, more
aggressive immunotherapies may be encouraging, but control trials are needed
to
prove efficacy.
PMID: 15367860 [PubMed - in process]
25: J Virol. 2004 Oct;78(19):10320-7.
Direct evidence for a chronic CD8+-T-cell-mediated immune reaction to tax within
the muscle of a human T-cell leukemia/lymphoma virus type 1-infected patient
with sporadic inclusion body myositis.
Ozden S, Cochet M, Mikol J, Teixeira A, Gessain A, Pique C.
Unite d'Epidemiologie et Physiopathologie des Virus Oncogenes, Paris, France.
Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection can lead to
the
development of HTLV-1-associated myelopathy/tropical spastic paraparesis
(HAM/TSP), concomitantly with or without other inflammatory disorders such as
myositis. These pathologies are considered immune-mediated diseases, and it
is
assumed that migration within tissues of both HTLV-1-infected CD4(+) T cells
and
anti-HTLV-1 cytotoxic T cells represents a pivotal event. However, although
HTLV-1-infected T cells were found in inflamed lesions, the antigenic
specificity of coinfiltrated CD8(+) T cells remains to be determined. In this
study, we performed both ex vivo and in situ analyses using muscle biopsies
obtained from an HTLV-1-infected patient with HAM/TSP and sporadic inclusion
body myositis. We found that both HTLV-1-infected CD4(+) T cells and CD8(+)
T
cells directed to the dominant Tax antigen can be amplified from muscle cell
cultures. Moreover, we were able to detect in two successive muscle biopsies
both tax mRNA-positive mononuclear cells and T cells recognized by the
Tax11-19/HLA-A*02 tetramer and positive for perforin. These findings provide
the
first direct demonstration that anti-Tax cytotoxic T cells are chronically
recruited within inflamed tissues of an HTLV-1 infected patient, which validates
the cytotoxic immune reaction model for the pathogenesis of HTLV-1-associated
inflammatory disease.
Publication Types:
Case Reports
PMID: 15367598 [PubMed - indexed for MEDLINE]
26: Neurology. 2004 Aug 24;63(4):718-20.
Randomized pilot trial of high-dose betaINF-1a in patients with inclusion body
myositis.
Muscle Study Group.
Neuromuscular Disease Center, 601 Elmwood Avenue, Box 673, Rochester, NY
14642-8673. Rabi_Tawil@URMC.Rochester.edu
Beta-interferon-1a (betaINF-1a) is well tolerated at low dose (30 microg
IM/week) in inclusion body myositis (IBM). The authors investigated the safety
and tolerability of high-dose (60 microg IM/week) betaINF-1a in a randomized,
placebo-controlled trial in IBM. Twenty-seven of the 30 subjects enrolled
completed the study. The adverse event profile was similar for the placebo and
betaINF-1a groups. betaINF-1a, at a dose of 60 microg IM/week, is well tolerated
in IBM, but no differences in muscle strength or mass were observed between
the
placebo and betaINF-1a groups at 6 months in this pilot study.
PMID: 15326251 [PubMed - in process]
27: Neurology. 2004 Aug 10;63(3):587-8.
Interferon beta-responsive inclusion body myositis in a hepatitis C virus
carrier.
Yakushiji Y, Satoh J, Yukitake M, Yamaguchi K, Nakamura I, Nishino I, Kuroda Y.
The Division of Neurology, Department of Internal Medicine, Saga University
School of Medicine, Saga, Japan. yakushij@hsp.ncvc.go.jp
PMID: 15304605 [PubMed - in process]
28: Neurology. 2004 Jul 27;63(2):402-3; author reply 403.
Comment on:
Neurology. 2003 Aug 12;61(3):316-21.
Polymyositis: an overdiagnosed entity.
Hengstman GJ, van Engelen BG.
Publication Types:
Comment
Letter
PMID: 15282847 [PubMed - indexed for MEDLINE]
29: Neurology. 2004 Jul 27;63(2):402; author reply 403.
Comment on:
Neurology. 2003 Aug 12;61(3):316-21.
Polymyositis: an overdiagnosed entity.
Bradley WG.
Publication Types:
Case Reports
Comment
Letter
PMID: 15282846 [PubMed - indexed for MEDLINE]
30: Neurology. 2004 Jul 27;63(2):403-4; author reply 404.
Comment on:
Neurology. 2003 Aug 12;61(3):288-9.
Unicorns, dragons, polymyositis, and other mythical beasts.
Askanas V, Engel WK.
Publication Types:
Comment
Letter
PMID: 15277658 [PubMed - indexed for MEDLINE]
31: J Chem Neuroanat. 2004 Jul;27(4):237-46.
Transgenic mice expressing the human C99 terminal fragment of betaAPP: effects
on cytochrome oxidase activity in skeletal muscle and brain.
Strazielle C, Dumont M, Fukuchi K, Lalonde R.
Laboratoire de Pathologie Moleculaire et Cellulaire en Nutrition (EMI-INSERM
0014) and Service de Microscopie Electronique, Faculte de Medecine, Universite
Henri Poincare, Nancy I, France. straziel@persmail.uhp-nancy.fr
In order to furnish a combined model of relevance to human inclusion-body
myopathy and Alzheimer's disease, transgenic mice expressing human betaAPP-C99
in skeletal muscle and brain under the control of the cytomegalovirus/beta-actin
promoter were produced (Tg13592). These transgenic mice develop Abeta deposits
in muscles but not in brain. Cell metabolic activity was analyzed in brain
regions and muscle by cytochrome oxidase (CO) histochemistry, the terminal
enzyme of the electron transport chain. By comparison to age-matched controls
of
the C57BL/6 strain, CO activity was selectively increased in dark skeletal
muscle fibers of Tg13592 mice. In addition, only increases in CO activity were
obtained in those brain regions where a significant difference appeared. The
CO
activity of Tg13592 mice was elevated in several thalamic nuclei, including
laterodorsal, ventromedial, and midline as well as submedial, intralaminar,
and
reticular. In contrast, the groups did not differ in most cortical regions,
except for prefrontal, secondary motor, and auditory cortices, and in most
brainstem regions, except for cerebellar (fastigial and interpositus) nuclei
and
related areas (red and lateral vestibular nuclei). No variation in cell density
and surface area appeared in conjunction with these enzymatic alterations. The
overproduction of betaAPP-C99 fragments in brain without (amyloidosis did not
appear to affect the metabolic activity of structures particularly vulnerable
in
Alzheimer's disease.
PMID: 15261330 [PubMed - indexed for MEDLINE]
32: Pharmacol Ther. 2004 Jun;102(3):177-93.
The use of intravenous immunoglobulin in the treatment of autoimmune
neuromuscular diseases: evidence-based indications and safety profile.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Diseases
and
Stroke, National Institutes of Health, MSC 1382, Room 4N248, Building 10, 10
Center Drive, Bethesda, MD 20892-1382, USA. dalakasm@ninds.nih.gov
Intravenous immunoglobulin (i.v.Ig) has multiple actions on the immunoregulatory
network that operate in concert with each other. For each autoimmune
neuromuscular disease, however, there is a predominant mechanism of action that
relates to the underlying immunopathogenetic cause of the respective disorder.
The best understood actions of i.v.Ig include the following: (a) modulation
of
pathogenic autoantibodies, an effect relevant in myasthenia gravis (MG),
Lambert-Eaton myasthenic syndrome (LEMS), Guillain-Barre syndrome (GBS), chronic
inflammatory demyelinating polyneuropathy (CIDP), and stiff-person syndrome
(SPS); (b) inhibition of complement activation and interception of membranolytic
attack complex (MAC) formation, an action relevant to the complement-mediated
mechanisms involved in GBS, CIDP, MG, and dermatomyositis (DM); (c) modulation
of the inhibitory or activation Fc receptors on macrophages invading targeted
tissues in nerve and muscle, as seen in CIDP, GBS, and inflammatory myopathies;
(d) down-regulation of pathogenic cytokines and adhesion molecules; (e)
suppression of T-cell functions; and (f) interference with antigen recognition.
Controlled clinical trials have shown that i.v.Ig is effective as first-line
therapy in patients with GBS, CIDP, and multifocal motor neuropathy (MMN), and
as second-line therapy in DM, MG, LEMS, and SPS. In paraproteinemic IgM anti-MAG
(myelin-associated glycoprotein) demyelinating polyneuropathies and inclusion
body myositis (IBM), the benefit is variable, marginal, and not statistically
significant. i.v.Ig has a remarkably good safety record for long-term
administration, however, the following side effects have been observed: mild,
infusion-rate-related reactions, such as headaches, myalgia, or fever; moderate
but inconsequential events, such as aseptic meningitis and skin rash; and
severe, but rare, complications, such as thromboembolic events and renal tubular
necrosis. Future studies are needed to (a) find the appropriate dose and
frequency of infusions that maintain a response; (b) address pharmacoeconomics,
comparing the high cost of i.v.Ig to the cost of the other therapies, which,
although less expensive, cause significantly more long-term side effects; (c)
determine why some patients respond better than others; and (d) examine the
merits of combining i.v.Ig with other immunosuppressive drugs.
Publication Types:
Review
Review, Tutorial
PMID: 15246245 [PubMed - indexed for MEDLINE]
33: Muscle Nerve. 2004 Jul;30(1):102-10.
Annexin expression in inflammatory myopathies.
Probst-Cousin S, Berghoff C, Neundorfer B, Heuss D.
Center of Neuromuscular Disorders, Department of Neurology,
Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, D-91054
Erlangen, Germany. stefan.probst-cousin@neuro.imed.uni-erlangen.de
The pathogenesis of the inflammatory myopathies is still unclear, making their
treatment largely empirical. Improved understanding of the molecular mechanisms
of inflammatory muscle injury may, however, lead to the development of more
specific immunotherapies. To elucidate a possible pathogenic contribution of
calcium-binding proteins such as the annexins, we immunohistochemically
investigated muscle biopsy specimens from patients with dermatomyositis (10
cases), polymyositis (9 cases), and inclusion-body myositis (4 cases), compared
to control cases comprising sarcoid myopathy (3 cases), Duchenne muscular
dystrophy (DMD; 4 cases), and normal muscle (3 cases). We found expression of
annexins A1, A2, A4, and A6 in the vascular endothelium of all cases. Myofibers
expressed annexins A5, A6, and A7 diffusely and weakly in the cytosol, whereas
annexins A5 and A7 were also particularly localized to the sarcolemma. In the
inflammatory myopathies, in areas of myonecrosis in DMD, and in granulomatous
lesions of sarcoid myopathy, reactivity of annexins A1, A2, A4, A5, and A6 was
observed in macrophages and T-lymphocytes. Whereas the latter annexins appear
to
be nonspecific indicators of activation, annexin A1 upregulation may represent
endogenous anti-inflammatory mechanisms that merit further investigation.
PMID: 15221885 [PubMed - indexed for MEDLINE]
34: Acta Neuropathol (Berl). 2004 Sep;108(3):257-9. Epub 2004 Jun 24.
Rimmed vacuoles in facioscapulohumeral muscular dystrophy: a unique
ultrastructural feature.
Neudecker S, Krasnianski M, Bahn E, Zierz S.
Department of Neurology, Martin-Luther-University Halle-Wittenberg,
Ernst-Grube-Str. 40, 06097, Halle (Saale), Germany.
Rimmed vacuoles (RV) are a characteristic pathological feature in inclusion
body
myositis, but may also occur in other neuromuscular disorders, such as distal
myopathies, oculopharyngeal myopathy, polymyositis, rigid spine syndrome,
congenital myopathies, and some limb girdle muscular dystrophies, as well as
in
various neurogenic diseases. We describe a patient with RV in familial
facioscapulohumeral muscular dystrophy (FSHD) associated with an FSHD-typical
deletion on chromosome 4q35. Thus, FSHD should be included in the differential
diagnosis of neuromuscular disorders with RV.
Publication Types:
Case Reports
PMID: 15221332 [PubMed - indexed for MEDLINE]
35: J Neuropathol Exp Neurol. 2004 Jun;63(6):650-9.
Insulin-like growth factor I in inclusion-body myositis and human muscle
cultures.
Broccolini A, Ricci E, Pescatori M, Papacci M, Gliubizzi C, D'Amico A, Servidei
S, Tonali P, Mirabella M.
Department of Neuroscience, Catholic University, Rome, Italy.
a.broccolini@rm.unicatt.it
Possible pathogenic mechanisms of sporadic inclusion-body myositis (sIBM)
include abnormal production and accumulation of amyloid beta (A beta), muscle
aging, and increased oxidative stress. Insulin-like growth factor I (IGF-I),
an
endocrine and autocrine/paracrine trophic factor, provides resistance against
A
beta toxicity and oxidative stress in vitro and promotes cell survival. In this
study we analyzed the IGF-I signaling pathway in sIBM muscle and found that
16.2% +/- 2.5% of nonregenerating fibers showed increased expression of IGF-I,
phosphatidylinositide 3'OH-kinase, and Akt. In the majority of sIBM abnormal
muscle fibers, increased IGF-I mRNA and protein correlated with the presence
of
A beta cytoplasmic inclusions. To investigate a possible relationship between
A
beta toxicity and IGF-I upregulation, normal primary muscle cultures were
stimulated for 24 hours with the A beta(25-35) peptide corresponding to the
biologically active domain of A beta. This induced an increase of IGF-I mRNA
and
protein in myotubes at 6 hours, followed by a gradual reduction thereafter.
The
level of phosphorylated Akt showed similar changes. We suggest that in sIBM.
IGF-I overexpression represents a reactive response to A beta toxicity, possibly
providing trophic support to vulnerable fibers. Understanding the signaling
pathways activated by IGF-I in sIBM may lead to novel therapeutic strategies
for
the disease.
PMID: 15217093 [PubMed - indexed for MEDLINE]
36: J Neuropathol Exp Neurol. 2004 May;63(5):484-98.
Proteasomal expression, induction of immunoproteasome subunits, and local MHC
class I presentation in myofibrillar myopathy and inclusion body myositis.
Ferrer I, Martin B, Castano JG, Lucas JJ, Moreno D, Olive M.
Instituto de Neuropatologia, Servicio de Anatomia Patologica, Hospital
Universitario de Bellvitge, Hospitalet de Llobregat, Spain. 8082ifa@comb.es
Inclusion body myositis (IBM) and myofibrillar myopathy (MM) are diseases
characterized by the abnormal accumulation of proteins in muscle fibers,
including desmin, alphaB-crystallin, gelsolin, actin, kinases, and phospho-tau,
along with ubiquitin in muscle fibers, suggesting abnormal protein degradation
as a possible cause of the surplus myopathy. Since the ubiquitin-proteasome
system plays a crucial role in non-lysosomal protein degradation, the present
study has examined by immunohistochemistry the expression of components of the
catalytic core of 20S proteasomes and its regulators: 19S and PA28alpha/beta,
and the expression of immunoproteasome subunits LMP2, LMP7, and MECL1 in 8
patients with MM and 10 patients with IBM. The patients with MM were from 6
unrelated families, 2 sporadic cases, I with autosomal recessive and 5 with
autosomal dominant inheritance. One sporadic patient had a de novo R406W
mutation in the desmin gene, and 1 patient with autosomal dominant MM had a
single amino acid deletion at position 366 in the desmin gene. Increased
immunoreactivity to 20S, 19S, and PA28alpha/beta colocalizing abnormal protein
deposits, as revealed in consecutive serial sections, was seen in all cases
with
MM and IBM. In all cases, the subunits of the immunoproteasome LMP2, LMP7, and
MECL1 colocalized with proteasomal immunoreactivity and abnormal protein
accumulation. Immunohistochemistry revealed focal MHC class I immunoreactivity
in the cytoplasmic membrane of muscle fibers in IBM and in association with
protein aggregates in IBM, and to a lesser degree, in MM. The present findings
provide a link between abnormal protein accumulation and altered proteasomal
expression in IBM and MM.
PMID: 15198127 [PubMed - indexed for MEDLINE]
37: Can J Gastroenterol. 2004 Jun;18(6):397-9.
Injection of botulinum toxin A to the upper esophageal sphincter for
oropharyngeal dysphagia in two patients with inclusion body myositis.
Liu LW, Tarnopolsky M, Armstrong D.
Hamilton Health Sciences, Hamilton, Ontario, Canada. liuwc@mcmaster.ca
Inclusion body myositis (IBM) is a progressive degenerative skeletal muscle
disease leading to weakening and atrophy of both proximal and distal muscles.
Dysphagia is reported in up to 86% of IBM patients. Surgical cricopharyngeal
myotomy may be effective for cricopharyngeal dysphagia and there is one
published report that botulinum toxin A, injected into the cricopharyngeus
muscle using a hypopharyngoscope under general anesthesia, relieved
IBM-associated dysphagia. This report presents the first documentation of
botulinum toxin A injection into the upper esophageal sphincter using a flexible
esophagogastroduodenoscope under conscious sedation, to reduce upper esophageal
sphincter pressure and successfully alleviate oropharyngeal dysphagia in two
IBM
patients.
Publication Types:
Case Reports
PMID: 15190396 [PubMed - indexed for MEDLINE]
38: Rev Med Interne. 2004 Jun;25 Suppl 1:S14-6.
The molecular pathophysiology in inflammatory myopathies.
Dalakas MC.
Neuromuscular Diseases Section, NINDS, National Institutes of Health, NIH,
National Institute of Neurological Diseases and Stroke, 10 Center Drive, MSC
1382, Building 10, Room 4N248, Bethesda, MD 20892-1382, USA.
dalakasm@ninds.nih.gov
Publication Types:
Review
PMID: 15165685 [PubMed - indexed for MEDLINE]
39: Eur Neurol. 2004;51(4):215-20. Epub 2004 May 17.
Apolipoprotein E and alpha-1-antichymotrypsin polymorphisms in sporadic
inclusion body myositis.
Gossrau G, Gestrich B, Koch R, Wunderlich C, Schroder JM, Schroeder S, Reichmann
H, Lampe JB.
Department of Neurology, Medical Clinic II, Technical University Dresden,
Dresden, Germany. ggossrau@uni-bonn.de
Sporadic inclusion body myositis (s-IBM) is a progressive muscle disease of
unknown aetiology. Characteristically, intracellular amyloid deposits are
detectable, including beta-amyloid precursor protein, phosphorylated tau,
alpha1-antichymotrypsin (alpha1-ACT) and apolipoprotein E (ApoE). Polymorphisms
and mutations of the encoding genes have been identified in a variety of
neurodegenerative diseases including Alzheimer's disease (AD). Beside other
factors, polymorphisms may lead to protein accumulation in both diseases. In
particular, polymorphisms within the ApoE and alpha1-ACT gene have been
implicated in the aetiology of AD and s-IBM. We analysed ApoE and alpha1-ACT
gene polymorphisms in 35 s-IBM patients. We could not identify any statistical
significant correlation between distinct ApoE and alpha1-ACT genotypes and the
risk of developing s-IBM. Additionally, ApoE and alpha1-ACT genotypes seem not
to influence the onset age of s-IBM. A combination of different alpha1-ACT and
ApoE genotypes appears not to enhance the risk of developing s-IBM. Therefore,
allelic variations of alpha1-ACT and ApoE are unlikely to be genetic key factors
in the aetiology of s-IBM. Copyright 2004 S. Karger AG, Basel
PMID: 15159602 [PubMed - indexed for MEDLINE]
40: Best Pract Res Clin Rheumatol. 2004 Jun;18(3):345-58.
Paediatric idiopathic inflammatory muscle disease.
Wedderburn LR, Li CK.
Rheumatology Unit, Institute of Child Health, University College London, 30
Guilford Street, London WC1N 1EH, UK. l.wedderburn@ich.ucl.ac.uk
The paediatric idiopathic inflammatory myopathies (IIMs) are a group of rare
but
serious systemic autoimmune conditions of childhood. The most common of the
paediatric IIMs is juvenile dermatomyositis (JDM), while polymyositis and
inclusion body myositis are rare in children. JDM has a significantly different
spectrum of disease from adult dermatomyositis. Juvenile myositis can also occur
as part of other systemic autoimmune diseases such as scleroderma and systemic
lupus erythematosus. There has recently been significant progress towards the
development and validation of tools to measure disease activity and damage in
the paediatric IIMs. In addition, several new therapeutic avenues have been
used
to treat JDM. This review will discuss developments in the diagnostic criteria
for JDM, the clinical types and course of these conditions, recent progress
in
disease assessment, treatment options and new developments in research into
the
pathogenesis of paediatric IIM.
Publication Types:
Review
Review, Tutorial
PMID: 15158745 [PubMed - indexed for MEDLINE]
41: Best Pract Res Clin Rheumatol. 2004 Jun;18(3):331-44.
Adult inflammatory myopathies.
Christopher-Stine L, Plotz PH.
Division of Rheumatology, Department of Medicine, Johns Hopkins University
School of Medicine, Baltimore, MD 21205, USA.
The major inflammatory myopathies of adults-dermatomyositis, polymyositis and
inclusion body myositis-are uncommon and can be difficult to distinguish from
many conditions that mimic them clinically. They have a high morbidity; they
are
not infrequently the first sign of an associated malignancy; and they may be
a
part of another connective tissue disease. Their pathogenetic features suggest
that they are different illnesses. Dermatomyositis and polymyositis are clearly
inflammatory, both clinically and histologically, and both generally respond
to
therapy directed towards inflammation. Inclusion body myositis is now generally
recognized as the most common myopathy presenting in patients over the age of
50
years, and it responds only modestly and sometimes not at all to
immunosuppressive therapy. In this review, we have summarised the major newly
recognized features of pathogenesis, the involvement of extramuscular organs,
the differential diagnosis, diagnostic approaches and the main lines of therapy.
Publication Types:
Review
Review, Tutorial
PMID: 15158744 [PubMed - indexed for MEDLINE]
42: JAMA. 2004 May 19;291(19):2367-75.
Comment in:
JAMA. 2004 Sep 22;292(12):1429; author reply 1429-30.
Intravenous immunoglobulin in autoimmune neuromuscular diseases.
Dalakas MC.
Neuromuscular Diseases Section, National Institutes of Health, National
Institute of Neurological Disorders and Stroke, Bethesda, Md 20892, USA.
dalakasm@ninds.nih.gov
CONTEXT: Intravenous immunoglobulin (IVIG) enhances immune homeostasis by
modulating expression and function of Fc receptors, interfering with activation
of complement and production of cytokines, providing anti-idiotypic antibodies,
and affecting the activation and effector functions of T and B cells. These
mechanisms may explain the effectiveness of IVIG in autoimmune neuromuscular
disorders. OBJECTIVE: To systematically review the current status of the
treatment of autoimmune neuromuscular diseases with IVIG, with emphasis on
controlled trials. DATA SOURCES: Peer-reviewed publications identified through
MEDLINE (1966-2003), EMBASE (1974-2003), and references from bibliographies
of
pertinent articles. Each autoimmune neuromuscular disease term was searched
in
combination with the term intravenous immunoglobulin. STUDY SELECTION AND DATA
EXTRACTION: Criteria for selection of studies included controlled study design,
English language, and clinical pertinence. Data quality was based on venue of
publication and relevance to clinical care. DATA SYNTHESIS: Outcomes of
controlled trials indicate that IVIG at a total dose of 2 g/kg is effective
as
first-line therapy in Guillain-Barre syndrome, chronic inflammatory
demyelinating polyneuropathy, and multifocal motor neuropathy and as second-line
therapy in stiff-person syndrome, dermatomyositis, myasthenia gravis, and
Lambert-Eaton myasthenic syndrome. In other controlled studies, IVIG produced
a
modest, variable, and transient but not statistically significant benefit in
patients with inclusion body myositis and paraproteinemic anti-myelin-associated
glycoprotein antibody demyelinating polyneuropathy. Intravenous immunoglobulin
is not effective in patients with multiple sclerosis who have established
weakness or optic neuritis. In myasthenia gravis, it should be reserved for
difficult cases or before thymectomy in lieu of plasma exchange. CONCLUSION:
Intravenous immunoglobulin is effective in many autoimmune neurologic diseases,
but its spectrum of efficacy, especially as first-line therapy, and the
appropriate dose for long-term maintenance therapy are not fully established.
Further controlled studies of IVIG, combined with a dose-finding effect,
pharmacoeconomics, and quality-of-life assessments, are warranted to improve
the
evidence base for clinical practice.
Publication Types:
Review
PMID: 15150209 [PubMed - indexed for MEDLINE]
43: FEBS Lett. 2004 May 21;566(1-3):105-9.
The homozygous M712T mutation of UDP-N-acetylglucosamine
2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities
but
not in altered overall cellular sialylation in hereditary inclusion body
myopathy.
Hinderlich S, Salama I, Eisenberg I, Potikha T, Mantey LR, Yarema KJ, Horstkorte
R, Argov Z, Sadeh M, Reutter W, Mitrani-Rosenbaum S.
Charite - Universitatsmedizin Berlin, Campus Benjamin Franklin, Institut fur
Biochemie und Molekularbiologie, Arnimallee 22, 14195 Berlin-Dahlem, Germany.
stephan.hinderlich@charite.de
Hereditary inclusion body myopathy (HIBM) is a neuromuscular disorder, caused
by
mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase,
the
key enzyme of sialic acid biosynthesis. In Middle Eastern patients a single
homozygous mutation occurs, converting methionine-712 to threonine. Recombinant
expression of the mutated enzyme revealed slightly reduced N-acetylmannosamine
kinase activity, in agreement with the localization of the mutation within the
kinase domain. B lymphoblastoid cell lines derived from patients expressing
the
mutated enzyme also display reduced UDP-N-acetylglucosamine 2-epimerase
activity. Nevertheless, no reduced cellular sialylation was found in those cells
by colorimetric assays and lectin analysis, indicating that HIBM is not directly
caused by an altered overall expression of sialic acids.
PMID: 15147877 [PubMed - indexed for MEDLINE]
44: Hum Mutat. 2004 Jun;23(6):632.
Novel GNE mutations in Italian families with autosomal recessive hereditary
inclusion-body myopathy.
Broccolini A, Ricci E, Cassandrini D, Gliubizzi C, Bruno C, Tonoli E, Silvestri
G, Pescatori M, Rodolico C, Sinicropi S, Servidei S, Zara F, Minetti C, Tonali
PA, Mirabella M.
Department of Neuroscience, Catholic University, Rome, Italy.
a.broccolini@rm.unicatt.it
The most common form of autosomal recessive (AR) hereditary inclusion-body
myopathy (HIBM), originally described in Persian-Jewish families, is
characterized by onset in early adult life with weakness and atrophy of distal
lower limb muscles, which progress proximally and relatively spare the
quadriceps. AR HIBM is associated with mutations in the UDP-N-acetylglucosamine
2-epimerase/N-acetylmannosamine kinase gene (GNE) on chromosome 9p12-13. In
the
present study we have identified seven novel GNE mutations in patients from
five
unrelated Italian families with clinical and pathologic features indicative
of
AR HIBM. Four were missense mutations (c.1556A>G [p.N519S], c.79C>T [p.P27S],
c.1798G>A [p.A600T] and c.616G>A [p.G206S]), two consisted in a single-base
deletion (c.616delG [p.G206fsX4] and c.1130delT [p.I377fsX16]) and one in an
intronic single-base insertion (c.1070+2dupT). These latter findings further
extend the type of GNE mutations associated with HIBM. Furthermore, in one
patient we also identified the c.737G>A [p.R246Q] missense mutation that
corresponds to the one previously reported in a family from the Bahamas.
Interestingly, in two of our families distinct mutations affected nucleotide
c.616 in exon 3 (c.616delG and c.616G>A). The possibility of specific portions
of the gene being more prone to mutations remains to be elucidated. Copyright
2004 Wiley-Liss, Inc.
PMID: 15146476 [PubMed - indexed for MEDLINE]
45: J Neurol Neurosurg Psychiatry. 2004 Jun;75(6):917-20.
Sporadic inclusion body myositis: morphology, regeneration, and cytoskeletal
structure of muscle fibres.
Arnardottir S, Borg K, Ansved T.
Department of Clinical Neuroscience, Division of Neurology, Karolinska Hospital,
Stockholm, Sweden. snjolaug.arnardottir@ks.se
OBJECTIVE: To characterise morphological abnormalities in relation to muscle
fibre type in sporadic inclusion body myositis (s-IBM). METHODS: 14 muscle
biopsies from 11 patients with s-IBM were characterised for morphological
abnormalities and fibre type composition as well as muscle fibre regeneration
and cytoskeletal structure, using histochemical and immunohistochemical
techniques. RESULTS: Morphological abnormalities included inflammatory
infiltrates and "rimmed vacuoles," and pronounced variation in fibre
size. There
were no significant differences in fibre type composition between s-IBM patients
and controls based on the myofibrillar ATPase staining. A differential effect
on
muscle fibre sizes was noted, type II fibres being smaller in the s-IBM patients
than in the controls. Conversely, the mean type I muscle fibre diameter in the
s-IBM patients was larger than in the controls, though this difference was not
significant. An ongoing intense regeneration process was present in s-IBM
muscle, as indicated by the expression of neonatal myosin heavy chain, vimentin,
and CD56 (Leu-19) in most of the muscle fibres. The cytoskeletal proteins
dystrophin and desmin were normally expressed in s-IBM muscle fibres that were
not undergoing degeneration or regeneration. CONCLUSIONS: There are extensive
morphological and morphometric alterations in s-IBM, affecting different muscle
fibre types in different ways. The cytoskeletal structure of type I and II
muscle fibres remains unaffected in different stages of the disease.
PMID: 15146016 [PubMed - indexed for MEDLINE]
46: Acta Neuropathol (Berl). 2004 Jul;108(1):37-42. Epub 2004 May 08.
Expression and distribution of the nitric oxide synthases in idiopathic
inflammatory myopathies.
De Paepe B, Racz GZ, Schroder JM, De Bleecker JL.
Department of Neurology, Ghent University Hospital, De Pintelaan 185, 9000,
Belgium.
Different immune effector mechanisms have been characterised in the idiopathic
inflammatory myopathies (IIM): in polymyositis (PM) and sporadic inclusion body
myositis (sIBM), T-cell-mediated cytotoxicity targets nonnecrotic muscle fibres,
whereas in dermatomyositis (DM) the complement-mediated immune response is
directed against the microvasculature. As nitric oxide (NO) has an important
function in cell signalling and in the cytotoxicity displayed by activated
macrophages, it is potentially involved in the immunopathogenesis of IIM. Using
immunohistochemical, in situ hybridisation and Western blotting techniques,
we
visualised the three isoforms of NO synthase (NOS) in muscle tissues from normal
controls and from patients diagnosed with IIM. The levels of both constitutive
isoforms of NOS (endothelial, i.e., eNOS, and neuronal, i.e., nNOS) were
unchanged in IIM as compared with normal muscle. Both protein and mRNA of the
inducible form (iNOS) were detected in half of the control biopsies. Constant
and increased iNOS protein expression was found in endomysial infiltrates of
PM
and sIBM, whereas perimysial inflammatory cells in DM were largely negative.
We
developed a quantitative Western blotting protocol which confirmed the
constitutive nature of nNOS and eNOS and the significant induction of iNOS in
PM. Our results appoint iNOS with a dual function: a limited and transient role
in normal muscle physiology and an active cytotoxic role in PM and sIBM.
PMID: 15138776 [PubMed - indexed for MEDLINE]
47: Neuromuscul Disord. 2004 May;14(5):337-45.
119th ENMC international workshop: trial design in adult idiopathic inflammatory
myopathies, with the exception of inclusion body myositis, 10-12 October 2003,
Naarden, The Netherlands.
Hoogendijk JE, Amato AA, Lecky BR, Choy EH, Lundberg IE, Rose MR, Vencovsky
J,
de Visser M, Hughes RA.
Department of Neurology, University Medical Center, Heidelberg laan 100,
Utrecht, CX 3584, The Netherlands. j.hoogendijk@neuro.azu.nl
Publication Types:
Congresses
PMID: 15099594 [PubMed - indexed for MEDLINE]
48: Clin Neuropathol. 2004 Mar-Apr;23(2):76-9.
Necrotizing myopathy with microvascular deposition of the complement membrane
attack complex.
De Bleecker J, Vervaet V, Van den Bergh P.
Department of Neurology, Ghent University Hospital, Ghent, Belgium.
jan.debleecker@Ugent.be
Necrotizing myopathy without prominent inflammatory changes is increasingly
being recognized as a form of inflammatory myopathy, different from
dermatomyositis, polymyositis and sporadic inclusion-body myositis. We report
a
patient with a chronic steroid-responsive myopathy and an ill-defined overlap
syndrome. The muscle biopsy showed thickened capillaries and arterioles and
deposition of the membrane attack complex in the replicated mural elements of
some vessels. The surface of all muscle fibers showed major histocompatibility
class I immunoreactivity. Similar patients have rarely been reported, either
suffering from an undifferentiated connective tissue disorder or a carcinoma.
The link between the muscle fiber necrosis and the microangiopathy is unclear.
Absence of prominent inflammatory changes in a diagnostic muscle biopsy does
not
exclude the diagnosis of a treatable autoimmune inflammatory myopathy.
Publication Types:
Case Reports
PMID: 15074581 [PubMed - indexed for MEDLINE]
49: Brain. 2004 May;127(Pt 5):1182-90. Epub 2004 Mar 26.
Upregulated inducible co-stimulator (ICOS) and ICOS-ligand in inclusion body
myositis muscle: significance for CD8+ T cell cytotoxicity.
Schmidt J, Rakocevic G, Raju R, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
j.schmidt@gmx.org
Interactions between inducible co-stimulatory molecule (ICOS) and ICOS-ligand
(ICOS-L) are crucial for T-cell co-stimulation, effector cell differentiation
and memory CD8+ T-cell activation. Because in the muscle of patients with
sporadic inclusion body myositis (sIBM) clonally expanded CD8+ T cells invade
major histocompatibility complex (MHC) class I-expressing muscle fibres, we
investigated ICOS.ICOS-L interactions and correlated their expression with
perforin, a marker for cytotoxic effector function by autoinvasive CD8+ T cells.
The mRNA from 20 muscle biopsies of sIBM, 20 non-inflammatory or dystrophic
controls, two dermatomyositis (DM) and two polymyositis (PM) patients was
reverse transcribed and reamplified by semi-quantitative and quantitative
reverse transcription-polymerase chain reaction (RT-PCR), using primers for
ICOS, ICOS-L and perforin. The glyceraldehyde 3-phosphate dehydrogenase
(GAPDH)-normalized ratio of ICOS, ICOS-L and perforin expression was compared
with the degree of endomysial inflammation. Protein expression of ICOS, ICOS-L
and perforin was confirmed by immunohistochemistry. We demonstrate that ICOS-L
mRNA was upregulated in sIBM (arbitrary units, median +/- SEM: 48.6 +/- 14.9)
compared with controls (6.2 +/- 17.8, P < 0.05) and significantly correlated
with the expression of ICOS (53.9 +/- 16.6 versus 6.7 +/- 8.9 in controls, P
<
0.001). By triple labelling immunohistochemistry, the CD8+ T cells in sIBM and
PM were found to invade ICOS-L- and MHC class I-co-expressing muscle fibres.
Among the autoinvasive CD8+ T cells, however, only a subset of approximately
5-10% were ICOS positive, and thereby perceptive for ICOS.ICOS-L signalling
at
the immunological synapse. In contrast, in Duchenne muscular dystrophy and DM,
although ICOS and ICOS-L mRNA expression was also increased, the majority of
ICOS-L- and ICOS-positive cells were in the perimysial regions and connective
tissue. The mRNA for perforin was increased in sIBM (28.1 +/- 8.7) compared
with
controls (4.3 +/- 11.2, P = 0.18), and significantly correlated with mRNA of
ICOS, ICOS-L and the degree of endomysial inflammation as assessed in coded
haematoxylin/eosin tissue sections. By triple immunohistochemical staining and
cell counting, perforin granules were found in 71% of the autoinvasive CD8+
T
cells that were also ICOS positive. Our data indicate that in sIBM there is
upregulation of ICOS.ICOS-L co-stimulatory signalling in association with
enhanced perforin expression by the autoinvasive CD8+ T cells. The findings
support previous suggestions that in IBM, the muscle fibres have the capacity
for antigen presentation, thereby activating a specific subset among the
autoinvasive CD8+ T cells to exert a cytotoxic effect. The observations
strengthen the immunopathogenesis of sIBM, and offer the basis for future
therapeutic interventions targeting ICOS.ICOS-L co-stimulatory interactions.
PMID: 15047591 [PubMed - indexed for MEDLINE]
50: Neuromuscul Disord. 2004 Apr;14(4):265-73.
Localization of the alpha-chemokine SDF-1 and its receptor CXCR4 in idiopathic
inflammatory myopathies.
De Paepe B, Schroder JM, Martin JJ, Racz GZ, De Bleecker JL.
Department of Neurology, Ghent University Hospital, De Pintelaan 185, B-9000
Ghent, Belgium.
We studied the distribution of stromal cell-derived factor 1 isoforms alpha
and
beta, and their receptor CXCR4, in polymyositis, sporadic inclusion body
myositis and dermatomyositis using in situ hybridization, immunohistochemistry,
immunofluorescence and Western blotting. In control muscle, polymyositis and
sporadic inclusion body myositis, stromal cell-derived factor-1alpha expression
was noted in muscle fibers, while stromal cell-derived factor-1beta and CXCR4
were predominantly localized to capillaries and arterioles. In dermatomyositis,
stromal cell-derived factor-1beta immunoreactivity of blood vessels was focally
increased. The vast majority of inflammatory cells in idiopathic inflammatory
myopathies were CXCR4 positive. A subset of helper T-cells and macrophages
expressed stromal cell-derived factor-1alpha, while only rare inflammatory cells
expressed stromal cell-derived factor-1beta. A significant increase of stromal
cell-derived factor-1alpha and CXCR4 was observed in protein extracts of
idiopathic inflammatory myopathies in comparison with normal controls. The
abundance of both CXCR4 and its ligand stromal cell-derived factor-1 implicates
their interaction in the pathogenesis of idiopathic inflammatory myopathies
and
identifies these proteins as possible targets for selective immune therapy.
PMID: 15019705 [PubMed - indexed for MEDLINE]
51: Neuromuscul Disord. 2004 Apr;14(4):246-52.
Childhood macrophagic myofasciitis-consanguinity and clinicopathological
features.
Nevo Y, Kutai M, Jossiphov J, Livne A, Neeman Z, Arad T, Popovitz-Biro R, Atsmon
J, Shapira Y, Soffer D.
The Institute for Child Development and Pediatric Neurology Unit, Tel Aviv
Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Beit
Habriut Strauss, 14 Balfour Street, Tel Aviv 65211, Israel.
nevo@tasmc.health.gov.il
Macrophagic myofasciitis has been almost exclusively detected in adults only.
We
describe six children of Arab Moslem origin with this disorder. Three presented
with hypotonia, developmental delay and seizures and were evaluated for a
mitochondrial disorder. The other three children had hypotonia and predominantly
motor delay. Five of the six families were consanguineous. A massive collection
of macrophages was present in the fascia and adjacent epimysium in all biopsies.
The macrophages were periodic-acid-Schiff positive and immunoreactive for CD68.
One biopsy which was evaluated by electron microscopy and energy-dispersive
X-ray microanalysis showed crystalline structures containing aluminum in
macrophages. Two children with motor delay and hypotonia were treated with oral
prednisone for 3 months with no clinical improvement. Genetic predisposition
probably accounts for the variability in the prevalence of macrophagic
myofasciitis in different populations. At least in childhood, there seems to
be
no connection between macrophagic myofasciitis as a pathological entity and
the
clinical symptoms and signs.
PMID: 15019702 [PubMed - indexed for MEDLINE]
52: Mol Genet Metab. 2004 Mar;81(3):196-202.
Hypoglycosylation of alpha-dystroglycan in patients with hereditary IBM due
to
GNE mutations.
Huizing M, Rakocevic G, Sparks SE, Mamali I, Shatunov A, Goldfarb L, Krasnewich
D, Gahl WA, Dalakas MC.
Medical Genetics Branch, National Human Genome Research Institute/NIH, Bethesda,
MD, USA.
Hereditary inclusion body myopathy (HIBM) is an adult onset neuromuscular
disorder associated with mutations in the gene
UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), whose
product is the rate limiting bi-functional enzyme catalyzing the first two steps
of sialic acid biosynthesis. Loss of GNE activity in HIBM is thought to impair
sialic acid production and interfere with proper sialylation of glycoconjugates,
but it remains unclear how such a defect would lead to muscle destruction and
muscle weakness. Hypoglycosylation of alpha-dystroglycan, a central protein
of
the skeletal muscle dystrophin-glycoprotein complex, results in disturbed
interactions with extracellular matrix proteins. This has recently been
identified as the pathomechanism involved in several congenital muscular
dystrophies. We examined the glycosylation status of alpha-dystroglycan in
muscle biopsies of four HIBM patients of non-Iranian Jewish origin (one
American, two Indians, and one Greek). Two of these patients carry novel
compound heterozygous GNE mutations on exon 2 and exon 9. All four muscle
biopsies showed absent or markedly reduced immunolabeling with two different
antibodies (VIA4 and IIH6) to glycosylated epitopes of alpha-dystroglycan.
Normal labeling was found using antibodies to the core alpha-dystroglycan
protein, beta-dystroglycan, and laminin alpha-2. These findings resemble those
found for other congenital muscular dystrophies, suggesting that HIBM may be
a
"dystroglycanopathy," and providing an explanation for the muscle
weakness of
patients with GNE mutations.
PMID: 14972325 [PubMed - indexed for MEDLINE]
53: Ann Rheum Dis. 2004 Mar;63(3):297-301.
Comment in:
Ann Rheum Dis. 2004 Aug;63(8):1005; discussion 1005-6.
Interstitial lung disease, a common manifestation of newly diagnosed polymyositis
and dermatomyositis.
Fathi M, Dastmalchi M, Rasmussen E, Lundberg IE, Tornling G.
Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet,
Stockholm, Sweden. Maryam.Fathi@ks.se
OBJECTIVES: To estimate the prevalence and predictors of interstitial lung
disease in newly diagnosed polymyositis and dermatomyositis. METHODS: A
prospective study in which consecutive patients with newly diagnosed poly- and
dermatomyositis, regardless of clinical symptoms of pulmonary disease, were
investigated with chest x ray, high resolution computed tomography (HRCT),
pulmonary function tests, and biochemical and autoantibody analysis. Patients
with inclusion body myositis, malignancy, other defined inflammatory connective
tissue diseases (CTDs), or antibody profile indicating other CTDs were excluded.
RESULTS: Between March 1998 and September 2000, 26 new cases of poly- or
dermatomyositis were diagnosed; 17 of those patients were included in the study.
Interstitial lung disease (ILD), defined as radiological signs on chest x ray
examination/HRCT or restrictive ventilatory defect, were found in 11 (65%)
patients and were more common in men than in women. Arthritis and occurrence
of
anti-Jo-1 antibodies were found more often in patients with ILD than in those
without. There was no statistically significant association between respiratory
symptoms, other serological or laboratory variables and ILD. CONCLUSIONS: ILD
is
a common early manifestation in patients with poly- and dermatomyositis and
is
not always related to clinical symptoms. Chest x ray examination, HRCT,
pulmonary function tests, and analysis of anti-Jo-1 antibodies should be
included in the initial investigation of patients with myositis regardless of
respiratory symptoms.
PMID: 14962966 [PubMed - indexed for MEDLINE]
54: Curr Treat Options Neurol. 2004 Mar;6(2):155-161.
Inflammatory Myopathies.
Grogan PM, Katz JS.
Department of Neurology, Wilford Hall Medical Center, 2200 Bergquist Drive,
Suite 1,San Antonio, TX 78236, USA.
Therapies that suppress or modify the immune system remain the primary treatment
for the idiopathic inflammatory myopathies. Dermatomyositis (DM) and
polymyositis (PM) are the two conditions that respond best to immunotherapy.
Although there are no randomized controlled trials, corticosteroids,
specifically high-dose oral prednisone, remain the cornerstone of management.
Recent controlled clinical trials show that intravenous immunoglobulin (IVIg)
is
an efficacious treatment in DM. Expert clinicians are generally using this as
a
second-line agent or as an adjunct to prednisone. IVIg has a relatively benign
side effect profile compared with chronic steroid use, but the cost of
treatment, the need for repetitive treatment cycles, and the potential for
serious adverse effects have kept it from being a first-line agent in DM. There
have been no trials performed using IVIg in PM. Chronic immunosuppressant
medications, including azathioprine, cyclosporine, and methotrexate, are also
available for long-term management in patients with recalcitrant disease or
side
effects from extended corticosteroid use. These agents lack the troubling side
effects of prednisone and are less costly than IVIg, but require close medical
monitoring for adverse reactions to blood, kidney, lung, or liver. Newer
medications with potentially more benign side effect profiles, such as
mycophenolate mofetil and etanercept, are currently being studied, but knowledge
of how effective they are and how quickly they work are not yet available.
Inclusion body myositis has proven resistant to immunosuppressive medications.
The response has been so consistently poor and so easily contrasted with DM
that
the authors wonder why these conditions are so routinely lumped together in
chapters and review articles. Clearly, this is based solely on the common
pathologic feature of inflammation, rather than a clear understanding of how
these conditions occur, or why they do or do not respond to treatment.
PMID: 14759347 [PubMed - as supplied by publisher]
55: Muscle Nerve. 2004 Feb;29(2):261-6.
Overexpression of semicarbazide-sensitive amine oxidase in human myopathies.
Olive M, Unzeta M, Moreno D, Ferrer I.
Institut de Neuropatologia, Hospital Universitari de Bellvitge, 08907 Hospitalet
de Llobregat, Barcelona, Spain. 25169mop@comb.es
Oxidative stress has been implicated in the pathogenesis of several muscle
diseases. Semicarbazide-sensitive amine oxidase (SSAO) metabolizes oxidative
deamination of primary aromatic and aliphatic amines. In the oxidative
reactions, amine substrates are converted into the aldehyde, followed by the
production of ammonia and H(2)O(2). Although normal levels in muscle are very
low, SSAO is expressed in almost all mammalian tissues. In this study, we
examined the possible implication of SSAO as an additional source of oxidative
stress in the pathogenesis of muscle disorders. The expression of SSAO was
examined immunohistochemically in muscle biopsy specimens from patients with
inclusion-body myositis (IBM; n = 5), desmin-related myopathy (DRM; n = 3),
dermatomyositis (n = 3), granulomatous (sarcoid) myopathy (n = 2), muscle
denervation-reinnervation (n = 3), and rhabdomyolysis (n = 2), as well as from
control subjects (n = 3). Strong SSAO immunoreactivity was present in vacuolated
and nonvacuolated fibers in IBM, in abnormal fibers in DRM, and in degenerating
and regenerating fibers in dermatomyositis and rhabdomyolysis. In addition,
SSAO
overexpression was observed in muscle fibers adjacent to granulomas in sarcoid
myopathy. These results suggest that SSAO is a source of oxidative stress in
diseased human skeletal muscle and that it contributes to oxidative
stress-induced damage in various inflammatory and other myopathies.
Alternatively, the expression of SSAO in muscle fibers may be a consequence
of
muscle fiber injury.
PMID: 14755492 [PubMed - indexed for MEDLINE]
56: Immunol Allergy Clin North Am. 2003 Nov;23(4):699-712.
Aluminum inclusion macrophagic myofasciitis: a recently identified condition.
Gherardi RK, Authier FJ.
Muscle and Nerve Group, Henri Mondor University Hospital, Creteil, France.
lauret@univ-paris12.fr
The authors conclude that the persistence of aluminum hydroxide at the site
of
intramuscular injection is a novel finding which has an exact significance that
remains to be established fully. It seems mandatory to evaluate possible
long-term adverse effects induced by this compound, because this issue has not
been addressed (in the past, aluminum hydroxide was believed to be cleared
quickly from the body). If safety concerns about the long-term effects of
aluminum hydroxide are confirmed, novel and alternative vaccine adjuvants to
rescue vaccine-based strategies should be proposed to ensure the enormous
benefit for public health that these vaccines provide worldwide.
Publication Types:
Review
Review, Tutorial
PMID: 14753387 [PubMed - indexed for MEDLINE]
57: Arch Neurol. 2004 Jan;61(1):132-5.
Polymyositis: an ongoing discussion about a disease entity.
Bronner IM, Linssen WH, van der Meulen MF, Hoogendijk JE, de Visser M.
Department of Neurology, Sint Lucas Andreas Hospital, Jan Tooropstraat 164,
1061
AE Amsterdam, the Netherlands. i.bronner@slaz.nl
Since its first description more than a century ago, there has been much debate
about the diagnostic entity polymyositis. Because initial observations were
of
individuals with dermatomyositis, it appeared that polymyositis was not possible
without skin lesions. Distinctive clinical and histologic features of
polymyositis were not established until the late 20th century. The
identification of inclusion body myositis as a distinct entity has further
refined nosographic classification.
Publication Types:
Historical Article
PMID: 14732633 [PubMed - indexed for MEDLINE]
58: Acta Neuropathol (Berl). 2004 Mar;107(3):197-203. Epub 2004 Jan 08.
Coexistence of X-linked recessive Emery-Dreifuss muscular dystrophy with
inclusion body myositis-like morphology.
Fidzianska A, Rowinska-Marcinska K, Hausmanowa-Petrusewicz I.
Neuromuscular Unit, MRC, Polish Academy of Science, 1a Banacha Str., 02-097
Warsaw, Poland. neurmyol@cmdik.pan.pl
We reported three cases (two familial and one sporadic) of X-linked
Emery-Dreifuss muscular dystrophy (EDMD), genetically documented. Two patients
demonstrated a typical inclusion body myositis (IBM)-like morphology. The third
patient had only minor changes. Patients had elbow and ankle contractures,
progressive wasting of humeroperoneal muscles and cardiac failure (pacemaker
implantation in all). There was a mutation within the Xq28 gene and complete
absence of emerin in the nuclear membrane. Mononuclear cell infiltrations,
rimmed vacuoles, amyloid deposits, as well as cytoplasmic and nuclear
tubulofilamentous muscle inclusions were most unusual findings. Coexistence
of
IBM-like morphology and X-linked recessive EDMD might indicate that pathological
features of IBM are nonspecific and may be present in other neuromuscular
disorders.
PMID: 14712398 [PubMed - indexed for MEDLINE]
59: J Neurol Neurosurg Psychiatry. 2004 Jan;75(1):136-9.
Diagnostic value of MHC class I staining in idiopathic inflammatory myopathies.
van der Pas J, Hengstman GJ, ter Laak HJ, Borm GF, van Engelen BG.
Neuromuscular Centre, Institute of Neurology, University Medical Centre,
Nijmegen, Netherlands.
BACKGROUND: Identification of mononuclear cellular infiltrates in skeletal
muscle tissue is the histological cornerstone of the diagnosis of idiopathic
inflammatory myopathy (IIM). However, these infiltrates are not always present.
OBJECTIVE: To determine whether MHC class I antigen expression on the
sarcolemma, which is absent in normal muscle tissue, is upregulated in IIM and
could serve as an additional diagnostic test. METHODS: Expression of MHC class
I
antigens was studied in 224 muscle samples of 61 adult patients with IIM (9
dermatomyositis, 23 polymyositis, 29 inclusion body myositis) and 163 controls
(normal subjects and patients with various neuromuscular disorders) in a
prospective blinded manner. RESULTS: The sensitivity of the test for diagnosing
IIM was 78% (95% confidence interval (CI), 66% to 88%), with a specificity of
95% (91% to 98%). The sensitivity before the start of immunosuppressive
treatment was 89% (76% to 96%). The sensitivity was not changed by including
all
patients who had been on immunosuppressive treatment for less than four weeks
before muscle biopsy (sensitivity 90% (79% to 97%)). False positive results
were
found in only seven controls (4%), six of whom had a muscular dystrophy.
CONCLUSIONS: Detection of sarcolemmal MHC class I is a valid test for IIM. It
is
not affected by the short term use of immunosuppressive agents (less than four
weeks) and it should be incorporated in the histological evaluation when the
diagnosis of IIM is under consideration or needs to be excluded.
Publication Types:
Clinical Trial
PMID: 14707323 [PubMed - indexed for MEDLINE]
60: Ann Neurol. 2004 Jan;55(1):121-5.
Creutzfeldt-Jakob disease and inclusion body myositis: abundant
disease-associated prion protein in muscle.
Kovacs GG, Lindeck-Pozza E, Chimelli L, Araujo AQ, Gabbai AA, Strobel T, Glatzel
M, Aguzzi A, Budka H.
Institute of Neurology, University of Vienna, and Austrian Reference Centre
for
Human Prion Diseases, Vienna, Austria.
Pathologicalprion protein (PrP(Sc)) is the hallmark of prion diseases affecting
primarily the central nervous system. Using immunohistochemistry,
paraffin-embedded tissue blot, and Western blot, we demonstrated abundant
PrP(Sc) in the muscle of a patient with sporadic Creutzfeldt-Jakob disease and
inclusion body myositis. Extraneural PrP(C)-PrP(Sc) conversion in
Creutzfeldt-Jakob disease appears to become prominent when PrP(C) is abundantly
available as substrate, as in inclusion body myositis muscle.
Publication Types:
Case Reports
PMID: 14705121 [PubMed - indexed for MEDLINE]
61: Am J Pathol. 2004 Jan;164(1):1-7.
Endoplasmic reticulum stress and unfolded protein response in inclusion body
myositis muscle.
Vattemi G, Engel WK, McFerrin J, Askanas V.
Department of Neurology, University of Southern California Neuromuscular Center,
University of Southern California Keck School of Medicine, Good Samaritan
Hospital, Los Angeles, California 90017-1912, USA.
Proteins in the endoplasmic reticulum (ER) require an efficient system of
molecular chaperones whose role is to assure their proper folding and to prevent
accumulation of unfolded proteins. The response of cells to accumulation of
unfolded proteins in the ER is termed "unfolded protein response"
(UPR). UPR is
a functional mechanism by which cells attempt to protect themselves against
ER
stress, resulting from the accumulation of the unfolded/misfolded proteins.
Because intracellular inclusions, containing either amyloid-beta (Abeta) or
phosphorylated tau, are the characteristic feature of sporadic inclusion body
myositis (s-IBM) muscle biopsies, we studied expression and immunolocalization
of five ER chaperones, calnexin, calreticulin, GRP94, BiP/GRP78, and ERp72,
in
s-IBM and control muscle biopsies. Physical interaction of the ER chaperones
with amyloid-beta precursor protein (AbetaPP) was studied by a combined
immunoprecipitation/immunoblotting technique in s-IBM and control muscle
biopsies, and in AbetaPP-overexpressing cultured human muscle fibers. In all
s-IBM muscle biopsies, all five of the ER chaperones were immunodetected in
the
form of inclusions that co-localized with amyloid-beta. By immunoblotting,
expression of ER chaperones was greatly increased as compared to the controls.
By immunoprecipitation/immunoblotting experiments, ER chaperones
co-immunoprecipitated with AbetaPP. Our studies provide evidence of the UPR
in
s-IBM muscle and demonstrate for the first time that the ER chaperones calnexin,
calreticulin, GRP94, BiP/GRP78, and ERp72 physically associate with AbetaPP
in
s-IBM muscle, suggesting their playing a role in AbetaPP folding and processing.
PMID: 14695312 [PubMed - indexed for MEDLINE]
62: Neuromuscul Disord. 2003 Dec;13(10):830-4.
A novel homozygous missense mutation in the GNE gene of a patient with
quadriceps-sparing hereditary inclusion body myopathy associated with muscle
inflammation.
Krause S, Schlotter-Weigel B, Walter MC, Najmabadi H, Wiendl H, Muller-Hocker
J,
Muller-Felber W, Pongratz D, Lochmuller H.
Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians
University, Munich, Germany.
An adult-onset hereditary inclusion body myopathy with sparing of the quadriceps
muscle was originally described in Iranian Jews and assigned to a locus on
chromosome 9p12-p13. Recently, mutations of the
UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene were
reported to cause hereditary inclusion body myopathy and one type of distal
myopathy in a world-wide distribution. Importantly, the lack of muscle
inflammation was used to distinguish hereditary inclusion body myopathy from
the
sporadic form of inclusion body myopathy. We report a case of a
quadriceps-sparing myopathy in a non-Jewish, Iranian patient with a high degree
of muscle inflammation. A novel homozygous G-to-A mutation (128933G-->A)
in exon
7 changing a valine to isoleucine (V367I) in the epimerase domain of the GNE
gene was found. We conclude that muscle inflammation is not sufficient to
exclude the diagnosis of hereditary inclusion body myopathy.
Publication Types:
Case Reports
PMID: 14678807 [PubMed - indexed for MEDLINE]
63: J Neurol. 2003 Nov;250(11):1313-7.
Analysis of HLA class I and II alleles in sporadic inclusion-body myositis.
Lampe JB, Gossrau G, Kempe A, Fussel M, Schwurack K, Schroder R, Krause S,
Kohnen R, Walter MC, Reichmann H, Lochmuller H.
Klinik fur Neurologie, Technische Universitat Dresden, Fetscherstrasse 74,
01307, Dresden, Germany. johannes.lampe@schering.de
Sporadic inclusion body myositis (s-IBM) is characterised by progressive
weakness of proximal and distal limb muscles. Most patients are aged over 50
years at disease onset. Muscle biopsy reveals an inflammatory myopathy and
cytoplasmic amyloid deposits. The mononuclear infiltrate is dominated by CD8+
T-cells. Several investigators have described associations between s-IBM and
certain HLA antigens and alleles. However, to date neither HLA class I nor II
alleles have been analysed in a large series of patients. We typed various HLA
class I and II alleles in 47 patients suffering from s-IBM using sequence
specific-primer pairs (SSPPCR). The results were compared with published German
controls. Additional Bonferroni adjustment was performed over all allele groups
corresponding to serologically defined antigens within one HLA class I or II
locus. After Bonferroni adjustment, we found a significant increase in frequency
of the following HLA alleles for s-IBM patients when compared with normal
controls: A*03 (p = 0.0002), B*08 (p = 0.002), DRB1*03 (p = 0.0000002), and
DQB1*05 (p = 0.02). HLA typing may be helpful to distinguish between subgroups
of s-IBM patients. Moreover, HLA analysis may aid in identifying patients who
might profit from future therapeutic strategies.
PMID: 14648147 [PubMed - indexed for MEDLINE]
64: Lancet. 2003 Nov 22;362(9397):1762-3; author reply 1763.
Comment on:
Lancet. 2003 Sep 20;362(9388):971-82.
Diagnostic criteria for polymyositis and dermatomyositis.
Miller FW, Rider LG, Plotz PH, Isenberg DA, Oddis CV.
Publication Types:
Comment
Letter
PMID: 14643132 [PubMed - indexed for MEDLINE]
65: Muscle Nerve. 2003 Dec;28(6):659-82.
Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies.
Figarella-Branger D, Civatte M, Bartoli C, Pellissier JF.
Laboratoire de Biopathologie Nerveuse et Musculaire (EA 3281), Faculte de
Medecine Timone, Universite de la Mediterranee, 27 Boulevard Jean Moulin, 13385
Marseille, France. Dominique.Figarella-Branger@medecine.univ-mrs.fr
The inflammatory myopathies include dermatomyositis (DM), polymyositis (PM),
and
sporadic inclusion-body myositis (s-IBM). In DM, the main immune effector
response appears to be humoral and directed against the microvasculature,
whereas in both PM and s-IBM, cytotoxic CD8+ T cells and macrophages invade
and
eventually destroy nonnecrotic muscle fibers expressing major histocompatibility
complex class I. The need for more specific and safer therapies in inflammatory
myopathies has prompted researchers to better decipher the molecular events
associated with inflammation and muscle fiber loss in these diseases. The
complex specific migration of leukocyte subsets to target tissues requires a
coordinated series of events, namely activation of leukocytes, adhesion to the
vascular endothelium, and migration. Cell adhesion molecules (CAM) and
chemokines play a major role in this multistep process. In addition, cytokines
by stimulating CAM expression and orchestrating T-cell differentiation also
influence the immune response. This review focuses on recent advances in
defining the molecular events involved in leukocyte trafficking in inflammatory
myopathies. Specific topics include a concise summary of clinical features,
pathological findings and immunopathology observed in inflammatory myopathies,
background information about cytokines, chemokines and cell adhesion molecules,
and the expression of these molecules in inflammatory myopathies.
Publication Types:
Review
PMID: 14639580 [PubMed - indexed for MEDLINE]
66: Eur Neurol. 2004;51(1):10-4. Epub 2003 Nov 18.
Increase in transglutaminase 2 in idiopathic inflammatory myopathies.
Choi YC, Kim TS, Kim SY.
Department of Neurology, Brain Korea 21 Project for Medicine, Yonsei University,
College of Medicine, Seoul, Republic of Korea. ycchoi@yumc.yonsei.ac.kr
Idiopathic inflammatory myopathies (IMs), including dermatomyositis (DM),
polymyositis (PM), and sporadic inclusion body myositis (s-IBM), are
characterized by inflammatory cell infiltration in muscle tissue and muscle
fiber destruction, which leads to muscle weakness. Although the cause of IMs
is
unclear, an autoimmune pathogenesis may be involved in initiating the muscle
inflammation. Recently, we have found an aberrant expression of transglutaminase
2 (TGase 2) in s-IBM, which is closely associated with insoluble inclusion body
formation. TGase 2 is a cross-linking enzyme that generates a conformational
change of molecules via a covalent isopeptide bond. The increase in the level
of
TGase 2 expression and the inappropriate presentation of substrates/cross-linked
aggregates to the immune system may contribute to the autoimmune aspects of
IMs.
We investigated whether or not an increase in TGase 2 expression is a common
factor in muscle inflammation. Duchenne muscular dystrophy (DMD) and normal
tissues were employed as controls. Using immunocytochemistry and quantitative
RT-PCR, the level of TGase 2 expression was found to be specifically increased
in PM and DM, but not in DMD and normal controls. Therefore, the targeting of
TGase inhibition in IMs will be a challenging therapeutic approach that should
be investigated in the near future. Copyright 2004 S. Karger AG, Basel
PMID: 14631123 [PubMed - indexed for MEDLINE]
67: Intern Med. 2003 Oct;42(10):1035-8.
Comment in:
Intern Med. 2003 Oct;42(10):928-9.
Familial inclusion body myositis: a report on two Japanese sisters.
Tateyama M, Saito N, Fujihara K, Shiga Y, Takeda A, Narikawa K, Hasegawa T,
Taguchi Y, Sakuma R, Onodera Y, Ohnuma A, Tobita M, Itoyama Y.
Department of Neurology, Tohoku University School of Medicine, Sendai.
Familial occurrence of inclusion body myositis is extremely rare, and only
a few
cases in Western countries have been reported. In these reports, a strong
association of this disease with DR3 (DRB1*0301/0302) and the efficacy of
immunosuppressants suggested that an immune pathomechanism is involved in the
disease. We, for the first time, report two Japanese sisters who suffered
myopathy clinicopathologically similar to inclusion body myositis. One sister
received corticosteroid and azathioprine and the therapy relieved dysphagia.
Both of our patients had DR15(2)/4 (DRB1*1502/0405), suggesting a distinct
genetic association with the disease in the Japanese population.
Publication Types:
Case Reports
PMID: 14606722 [PubMed - indexed for MEDLINE]
68: Intern Med. 2003 Oct;42(10):928-9.
Comment on:
Intern Med. 2003 Oct;42(10):1035-8.
The familial occurrence may give a clue to the pathogenesis of inclusion body
myositis.
Mizusawa H.
Publication Types:
Comment
Editorial
PMID: 14606702 [PubMed - indexed for MEDLINE]
69: Neurol Sci. 2003 Oct;24 Suppl 4:S256-9.
High-dose intravenous immunoglobulin in inflammatory myopathies: experience
based on controlled clinical trials.
Dalakas MC.
Neuromuscular Diseases, Section National Institute of Neurological Disorders
and
Stroke National Institutes of Health, Bethesda, MD 20892-1382, USA.
Controlled clinical trials with high-dose intravenous immunoglobulin (IVIg)
have
been conducted in patients with DM and IBM, but not PM. A double-blind
placebo-controlled study in DM patients, resistant or partially responsive to
conventional therapies, showed that IVIg is very effective in improving both
the
muscle strength and the skin rash. The clinical benefit, which was impressive
in
patients with early disease, was associated with improvement in the muscle
cytoarchitecture. Quantitative histological studies in repeated muscle biopsies
showed a statistically significant increased in the size of muscle fibers and
the number of capillaries with normalization of the capillary diameter.
Resolution of the aberrant immunopathological parameters including interception
of complement activation products and downregulation of T cells, ICAM-I, VCAM,
TGF-beta and MHC-I molecules was also noted. In IBM, IVIg showed marginal, and
non statistically significant, improvements in muscle strength. Up to 20% of
patients however, demonstrated clinical improvement with increased activities
of
daily living while certain muscle groups, such as the muscles of swallowing,
showed significant improvements compared to placebo implying mild regional
benefits. In PM, small uncontrolled series have shown improvements in muscle
strength in up to 70% of the IVIg-treated patients. Because PM, as a stand-alone
clinical entity, is a very rare disease, completion of controlled trials will
be
very difficult.
Publication Types:
Review
Review, Tutorial
PMID: 14598055 [PubMed - indexed for MEDLINE]
70: Clin Rheumatol. 2003 Oct;22(4-5):324-8.
Inclusion body myositis in connective tissue disorders: case report and review
of the literature.
Derk CT, Vivino FB, Kenyon L, Mandel S.
Thomas Jefferson University Hospital, Pennsylvania, Philadelphia, USA.
chris.derk@mail.tju.edu
We report a patient with systemic lupus erythematosus (SLE) and secondary
Sjogren's syndrome (SS) who developed inclusion body myositis (IBM) which,
contrary to the typical presentation of this disorder, was symmetrical in nature
although the diagnosis was only made after electron microscopy was performed.
Therapy with increased doses of methotrexate proved to be beneficial, with the
patient having full recovery after 8 months of therapy. It appears that a subset
of IBM may be related to autoimmune disorders, an issue that was disputed in
the
past, and these patients may have a better prognosis than typical IBM patients.
This is the first case report of IBM in a patient who had the dual diagnosis
of
SLE and SS.
Publication Types:
Case Reports
Review
Review of Reported Cases
PMID: 14576992 [PubMed - indexed for MEDLINE]
71: Curr Opin Rheumatol. 2003 Nov;15(6):737-44.
Proposed pathogenetic cascade of inclusion-body myositis: importance of
amyloid-beta, misfolded proteins, predisposing genes, and aging.
Askanas V, Engel WK.
Department of Neurology, University of Southern California, Keck School of
Medicine, Good Samaritan Hospital, Los Angeles, California 90017-1912, USA.
askanas@hsc.usc.edu
PURPOSE OF REVIEW: Sporadic inclusion-body myositis, the most common muscle
disease of older persons, is of unknown cause, and there is no successful
treatment. Interest in sporadic inclusion-body myositis has been enhanced by
the
recent identification within the sporadic inclusion-body myositis muscle fibers
of several abnormally accumulated proteins, which provides novel and important
clues to the pathogenesis of sporadic inclusion-body myositis. RECENT FINDINGS:
This article summarizes the most recent findings leading to better understanding
of the players in the pathogenetic cascade. It is suggested that lymphocytic
inflammatory component is probably secondary, and it may contribute only
slightly to muscle fiber damage in sporadic inclusion-body myositis. However,
it
is proposed that the identified abnormal accumulation, aggregation, and
misfolding of proteins, combined with and perhaps provoked by an aging
intracellular milieu, more essentially lead to the vacuolar degeneration and
atrophy of the muscle fibers that are specific to sporadic inclusion-body
myositis. Abnormal accumulations of the amyloid-beta precursor protein and of
its proteolytic fragment, amyloid-beta, associated with the aging cellular
muscle fiber environment, appear to be key pathogenic events. SUMMARY: In
conceptualizing a treatment for sporadic inclusion-body myositis, the
accumulations of amyloid-beta42 and other unfolded proteins are now phenomena
to
be reckoned with. One would like to stop intracellular increase of the
unfolded/misfolded proteins by reducing their formation and/or increasing their
disposal. In addition, the identification of factors that would decrease
intra-muscle fiber expressions of beta- and gamma-secretases might lead to
decreased production of putatively myotoxic oligomeric amyloid-beta42. Better
understanding of the mechanisms and consequences of genes that predispose to
sporadic inclusion-body myositis, and of human muscle fiber aging, could also
provide new avenues toward the therapy of sporadic inclusion-body myositis.
How
to therapeutically capitalize on the new findings is now the challenge.
Publication Types:
Review
Review, Tutorial
PMID: 14569203 [PubMed - indexed for MEDLINE]
72: Curr Opin Rheumatol. 2003 Nov;15(6):679-90.
Physical activity and disablement in the idiopathic inflammatory myopathies.
Harris-Love MO.
Rehabilitation Medicine Department, National Institute of Health, Bethesda,
MD
20892, USA. mlove@nih.gov
PURPOSE OF REVIEW: The sequelae associated with idiopathic inflammatory myopathy
(IIM) often result in disability and decreased quality of life. Our
understanding of how exercise mitigates disability may be facilitated through
the use of a conceptual model. This review describes the enablement-disablement
model applied to myositis and explores the role of physical activity in the
enablement process. RECENT FINDINGS: National and international organizations
have revised their disablement models by acknowledging disability as a
relational concept, refining the relationship of disability to quality of life,
and incorporating the role of intervention through the enablement process.
Disability associated with IIM may be complicated by aging-related comorbidities
and decreased physical activity. However, data indicate that both short-term
and
long-term aerobic training results in improved aerobic capacity and decreased
disability in adults with IIM. Strengthening regimens have also resulted in
decreased functional limitations and disability for adults with polymyositis
and
dermatomyositis. While comprehensive exercise programs have not been shown to
exacerbate disease activity or damage in people with IIM, their effectiveness
for individuals with inclusion body myositis (IBM) remains uncertain. SUMMARY:
Physical activity constitutes a valuable enablement strategy that can reduce
disability in adults with IIM. Use of the disablement-enablement model and ICF
taxonomy in conjunction with outcomes across disablement domains may augment
further investigation of the effectiveness of exercise interventions. Additional
research is needed to better understand the relationship between disease
severity and optimal exercise dosage, the effects of long-term exercise in
children with IIM, and the physiologic response to exercise in people with IBM.
Publication Types:
Review
Review, Tutorial
PMID: 14569196 [PubMed - indexed for MEDLINE]
73: Eur Neurol. 2003;50(3):172-5.
Therapy with intravenous immunoglobulins: complications and side-effects.
Wittstock M, Benecke R, Zettl UK.
Department of Neurology, University of Rostock, Rostock, Germany.
matthias.wittstock@med.uni-rostock.de
Therapy with intravenous immunoglobulins (IVIG) is thought to be a safe
treatment for a number of immune-mediated neurological diseases. Published data
about prevalence of adverse effects range from 11 to 81%. The purpose of our
study was to present a representative view on adverse effects by analysis of
a
large cohort of patients treated by IVIG. In a prospective study, we analysed
117 patients (age 17-79 years) who were treated with IVIG for various
neurological diseases including chronic inflammatory demyelinating
polyneuropathy, diabetic amyotrophy, inclusion body myositis, multiple
sclerosis, Guillain-Barre syndrome, Miller-Fisher syndrome, multifocal motor
neuropathy, myasthenia gravis and polymyositis. IVIG therapy was applied at
a
dose of 0.4 g/kg body weight/day in a total of 408 therapy courses. 42.7% showed
adverse events. The majority of patients presented with minor adverse effects,
mostly asymptomatic laboratory changes. Rash or mild headache occurred in 8
patients, especially when IVIG was given with infusion flow higher than 10 g/h.
Two patients showed a severe complication with deep vein thrombosis. In summary,
beside its effectiveness in immune mediated neurological diseases, therapy with
IVIG seems to be a safe therapy. Most patients show no or minor adverse effects.
Patients with pre-existent disorders like heart or renal insufficiency or
immobilised patients, however, may be at higher risk for complications.
Copyright 2003 S. Karger AG, Basel
PMID: 14530624 [PubMed - indexed for MEDLINE]
74: Acta Neuropathol (Berl). 2004 Jan;107(1):59-65. Epub 2003 Sep 26.
Expression of lysosome-related proteins and genes in the skeletal muscles of
inclusion body myositis.
Kumamoto T, Ueyama H, Tsumura H, Toyoshima I, Tsuda T.
Division of Neurology and Neuromuscular Disorders, Department of Immunology
and
Allergy, Oita Medical University, Idaigaoka 1-1, Hasama, 879-5593, Oita, Japan.
kumagoro@oita-med.ac.jp
Despite the unknown etiology and pathogenesis of sporadic inclusion body
myositis (s-IBM), investigators have speculated that the lysosome system in
muscle fiber plays a central role in rimmed vacuole formation, a hallmark of
s-IBM. We explored the role of receptor-mediated intracellular transport and
autophagy in the lysosomal system in the abnormal accumulation of rimmed
vacuoles in s-IBM. Expressions of mannose 6-phosphate receptor (M6PR), clathrin
and hApg5 and hApg12 were analyzed in muscle biopsy specimens from patients
with
s-IBM, amyotrophic lateral sclerosis (ALS) or peripheral neuropathy and in
normal human muscle specimens by means of immunohistochemistry and reverse
transcriptase-polymerase chain reaction (RT-PCR). Most muscle fibers in control
specimens showed little or no immunoreactivity for clathrin and M6PR, which
are
involved in the receptor-mediated intracellular transport. Abnormal increases
in
both proteins were observed mainly in the sarcoplasm of atrophic fibers in all
diseased specimens. In s-IBM muscles in particular, clathrin and M6PR were often
observed inside rimmed vacuoles and in the sarcoplasm of vacuolated or
non-vacuolated fibers. mRNA levels of hApg5 and hApg12, which are involved in
autophagic vacuole formation, as well as of M6PR and clathrin were significantly
increased in s-IBM muscles in comparison to levels in normal and ALS/peripheral
neuropathy muscles. Our results suggest that the transport of newly synthesized
lysosomal enzymes from the secretory pathway via the trans-Golgi network of
the
Golgi apparatus and autophagic vacuole formation (i.e., autophagy) in the
lysosome system are activated in s-IBM muscles. Remarkable accumulation of
rimmed vacuoles is thought to occur because of abnormal lysosome function,
especially the formation or turnover of autolysosomes after the fusion of
autophagic vacuoles with the early endosomes or because of the increase in the
rate of muscle fiber breakdown.
PMID: 14513262 [PubMed - indexed for MEDLINE]
75: Lancet. 2003 Sep 20;362(9388):971-82.
Comment in:
Lancet. 2003 Nov 22;362(9397):1762-3; author reply 1763.
Polymyositis and dermatomyositis.
Dalakas MC, Hohlfeld R.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, MD 20892-1382, USA.
dalakasm@ninds.nih.gov
The inflammatory myopathies, commonly described as idiopathic, are the largest
group of acquired and potentially treatable myopathies. On the basis of unique
clinical, histopathological, immunological, and demographic features, they can
be differentiated into three major and distinct subsets: dermatomyositis,
polymyositis, and inclusion-body myositis. Use of new diagnostic criteria is
essential to discriminate between them and to exclude other disorders.
Dermatomyositis is a microangiopathy affecting skin and muscle; activation and
deposition of complement causes lysis of endomysial capillaries and muscle
ischaemia. In polymyositis and inclusion-body myositis, clonally expanded
CD8-positive cytotoxic T cells invade muscle fibres that express MHC class I
antigens, which leads to fibre necrosis via the perforin pathway. In
inclusion-body myositis, vacuolar formation with amyloid deposits coexists with
the immunological features. The causative autoantigen has not yet been
identified. Upregulated vascular-cell adhesion molecule, intercellular adhesion
molecule, chemokines, and their receptors promote T-cell transgression, and
various cytokines increase the immunopathological process. Early initiation
of
therapy is essential, since both polymyositis and dermatomyositis respond to
immunotherapeutic agents. New immunomodulatory agents currently being tested
in
controlled trials may prove promising for difficult cases.
Publication Types:
Review
PMID: 14511932 [PubMed - indexed for MEDLINE]
76: Curr Opin Neurol. 2003 Oct;16(5):569-75.
Treatment of idiopathic inflammatory myopathies.
Amato AA, Griggs RC.
Department of Neurology, Brigham and Women's Hospital and Harvard Medical
School, Boston, Massachusetts 02115, USA. aamato@partners.org
PURPOSE OF REVIEW: This article reviews the results of recent therapeutic trials
in dermatomyositis, polymyositis, and inclusion body myositis and suggests an
approach to treating patients with inflammatory myopathy. RECENT FINDINGS: We
reviewed 10 double-blind, placebo-controlled therapeutic trials in patients
with
inflammatory myopathy. Only one, using intravenous immunoglobulin in refractory
dermatomyositis, indicated benefit. A brief trial of azathioprine in
polymyositis and eight studies using various treatments in inclusion body
myositis did not show benefit. SUMMARY: There have been no adequate
double-blind, placebo-controlled therapeutic trials of dermatomyositis and
polymyositis. It is generally accepted, however, that these disorders respond
to
immunosuppressive agents. Prednisone is usually the initial treatment. There
is
no agreement on how prednisone should be administered and even less agreement
about other agents. Inclusion body myositis, which now appears to be the most
common (in adults), is unresponsive to immunosuppressive and immunomodulating
therapies. There are candidate treatments for inclusion body myositis and a
need
for additional double-blind, placebo-controlled therapeutic trials in all
patients with inflammatory myopathy.
Publication Types:
Review
Review, Tutorial
PMID: 14501840 [PubMed - indexed for MEDLINE]
77: J Neuroimmunol. 2003 Aug;141(1-2):125-31.
Expression of IFN-gamma-inducible chemokines in inclusion body myositis.
Raju R, Vasconcelos O, Granger R, Dalakas MC.
National Institute of Neurological Disorders and Stroke, National Institutes
of
Health, Bethesda, MD 20892-1382, USA.
Because IFN-gamma-inducible chemokines, Mig (CXCL9), IP-10 (CXCL10), I-TAC
(CXCL11) and their receptor, CXCR3, are critical molecules in T cell trafficking
and generation of effector T cells, we examined their expression in the muscle
biopsies of patients with sporadic inclusion body myositis (s-IBM) and disease
controls. The functional role of these molecules was also studied by examining
the effect and time kinetics of IFN-gamma in inducing Mig and IP-10 expression
in human myotubes in vitro. We found significantly high levels of Mig and IP-10
mRNA expression in s-IBM muscles compared to controls. IFN-gamma upregulated
the
mRNA expression of Mig and IP-10 by human myotubes in a dose-dependent manner.
By double-label immunohistochemistry, Mig was expressed on a subset of CD8(+)
cells and the areas of the muscle fiber in contact or contiguous to the T cells;
CXCR3 was expressed only on a subset of the autoinvasive CD8(+) T cells but
not
the myofibers. IP-10 and I-TAC were not detected by immunocytochemistry. The
findings indicate that in s-IBM, IFN-gamma is involved in the upregulation and
in situ production of proinflammatory chemokines, which, in turn, participate
in
the recruitment of activated T cells and contribute to the self-sustaining
nature of endomysial inflammation.
PMID: 12965263 [PubMed - indexed for MEDLINE]
78: South Med J. 2003 Jul;96(7):721-3.
Inclusion body myositis associated with celiac sprue and idiopathic
thrombocytopenic purpura.
Williams SF, Mincey BA, Calamia KT.
Division of General Internal Medicine, Mayo Clinic Jacksonville, Jacksonville,
FL 32224, USA.
We report an unusual case of a 51-year-old woman with inclusion body myositis
associated with celiac sprue and idiopathic thrombocytopenic purpura. We propose
that the presence of all three disorders together suggests that they may share
an interrelated immune mechanism.
Publication Types:
Case Reports
PMID: 12940332 [PubMed - indexed for MEDLINE]
79: Am J Pathol. 2003 Sep;163(3):947-56.
Erratum in:
Am J Pathol. 2003 Dec;163(6):2645.
Expression of calcium-binding proteins MRP8 and MRP14 in inflammatory muscle
diseases.
Seeliger S, Vogl T, Engels IH, Schroder JM, Sorg C, Sunderkotter C, Roth J.
Institute of Experimental Dermatology, Department of Pediatrics, University
Hospital, Aachen, Germany.
The pathophysiological role of infiltrating macrophages and their subtypes
in
idiopathic inflammatory myopathies such as dermatomyositis, polymyositis, and
inclusion body myositis is not fully clear. Monocytes exhibit various phenotypes
with different functional properties such as release of pro- or
anti-inflammatory mediators. Expression of myeloid-related proteins MRP8 and
MRP14, two calcium-binding S100-proteins, characterizes a proinflammatory
subtype of macrophages. We immunohistochemically investigated expression of
MRP8
and MRP14 in muscle biopsies of 33 patients with dermatomyositis, polymyositis,
and inclusion body myositis. We found a clear association of expression of MRP8
and MRP14 by infiltrating macrophages with degeneration of myofibers. Because
MRP8 and MRP14 are secreted by activated macrophages we investigated if these
proteins would have direct extracellular effects on myocytes. We found that
the
purified MRP8/MRP14 complex inhibited proliferation and differentiation of C2C12
myoblasts and that it induced apoptosis via activation of caspase-3 in a time-
and dose-dependent manner. These results indicate that in the course of
inflammatory myopathies, activated macrophages can promote destruction and
impair regeneration of myocytes via secretion of MRP8/MRP14.
PMID: 12937135 [PubMed - indexed for MEDLINE]
80: FASEB J. 2003 Oct;17(13):1892-4. Epub 2003 Aug 15.
Human muscle cells express a B7-related molecule, B7-H1, with strong negative
immune regulatory potential: a novel mechanism of counterbalancing the immune
attack in idiopathic inflammatory myopathies.
Wiendl H, Mitsdoerffer M, Schneider D, Chen L, Lochmuller H, Melms A, Weller M.
Department of Neurology, University of Tubingen, Medical School, D-72076
Tubingen, Germany. heinz.wiendl@uni-tuebingen.de
B7-H1 is a novel B7 family protein attributed to costimulatory and immune
regulatory functions. Here we report that human myoblasts cultured from control
subjects and patients with inflammatory myopathies as well as TE671 muscle
rhabdomyosarcoma cells express high levels of B7-H1 after stimulation with the
inflammatory cytokine IFN-gamma. Coculture experiments of MHC class
I/II-positive myoblasts with CD4 and CD8 T cells in the presence of antigen
demonstrated the functional consequences of muscle-related B7-H1 expression:
production of inflammatory cytokines, IFN-gamma and IL-2, by CD4 as well CD8
T
cells was markedly enhanced in the presence of a neutralizing anti-B7-H1
antibody. This observation was paralleled by an augmented expression of the
T
cell activation markers CD25, ICOS, and CD69, thus showing B7-H1-mediated
inhibition of T cell activation. Further, we investigated 23 muscle biopsy
specimens from patients with polymyositis (PM), inclusion body myositis (IBM),
dermatomyositis (DM), and nonmyopathic controls for B7-H1 expression by
immunohistochemistry: B7-H1 was expressed in PM, IBM, and DM specimens but not
in noninflammatory and nonmyopathic controls. Staining was predominantly
localized to areas of strong inflammation and to muscle cells as well as
mononuclear cells. These data highlight the immune regulatory properties of
muscle cells and suggest that B7-H1 expression represents an inhibitory
mechanism induced upon inflammatory stimuli and aimed at protecting muscle
fibers from immune aggression.
PMID: 12923066 [PubMed - indexed for MEDLINE]
81: Neuromuscul Disord. 2003 Sep;13(7-8):559-67.
Clinical and genetic heterogeneity in chromosome 9p associated hereditary
inclusion body myopathy: exclusion of GNE and three other candidate genes.
Watts GD, Thorne M, Kovach MJ, Pestronk A, Kimonis VE.
Division of Genetics and Metabolism, Children's Hospital, Harvard Medical
School, 300 Longwood Avenue, Fegan 5, Boston, MA 02115, USA.
We have previously reported a new autosomal dominant inclusion body myopathy
clinically resembling limb girdle muscular dystrophy, associated with Paget
disease of bone in the majority and frontotemporal dementia in a third of
individuals. The critical locus for this unique disorder now termed IBMPFD is
9
p21.1-p12, spans 5.5 Mb and contains the gene responsible for the recessive
quadriceps-sparing inclusion body myopathy (IBM2). Mutation analysis of the
GNE
gene associated with IBM2 in affected individuals from four IBMPFD families
did
not identify any mutations, indicating that the two disorders are not allelic.
Expression studies indicate that GNE has a tissue-specific splice pattern, with
four splice variants. Mutation analysis in three other candidate genes
(beta-tropomyosin, NDUFB6 and SMU1) did not identify any mutations.
PMID: 12921793 [PubMed - indexed for MEDLINE]
82: J Rheumatol. 2003 Aug;30(8):1892.
Comment on:
J Rheumatol. 2002 Sep;29(9):1897-906.
Magnetic resonance imaging criteria to differentiate inclusion body myositis
from
polymyositis.
Hengstman GJ.
Publication Types:
Comment
Letter
PMID: 12913890 [PubMed - indexed for MEDLINE]
83: Neurology. 2003 Aug 12;61(3):322-6.
MAP kinase phosphatase-1 is induced in abnormal fibers in inclusion body
myositis.
Nakano S, Shinde A, Ito H, Ito H, Kusaka H.
Department of Neurology, Kansai Medical University, Moriguchi-city, Japan.
nakanos@takii.kmu.ac.jp
OBJECTIVE: To investigate alterations in protein kinases and phosphatases that
regulate the activity of mitogen activated protein kinase (MAPK) in sporadic
inclusion body myositis (IBM). BACKGROUND: In vacuolated fibers in IBM, several
studies reported upregulation of the extracellular regulated kinase (ERK)
subclass of MAPK family. Whereas MAPK kinases (MKK) activate MAPK, MAPK
phosphatases (MKP) inactivate MAPK. MKP-1 is involved in muscle fiber
differentiation and it is downregulated during myotube formation. METHODS:
Immunolocalization of MKK1 through MKK4 and MKP-1 to MKP-3 was tested in muscle
specimens from 10 patients with IBM and controls. RESULTS: In IBM, strong and
focal deposits of MKP-1 were observed in vacuolated fibers. The MKP-1-positive
deposits were colocalized with ERK. MKP-2, MKP-3, and MKK were not associated
with vacuolated fibers. CONCLUSIONS: In IBM, MKP-1 is abnormally induced in
vacuolated fibers probably to inactivate ERK. Although direct activators other
than those tested in the current study might induce ERK, the absence of
activation of MKK suggests that the aggregation of ERK protein itself causes
the
seeming upregulation of the protein kinase in IBM. Like ERK and its nuclear
substrate, MKP-1 is an enzyme that forms aggregates in vacuolated fibers and
is
involved in myogenesis.
PMID: 12913191 [PubMed - indexed for MEDLINE]
84: Neurology. 2003 Aug 12;61(3):316-21.
Comment in:
Neurology. 2003 Aug 12;61(3):288-9.
Neurology. 2004 Jul 27;63(2):402-3; author reply 403.
Neurology. 2004 Jul 27;63(2):402; author reply 403.
Neurology. 2004 Jul 27;63(2):402; author reply 403.
Polymyositis: an overdiagnosed entity.
van der Meulen MF, Bronner IM, Hoogendijk JE, Burger H, van Venrooij WJ, Voskuyl
AE, Dinant HJ, Linssen WH, Wokke JH, de Visser M.
Rudolf Magnus Institute of Neuroscience, Department of Neurology, University
Medical Center, Utrecht, The Netherlands. M.F.G.vdMeulen@neuro.azu.nl
BACKGROUND: According to widely used criteria (Bohan and Peter criteria, 1975),
dermatomyositis (DM) is differentiated from polymyositis (PM) only by skin
changes. More recent criteria also include histopathologic characteristics
enabling the distinction between PM and DM and the differentiation of sporadic
inclusion body myositis (s-IBM) from PM. The authors investigated the
applicability of diagnostic features for diagnosing PM and DM. METHODS: The
authors performed a retrospective follow-up study of 165 patients with 1) a
previous diagnosis of myositis; 2) subacute onset of symmetric, proximal
weakness; and 3) an evaluation between 1977 and 1998 excluding other
neuromuscular disorders. RESULTS: The diagnoses at initial evaluation based
on
clinical, laboratory, and histopathologic criteria were PM, 9 (5%); DM, 59 (36%;
54 isolated, 3 with associated connective tissue disease [CTD], 2 with
associated malignancy); unspecified myositis (perimysial/perivascular
infiltrates, no PM or DM), 65 (39%; 38 isolated myositis, 26 with associated
CTD, 1 with malignancy); and possible myositis (necrotizing myopathy, no
inflammatory infiltrates), 32 (19%; 29 isolated myositis, 3 with associated
CTD). At follow-up evaluation, five of the nine patients with PM had typical
s-IBM features. None of the remaining four patients complied with the assumed
typical signs of PM. Ten of the 38 patients with isolated unspecified myositis
had been diagnosed with a CTD. CONCLUSIONS: Polymyositis is an overdiagnosed
entity. At evaluation, more than half the patients with autoimmune myositis
cannot be specifically diagnosed with polymyositis or dermatomyositis. A quarter
of patients with isolated unspecified myositis subsequently developed connective
tissue disease.
PMID: 12913190 [PubMed - indexed for MEDLINE]
85: Neurology. 2003 Aug 12;61(3):288-9.
Comment in:
Neurology. 2004 Jul 27;63(2):403-4; author reply 404.
Comment on:
Neurology. 2003 Aug 12;61(3):316-21.
Neurology. 2003 Aug 12;61(3):384-6.
Unicorns, dragons, polymyositis, and other mythological beasts.
Amato AA, Griggs RC.
Publication Types:
Comment
Editorial
PMID: 12913184 [PubMed - indexed for MEDLINE]
86: Semin Neurol. 2003 Jun;23(2):199-206.
Therapeutic approaches in patients with inflammatory myopathies.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Building 10, Room 4N248, 10 Center Drive,
MSC 1382, Bethesda, MD 20892-1382, USA.
Among the group of inflammatory myopathies, dermatomyositis (DM) remains the
most treatable subset responding, in the majority of the cases, to steroids,
intravenous immunoglobulin (IVIg), or immunosuppressants. Inclusion-body
myositis (IBM) remains the most difficult disease to treat; in uncontrolled
studies immunosuppressants and steroids have not helped, and controlled trials
with IVIg have been disappointing. Polymyositis (PM) is a very uncommon,
although still overdiagnosed, disorder and its rarity poses difficulties in
performing large-scale therapeutic studies; based on small series, however,
PM
seems to variably respond to immunotherapeutic interventions. The most
consistent problem in the treatment of inflammatory myopathies remains the
distinction of true PM from the difficult-to-treat cases of IBM, or from
necrotizing myopathies and dystrophic processes where secondary endomysial
inflammation may be prominent. The future in the management of PM, DM, and IBM
seems promising because of the availability of new agents directed at T-cell
activation molecules, cytokines, chemokines, and adhesion receptors. In IBM,
the
use of such immunomodulatory drugs may be combined with agents that block
cytokine-enhancing amyloid or with agents that inhibit the formation and
polymerization of amyloid fibrils.
Publication Types:
Review
Review, Tutorial
PMID: 12894385 [PubMed - indexed for MEDLINE]
87: Neurology. 2003 Jul 22;61(2):260-2.
Anti-T-lymphocyte globulin treatment in inclusion body myositis: a randomized
pilot study.
Lindberg C, Trysberg E, Tarkowski A, Oldfors A.
Department of Neurology, Sahlgrenska University Hospital/Molndal, Sahlgrenska
NeuroMuscular Center, Gothenburg, Sweden. christopher.lindberg@vgregion.se
The authors performed an open, randomized trial in patients with inclusion
body
myositis comparing 1) 12-month treatment with oral methotrexate 7.5 mg/week
alone (MTX group) with 2) 12-month MTX treatment preceded by 7 days of IV
anti-T-lymphocyte immunoglobulin treatment (ATG group). Eleven patients were
randomized; 10 patients completed 12 months follow-up. Myometry showed that
patients in the ATG group (n = 6) increased in mean muscle strength by 1.4%
compared with the MTX group (n = 5), whose muscle strength decreased by 11.1%
(p
= 0.021).
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12874415 [PubMed - indexed for MEDLINE]
88: Neurology. 2003 Jul 22;61(2):257-60.
Transthyretin Val122Ile, accumulated Abeta, and inclusion-body myositis aspects
in cultured muscle.
Askanas V, Engel WK, McFerrin J, Vattemi G.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, Los Angeles
90017-1912, USA. askanas@hsc.usc.edu
Cultured muscle fibers (CMF) from a patient with inclusion-body myositis (IBM)
and cardiac amyloidosis associated with the transthyretin (TTR) Val122Ile
mutation contained aspects of the IBM phenotype: vacuolation, congophilic
inclusions, and clusters of immunocolocalizing amyloid beta-peptide (Abeta)
and
TTR accumulations. These abnormalities are never present in normal human CMF.
These perturbations were greatly increased after Abeta precursor protein gene
transfer. The TTR mutation may be a genetic predisposition factor for the
patient's IBM.
Publication Types:
Case Reports
PMID: 12874414 [PubMed - indexed for MEDLINE]
89: Rheumatology (Oxford). 2003 Aug;42(8):1016-8.
Anti-PM-Scl antibodies in a patient with inclusion body myositis.
Selva-O'Callaghan A, Mijares-Boeckh-Behrens T, Labrador-Horrillos M,
Solans-Laque R, Ma Grau-Junyent J, Vilardell-Tarres M.
Publication Types:
Case Reports
Letter
Review
Review of Reported Cases
PMID: 12869677 [PubMed - indexed for MEDLINE]
90: Rheumatology (Oxford). 2003 Aug;42(8):1012-4.
Inclusion body myositis evolving in systemic lupus erythrematosus? A case
report.
Massawi G, Hickling P, Hilton D, Patterson C.
Publication Types:
Case Reports
Letter
Review
Review of Reported Cases
PMID: 12869675 [PubMed - indexed for MEDLINE]
91: Scand J Immunol. 2003 Aug;58(2):195-200.
Inclusion body myositis: clonal expansions of muscle-infiltrating T cells
persist over time.
Muntzing K, Lindberg C, Moslemi AR, Oldfors A.
Department of Pathology, Sahlgrenska University Hospital, SE-413 45 Goteborg,
Sweden.
Inclusion body myositis (IBM) is a chronic inflammatory myopathy. The muscle
histology is characterized by infiltration of T cells, which invade and
apparently destroy muscle fibres. This study was performed to investigate
whether predominant clones of muscle-infiltrating T cells are identical in
different muscles and whether they persist over time in IBM. By reverse
transcriptase-polymerase chain reaction, 25 T-cell receptor (TCR) variable beta
(Vbeta) chain families and the complementarity-determining region 3 (CDR3) of
the TCR were analysed in two different muscle biopsies of four patients with
IBM. In two of the patients, the muscle biopsies were obtained from different
muscles at one time point, whereas in two patients, the second biopsy was
obtained 9 years after the first biopsy. T cells expressing predominant Vbeta
families were analysed for clonality by fragment length analysis of the CDR3.
Predominant Vbeta families were analysed by DNA sequencing to identify identical
clones. Immunohistochemical staining of Vbeta families was performed to study
the distribution of T cells expressing identified predominant Vbeta families.
The muscle-infiltrating lymphocytes showed restricted expression of TCR Vbeta
families. DNA sequencing proved that clonally expanded T cells were identical
in
different muscles and persisted 9 years after the first biopsy.
Immunohistochemical analysis with Vbeta family-specific antibodies demonstrated
the endomysial localization of these T cells in inflammatory cell infiltrates.
Our results show that in IBM there is clonal restriction of TCR expression in
muscle-infiltrating lymphocytes. Identical T-cell clones predominate in
different muscles, and these clones persist for many years. These results
indicate an important, continuous, antigen-driven inflammatory reaction in IBM.
PMID: 12869141 [PubMed - indexed for MEDLINE]
92: Rheumatology (Oxford). 2004 Jan;43(1):49-54. Epub 2003 Jul 16.
International consensus outcome measures for patients with idiopathic
inflammatory myopathies. Development and initial validation of myositis activity
and damage indices in patients with adult onset disease.
Isenberg DA, Allen E, Farewell V, Ehrenstein MR, Hanna MG, Lundberg IE, Oddis
C,
Pilkington C, Plotz P, Scott D, Vencovsky J, Cooper R, Rider L, Miller F;
International Myositis and Clinical Studies Group (IMACS).
Center for Rheumatology, Department of Medicine, The Middlesex Hospital,
University College London, London, UK. d.isenberg@ucl.ac.uk
OBJECTIVE: To devise new tools to assess activity and damage in patients with
idiopathic myopathies (IIM). METHODS: An international multidisciplinary
consensus effort to standardize the conduct and reporting of the myositis
clinical trials has been established. Two tools, known as the myositis intention
to treat index (MITAX) and the myositis disease activity assessment visual
analogue scale (MYOACT), have been developed to capture activity in patients
with IIM. In addition, the myositis damage index (MDI) has been devised to
assess the extent and severity of damage developing in different organs and
systems. These measures have been reviewed by the myositis experts participating
in the International Myositis Assessment and Clinical Studies (IMACS) group
and
have been found to have good face validity and to be comprehensive. The
instruments were assessed in two real patient exercises involving patients with
adult dermatomyositis and inclusion body myositis. RESULTS: The reliability
of
MITAX, MYOACT and MDI, measured by the intraclass correlation coefficient among
the physicians, and the inter-rater reliability, as assessed by variation in
the
physicians' rating of patients, was fair to good for most aspects of the tools.
Reliability and inter-rater agreement improved at the second exercise after
the
participants had completed additional training. CONCLUSIONS: The MITAX, MYOACT
and MDI tools, which are now undergoing validity testing, should enhance the
consistency, comprehensiveness and reliability of disease activity and damage
assessment in patients with myositis.
Publication Types:
Consensus Development Conference
Multicenter Study
Review
PMID: 12867580 [PubMed - indexed for MEDLINE]
93: Neurology. 2003 Jul 8;61(1):145; author reply 145.
Comment on:
Neurology. 2002 Dec 10;59(11):1689-93.
Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body
myopathy.
Hinderlich S, Salama I, Eisenberg I, Mitrani-Rosenbaum S.
Publication Types:
Comment
Letter
PMID: 12847185 [PubMed - indexed for MEDLINE]
94: AIDS. 2003 May 23;17(8):1266-7.
Inclusion body myositis: another possible manifestation of
antiretroviral-associated mitochondrial toxicity.
Loutfy MR, Sheehan NL, Goodhew JE, Walmsley SL.
Publication Types:
Case Reports
Letter
PMID: 12819534 [PubMed - indexed for MEDLINE]
95: J Neurol. 2003 May;250(5):619-21.
Inclusion body myositis in a patient with a presumed diagnosis of post-polio
syndrome.
Parissis D, Karkavelas G, Taskos N, Milonas I.
Publication Types:
Case Reports
Letter
PMID: 12814114 [PubMed - indexed for MEDLINE]
96: Muscle Nerve. 2003 Jul;28(1):113-7.
Novel missense mutation and large deletion of GNE gene in autosomal-recessive
inclusion-body myopathy.
Del Bo R, Baron P, Prelle A, Serafini M, Moggio M, Fonzo AD, Castagni M,
Bresolin N, Comi GP.
Dipartimento di Scienze Neurologiche, Centro Dino Ferrari, Universita degli
Studi di Milano, IRCCS Ospedale Maggiore Policlinico, Via F Sforza 35, Milano
20122, Italy.
The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene
is
the causative gene for autosomal-recessive hereditary inclusion-body myopathy
(h-IBM). Two sisters affected with autosomal-recessive h-IBM were shown to be
compound heterozygous for two novel GNE mutations: a large deletion involving
exons 1-9, and a R162C amino acid change in the epimerase domain. This is the
first deletion event observed in a GNE allele and expands the molecular
pathogenesis of autosomal-recessive h-IBM. Copyright 2003 Wiley Periodicals,
Inc.
Publication Types:
Case Reports
PMID: 12811782 [PubMed - indexed for MEDLINE]
97: Acta Neurol Scand. 2003 Jul;108(1):22-7.
Inclusion body myositis--sensory dysfunction revealed with quantitative
determination of somatosensory thresholds.
Arnardottir S, Svanborg E, Borg K.
Department of Clinical Neuroscience, division of Neurology, Karolinska Hospital,
Stockholm, Sweden.
In order to evaluate sensory function in inclusion body myositis (IBM), nine
patients were subjected to sensibility screening and quantitative determination
of somatosensory thresholds. Data were compared with results from
electrophysiological examination and muscle biopsy. On sensibility screening
all
but one of the IBM patients had abnormal findings in hands and/or feet mostly
affecting thermal sensibility. Vibratory thresholds were abnormal in five and
thermal thresholds in four of the patients. Mean vibratory thresholds were
significantly (P < 0.05) higher in the IBM patients when compared with the
controls. Significantly increased heat pain thresholds were found in hands and
feet when compared with the controls while thermal thresholds were normal. Nerve
conduction velocities were decreased in three patients, EMG showed both
myopathic and neuropathic abnormalities in six patients. Eight patients had
neuropathic abnormalities on muscle biopsy. The sensory dysfunction found
suggests an affection of peripheral nerves in IBM mainly affecting large
diameter myelinated nerve fibres corroborating earlier findings of a peripheral
neuropathy in IBM.
PMID: 12807389 [PubMed - indexed for MEDLINE]
98: J Neurochem. 2003 Jun;85(6):1539-46.
Cystatin C colocalizes with amyloid-beta and coimmunoprecipitates with
amyloid-beta precursor protein in sporadic inclusion-body myositis muscles.
Vattemi G, Engel WK, McFerrin J, Askanas V.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, Los Angeles,
California 90017-1912, USA.
Cystatin C (CC), an endogenous cysteine protease inhibitor, is accumulated
within amyloid-beta (A beta) amyloid deposits in Alzheimer's disease (AD) brain
and was proposed to play a role in the AD pathogenesis. Because the
chemo-morphologic muscle phenotype of sporadic inclusion-body myositis (s-IBM)
has several similarities with the phenotype of AD brain, including abnormal
accumulation of A beta deposits, we studied expression and localization of CC
in
muscle biopsies of 10 s-IBM, and 16 disease- and five normal-control muscle
biopsies. Physical interaction of CC with amyloid-beta precursor protein (A
beta
PP) was studied by a combined immunoprecipitation/immunoblotting technique in
the s-IBM muscle biopsies and in A beta PP-overexpressing cultured human muscle
fibers. In all s-IBM muscle biopsies, CC-immunoreactivity either colocalized
with, or was adjacent to, the A beta-immunoreactive inclusions in 80-90% of
the
vacuolated muscle fibers, mostly in non-vacuolated regions of their cytoplasm.
Ultrastructurally, CC immunoreactivity-colocalized with A beta on 6-10 nm
amyloid-like fibrils and floccular material. By immunoblotting, CC expression
was strongly increased in IBM muscle as compared to the controls. By
immunoprecipitation/immunoblotting experiments, CC coimmunoprecipitated with
A
beta PP, both in s-IBM muscle and in A beta PP-overexpressing cultured normal
human muscle fibers. Our studies (i) demonstrate for the first time that CC
physically associates with A beta PP, and (ii) suggest that CC may play a novel
role in the s-IBM pathogenesis, possibly by influencing A beta PP processing
and
A beta deposition.
PMID: 12787072 [PubMed - indexed for MEDLINE]
99: Neurology. 2003 May 13;60(9):1519-23.
Hereditary inclusion body myopathy: the Middle Eastern genetic cluster.
Argov Z, Eisenberg I, Grabov-Nardini G, Sadeh M, Wirguin I, Soffer D,
Mitrani-Rosenbaum S.
Department of Neurology and Agnes Ginges Center for Human Neurogenetics,
Hadassah University Hospital and Hebrew University-Hadassah Medical School,
Jerusalem. zargov@md2.huji.ac.il
BACKGROUND: Recessively inherited hereditary inclusion body myopathy (HIBM)
with
quadriceps sparing was initially described only in Jews originating from the
region of Persia. The recent identification of the gene responsible for this
myopathy and the common "Persian Jewish mutation" (M712T) enabled
the
re-evaluation of atypical phenotypes and the epidemiology of HIBM in various
communities in the Middle East. OBJECTIVE: To test for the M712T mutation in
the
DNA from HIBM patients in the Middle East. METHODS: DNA from all suspected HIBM
patients was tested for the M712T mutation. Unaffected members of families with
genetically proven HIBM were studied too. In the majority of families, haplotype
construction with markers spanning the 700-kb region of the HIBM gene was
performed. RESULTS: One hundred twenty-nine HIBM patients of 55 families (Middle
Eastern Jews, Karaites, and Arab Muslims of Palestinian and Bedouin origin)
were
homozygous for the M712T mutation, and all carried the same haplotype. Five
clinically unaffected subjects were also homozygous for the common mutation
and
haplotype, including two older adults (ages 50 and 68 years). Atypical features
with this same mutation were marked quadriceps weakness in five patients,
proximal weakness only in two patients, facial weakness in three patients, and
a
muscle biopsy showing perivascular inflammation in one patient. CONCLUSIONS:
The
phenotypic spectrum of recessive HIBM is wider than previously described, and
the diagnostic criteria for this myopathy must be changed. The Middle Eastern
cluster is the result of a founder mutation, with incomplete penetrance, that
is
approximately 1,300 years old and is not limited to Jews.
Publication Types:
Case Reports
Historical Article
PMID: 12743242 [PubMed - indexed for MEDLINE]
100: J Child Neurol. 2003 Mar;18(3):185-90.
Unfolding story of inclusion-body myositis and myopathies: role of misfolded
proteins, amyloid-beta, cholesterol, and aging.
Askanas V, Engel WK.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA
90017-1912, USA. askanas@hsc.usc.edu
Sporadic inclusion-body myositis and hereditary inclusion-body myopathies are
progressive muscle diseases leading to severe disability. We briefly summarize
their clinical pictures and pathologic diagnostic criteria and discuss the
latest advances in illuminating their pathogenic mechanism(s). We emphasize
how
different etiologies might lead to the strikingly similar pathology and possibly
similar pathogenic cascade. On the basis of our research, several processes
seem
to be important in relation to the still speculative pathogenesis, including
(a)
increased transcription and accumulation of amyloid-beta precursor protein and
accumulation of its proteolytic fragment amyloid-beta; (b) abnormal accumulation
of components related to lipid metabolism, for example, cholesterol,
accumulation of which is possibly owing to its abnormal trafficking; (c)
oxidative stress; (d) accumulations of other Alzheimer's disease-related
proteins; and (e) a milieu of muscle cellular aging in which these changes
occur. We discuss a potentially very important role of unfolded and/or misfolded
proteins as a possible mechanism in the formations of the inclusion bodies and
other abnormalities.
Publication Types:
Lectures
PMID: 12731644 [PubMed - indexed for MEDLINE]
101: Neuropediatrics. 2003 Feb;34(1):40-4.
Congenital myopathy with abundant ring fibres, rimmed vacuoles and inclusion
body myositis-type inclusions.
Fidzianska A, Kaminska A.
Neuromuscular Unit, Medical Research Centre, Polish Academy of Sciences, Warsaw,
Poland.
We report a 17-year-old girl with an unusual neuromuscular disorder
characterised by slowly progressive proximal muscle weakness whose muscle biopsy
showed multiple ring fibres and numerous rimmed vacuoles as well as
intracytoplasmic and intranuclear inclusions of the inclusion body
myositis-type. The clinical features of the presented case, manifested by the
onset of the disease in early childhood, delayed motor development, short
stature, lordosis and joint contractures were suggestive of congenital myopathy.
The coexistence of ring fibres, rimmed vacuoles and inclusion-body myositis-type
inclusions in a child with congenital myopathy has not been previously reported.
Publication Types:
Case Reports
PMID: 12690567 [PubMed - indexed for MEDLINE]
102: Brain. 2003 May;126(Pt 5):1026-35.
Muscle fibres and cultured muscle cells express the B7.1/2-related inducible
co-stimulatory molecule, ICOSL: implications for the pathogenesis of
inflammatory myopathies.
Wiendl H, Mitsdoerffer M, Schneider D, Melms A, Lochmuller H, Hohlfeld R, Weller
M.
Department of Neurology, University of Tubingen, Medical School, Tubingen,
Germany. heinz.wiendl@uni-tuebingen.de
Inducible co-stimulator ligand (ICOSL), a member of the B7 family of
co-stimulatory molecules related to B7.1/2, regulates CD4 as well as CD8 T-cell
responses via interaction with its receptor ICOS on activated T cells. Here
we
examined the expression and the functional relevance of ICOSL in human muscle
cells in vivo and in vitro. We investigated 25 muscle biopsy specimens from
patients with polymyositis, dermatomyositis, inclusion body myositis, Duchenne
muscular dystrophy and non-myopathic controls for ICOSL expression by
immunohistochemistry. Normal muscle fibres constitutively express low levels
of
ICOSL. However, ICOSL expression is markedly increased in muscle fibres in
inflammatory myopathies. Cell surface staining was most prominent in the contact
areas between muscle fibres and inflammatory cells, which in turn show
expression of ICOS as a marker of T-cell activation. Muscle endothelial cells
show constitutive expression of ICOSL under normal and pathological conditions.
We also detected mRNA and cell surface protein expression of ICOSL on myoblasts
cultured from control subjects and patients as well as in TE671 muscle
rhabdomyosarcoma cells. ICOSL expression was upregulated by tumour necrosis
factor-alpha (TNF-alpha), whereas interferon-gamma (IFN-gamma) had no such
effect. Co-culture experiments of major histocompatibility complex (MHC) class
II-positive myoblasts with CD4 T cells together with superantigen demonstrated
that the expression of muscle-related ICOSL has functional consequences: the
production of Th1 (IFN-gamma) and Th2 cytokines [interleukin (IL)-4 and IL-10]
by CD4 T cells was markedly reduced in the presence of a neutralizing anti-ICOSL
monoclonal antibody (mAb HIL-131), thus showing the importance of ICOSL
co-stimulation for T-cell activation. Taken together, our results demonstrate
that human muscle cells express ICOSL, a functional co-stimulatory molecule
distinct from B7.1 and B7.2. ICOSL-ICOS interactions may play an important role
in inflammatory myopathies, providing further evidence for the
antigen-presenting capacity of muscle cells.
PMID: 12690043 [PubMed - indexed for MEDLINE]
103: Acta Neuropathol (Berl). 2003 Jul;106(1):1-7. Epub 2003 Apr 01.
Expression of the intermediate filament protein synemin in myofibrillar
myopathies and other muscle diseases.
Olive M, Goldfarb L, Dagvadorj A, Sambuughin N, Paulin D, Li Z, Goudeau B,
Vicart P, Ferrer I.
Institut de Neuropatologia, Ciutat Sanitaria i Universitaria de Bellvitge,
C/Feixa Llarga s/n masculine, 08907 Hospitalet de Llobregat, Spain.
25169mop@comb.es
Synemin is a member of the intermediate protein superfamily. Previous studies
in
avian and rodent skeletal and cardiac muscles have demonstrated that synemin
localises at the Z-band, where it associates with desmin and alpha-actinin.
In
the present study, the distribution of synemin was examined using
immunohistochemistry in muscle biopsy specimens from patients suffering from
myofibrillar myopathy (MM, n=6), dermatomyositis (DM, n=3), inclusion body
myositis (IBM, n=5), oculopharyngeal muscular dystrophy (OPD, n=3) and
denervation atrophy (DA, n=3), to investigate the possible participation of
this
protein in the pathogenesis of various muscular diseases. Of patients affected
by MM, two showed the presence of mutations in the desmin gene; none had
mutations in the alphaB-crystallin gene; and no mutations were identified in
synemin or syncoilin genes of three patients. Synemin immunohistochemistry
disclosed a faint staining corresponding to the Z-bands in the cytoplasm of
control muscle fibres; in contrast, focal aggregates of synemin were seen in
patients with MM. Increased synemin immunoreactivity was identified diffusely
or
in the subsarcolemmal space of scattered fibres in patients with DM, and in
vacuolated fibres of patients with IBM and OPD. Strong synemin immunoreactivity
was observed in target formations and atrophic fibres of patients with
denervating disorders, as well as in atrophic fibres, regardless of their
origin, in all patients studied. Synemin co-localised with desmin, as seen on
consecutive serial sections immunostained with anti-synemin or anti-desmin
antibodies. These observations demonstrate abnormal accumulations containing
both synemin and desmin in muscle fibres in patients with MM, IBM, DM, OPD and
DA. Considering the important role of synemin as one of intermediate filaments
of skeletal and cardiac muscle, its destruction and accumulation in the
intracellular debris suggest that synemin may participate in the pathogenesis
of
these disorders.
PMID: 12669240 [PubMed - indexed for MEDLINE]
104: Muscle Nerve. 2003 Apr;27(4):407-25.
Inflammatory myopathies: clinical, diagnostic and therapeutic aspects.
Mastaglia FL, Garlepp MJ, Phillips BA, Zilko PJ.
Centre for Neuromuscular and Neurological Disorders, University of Western
Australia, Queen Elizabeth II Medical Centre, Nedlands, Australia.
flmast@cyllene.uwa.edu.au
The three major forms of immune-mediated inflammatory myopathy are
dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM).
They
each have distinctive clinical and histopathologic features that allow the
clinician to reach a specific diagnosis in most cases. Magnetic resonance
imaging is sometimes helpful, particularly if the diagnosis of IBM is suspected
but has not been formally evaluated. Myositis-specific antibodies are not
helpful diagnostically but may be of prognostic value; most antibodies have
low
sensitivity. Muscle biopsy is mandatory to confirm the diagnosis of an
inflammatory myopathy and to allow unusual varieties such as eosinophilic,
granulomatous, and parasitic myositis, and macrophagic myofasciitis, to be
recognized. The treatment of the inflammatory myopathies remains largely
empirical and relies upon the use of corticosteroids, immunosuppressive agents,
and intravenous immunoglobulin, all of which have nonselective effects on the
immune system. Further controlled clinical trials are required to evaluate the
relative efficacy of the available therapeutic modalities particularly in
combinations, and of newer immunosuppressive agents (mycophenolate mofetil and
tacrolimus) and cytokine-based therapies for the treatment of resistant cases
of
DM, PM, and IBM. Improved understanding of the molecular mechanisms of muscle
injury in the inflammatory myopathies should lead to the development of more
specific forms of immunotherapy for these conditions.
Publication Types:
Review
PMID: 12661042 [PubMed - indexed for MEDLINE]
105: Neurology. 2003 Mar 25;60(6):993-7.
Activation of nuclear factor-kappaB in inflammatory myopathies and Duchenne
muscular dystrophy.
Monici MC, Aguennouz M, Mazzeo A, Messina C, Vita G.
Department of Neurosciences, Psychiatry, and Anaesthesiology, University of
Messina, Italy.
OBJECTIVE: To investigate the immunolocalization and activation of nuclear
factor-kappaB (NF-kappaB) in polymyositis, dermatomyositis, and Duchenne
muscular dystrophy (DMD). BACKGROUND: NF-kappaB is a major transcription factor
modulating the cellular immune, inflammatory, and proliferative responses. In
skeletal muscle it was demonstrated to play a role in the expression of
inducible genes in response to oxidative stress and ischemia/reperfusion injury,
and also in myonuclear apoptosis and muscle catabolism. Some data suggest that
NF-kappaB may play a role in the pathogenesis of inclusion body myositis.
METHODS: Muscle samples from five patients each with polymyositis,
dermatomyositis, and DMD and 10 normal controls were studied by
immunocytochemistry and Western blot of nuclear extracts for the activated form
of NF-kappaB. NF-kappaB DNA binding activity was studied by electrophoretic
mobility shift assay (EMSA). RESULTS: Immunoreactivity for NF-kappaB was found
in the cytoplasm of all regenerating fibers and in 20 to 40% of necrotic fibers.
Western blot analysis of nuclear extracts showed a single band corresponding
to
65 kd in all patients. EMSA analysis confirmed activation of NF-kappaB pathway
in inflammatory myopathies and, to a lesser extent, also in DMD. CONCLUSIONS:
These data indicate that nuclear factor-kappaB pathway is activated in
polymyositis, dermatomyositis, and Duchenne muscular dystrophy. It may play
a
role in modulating the immune response and in regulating myogenesis and muscle
repair.
PMID: 12654966 [PubMed - indexed for MEDLINE]
106: Exp Neurol. 2003 Feb;179(2):150-8.
BACE1 and BACE2 in pathologic and normal human muscle.
Vattemi G, Engel WK, McFerrin J, Pastorino L, Buxbaum JD, Askanas V.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, Los Angeles
90017-1912, USA.
BACE1 and BACE2 are recently discovered enzymes participating in processing
of
amyloid beta precursor protein (AbetaPP). Their discovery is contributing
importantly to understanding the mechanism of amyloid-beta generation, and hence
the pathogenesis of Alzheimer's disease (AD). Sporadic inclusion-body myositis
(s-IBM) and hereditary inclusion-body myopathy (h-IBM) are progressive muscle
diseases in which overproduction of AbetaPP and accumulation of its presumably
toxic proteolytic product amyloid-beta (Abeta) in abnormal muscle fibers appear
to play an important upstream role in the pathogenic cascade. In normal human
muscle AbetaPP was also shown to be present and presumably playing a role (a)
at
neuromuscular junctions and (b) during muscle development. To investigate
whether BACE1 and BACE2 play a role in normal and diseased human muscle, we
have
now studied them by immunocytochemistry and immunoblotting in 35 human muscle
biopsies, including: 5 s-IBM; 5 chromosome-9p1-linked quadriceps-sparing h-IBM;
and 25 control muscle biopsies. In addition, expression of BACE1 and BACE2 was
studied in normal cultured human muscle. Our studies demonstrate that BACE1
and
BACE2 (a) are expressed in normal adult muscle at the postsynaptic domain of
neuromuscular junctions, and in cultured human muscle; (b) are accumulated in
the form of plaque-like inclusions in both s-IBM and h-IBM vacuolated muscle
fibers; and (c) are immunoreactive in necrotizing muscle fibers. Accordingly,
BACE1 and BACE2 participate in normal and abnormal processes of human muscle,
suggesting that their functions are broader than previously thought.
PMID: 12618121 [PubMed - indexed for MEDLINE]
107: J Rehabil Med. 2003 Jan;35(1):31-5.
Sporadic inclusion body myositis: pilot study on the effects of a home exercise
program on muscle function, histopathology and inflammatory reaction.
Arnardottir S, Alexanderson H, Lundberg IE, Borg K.
Department of Clinical Neuroscience Division of Neurology, Karolinska Hospital,
SE-171 76 Stockholm, Sweden. snjolaug.arnardottir@ks.se
OBJECTIVE: To evaluate the safety and effect of a home training program on
muscle function in 7 patients with sporadic inclusion body myositis. DESIGN:
The
patients performed exercise 5 days a week over a 12-week period. METHODS: Safety
was assessed by clinical examination, repeated muscle biopsies and serum levels
of creatine kinase. Muscle strength was evaluated by clinical examination,
dynamic dynamometer and by a functional index in myositis. RESULTS: Strength
was
not significantly improved after the exercise, however none of the patients
deteriorated concerning muscle function. The histopathology was unchanged and
there were no signs of increased muscle inflammation or of expression of
cytokines and adhesion molecules in the muscle biopsies. Creatine kinase levels
were unchanged. A significant decrease was found in the areas that were
positively stained for EN-4 (a marker for endothelial cells) in the muscle
biopsies after training. CONCLUSION: The home exercise program was considered
as
not harmful to the muscles regarding muscle inflammation and function. Exercise
may prevent loss of muscle strength due to disease and/or inactivity.
Publication Types:
Evaluation Studies
PMID: 12610846 [PubMed - indexed for MEDLINE]
108: J Allergy Clin Immunol. 2003 Feb;111(2 Suppl):S659-68.
20. Immunologic neuromuscular disorders.
Chitnis T, Khoury SJ.
Center for Neurologic Disease, Brigham and Women's Hospital, Harvard Medical
School, 77 Louis Pasteur Avenue, LMRC 1st Floor, Boston, MA 02215, USA.
Immune-mediated disorders of each of the structural subdivisions of the nervous
and neuromuscular system have been described. Despite the immune privilege of
the central nervous system, and to a lesser extent the peripheral nervous
system, immune dysregulation is not uncommon. Environmental, genetic, and
immunologic factors have been postulated to be involved in the development of
these disorders. Major immune-mediated neurologic diseases of the central
nervous system include multiple sclerosis and acute disseminated
encephalomyelitis. Immune-mediated diseases of the peripheral nervous system
include myasthenia gravis, Guillain-Barre syndrome, chronic inflammatory
demyelinating polyneuropathy, idiopathic polymyositis, dermatomyositis, and
inclusion body myositis. Some of these disorders, such as myasthenia gravis
and
certain forms of acute inflammatory demyelinating polyneuropathy, are clearly
autoimmune in nature, whereas the immune system plays an important role in
pathogenesis in others. Understanding the immune mechanisms of disease and
uncovering potential therapeutic targets are essential for the design of new
treatments. The epidemiology, pathogenesis, diagnostic criteria, and current
therapeutic approaches to the major neuroimmunologic diseases are reviewed.
Publication Types:
Review
Review, Tutorial
PMID: 12592311 [PubMed - indexed for MEDLINE]
109: Rheum Dis Clin North Am. 2002 Nov;28(4):723-41.
Idiopathic inflammatory myopathies: epidemiology, classification, and diagnostic
criteria.
Mastaglia FL, Phillips BA.
Centre for Neuromuscular and Neurological Disorders, QEII Medical Centre,
Department of Medicine, University of Western Australia.
flmast@cyllene.uwa.edu.au
Epidemiologic studies have helped to define the prevalence and incidence of
PM,
DM, and IBM and have highlighted differences in risk between men and women and
in the age at onset for the different forms of myositis. Additionally, these
studies have shown that there is a substantially higher risk of PM and DM in
certain racial groups which is likely to be genetically determined. These
differences are all likely to be fundamental in terms of the pathogenesis of
these diseases but, as yet, their full significance remains uncertain. They
do,
however, suggest that the interplay between genetic and environmental initiating
factors is different in the three disorders. Additional population-based studies
in homogeneous racial groups, in parallel with studies of susceptibility genes
for autoimmune disease, such as those encoding the MHC and inflammatory
cytokines, are needed to throw further light on the role of genetic factors
in
the pathogenesis of the IIMs [47]. Because of the paucity of epidemiologic data
on IBM, further studies are required to determine the degree of variation in
prevalence in different populations and racial groups, as well as the
consistency of the male association and age spectrum of manifestations of the
disease. The particularly strong association with DR3 in this form of IIM [48]
clearly points to the importance of genetic factors in pathogenesis, but further
studies of DR3-associated genes in the MHC and of other candidate genes are
needed to define more precisely the genes that convey susceptibility to the
disease in different racial groups. Epidemiologic studies also have the
potential to identify environmental factors that may play a part in disease
initiation in genetically susceptible individuals. Seasonal patterns of disease
onset have been reported, particularly in patients with DM [49-51] as well as
seasonal variation in the frequency of relapses [52], pointing to the probable
involvement of intercurrent infections, ultraviolet light exposure, or other
environmental factors in disease initiation and reactivation. Further
prospective studies are required to determine the contribution of environmental
exposures and how they interact with genetic susceptibility factors to lead
to
myositis. One of the major limitations of a number of the previous epidemiologic
studies is the lack of precision in the diagnostic criteria used and the
classification of cases of IIM. The Bohan and Peter criteria [1] which were
used
in most studies after 1975, were introduced before IBM was recognized as an
entity distinct from PM; most of the published incidence and prevalence figures
for PM are therefore likely to be inaccurate. Multicentered, interdisciplinary,
prospective studies, incorporating comprehensive clinical, laboratory, and
pathologic information, are needed to develop and validate better diagnostic
and
classification criteria and to determine the true prevalence and incidence of
the many forms of IIM.
Publication Types:
Review
Review, Tutorial
PMID: 12510664 [PubMed - indexed for MEDLINE]
110: Rheum Dis Clin North Am. 2002 Nov;28(4):823-32.
Clinical presentation of the idiopathic inflammatory myopathies.
Yazici Y, Kagen LJ.
Hospital for Special Surgery, Weill Medical College of Cornell University,
535
East 70th Street, New York, NY 10021, USA. yaziciy@hss.edu
The hallmark of the inflammatory myopathies is muscle weakness. Although this
feature can lead to significant disability and impairment of activities of daily
living, its initial presentation may not be recognized early. Older individuals,
in particular, may feel that the changes caused by myositis reflect the effects
of aging rather than those of a disease process, and diagnosis, therefore, may
be delayed. This factor has negative impact on the response to therapy.
Inclusion body myositis, with its insidious onset in older people, and
laboratory findings which may not be markedly abnormal, presents a diagnostic
challenge. DM, with its characteristic symptomatic rash, is generally brought
to
medical attention more quickly. Another area of diagnostic concern occurs when
associated organ involvement precedes myopathy. This has been observed, for
example, with interstitial lung disease, and again represents a challenge to
physicians. In this connection, the antisynthetase syndrome presenting with
fevers, Raynaud's features, arthritis, or pulmonary involvement may not
initially be recognized as a manifestation of inflammatory muscle disease. Each
subgroup of IIM may present with a variety of extramuscular features that can
complicate diagnosis and alter therapy and prognosis. This is particularly true
for the pulmonary, GI, and cardiac manifestations and when cancer is associated
with myositis. For these reasons, such features of IIM should be carefully
evaluated, treated, and monitored over the course of the illness; in some cases
these may play a greater role in determining the outcome of patients with IIM
than the muscle involvement itself. It is hoped that in the future increased
familiarity with the manifestations of the inflammatory myopathies, together
with a better understanding of the underlying pathogenesis, will lead to more
rapid diagnosis and more effective treatments.
Publication Types:
Review
Review, Tutorial
PMID: 12506774 [PubMed - indexed for MEDLINE]
111: Rheum Dis Clin North Am. 2002 Nov;28(4):779-98, vi.
Muscle biopsy findings in inflammatory myopathies.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Building 10, Room 4N248, 10 Center Drive,
MSC 1382, Bethesda, MD 20892-1382, USA. dalakasm@ninds.nih.gov
The inflammatory myopathies encompass a heterogeneous group of acquired muscle
diseases characterized clinically, by muscle weakness, and histologically, by
inflammatory infiltrates within the skeletal muscles. The group of these
myopathies comprise three major and discrete subsets: polymyositis (PM),
dermatomyositis (DM), and inclusion body myositis (IBM). Each subset retains
its
characteristic clinical, immunopathologic, and morphologic features regardless
of whether it occurs separately or in connection with other systemic diseases.
Although the diagnosis of these disorders is based on the combination of
clinical examination, electromyographic data, serum muscle enzyme levels,
various autoantibodies, and the muscle biopsy findings, the muscle biopsy offers
the most definitive diagnostic information in the majority of the cases. This
article summarizes the main histologic features that characterize PM, DM, or
IBM
and emphasizes the main pitfalls associated with interpretation of the biopsies.
Publication Types:
Review
Review, Tutorial
PMID: 12506772 [PubMed - indexed for MEDLINE]
112: Hum Mutat. 2003 Jan;21(1):99.
Mutations spectrum of GNE in hereditary inclusion body myopathy sparing the
quadriceps.
Eisenberg I, Grabov-Nardini G, Hochner H, Korner M, Sadeh M, Bertorini T, Bushby
K, Castellan C, Felice K, Mendell J, Merlini L, Shilling C, Wirguin I, Argov
Z,
Mitrani-Rosenbaum S.
Molecular Biology Unit, Hadassah Hospital, The Hebrew University-Hadassah
Medical School, Jerusalem, Israel.
Hereditary Inclusion Body Myopathy (HIBM) is a unique group of neuromuscular
disorders characterized by adult onset and a typical muscle pathology. We have
recently identified the gene encoding for a bifunctional enzyme,
UDP-N-acetylglucosamine 2 epimerase/N-acetylmannosamine kinase (GNE), as the
mutated gene in the prototype form of the disease presenting quadriceps sparing,
particularly common in Middle Eastern Jews. Interestingly, we have identified
the homozygous M712T Middle Eastern Jewish mutation also in two unrelated Middle
Eastern Moslem families. We have also evaluated the involvement of GNE in
several families from worldwide non-Jewish ethnic origins presenting symptoms
similar to the Middle Eastern HIBM prototype. A total of 14 GNE mutations were
identified (one nonsense and 13 missense), of which six are novel: an homozygous
missense mutation in a consanguineous family from Italy and in a non
consanguineous family from USA, and distinct compound heterozygotes in families
from Germany, Italy, Ireland, Bahamas, USA and East India. This study brings
to
17 the number of reported GNE mutations in quadriceps sparing myopathy,
occurring either in the epimerase or the kinase domain of the enzyme. The
mechanism leading to this unique phenotype still remains to be elucidated.
Copyright 2002 Wiley-Liss, Inc.
PMID: 12497639 [PubMed - indexed for MEDLINE]
113: Neurology. 2002 Dec 10;59(11):1808-9.
Comment in:
Neurology. 2002 Dec 10;59(11):1674-6.
An Italian family with autosomal recessive inclusion-body myopathy and mutations
in the GNE gene.
Broccolini A, Pescatori M, D'Amico A, Sabino A, Silvestri G, Ricci E, Servidei
S, Tonali PA, Mirabella M.
Institute of Neurology, Catholic University, Rome, Italy. abroccolini@tiscali.it
Publication Types:
Case Reports
PMID: 12473780 [PubMed - indexed for MEDLINE]
114: Neurology. 2002 Dec 10;59(11):1776-9.
Comment in:
Neurology. 2002 Dec 10;59(11):1674-6.
GNE mutations in an American family with quadriceps-sparing IBM and lack of
mutations in s-IBM.
Vasconcelos OM, Raju R, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Analysis for GNE mutations was performed in an American, non-Iranian Jewish,
family with quadriceps-sparing inclusion body myopathy (QS-IBM) and in 11
patients with sporadic IBM (s-IBM). Two novel nonallosteric site missense
mutations were found in the QS-IBM kinship. No mutations were identified in
s-IBM patients. After 8 years of follow-up and severe disease progression, the
quadriceps muscle in the QS-IBM patient remains strong despite subclinical
involvement documented with repeat MRI and muscle biopsy.
Publication Types:
Case Reports
PMID: 12473769 [PubMed - indexed for MEDLINE]
115: Neurology. 2002 Dec 10;59(11):1689-93.
Comment in:
Neurology. 2002 Dec 10;59(11):1674-6.
Neurology. 2003 Jul 8;61(1):145; author reply 145.
Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body
myopathy.
Nishino I, Noguchi S, Murayama K, Driss A, Sugie K, Oya Y, Nagata T, Chida
K,
Takahashi T, Takusa Y, Ohi T, Nishimiya J, Sunohara N, Ciafaloni E, Kawai M,
Aoki M, Nonaka I.
Department of Neuromuscular Research, National Institute of Neuroscience,
Kodaira, Tokyo, Japan. nishino@ncnp.go.jp
BACKGROUND: Distal myopathy with rimmed vacuoles (DMRV) is an
autosomal-recessive disorder with preferential involvement of the tibialis
anterior muscle that starts in young adulthood and spares quadriceps muscles.
The disease locus has been mapped to chromosome 9p1-q1, the same region as the
hereditary inclusion body myopathy (HIBM) locus. HIBM was originally described
as rimmed vacuole myopathy sparing the quadriceps; therefore, the two diseases
have been suspected to be allelic. Recently, HIBM was shown to be associated
with the mutations in the gene encoding the bifunctional enzyme,
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). OBJECTIVE:
To determine whether DMRV and HIBM are allelic. METHODS: The GNE gene was
sequenced in 34 patients with DMRV. The epimerase activity in lymphocytes from
eight DMRV patients was also measured. RESULTS: The authors identified 27
unrelated DMRV patients with homozygous or compound-heterozygous mutations in
the GNE gene. DMRV patients had markedly decreased epimerase activity.
CONCLUSIONS: DMRV is allelic to HIBM. Various mutations are associated with
DMRV
in Japan. The loss-of-function mutations in the GNE gene appear to cause
DMRV/HIBM.
PMID: 12473753 [PubMed - indexed for MEDLINE]
116: Best Pract Res Clin Rheumatol. 2002 Dec;16(5):817-32.
Idiopathic inflammatory myopathies - myositis.
Dorph C, Lundberg IE.
Rheumatology Unit, Karolinska Hospital, SE- 171 76, Stockholm, Sweden.
Ingrid.Lundberg@medks.ki.se
The inflammatory myopathies - myositis - encompass a heterogeneous group of
chronic muscle disorders of unknown origin and with varying prognoses. New
clinical phenotypes of myositis have been identified since the most widely used
classification criteria were proposed in 1975. Based on clinical and
histopathological features, inclusion body myositis was identified. Furthermore,
the myositis-specific autoantibodies may also identify different clinical
phenotypes and serve as prognostic markers. The different classifications and
inclusion criteria that have been used in different studies make some
epidemiological data uncertain. In order to improve our knowledge of causative
factors, as well as of pathogenic mechanisms, there is a need for revision and
also for an international acceptance of the classification criteria. During
recent years, our knowledge has increased regarding the role of some genetic
and
environmental factors that could affect susceptibility for developing myositis
as well as the prognosis. Whether there is an association between myositis and
malignancies has been a subject of controversy for many years and recent
epidemiological data have brought some clarification on this issue.
Publication Types:
Review
Review, Tutorial
PMID: 12473276 [PubMed - indexed for MEDLINE]
117: J Clin Neurosci. 2003 Jan;10(1):99-101.
Inflammatory myopathies: how to treat the difficult cases.
Mastaglia FL, Zilko PJ.
Centre for Neuromuscular and Neurological Disorders, and Department of Medicine,
University of Western Australia, Nedlands, WA, Australia.
flmast@cyllene.uwa.edu.au
The initial approach to the treatment of patients with inflammatory myopathy
is
critical in determining the subsequent course and outcome. Prolonged
administration of high doses of corticosteroids should be avoided and a
second-line agent such as methotrexate or azathioprine should be introduced
earlier rather than later. Intravenous immunoglobulin therapy has an important
place if the myositis remains active, particularly in patients with
dermatomyositis, and is the treatment of choice in patients with
immunodeficiency who are not controlled by corticosteroids. In more resistant
cases of polymyositis or dermatomyositis it may be necessary to use
cyclophosphamide, cyclosporin or the promising newer immunosuppressive agents
mycophenolate mofetil or tacrolimus to achieve disease control. The treatment
of
inclusion body myositis remains unsatisfactory but a trial of prednisolone and
methotrexate is warranted in selected patients.
Publication Types:
Review
Review, Tutorial
PMID: 12464534 [PubMed - indexed for MEDLINE]
118: Med Hypotheses. 2003 Jan;60(1):94-101.
Magnesium may help patients with recessive hereditary inclusion body myopathy,
a
pathological review.
Darvish D.
HIBM Research Group, Encino, CA 91434, USA. dd@hibm.org
Recently, bi-allelic mutations in the gene coding for the bi-functional enzyme
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK), symbol
GNE or GLCNE (MIM: 603824), were associated with the recessively inherited
phenotype of IBM2 (MIM: 600737). All patients tested so far have bi-allelic
missense mutation(s) of epimerase and/or kinase domains of GNE gene, which
clearly explains the recessive inheritance pattern of this phenotype. Single
allelic mutations of codons 263-266 of GNE have been implicated as the cause
of
French type sialuria (MIM: 269921). The dominantly inherited French type
sialuria seems to result from defective allosteric feedback inhibitory
regulation of GNE/MNK by cytidine monophosphate-N-acetylneuraminic acid
(CMP-NANA), resulting in overproduction of cytosolic N-acetylneuraminic acid,
and massive urinary excretion of free sialic acid. Because GNE is relatively
weakly expressed in skeletal muscle cells, and involvement of other organs are
not clinically evident in patients affected with IBM2, it is likely that the
missense mutation(s) found in these patients cause a partial reduction of the
efficiency of either the epimerase or the kinase activity of this enzyme.
Therapeutic dietary modifications are recommended including reduction of ethanol
consumption, avoidance of excess selenium, copper, and zinc, and dietary
promotion of magnesium (Mg(2+)), which is an essential co-factor for this
enzyme.
Publication Types:
Review
Review, Tutorial
PMID: 12450772 [PubMed - indexed for MEDLINE]
119: J Neuroimmunol. 2002 Dec;133(1-2):198-204.
Evidence for heterogeneity of T cell expansion in polymyositis and inclusion
body myositis.
van der Meulen MF, van Wichen DF, van Blokland WT, van den Berg LH, Wokke JH,
Hoogendijk JE, de Weger RA.
Department of Neurology, G03.228, Division of Neuromuscular Disorders,
University Medical Center Utrecht, P.O. Box 85500 3508 GA, Utrecht, The
Netherlands. M.F.G.vdMeulen@neuro.zau.nl
Vbeta usage of muscle-infiltrating T lymphocytes in polymyositis (PM) and
sporadic inclusion body myositis (s-IBM) was correlated with clinical and
histopathological features. Immunohistochemical analysis was combined with
complementarity-determining region 3 (CDR3) length analysis in nine muscle
biopsies of eight PM patients and six biopsies of five s-IBM patients. Vbeta
usage was heterogeneous in seven patients. Four of these patients had definite
PM with endomysial located T cell infiltrates, but T cells specifically
surrounding and invading individual non-necrotic fibers were not found. In two
s-IBM patients, Vbeta 2 usage was increased. In one of them, a repeat biopsy
showed a heterogeneous Vbeta usage. We conclude that clonal expansion of
muscle-infiltrating T cells could only be detected in part of the patients.
Explanations may be that clonal expansion does not take place in all disease
phases and that PM is a heterogeneous disease with respect to pathogenesis.
PMID: 12446023 [PubMed - indexed for MEDLINE]
120: J Vet Diagn Invest. 2002 Nov;14(6):501-3.
Inclusion body myositis in spring peepers (Pseudacris crucifer).
Raymond JT, Reichard T, Shellabarger W, Nordhausen R, Garner MM.
Northwest ZooPath, Snohomish, WA 98296-4815, USA.
In 2000, 2 adult captive spring peepers (Pseudacris crucifer) from the same
zoological park were humanely euthanized. Histologically, both frogs had
degeneration, atrophy, and necrosis of striated myofibers of the tongue admixed
with chronic lymphohistiocytic inflammation. One frog had similar lesions in
the
skeletal muscles of the body wall. Several degenerate and necrotic myofibers
contained single, eosinophilic, intranuclear inclusion bodies. Ultrastructural
examination of the inclusions revealed nonenveloped, icosahedral, virus-like
particles averaging 20-24 nm in diameter. This is the first reported case of
inclusion body myositis in frogs and is believed to be due to parvoviral
infection.
Publication Types:
Case Reports
PMID: 12423034 [PubMed - indexed for MEDLINE]
121: Curr Opin Rheumatol. 2002 Nov;14(6):653-7.
Inclusion body myositis.
Tawil R, Griggs RC.
Department of Neurology, University of Rochester, Rochester, New York 14642,
USA. Rabi_Tawil@urmc.rochester.edu
Inclusion body myositis (IBM) is an inflammatory myopathy with distinctive
clinicopathologic features. The etiology of IBM remains elusive. The
immune-mediated basis for this disease has been challenged by evidence
implicating a number of divergent etiologic factors. These factors include
mitochondrial deletions, nitric oxide induced oxidative stress, myonuclear
breakdown, and abnormal accumulation within muscle fibers of brain-specific
Alzheimer type proteins. The treatment of IBM with conventional
immunosuppressive agents has been disappointing. Therapeutic approaches
currently under study or consideration are beta-interferon and synthetic
anabolic hormones.
Publication Types:
Review
Review, Tutorial
PMID: 12410086 [PubMed - indexed for MEDLINE]
122: Mol Genet Metab. 2002 Nov;77(3):252-6.
Four novel mutations associated with autosomal recessive inclusion body myopathy
(MIM: 600737).
Darvish D, Vahedifar P, Huo Y.
HIBM Research Group, 16661 Ventura Blvd., #311, Encino, CA 91436, USA.
ddarvish@hibm.org
Recently, mutations in the gene encoding for the bi-functional enzyme
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK), symbol
GNE or GLCNE (MIM: 603824) [EC 5.1.3.14], were associated with IBM2 (MIM:
600737). IBM2 is a recessively inherited vacuolar myopathy with a prevalence
rate of 1-2/1000 amongst people of Iranian-Jewish descent. Seven missense
mutations were previously described by Eisenberg et al. All families tested
from
Iranian and Middle Eastern Jewish ancestry have the same homozygous mutation
(bp2186t>c). Here we review the mutations in GNE associated with IBM2, and
we
describe additional four mutations found in individuals suffering from
clinically similar disorder who are not of Iranian or Jewish descent. These
findings further confirm that homozygous or compound heterozygous mutations
of
GNE/MNK gene associated with IBM2 are not confined to any single specific region
of the enzyme outside its negative feedback regulatory domain located at codons
249-275.
PMID: 12409274 [PubMed - indexed for MEDLINE]
123: Rev Neurol (Paris). 2002 Oct;158(10 Pt 1):948-58.
Understanding the immunopathogenesis of inclusion-body myositis: present and
future prospects.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, USA.
Sporadic Inclusion Body Myositis (s-IBM) is the most common acquired
inflammatory myopathy. It has a stereotypic clinical presentation and a
predictably progressive course that leads to severe muscle weakness and
permanent disability. The combination of primary endomysial inflammation with
autoimmune features identical to those seen in Polymyositis, and degenerative
features with vacuolization of muscle fibers and deposits of tiny speckles of
amyloid, are characteristic for the disease. In this review, the immunopathology
of IBM is detailed. The inflammation which is prominent even late in the
disease, is characterized by activated, CD8+ cytotoxic T cells that secrete
perforin and invade MHC-I-expressing muscle fibers. The autoinvasive T cells
are
probably antigen driven because of specific rearrangement of their T Cell
Receptor profile, restriction of the CDR3 region, upregulation of co-stimulatory
molecules and their ligands on the muscle fibers, and activation of various
cytokines, chemokines and adhesion molecules. The disease can be seen in
association with HIV and HTLV-I infection, but viruses have not been amplified
from the muscle fibers and the antigen or the factors that trigger inflammation
are still unknown. The disease is mysteriously resistant to conventional
immunotherapies in spite of the immunopathologic similarities with PM. The cause
of the vacuolar formation in IBM is also unknown and the role, that the tiny
amyloid deposits play in the disease remain unclear. The treatment approaches
and the prospects for future immunotherapeutic interventions are discussed.
Publication Types:
Review
Review, Tutorial
PMID: 12407303 [PubMed - indexed for MEDLINE]
124: Neuromuscul Disord. 2002 Nov;12(9):853-7.
Inclusion body myositis: morphological clues to correct diagnosis.
Dahlbom K, Lindberg C, Oldfors A.
Department of Neurology and Clinical Neurophysiology, Orebro University
Hospital, S-701 85, Orebro, Sweden.
The aim of this study was to investigate variability of morphological changes
found in patients with sporadic inclusion body myositis, to assess the
diagnostic value of muscle biopsy. The study included all 43 definite inclusion
body myositis patients (86 biopsies) diagnosed at Sahlgrenska University
Hospital, Gothenburg, Sweden, between 1984 and 2000. Invasion of mononuclear
inflammatory cells in non-necrotic muscle fibres was found in 72 of 86
specimens, while all investigated biopsies showed up-regulation of major
histocompatibility complex class I. Cytochrome c oxidase-negative muscle fibres
were demonstrated in 84 of 86 biopsies. Rimmed vacuoles were present in all
specimens from the vastus lateralis and tibialis muscles, and in 43 of 51
biopsies from the deltoid muscle. In cases with clinical suspicion of inclusion
body myositis, where the muscle biopsy does not show inflammatory cell
infiltration and rimmed vacuoles, inclusion body myositis should still be
considered if there are cytochrome c oxidase-negative fibres and up-regulation
of major histocompatibility complex class I. In such cases repeat muscle biopsy
may be helpful.
PMID: 12398837 [PubMed - indexed for MEDLINE]
125: Neurology. 2002 Oct 22;59(8):1170-82.
Comment in:
Neurology. 2002 Oct 22;59(8):1128-9.
Molecular profiles of inflammatory myopathies.
Greenberg SA, Sanoudou D, Haslett JN, Kohane IS, Kunkel LM, Beggs AH, Amato AA.
Department of Neurology, Brigham and Women's Hospital, 75 Francis Street,
Boston, MA 02115, USA. sagreenberg@partners.org
OBJECTIVE: To describe the use of large-scale gene expression profiles to
distinguish broad categories of myopathy and subtypes of inflammatory myopathies
(IM) and to provide insight into the pathogenesis of inclusion body myositis
(IBM), polymyositis, and dermatomyositis. METHODS: Using Affymetrix GeneChip
microarrays, the authors measured the simultaneous expression of approximately
10,000 genes in muscle specimens from 45 patients in four major disease
categories (dystrophy, congenital myopathy, inflammatory myopathy, and normal).
The authors separately analyzed gene expression in 14 patients limited to the
three major subtypes of IM. Bioinformatics techniques were used to classify
specimens with similar expression profiles based on global patterns of gene
expression and to identify genes with significant differential gene expression
compared with normal. RESULTS: Ten of 11 patients with IM, all normals and
nemaline myopathies, and 10 of 12 patients with Duchenne muscular dystrophy
were
correctly classified by this approach. The various subtypes of inflammatory
myopathies have distinct gene expression signatures. Specific sets of
immune-related genes allow for molecular classification of patients with IBM,
polymyositis, and dermatomyositis. Analysis of differential gene expression
identifies as relevant to disease pathogenesis previously reported cytokines,
major histocompatibility complex class I and II molecules, granzymes, and
adhesion molecules, as well as newly identified members of these categories.
Increased expression of actin cytoskeleton genes is also identified.
CONCLUSIONS: The molecular profiles of muscle tissue in patients with
inflammatory myopathies are distinct and represent molecular signatures from
which diagnostic insight may follow. Large numbers of differentially expressed
genes are rapidly identified.
Publication Types:
Validation Studies
PMID: 12391344 [PubMed - indexed for MEDLINE]
126: Curr Opin Neurol. 2002 Oct;15(5):525-31.
Inclusion-body myositis and myopathies: different etiologies, possibly similar
pathogenic mechanisms.
Askanas V, Engel WK.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, Los Angeles,
California 90017, USA. askanas@hsc.usc.edu
PURPOSE OF REVIEW: Sporadic inclusion-body myositis (s-IBM) and hereditary
inclusion body myopathies are progressive muscle diseases that lead to severe
disability. We discuss recent advances in illuminating their pathogenic
mechanism(s). RECENT FINDINGS: We emphasize how different etiologies might lead
to the strikingly similar pathology and possibly similar pathogenic cascade.
Our
basic hypothesis is that over-expression of amyloid-beta precursor protein
within aging muscle fibers is an early upstream event causing the subsequent
pathogenic cascade. On the basis of our research, several processes seem to
be
important in relation to the still speculative pathogenesis: (a) increased
transcription and accumulation of amyloid-beta precursor protein, and
accumulation of its proteolytic fragment Abeta; (b) accumulations of
phosphorylated tau and other Alzheimer-related proteins; (c) accumulation of
cholesterol and low-density lipoprotein receptors, the cholesterol accumulation
possibly due to its abnormal trafficking; (d) oxidative stress; and (e) a milieu
of muscle cellular aging in which these changes occur. We discuss unfolded
and/or misfolded proteins as a possible mechanism in formation of the inclusion
bodies and their consequences. The remarkable pathologic similarities between
s-IBM muscle and Alzheimer disease brain are discussed. SUMMARY: Unfolding
knowledge of the various pathogenetic aspects of the s-IBMs and hereditary
inclusion body myopathies may lead to new therapeutic avenues.
Publication Types:
Review
Review, Tutorial
PMID: 12351995 [PubMed - indexed for MEDLINE]
127: J Rheumatol. 2002 Sep;29(9):1897-906.
Comment in:
J Rheumatol. 2003 Aug;30(8):1892.
Magnetic resonance imaging criteria for distinguishing between inclusion body
myositis and polymyositis.
Dion E, Cherin P, Payan C, Fournet JC, Papo T, Maisonobe T, Auberton E, Chosidow
O, Godeau P, Piette JC, Herson S, Grenier P.
Department of Radiology, Institute of Myology, Paris, France.
elisabeth.dion@psl.ap-hop-paris.fr
OBJECTIVE: To develop diagnostic imaging criteria for polymyositis (PM) and
sporadic inclusion body myositis (sIBM). METHODS: We investigated 220 patients
with suspected inflammatory myopathies by magnetic resonance imaging (MRI).
Findings were compared with the results of clinical and biological examinations
and muscle biopsy. PM and IBM were diagnosed in 25 patients each. Quantitative
and qualitative MRI analysis of the 3 muscle groups of the 2 thighs included
fatty infiltration, atrophy, inflammation, and the type and distribution of
the
lesions. RESULTS: MRI was abnormal in all patients. Fatty infiltration and
atrophy were more frequent in patients with sIBM (p < 0.05). Inflammation
as the
sole abnormality was preferentially encountered in PM (p = 0.05). Widespread
abnormalities were more frequent in sIBM (p < 0.01). Abnormalities in PM
tended
to be distributed along the fascia. Involvement of the anterior group, an
asymmetrical distribution, and a distal predominance were all more frequent
in
sIBM (p < 0.001). CONCLUSION: Despite some overlap in MRI findings between
the 2
diseases, MRI was useful for distinguishing PM from sIBM.
PMID: 12233884 [PubMed - indexed for MEDLINE]
128: Curr Rheumatol Rep. 2002 Oct;4(5):427-33.
Newest pathogenetic considerations in inclusion-body myositis: possible role
of
amyloid-beta, cholesterol, relation to aging and to Alzheimer's disease.
Askanas V, Engel WK.
University of Southern California Neuromuscular Center, Good Samaritan Hospital,
637 South Lucas Avenue, Los Angeles, CA 90017-1912, USA. askanas@hsc.usc.edu
This report summarizes clinical features and diagnostic criteria, and the newest
advances related to seeking the pathogenic mechanism(s) of sporadic
inclusion-body myositis. On the basis of the authors' research, several
processes seem to be important in relation to the still-speculative
pathogenesis: increased transcription and accumulation of amyloid-b precursor
protein and accumulation of its proteolytic fragment amyloid-b; abnormal
accumulation of components related to lipid metabolism (eg, low-density
lipoprotein receptors and cholesterol; accumulation of cholesterol is possibly
caused by its abnormal trafficking); oxidative stress; accumulations of other
Alzheimer-related proteins including phosphorylated tau; a milieu of muscle
cellular aging in which these changes occur. The authors' basic hypothesis is
that overexpression of amyloid-b precursor protein within the aging muscle
fibers is an early upstream event causing the subsequent pathogenic cascade.
The
remarkable pathologic similarities between inclusion-body myositis muscle and
Alzheimer's disease brain are discussed.
Publication Types:
Review
Review, Tutorial
PMID: 12217248 [PubMed - indexed for MEDLINE]
129: Curr Rheumatol Rep. 2002 Oct;4(5):415-26.
Malignancy in patients with inflammatory myopathy.
Buchbinder R, Hill CL.
Cabrini Medical Centre, Suite 41, 183 Wattletree Road, Malvern, Victoria 3144,
Australia. rachelle.buchbinder@med.monash.edu.au
The most recent evidence from population-based cohort studies confirms the
association between malignancy and dermatomyositis and polymyositis. These
studies show an even stronger association between polymyositis and malignancy
than previous studies, suggesting less misclassification. This is particularly
true of one study that used pathologic criteria to distinguish between myositis
subtypes. Recent data also confirm that the association for dermatomyositis
and
polymyositis is not purely caused by diagnostic suspicion or surveillance bias.
More data are still required to determine individual cancer risks, although
it
appears that ovarian and lung cancer are associated with dermatomyositis while
lung cancer and non-Hodgkin's lymphoma are associated with polymyositis. An
association between malignant disease and inclusion body myositis has also been
verified for the first time. Of interest, too, is the increasing number of
reports documenting cases in which the clinical course of the myositis mirrors
that of the cancer, supporting the notion that in some instances, myositis is
a
paraneoplastic disorder.
Publication Types:
Review
Review, Tutorial
PMID: 12217247 [PubMed - indexed for MEDLINE]
130: Neurology. 2002 Aug 13;59(3):451-4.
Comment in:
Neurology. 2002 Dec 10;59(11):1674-6.
Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene.
Tomimitsu H, Ishikawa K, Shimizu J, Ohkoshi N, Kanazawa I, Mizusawa H.
Department of Neurology and Neurological Science, Graduate School, Tokyo Medical
and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
The authors present three novel missense mutations in the
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, the
causative gene for hereditary inclusion body myopathy, in Japanese patients
with
distal myopathy with rimmed vacuoles. Seven out of nine patients had homozygous
V572L mutation, one was a compound heterozygote with C303V and V572L mutations,
and the remaining patient bore homozygous A631V mutation.
PMID: 12177386 [PubMed - indexed for MEDLINE]
131: Acta Neuropathol (Berl). 2002 Sep;104(3):297-304. Epub 2002 Jun 08.
Expression, localization and functional divergence of alphaB-crystallin and
heat
shock protein 27 in core myopathies and neurogenic atrophy.
Fischer D, Matten J, Reimann J, Bonnemann C, Schroder R.
Department of Neurology, University Hospital Bonn, Rheinische
Friedrich-Wilhelms-Universitat, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
AlphaB-crystallin (alphaBC) and heat shock protein 27 (hsp 27) are members
of
the family of small heat shock proteins (shsps), which exert a role as molecular
chaperones by binding unfolded or denatured proteins, thereby suppressing
irreversible protein aggregation and consecutive cell damage. The essential
role
of shsps in human neuromuscular disorders is highlighted by the observation
that
a mutation of the human alphaBC gene causes an autosomal dominant "myofibrillar
myopathy" characterized by alphaBC and desmin accumulation. Furthermore,
an
aberrant immunostaining of alphaBC was recently reported in sporadic inclusion
body myositis. In the present study we analyzed the expression and localization
of alphaB-crystallin and hsp 27 in various congenital myopathies by means of
indirect immunofluorescence, immunogold electron microscopy and Western
blotting. We demonstrate an increased immunoreactivity of alphaBC and hsp 27
in
central and minicore lesions as well as in target fibers, which renders both
shsps as reliable, but nonspecific, markers for core and target structures.
In
contrast, Western blotting demonstrated a normal expression level of alphaBC
and
hsp 27, which indicates that the increased immunostaining is not the result
of
an enhanced protein expression. Furthermore, thiocyanate-induced degradation
of
actin filaments led to a dramatic decrease of hsp 27 immunostaining in core
and
target lesions, whereas the increased alphaBC and desmin immunostaining was
found to be even more enhanced. The latter findings imply a functional diversity
of both shsps with a preferential association of hsp 27 with the actin
microfilament system and alphaBC with the intermyofibrillar desmin cytoskeleton
in human skeletal muscle.
PMID: 12172916 [PubMed - indexed for MEDLINE]
132: Semin Neurol. 2002 Mar;22(1):41-51.
Misunderstandings, misperceptions, and mistakes in the management of the
inflammatory myopathies.
Kissel JT.
Department of Neurology, Ohio State University, Columbus, Ohio 43210-1250, USA.
Many misconceptions persist concerning fundamental issues related to the
idiopathic inflammatory myopathies. Such misconceptions can lead to frank
mistakes in the diagnosis and management of these disorders. In some cases,
these misperceptions have resulted from overreliance on out-of-date information
and "classic" articles that are no longer classic! In other instances,
misperceptions persist because of the many voids in our understanding of these
diseases. This review uses case presentations to highlight important caveats
in
diagnosing and managing the common idiopathic inflammatory myopathies.
Publication Types:
Case Reports
Review
Review, Tutorial
PMID: 12170392 [PubMed - indexed for MEDLINE]
133: Neurology. 2002 Jun 25;58(12):1779-85.
Differential expression of chemokines in inflammatory myopathies.
De Bleecker JL, De Paepe B, Vanwalleghem IE, Schroder JM.
Department of Neurology, University Hospital, Gent, Belgium.
jan.debleecker@rug.ac.be
BACKGROUND: Chemokines represent a family of small-molecular-weight cytokines
that recruit and activate inflammatory cells in response to inflammation.
Invasion of cytotoxic memory T cells and macrophages in nonnecrotic muscle
fibers characterizes polymyositis and sporadic inclusion body myositis.
Dermatomyositis is a complement-mediated endotheliopathy. Elucidation of the
mechanisms guiding lymphocyte diapedesis and trafficking could lead to selective
therapeutic interventions. METHODS: Immunoblots and multistep immunofluorescence
studies with non-cross-reactive antibodies recognizing interleukin-8, monocyte
chemoattractant protein-1 (MCP-1), MCP-3, TARC (thymus and activation regulated
cytokine), and RANTES (regulated upon activation, normal T-cell expressed and
secreted), using appropriate positive and negative controls. In situ
hybridization was used to localize MCP-1 mRNA. RESULTS: MCP-1 protein was
strongly expressed on T cells and a subset of macrophages actively invading
a
proportion of the nonnecrotic muscle fibers in polymyositis and inclusion body
myositis alike. Capillaries and arterioles in the vicinity of endomysial
inflammatory foci were immunoreactive for MCP-1, with faint or no expression
in
unaffected parts of the tissue. By contrast, widespread and strong endothelial
MCP-1 expression occurred on perifascicular and perimysial endothelia in
dermatomyositis, also at sites remote from inflammatory infiltrates. In some
control specimens, a subset of capillaries also expressed MCP-1, possibly
reflecting a role of this chemokine in normal immune surveillance. MCP-1 mRNA
was detected in scattered macrophages in each inflammatory myopathy. All other
chemokines were absent. CONCLUSION: Chemokines are differentially expressed
in
the symptomatic stage of inflammatory myopathies. MCP-1 plays a major role in
the myocytotoxicity in polymyositis and inclusion body myositis. MCP-1 may be
induced by membranolytic attack complex binding to endothelial cells in
dermatomyositis.
PMID: 12084877 [PubMed - indexed for MEDLINE]
134: Acta Neurol Scand. 2002 May;105(5):403-7.
Expression of Bcl-2 in inclusion body myositis.
Fyhr IM, Lindberg C, Oldfors A.
Department of Pathology, Sahlgrenska University Hospital, Goteborg University,
S-413 45 Goteborg, Sweden. ingmarie.fyhr@path.gu.se
OBJECTIVES: On the background of the possible role of the anti-apoptotic protein
Bcl-2 to inhibit apoptosis induced by the Fas/Fas ligand system in inflammatory
myopathies we investigated the expression of Bcl-2 in inclusion body myositis
(IBM). MATERIAL AND METHODS: We examined muscle tissue from seven IBM patients
and controls by immunocytochemistry using antibodies against Bcl-2, Fas (a
member of the tumor necrosis factor receptor family) and the regeneration
marker, neural cell adhesion molecule (N-CAM). We also investigated the
occurrence of DNA fragmentation by the terminal deoxynucleotidyl transferase
(TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling
(TUNEL)-method. RESULTS: Both Bcl-2 and Fas were up-regulated in muscle fibers
in IBM and disease controls. Bcl-2 was expressed by regenerating muscle fibers
while Fas was expressed by non-regenerating muscle fibers associated with
inflammatory cell infiltrates. Bcl-2 and Fas were also expressed by inflammatory
cells. There were scattered TUNEL positive nuclei and most of these appeared
to
be inflammatory cells. CONCLUSION: The low occurrence of apoptotic myonuclei
is
not related to Bcl-2 expression, which is confined to regenerating muscle cells
in IBM and other myopathies.
PMID: 11982494 [PubMed - indexed for MEDLINE]
135: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6334-9. Epub 2002 Apr 23.
Inclusion body myositis-like phenotype induced by transgenic overexpression
of
beta APP in skeletal muscle.
Sugarman MC, Yamasaki TR, Oddo S, Echegoyen JC, Murphy MP, Golde TE, Jannatipour
M, Leissring MA, LaFerla FM.
Department of Neurobiology and Behavior, University of California, Irvine,
CA
92697, USA.
Inclusion body myositis (IBM), the most common age-related muscle disease in
the
elderly population, is an incurable disorder leading to severe disability.
Sporadic IBM has an unknown etiology, although affected muscle fibers are
characterized by many of the pathobiochemical alterations traditionally
associated with neurodegenerative brain disorders such as Alzheimer's disease.
Accumulation of the amyloid-beta peptide, which is derived from proteolysis
of
the larger amyloid-beta precursor protein (betaAPP), seems to be an early
pathological event in Alzheimer's disease and also in IBM, where in the latter,
it predominantly occurs intracellularly within affected myofibers. To elucidate
the possible role of betaAPP mismetabolism in the pathogenesis of IBM,
transgenic mice were derived in which we selectively targeted betaAPP
overexpression to skeletal muscle by using the muscle creatine kinase promoter.
Here we report that older (>10 months) transgenic mice exhibit intracellular
immunoreactivity to betaAPP and its proteolytic derivatives in skeletal muscle.
In this transgenic model, selective overexpression of betaAPP leads to the
development of a subset of other histopathological and clinical features
characteristic of IBM, including centric nuclei, inflammation, and deficiencies
in motor performance. These results are consistent with a pathogenic role for
betaAPP mismetabolism in human IBM.
PMID: 11972038 [PubMed - indexed for MEDLINE]
136: J Neurol Neurosurg Psychiatry. 2002 May;72(5):650-2.
Human T cell leukaemia virus type I associated neuromuscular disease causing
respiratory failure.
Littleton ET, Man WD, Holton JL, Landon DN, Hanna MG, Polkey MI, Taylor GP.
The National Hospital for Neurology and Neurosurgery, University College London
Hospitals NHS Trust, Queen Square, London, UK.
Polymyositis and inclusion body myositis have rarely been described in
association with human T cell leukaemia virus type I (HTLV-I) infection. Most
of
such patients have coexisting HTLV-I associated myelopathy (HAM). Two patients
with HTLV-I infection, myopathy, and respiratory failure are described. The
muscle biopsy specimen of the first patient bore the histological features of
inclusion body myositis and there was no evidence of concurrent myelopathy.
The
second patient had HAM, and her muscle biopsy showed non-specific myopathic
and
neuropathic changes. Both patients developed respiratory muscle weakness over
eight years after diagnosis of myopathy, leading to hypercapnic respiratory
failure requiring mechanical ventilatory support. Respiratory failure as a
complication of HTLV-I associated myopathy has not previously been described.
Publication Types:
Case Reports
PMID: 11971056 [PubMed - indexed for MEDLINE]
137: Rheumatology (Oxford). 2002 Apr;41(4):440-4.
Primary Sjogren's syndrome associated with inclusion body myositis.
Kanellopoulos P, Baltoyiannis C, Tzioufas AG.
Department of Pathophysiology, School of Medicine, University of Athens, Greece.
OBJECTIVE: To describe three new patients with inclusion body myositis (IBM)
associated with primary Sjogren's syndrome (pSS) and summarize the clinical
and
serological picture for all six patients reported so far. PATIENTS AND METHODS:
Three out of 518 (0.6%) pSS patients followed in our department over a period
of
15 yr (1985-2000) also presented IBM. The diagnosis was based on histological
criteria. Previous reports described four more patients with IBM associated
with
pSS. Five out of six were females; the mean age of IBM onset was 53.3+/-14.0
yr
and the disease duration 8.0+5.8 yr. RESULTS: Four out of six patients presented
IBM several years after the onset of pSS. Four out of six patients presented
extraglandular manifestations, such as arthralgias, vitamin B12 deficiency,
interstitial kidney disease and biliary cirrhosis. The serological picture did
not differ significantly from that observed in pSS alone. CONCLUSION: Although
rare, IBM may be seen in patients with pSS and it affects predominantly women.
The clinical and pathological pictures do not differ from those observed in
idiopathic IBM. A common autoimmune pathway in these two diseases, but no
definite conclusions can be drawn.
Publication Types:
Case Reports
PMID: 11961175 [PubMed - indexed for MEDLINE]
138: J Neurol. 2002 Jan;249(1):69-75.
Clinical and serological characteristics of 125 Dutch myositis patients.
Myositis specific autoantibodies aid in the differential diagnosis of the
idiopathic inflammatory myopathies.
Hengstman GJ, Brouwer R, Egberts WT, Seelig HP, Jongen PJ, van Venrooij WJ,
van
Engelen BG.
Neuromuscular Centre Nijmegen, Institute of Neurology, University Medical Centre
Nijmegen, The Netherlands. g.hengstman@czzoneu.azn.nl
The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of
systemic diseases that include the familiar disease entities of dermatomyositis
(DM), polymyositis (PM), and inclusion body myositis (IBM). A subset of patients
has unique autoantibodies which are specific for IIM (myositis specific
autoantibodies; MSAs). We studied the clinical and serological characteristics
of IIM in 125 Dutch patients. Sera were analysed by immunoblotting,
enzyme-linked immunosorbent assay, and immunoprecipitation. The most frequently
encountered MSA was the anti-Jo-1 autoantibody (20%), followed by anti-tRNAHis
(6%), anti-Mi-2 (6%), and anti-SRP (4%). The presence of certain MSAs was
clearly associated with specific clinical characteristics. Anti-Jo-1 and
anti-tRNAHis were associated with the anti-synthetase syndrome, anti-SRP with
PM
with severe myalgia and arthralgia and a moderate response to immunosuppressive
treatment. A novel finding was the presence of anti-Mi-2, not only in DM, but
also in PM. MSAs were frequently present in DM/PM sera, but were hardly ever
detected in the sera of IBM patients. The few IBM patients with MSAs
demonstrated a significant response to immunosuppressive treatment. It can be
concluded that MSAs define specific clinical syndromes within the spectrum of
IIM and that they can assist in the differential diagnosis and treatment plan
of
these enigmatic disorders by virtually excluding IBM by their presence, and
by
potentially identifying a subgroup of steroid-responsive IBM patients.
PMID: 11954871 [PubMed - indexed for MEDLINE]
139: J Rheumatol. 2002 Apr;29(4):717-25.
Subclinical myositis is common in primary Sjogren's syndrome and is not related
to muscle pain.
Lindvall B, Bengtsson A, Ernerudh J, Eriksson P.
Department of Clinical Neurosciences and Locomotion, University Hospital,
Linkoping, Sweden. Bjorn.Lindvall@lio.se
OBJECTIVE: Although muscle pain is common in primary Sjogren's syndrome (SS),
the underlying mechanisms are mainly unknown. We studied all patients with SS
at
our rheumatology unit with respect to muscle pain in general and to fibromyalgia
(FM), and correlated clinical data to muscle biopsy findings. METHODS: We
investigated 48 patients with SS according to the modified European diagnostic
criteria. The ACR criteria for FM were used to subgroup the patients. Muscle
biopsy was performed in 36 patients. Light microscope morphology and
immunohistochemical expression of MHC class I, MHC class II, and membrane attack
complex (MAC) were studied. RESULTS: We found 44% of patients complained of
muscle pain; 27% fulfilled the ACR criteria for FM, whereas 17% had other forms
of myalgia. Muscle pain could not be related to histopathological findings.
Signs of inflammation were found in 26 of 36 biopsies (72%), and inflammation
combined with degeneration/regeneration (i.e., histological signs of
polymyositis) in 17 biopsies (47%). However, only 5 patients (14%) had clinical
as well as histological signs of polymyositis. Eight muscle biopsies (22%)
showed histological features of inclusion body myositis (IBM). However, no
patient had clinical symptoms suggestive of this disease. Abnormal expression
of
MHC class I, MHC class II, and MAC was found in 18 (50%), 16 (44%), and 27 (75%)
patients, respectively. CONCLUSION: Muscle pain, especially FM, is common in
SS.
Histopathological signs of myositis are very common in SS. However, muscle
symptoms are not related to histological signs of muscle inflammation. IBM-like
findings may represent vacuolar myopathic degeneration due to previous
subclinical muscle inflammation rather than a specific clinical entity.
PMID: 11950012 [PubMed - indexed for MEDLINE]
140: Neurology. 2002 Apr 9;58(7):1081-7.
A pilot randomized trial of oxandrolone in inclusion body myositis.
Rutkove SB, Parker RA, Nardin RA, Connolly CE, Felice KJ, Raynor EM.
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical
School, Boston, MA 02215, USA. srutkove@caregroup.harvard.edu
BACKGROUND: Inclusion body myositis (IBM) remains without effective therapy.
As
anabolic steroids have myotrophic properties, the authors studied whether a
synthetic androgen, oxandrolone, would have efficacy in IBM. METHODS: A
double-blind, placebo-controlled, crossover design was used. Patients received
oxandrolone or placebo for 12 weeks followed by a minimum 2-month washout
period, followed by 12 weeks of the alternative treatment. Maximal voluntary
isometric contraction testing (MVICT), manual muscle testing (MMT), and
functional performance testing were obtained before and after each treatment
period, with the whole-body MVICT score as the primary outcome measure. RESULTS:
Of 19 patients enrolled, 16 (14 men, 2 women; median age 68.5 years) had
complete data for at least the first treatment period, with 13 completing the
entire study. Whole-body MVICT improved by a median of 15.5 kg with drug and
4.1
kg with placebo (p = 0.06), whereas MMT demonstrated a median increase of 2.0
Medical Research Council points with drug and 0.9 point with placebo (p = 0.33).
Upper-extremity MVICT demonstrated a significant treatment effect, with strength
increasing a median 6.3 kg with drug vs 2.5 kg with placebo (p = 0.006). Stair
climbing also increased a median of 1 step on average with drug versus no change
with placebo (p < 0.001). Minimal adverse effects occurred. CONCLUSIONS:
Oxandrolone had a borderline significant effect in improving whole-body strength
and a significant effect in improving upper-extremity strength as measured by
MVICT. Given these findings, further study of this drug, possibly in combination
with an immunomodulating agent, is warranted.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 11940697 [PubMed - indexed for MEDLINE]
141: Acta Neurol Scand. 2002 Apr;105(4):309-13.
Matrix metalloproteinases in inflammatory myopathies: enhanced immunoreactivity
near atrophic myofibers.
Schoser BG, Blottner D, Stuerenburg HJ.
Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximillians
University Munich, Munich, Germany. benedikt.schoser@fbs.med.uni-muenchen.de
OBJECTIVES: To further examine the role of proteolytic enzyme expression of
matrix metalloproteinases (MMP) and T-cell markers in inflammatory myopathies
and controls. MATERIAL AND METHODS: We studied the expression of MMP-2, MMP-7,
and MMP-9 in 19 cases of inflammatory myopathies and controls using
immunocytochemistry. RESULTS: Inflammatory myopathies showed distinct patterns
of up-regulation of MMP. MMP-9 was strongly expressed in atrophic myofibers
in
all inflammatory myopathies. MMP-2 immunoreactivity was similar in its
distribution, however, to a weaker intensity. In dermatomyositis the
perifascicular atrophy showed pronounced MMP-9 immunoreactivity, probably
reflecting denervated patterns of myofibers. Moreover, MMP-7 strongly
immunolabeled invaded myofibers in polymyositis cases only. CONCLUSION: These
patterns confirm, that MMP-7 up-regulation is prominent in PM, while MMP-2
immunoreactivity is only slightly elevated in inflamed muscle. In general, MMP-9
up-regulation appears to be an important additional molecular event in the
multistep process of all inflammatory myopathies.
PMID: 11939944 [PubMed - indexed for MEDLINE]
142: Pediatr Dev Pathol. 2002 Mar-Apr;5(2):151-8.
Aluminum phagocytosis in quadriceps muscle following vaccination in children:
relationship to macrophagic myofasciitis.
Lacson AG, D'Cruz CA, Gilbert-Barness E, Sharer L, Jacinto S, Cuenca R.
Departments of Pediatrics and Pathology, University of South Florida at All
Children's Hospital, 801 Sixth Street South 7020, St. Petersburg, FL 33731,
USA.
Macrophagic myofasciitis (MMF) is a rare, seemingly emerging entity among adult
patients in France. We encountered two children with the first two cases of
MMF
in North America. A 5-year-old male with chronic intestinal pseudo-obstruction
required nighttime parenteral nutrition. Abnormal pupillary reflexes and urinary
retention suggested a diffuse dysautonomia, which prompted a neurological
diagnostic work-up. A 3-year-old child had developmental delay and hypotonia.
Both children received age-appropriate immunizations. Quadriceps muscle biopsy
from each child showed the typical patchy, cohesive centripetal infiltration
of
alpha-1-antitrypsin+, alpha-1-antichymotrypsin+, CD68+, PAS+, CD1a-, S-100-,
factor XIII- granular macrophages with adjacent myofiber atrophy, dilated blood
vessels, and mild endomysial and perimysial fibrosis. No myonecrosis was
observed and no discrete granulomas were seen. A single aluminum peak was
demonstrated on energy dispersive X-ray microanalysis. The etiology of the
clinical symptoms in these cases and in cases reported as MMF remains
intriguing. Despite numerous stains to demonstrate organisms, most infectious
causes leading to macrophage activation were ruled out. These cases are being
reported to increase awareness of this condition and to encourage a systematic
epidemiologic and clinicopathologic study in North America.
Publication Types:
Case Reports
PMID: 11910509 [PubMed - indexed for MEDLINE]
143: Ann Neurol. 2002 Mar;51(3):369-72.
Comparison of weakness progression in inclusion body myositis during treatment
with methotrexate or placebo.
Badrising UA, Maat-Schieman ML, Ferrari MD, Zwinderman AH, Wessels JA, Breedveld
FC, van Doorn PA, van Engelen BG, Hoogendijk JE, Howeler CJ, de Jager AE,
Jennekens FG, Koehler PJ, de Visser M, Viddeleer A, Verschuuren JJ, Wintzen
AR.
Department of Neurology, Leiden University Medical Center, The Netherlands.
ubadrising@lumc.nl
We investigated whether 5 to 20mg per week oral methotrexate could slow down
disease progression in 44 patients with inclusion body myositis in a randomized
double-blind placebo-controlled study over 48 weeks. Mean change of quantitative
muscle strength testing sum scores was the primary study outcome measure.
Quantitative muscle strength testing sum scores declined in both treatment
groups, -0.2% for methotrexate and -3.4% for placebo (95% confidence interval
=
-2.5% to +9.1% for difference). There were also no differences in manual muscle
testing sum scores, activity scale scores and patients' own assessments after
48
weeks of treatment. Serum creatine kinase activity decreased significantly in
the methotrexate group. We conclude that oral methotrexate did not slow down
progression of muscle weakness but decreased serum creatine kinase activity.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 11891832 [PubMed - indexed for MEDLINE]
144: Neurology. 2002 Mar 12;58(5):780-6.
Myosin heavy chain IIa gene mutation E706K is pathogenic and its expression
increases with age.
Tajsharghi H, Thornell LE, Darin N, Martinsson T, Kyllerman M, Wahlstrom J,
Oldfors A.
Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
BACKGROUND: The authors recently described a new autosomal dominant myopathy
(OMIM 605637 inclusion body myopathy 3) associated with a missense mutation
in
the myosin heavy chain (MyHC) IIa gene (MyHC IIa, Human Gene Map [HGM] locus
MYH2). Young patients showed minor changes in their muscle biopsies, although
dystrophic alterations and rimmed vacuoles with 15- to 20-nm tubulofilaments
identical to those in sporadic inclusion body myositis (s-IBM) were observed
in
some of the adult (especially older) patients. The current study was undertaken
to investigate the relation between expression of the mutant MyHC IIa and
pathologic changes in muscle. METHODS: The expression of MyHC IIa in nine muscle
specimens from six individuals carrying the mutation was analyzed by
immunohistochemistry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
and a new reverse transcriptase--PCR method to measure the relative abundance
of
the various MyHC transcripts. RESULTS: Young patients with muscle weakness and
minor pathologic changes in muscle expressed MyHC IIa at undetectable levels.
MyHC IIa was expressed at high levels in adults with a progressive clinical
course and dystrophic muscle changes. In these cases, a large number of muscle
fibers were hybrids with expression of more than one MyHC isoform. Both MyHC
IIa
alleles were equally expressed. The relative level of MyHC IIa transcripts
exceeded that of the corresponding protein, indicating an increased turnover
of
mutated protein. MyHC IIa expression was a consistent finding in muscle fibers
with rimmed vacuoles. CONCLUSIONS: The clear correlation between pathologic
changes and expression of MyHC IIa indicates that defects in MyHC may lead not
only to muscle weakness but also to muscle degeneration. The consistent
expression of MyHC IIa in muscle fibers with rimmed vacuoles indicates that
the
breakdown of sarcomeric proteins is a key element in the pathogenesis of rimmed
vacuoles of s-IBM type.
PMID: 11889243 [PubMed - indexed for MEDLINE]
145: Muscle Nerve. 2002 Mar;25(3):390-7.
Localized bioimpedance analysis in the evaluation of neuromuscular disease.
Rutkove SB, Aaron R, Shiffman CA.
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical
School, 330 Brookline Avenue, TCC-810, Boston, Massachusetts 02215, USA.
Localized bioimpedance analysis is a novel, noninvasive technique with potential
application to neuromuscular disease. In this procedure, high-frequency
alternating current is passed through muscle, and parameters related to the
consequent voltage pattern are evaluated. Currents flowing perpendicular to
muscle fibers encounter many more cell membranes than do currents flowing
parallel to them, producing surface voltage patterns that are altered by
disease. Using this technique, 45 normal subjects and 25 patients with various
neuromuscular diseases were studied, including 4 with amyotrophic lateral
sclerosis, 4 with inflammatory myopathy, and 11 with inclusion-body myositis.
Two parameters, the spatially averaged phase and the effective longitudinal
resistivity, were altered in patients with neuromuscular disease. Reductions
in
phase correlated to disease progression, whereas normalization of phase
correlated with disease remission. In patients with inclusion-body myositis,
a
unique pattern of reduced phase and elevated resistivity was identified. These
findings suggest that localized bioimpedance analysis has the potential of
playing a substantial role in the diagnostic and therapeutic evaluation of
neuromuscular disease. Copyright 2002 Wiley Periodicals, Inc.
PMID: 11870716 [PubMed - indexed for MEDLINE]
146: Neurology. 2002 Feb 12;58(3):438-45.
Three lipoprotein receptors and cholesterol in inclusion-body myositis muscle.
Jaworska-Wilczynska M, Wilczynski GM, Engel WK, Strickland DK, Weisgraber KH,
Askanas V.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, 637 S. Lucas Ave.,
Los Angeles, CA 90017-1912, USA.
BACKGROUND: An important aspect of inclusion-body myositis (IBM) vacuolated
muscle fibers (VMF) is abnormal accumulation of amyloid-beta precursor protein
(AbetaPP) epitopes and its product, amyloid-beta (Abeta), and of phosphorylated
tau (p-tau) in the form of paired helical filaments. Lipoprotein receptors and
cholesterol are known to play an important role in AbetaPP processing, Abeta
production, and tau phosphorylation. METHODS: In 10 IBM and 22 control muscle
biopsies the authors immunolocalized low-density lipoprotein receptor (LDLR),
very low-density lipoprotein receptor (VLDLR), and low-density lipoprotein
receptor-related protein (LRP), and colocalized them with Abeta, p-tau, APOE,
and free cholesterol. RESULTS: In each biopsy, virtually all IBM VMF had strong
LDLR-immunoreactive inclusions, which colocalized with Abeta, APOE, p-tau, and
free cholesterol. VLDLR was increased mainly diffusely, but in approximately
50%
of the VMF it was also accumulated in the form of inclusions colocalizing with
Abeta, APOE, and free cholesterol, but not with p-tau. LRP inclusions were
present in a few VMF. In all myopathies, a subset of regenerating and
necrotizing muscle fibers had prominent diffuse accumulation of both LDLR and
free cholesterol. At normal neuromuscular junctions (NMJ) postsynaptically,
LDLR
and VLDLR, but not LRP, were immunoreactive. CONCLUSIONS: 1) Abnormal
accumulation of LDLR, VLDLR, LRP, and cholesterol within IBM vacuolated muscle
fibers suggests novel roles for them in the IBM pathogenesis. 2) Expression
of
LDLR and VLDLR at normal NMJ suggests physiologic roles for them in
transsynaptic signaling pathways, increased internalization of lipoproteins
there, or both. 3) Increased LDLR and free cholesterol in some regenerating
and
necrotizing muscle fibers suggest a role for them in human muscle fiber growth
and repair and necrotic death.
PMID: 11839845 [PubMed - indexed for MEDLINE]
147: Acta Neuropathol (Berl). 2002 Jan;103(1):59-65.
Increased expression of manganese superoxide dismutase is associated with that
of nitrotyrosine in myopathies with rimmed vacuoles.
Tsuruta Y, Furuta A, Taniguchi N, Yamada T, Kira J, Iwaki T.
Department of Neuropathology, Neurological Institute, Graduate School of Medical
Sciences, Kyushu University, Fukuoka, Japan.
Oxidative stress has been suggested as one of the pathogenetic mechanisms of
inclusion body myositis (IBM). To study the role of antioxidant enzymes in
myopathies with rimmed vacuoles, we examined expressions of copper, zinc
superoxide dismutase (Cu, Zn-SOD) and manganese superoxide dismutase (Mn-SOD),
and the relationship between SODs and other proteins localized in rimmed
vacuoles in muscle biopsy specimens from three cases of sporadic IBM and two
of
distal myopathy with rimmed vacuoles (DMRV) as well as eight control cases of
myopathies without rimmed vacuoles. Immunoblot analysis showed distinct protein
bands of both SODs in IBM and DMRV using subtype-specific antibodies.
Intensities of immunoreactive bands for Mn-SOD in IBM and DMRV were stronger
than those in the control cases. Immunohistochemistry disclosed accumulation
of
both SODs in vacuolated muscle fibers in all cases of IBM and DMRV.
Immunoreactivity for Mn-SOD was often colocalized with that of nitrotyrosine,
cytochrome oxidase, tau, and lysosome-associated membrane proteins 2 (LAMP-2)
in
vacuolated fibers. Some of the Cu, Zn-SOD-positive vacuolated fibers were
associated with ubiquitin. The two SODs may have different roles for cell
protection, and the expression of Mn-SOD is associated with nitric oxide-induced
oxidative damage in myopathies with rimmed vacuoles.
PMID: 11837748 [PubMed - indexed for MEDLINE]
148: Acta Paediatr Taiwan. 2001 Nov-Dec;42(6):367-9.
Stiff-Baby--an unusual manifestation of cytoplasmic body myopathy: report of
one
case.
Chen YD, Chen CH, Mak SC, Chi CS.
Department of Pediatrics, Taichung Veterans General Hospital, Taiwan.
A 2-month-old male baby was admitted to our hospital with episodic cyanosis
and
respiratory failure which required mechanical ventilation. He was found to have
upper limb flexion rigidity and poor weight gain since one month old.
Progressive muscle stiffness over the abdomen, chest wall, back and four limbs
were also noted. He could not be weaned from the ventilator smoothly due to
recurrent CO2 retention. Laboratory tests revealed a high serum creatine kinase
level. Cytoplasmic body myopathy was confirmed by muscle biopsy. The unusual
initial presentations of generalized stiffness and early onset of respiratory
failure were quite different from those of patients reported in the literature,
who had floppiness, muscular atrophy and weakness. Prednisolone and Vigabatrin
were given and the patient showed slight improvement in muscle stiffness and
spontaneous movement.
Publication Types:
Case Reports
PMID: 11811228 [PubMed - indexed for MEDLINE]
149: Neurology. 2002 Jan 22;58(2):326.
Intravenous immunoglobulin for dysphagia of inclusion body myositis.
Cherin P, Pelletier S, Teixeira A, Laforet P, Simon A, Herson S, Eymard B.
Service de Medecine Interne I, Hopital Salpetriere, Paris, France.
patrick.cherin@psl.ap-hop-paris.fr
Publication Types:
Case Reports
PMID: 11805271 [PubMed - indexed for MEDLINE]
150: Arch Pathol Lab Med. 2002 Jan;126(1):105-6.
Pathologic quiz case: male with chronic progressive painless muscle weakness.
Ciliberti EF, Prayson RA.
Department of Neurology, Cleveland Clinic Florida, Fort Lauderdale, USA.
Publication Types:
Case Reports
PMID: 11800662 [PubMed - indexed for MEDLINE]
151: J Neurol Neurosurg Psychiatry. 2002 Feb;72(2):203-10.
An expanded cortical representation for hand movement after peripheral motor
denervation.
Reddy H, Bendahan D, Lee MA, Johansen-Berg H, Donaghy M, Hilton-Jones D,
Matthews PM.
Centre for Functional Magnetic Resonance Imaging of the Brain (fMRIB),
Department of Clinical Neurology, University of Oxford, Oxford, UK.
OBJECTIVES: Functional reorganisation of the motor or sensory cortex has been
demonstrated in animals after section of mixed peripheral nerves. Here
functional changes in the motor cortex specifically after peripheral motor
denervation in humans are investigated. METHODS: Functional MRI (fMRI) was used
to study brain activation during a finger flexion-extension task in patients
with a late onset, acquired pure motor neuropathy (n=6), contrasting results
with those from patients with pure sensory neuropathies (n=4) or healthy
controls (n=7). RESULTS: Increases in the extent of activation in the motor
cortex both ipsilateral and contralateral to the hand moved were found in the
patients with motor neuropathy. The neuroanatomical localisation of the mixed
contralateral sensorimotor cortex activation volume was more posterior for the
patients with motor neuropathy than for the healthy controls (mean difference,
12 mm, p<0.05). The pure sensory neuropathy group by contrast showed no change
in the extent of activation relative to healthy controls and a trend for more
anterior primary sensorimotor cortex activation (p<0.06). To test whether
the
increased activation volumes found in patients with motor neuropathy were a
result simply of factors such as increased effort with movement rather than
the
motor denervation, patients with hand weakness from inclusion body myositis
(n=4) were studied while making similar hand movements. No differences in either
the numbers of significantly activated voxels or in their localisation were
found relative to healthy controls (n=10). CONCLUSIONS: These results provide
a
novel demonstration that peripheral denervation (as distinguished from factors
related to weakness) leads to functional reorganisation of the sensorimotor
cortex in the adult brain. This suggests that adaptive responses to motor
denervation involve the central as well as the peripheral nervous system.
PMID: 11796770 [PubMed - indexed for MEDLINE]
152: Rheumatology (Oxford). 2002 Jan;41(1):22-6.
Outcome in patients with idiopathic inflammatory myositis: morbidity and
mortality.
Sultan SM, Ioannou Y, Moss K, Isenberg DA.
Centre for Rheumatology, Department of Medicine, University College Hospital,
London W1P 9PG, UK.
OBJECTIVE: To assess the long-term outcome of a cohort of 46 patients with
idiopathic myositis by assessing both health status, as measured by the SF-36,
and cumulative survival probability over a 20-yr follow-up period at a single
rheumatology centre. Methods and results. Forty-six patients under long-term
follow-up from 1978 to 1999 were identified from our database. All patients
fulfilled three out of four of the Bohan and Peter criteria for myositis. We
excluded those with malignancy-associated disease and those with inclusion body
myositis. Twenty-three patients (50%) had adult-onset polymyositis, 14 (30.4%)
had adult-onset dermatomyositis, one had childhood-onset dermatomyositis and
eight (17.4%) had an overlap syndrome (associated with either systemic lupus
erythematosus or rheumatoid arthritis). During the course of the disease, seven
patients (15.2%) went into full remission, eight (17.4%) had monophasic illness,
nine (19.6%) had a relapsing-remitting course, 16 (34.8%) had chronic
progressive illness and six (13.04%) died. All patients had significantly lower
SF-36 scores in all aspects of health compared with the general population (P<
or =0.001). Patients with chronic progressive illness had significantly greater
bodily pain (P< or =0.05, t-test) than those with a relapsing-remitting illness,
but did not differ in other aspects of health. There was no significant
difference in the scores in the different domains of the SF-36 between the
patients with active disease and those with inactive disease (0.05<P<0.1).
Six
of the 46 patients died. Cumulative survival probability was calculated. The
five-year survival rate was 95% and the 10-yr survival rate 83.8%. CONCLUSION:
Patients with myositis report significantly poorer health compared with the
general population. Health status and disease activity are important outcome
measures in the assessment of patients with myositis.
PMID: 11792875 [PubMed - indexed for MEDLINE]
153: Fukuoka Igaku Zasshi. 2001 Nov;92(11):370-6.
Inclusion body myositis associated with hepatitis C virus infection.
Tsuruta Y, Yamada T, Yoshimura T, Satake M, Ogata K, Yamamoto T, Furuya H,
Kira
J.
Department of Neurology, Neurological Institute, Graduate School of Medical
Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582,
Japan.
Inclusion body myositis (IBM) is a chronic progressive inflammatory myopathy
in
elders. Three patients with chronic hepatitis C developed IBM. Their muscle
biopsies were examined by polymerase chain reaction (PCR) for two patients and
immunohistochemistry for three patients. The hepatitis C virus (HCV)-RNA genome
was detected in one of the two patients. The degenerated and atrophic muscle
fibers were immunoreactive for an anti-HCV antibody in all three patients.
Immunoreactivity for an anti-HCV antibody was not apparent in the muscle
specimen from an IBM patient without HCV infection. Our findings suggest that
HCV infection is related to the pathogenesis in some cases of IBM.
PMID: 11774706 [PubMed - indexed for MEDLINE]
154: Expert Opin Investig Drugs. 2001 Jul;10(7):1265-77.
Recent advances in the management of adult myositis.
Fam AG.
Division of Rheumatology, Sunnybrook and Women's College Health Sciences Centre,
University of Toronto, Toronto, Ontario, Canada. adel.fam.@swchsc.on.ca
Standard drug therapy of adult polymyositis, dermatomyositis and inclusion
body
myositis includes high-dose corticosteroids and cytotoxic drugs (methotrexate,
azathioprine (AZA) and cyclophosphamide). Recent data are in favour of the early
introduction of a cytotoxic or immunomodulating drug in addition to
corticosteroid therapy. In patients with corticosteroid- and cytotoxic-resistant
myositis, promising novel approaches to management include: iv. megadose pulse
methylprednisolone combined with cytotoxic drugs, combination therapy with both
methotrexate and AZA, cyclosporin, tacrolimus, fludarabine and iv.
immunoglobulin (IVIG). Recent advances in the understanding of the role of
cytokines and complement, in the pathogenesis of myositis, have led to
preliminary therapeutic trials of three biological agents: etanercept,
infliximab and anti-C5 monoclonal antibody.
Publication Types:
Review
Review, Tutorial
PMID: 11772250 [PubMed - indexed for MEDLINE]
155: Mol Genet Metab. 2001 Dec;74(4):458-75.
Clinical delineation and localization to chromosome 9p13.3-p12 of a unique
dominant disorder in four families: hereditary inclusion body myopathy, Paget
disease of bone, and frontotemporal dementia.
Kovach MJ, Waggoner B, Leal SM, Gelber D, Khardori R, Levenstien MA, Shanks
CA,
Gregg G, Al-Lozi MT, Miller T, Rakowicz W, Lopate G, Florence J, Glosser G,
Simmons Z, Morris JC, Whyte MP, Pestronk A, Kimonis VE.
Division of Genetics and Metabolism, Department of Pediatrics, Southern Illinois
University-School of Medicine, Springfield, Illinois, USA.
Autosomal dominant myopathy, Paget disease of bone, and dementia constitute
a
unique disorder (MIM 605382). Here we describe the clinical, biochemical,
radiological, and pathological characteristics of 49 affected (23 male, 26
female) individuals from four unrelated United States families. Among these
affected individuals 90% have myopathy, 43% have Paget disease of bone, and
37%
have premature frontotemporal dementia. EMG shows myopathic changes and muscle
biopsy reveals nonspecific myopathic changes or blue-rimmed vacuoles. After
candidate loci were excluded, a genome-wide screen in the large Illinois family
showed linkage to chromosome 9 (maximum LOD score 3.64 with marker D9S301).
Linkage analysis with a high density of chromosome 9 markers generated a maximum
two-point LOD score of 9.29 for D9S1791, with a maximum multipoint LOD score
of
12.24 between D9S304 and D9S1788. Subsequent evaluation of three additional
families demonstrating similar clinical characteristics confirmed this locus,
refined the critical region, and further delineated clinical features of this
unique disorder. Hence, autosomal dominant inclusion body myopathy (HIBM), Paget
disease of bone (PDB), and frontotemporal dementia (FTD) localizes to a
1.08-6.46 cM critical interval on 9p13.3-12 in the region of autosomal recessive
IBM2. Copyright 2001 Elsevier Science.
PMID: 11749051 [PubMed - indexed for MEDLINE]
156: Microsc Res Tech. 2001 Nov 15;55(4):249-58.
Oxides and apoptosis in inflammatory myopathies.
Stangel M, Mix E, Zettl UK, Gold R.
Department of Neurology, Universitatsklinikum Benjamin Franklin, Free University
Berlin, D-12200 Berlin, Germany.
Reactive oxygen intermediates (ROI) and nitric oxide (NO(.)) are produced in
abundance in the inflammatory muscle diseases of autoimmune origin polymyositis
(PM), dermatomyositis (DM), and inclusion body myositis (IBM). However, their
role in the pathogenesis of these diseases is so far not clear. In contrast
to
demyelinating neuropathies, there is no convincing evidence for oxide-induced
apoptosis either in myocytes or in lymphocytes and phagocytes in inflammatory
myopathies. On the contrary, NO(.) released at low concentrations at target
sites may even have cell-protective effects. A major mechanism of protection
from apoptosis in both myocytes and inflammatory cells seems to be the
upregulation of anti-apoptotic proteins like Bcl-2. Caution is warranted to
apply antioxidative and anti-apoptotic agents to patients with inflammatory
myopathies as long as the pathogenic role of oxides and apoptosis in the
individual case is not resolved. Copyright 2001 Wiley-Liss, Inc.
Publication Types:
Review
Review, Tutorial
PMID: 11748863 [PubMed - indexed for MEDLINE]
157: Lancet. 2001 Dec 8;358(9297):1962-4.
Presence of BACE1 and BACE2 in muscle fibres of patients with sporadic
inclusion-body myositis.
Vattemi G, Engel WK, McFerrin J, Buxbaum JD, Pastorino L, Askanas V.
Sporadic inclusion-body myositis (IBM) is the most common, progressive muscle
disease of older individuals. We investigated the presence of BACE1 and
BACE2-two beta secretases that cleave amyloid-beta-precursor protein-in
muscle-biopsy samples from patients with IBM and from controls. On
immunofluorescence, BACE1 and BACE2 co-localised with amyloid beta in IBM
vacuolated muscle fibres, but were not found in controls. Immunoblotting showed
increased BACE2 but not BACE1 in patients with IBM compared with controls. Our
study suggests that both of these proteases might participate in processing
of
amyloid-beta-precursor protein in IBM muscle fibres.
Publication Types:
Letter
PMID: 11747923 [PubMed - indexed for MEDLINE]
158: Muscle Nerve. 2001 Nov;24(11):1526-34.
Patterns of muscle involvement in inclusion body myositis: clinical and magnetic
resonance imaging study.
Phillips BA, Cala LA, Thickbroom GW, Melsom A, Zilko PJ, Mastaglia FL.
Centre for Neuromuscular and Neurological Disorders, Australian Neuromuscular
Research Institute, University of Western Australia, Perth, Western Australia,
Australia. b.phillips@unimelb.edu.au
The differential patterns of muscle involvement in the upper and lower limbs
in
sporadic inclusion body myositis (sIBM) were examined in 18 patients using both
quantitative and manual muscle testing as well as magnetic resonance imaging
(MRI) in 9 patients. Weakness of the quadriceps femoris and the forearm flexors
was present in most patients, but there was considerable variability in the
patterns and severity of muscle involvement. MRI disclosed preferential patterns
of muscle involvement within functional groups such as the quadriceps femoris,
in which there was severe involvement of the vasti with relative sparing of
the
rectus femoris, and the triceps surae, in which selective involvement of the
medial gastrocnemius was common. Involvement of flexor digitorum profundus on
MRI was found in only one third of patients. The results emphasize the
variability in the clinical phenotype and differential susceptibility of muscles
to the disease process in sIBM. Copyright 2001 John Wiley & Sons, Inc.
PMID: 11745956 [PubMed - indexed for MEDLINE]
159: Neurochem Int. 2002 Jan;40(1):85-103.
Transglutaminases in disease.
Kim SY, Jeitner TM, Steinert PM.
Laboratory of Skin Biology, NIAMS, NIH, MD, USA. sykim@burke.org
Transglutaminases (TGases) are enzymes that are widely used in many biological
systems for generic tissue stabilization purposes. Mutations resulting in lost
activity underlie several serious disorders. In addition, new evidence documents
that they may also be aberrantly activated in tissues and cells and contribute
to a variety of diseases, including neurodegenerative diseases such as
Alzheimer's and Huntington's diseases. In these cases, the TGases appear to
be a
factor in the formation of inappropriate proteinaceous aggregates that may be
cytotoxic. In other cases such as celiac disease, however, TGases are involved
in the generation of autoantibodies. Further, in diseases such as progressive
supranuclear palsy, Huntington's, Alzheimer's and Parkinson's diseases, the
aberrant activation of TGases may be caused by oxidative stress and
inflammation. This review will examine the role and activation of TGases in
a
variety of diseases.
Publication Types:
Review
Review, Tutorial
PMID: 11738475 [PubMed - indexed for MEDLINE]
160: Rheumatol Int. 2001 Oct;21(2):75-7.
Association of inclusion body myositis with subacute cutaneous lupus
erythematosus.
Wenzel J, Uerlich M, Gerdsen R, Bieber T, Boehm I.
Department of Dermatology, University of Bonn, Germany.
joerg.wenzel@ukb.uni-bonn.de
We present the case of a 71-year-old man with inclusion body myositis combined
with subacute cutaneous lupus erythematosus and dysphagia. Although inclusion
body myositis is usually resistant to immunosuppressive therapy, this patient
improved under treatment with corticosteroids. The presented case is discussed
in the context of earlier reports of inclusion body myositis and lupus
erythematosus.
Publication Types:
Case Reports
Review
Review of Reported Cases
PMID: 11732863 [PubMed - indexed for MEDLINE]
161: Dysphagia. 2001 Fall;16(4):244-8.
Cricopharyngeal muscle hypertrophy associated with florid myositis.
Bachmann G, Streppel M, Krug B, Neuen-Jacob E.
Klinik und Poliklinik fur Hals-Nasen-Ohrenheilkunde, Universitat zu Koln,
Germany. gregor.bachmann@rito.no
Hypertrophy of the cricopharyngeal muscle is a serious clinical condition that
can cause severe dysphagic symptoms, including prolonged deglutition and
postdeglutitive aspiration. Although the therapeutical concepts are well
established, the pathogenic mechanism of cricopharyngeal hypertrophy remains
unclear. We present a patient with a ten-year history of progressive dysphagia.
The neurological and MRI findings were normal. However, videocineradiography
showed severe hypertrophy of the cricopharyngeal muscle. This condition was
first treated by injections of botulinum toxin, which did not alleviate the
symptoms. Next, myotomy and muscle biopsy were performed. Histological
evaluation disclosed lymphoplasmacellular florid myositis, single-fiber atrophy,
and muscle fiber necrosis with phagocytosis. There were no signs of inclusion
body myositis or oculopharyngeal muscular dystrophy. Our finding of severe
cricopharyngeal muscle hypertrophy associated with myositis has been published
previously (n = 34). The study presented here shows cricopharyngeal dysphagia
associated with various systemic diseases, including motor neuron disease,
general granulomatous disease, dermatomyositis, or inclusion body myositis.
Isolated changes of the cricopharyngeal muscle were described in 65% of the
cases.
Publication Types:
Case Reports
Review
Review of Reported Cases
PMID: 11720399 [PubMed - indexed for MEDLINE]
162: Curr Opin Pharmacol. 2001 Jun;1(3):300-6.
The molecular and cellular pathology of inflammatory muscle diseases.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders,
National Institutes of Health, Bethesda, MD 20892-1382, USA.
dalakasm@ninds.nih.gov
The inflammatory muscle diseases dermatomyositis, polymyositis and inclusion
body myositis are of unknown cause, but immune mechanisms are strongly
implicated. Progress in the past two years has led to an improved understanding
of the main molecular events involved in the immunological synapse between
muscle and autoinvasive T cells. In particular, we now have a better
understanding of TCR gene rearrangement in endomysial T cells, regulation of
MHC
expression, activity of co-stimulatory molecules, and the signalling cascades
activated by cytokines, chemokines and metalloproteinases. Recent reports of
an
upregulation of strong anti-apoptotic molecules on the surface of muscle fibers
identifies the end result of these disease processes, loss of muscle cells,
as
through necrosis, and not apoptosis. Such progress in molecular immunopathology
has generated the interest to apply semispecific immunotherapies with the hope
of halting disease progression or improving the strength of patients
unresponsive to currently available non-specific immunotherapeutic
interventions.
Publication Types:
Review
Review, Tutorial
PMID: 11712755 [PubMed - indexed for MEDLINE]
163: Neurology. 2001 Nov 13;57(9):1566-70.
Erratum in:
Neurology 2002 Jan 22;58(2):334.
Randomized pilot trial of betaINF1a (Avonex) in patients with inclusion body
myositis.
Muscle Study Group.
Neuromuscular Disease Center, Rochester, NY 14642, USA.
BACKGROUND: Inclusion body myositis (IBM) is the most common acquired disease
of
muscle in adults over the age of 50 years. Although there is compelling evidence
for the importance of immunologic abnormalities in its pathogenesis, the cause
of the disease is not known, and it is considered to be resistant to treatment
with corticosteroids and other conventional immunosuppressive agents.
beta-Interferon (betaIFN), an immunomodulatory cytokine, is a candidate
therapeutic agent for IBM. METHOD: A 24-week, multicenter, randomized,
placebo-controlled, parallel-group clinical trial of 30 microg of
beta-interferon-1a (betaINF1a) administered IM once a week in 30 patients with
IBM was conducted. The primary goal was to establish the safety and tolerability
of betaINF1a in IBM. A secondary goal was to obtain preliminary data on the
efficacy of betaINF1a by measuring changes from baseline in muscle strength
and
muscle mass. RESULTS: Twenty-nine of the 30 subjects enrolled completed the
study. Two subjects (one in the placebo group, one in the betaINF1a group)
experienced severe adverse events. One subject, randomized to receive betaINF1a,
died from an ischemic bowel after resection of a colonic mass. No subjects
required dosage reductions, and the adverse event profile was similar for the
placebo and betaINF1a groups. There were no significant differences in the
changes in muscle strength and muscle mass between the placebo and betaINF1a
groups at 6 months. CONCLUSIONS: betaINF1a at a dose of 30 microg/week IM is
well tolerated in IBM. Further studies are needed to establish its therapeutic
usefulness in this inflammatory myopathy.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 11706093 [PubMed - indexed for MEDLINE]
164: Neurology. 2001 Nov 13;57(9):1561-5.
Production of IL-6 by human myoblasts stimulated with Abeta: relevance in the
pathogenesis of IBM.
Baron P, Galimberti D, Meda L, Scarpini E, Conti G, Cogiamanian F, Scarlato G.
Department of Neurological Sciences, Centro Dino Ferrari, University of Milan
School of Medicine, IRCCS Ospedale Maggiore, Milan, Italy.
neuromil@mailserver.unimi.it
OBJECTIVE: To determine whether amyloid-beta protein (Abeta) can induce the
production of proinflammatory cytokines by cultured normal muscle cells.
BACKGROUND: Sporadic inclusion body myositis (IBM) is characterized by the
presence of rimmed vacuoles and fibrillary inclusions of Abeta in muscle fibers,
and often inflammatory cells. Endomysial expression of proinflammatory molecules
has suggested an ongoing immune process, but the site of sensitization and the
mechanisms that trigger an inflammatory reaction is unknown. METHOD: The authors
used Northern blot analysis and specific immunoassays to study the expression
and secretion in cell-free supernatants of tumor necrosis factor-alpha
(TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) by purified
human myoblasts and C2C12 mouse skeletal muscle cells incubated with Abeta[1-42]
or Abeta[25-35] peptides. RESULTS: Nonstimulated muscle cells produced
detectable IL-6, whereas secretion of IL-1beta and TNFalpha was absent.
Incubation with Abeta peptides increased IL-6 production, whereas TNFalpha and
IL-1beta levels remained undetectable. Northern blot analysis of
Abeta-stimulated human myoblasts revealed an increase in IL-6 mRNA expression.
CONCLUSIONS: Cultured muscle cells increase the constitutive production of IL-6
in response to local deposition of Abeta in sporadic IBM. IL-6 could be a CD8(+)
proliferation and differentiation agent, an autocrine proteolysis-inducing
factor of damaged myotubes, and a proliferation-stimulating agent for satellite
cells to replace the destroyed myofibers in IBM.
PMID: 11706091 [PubMed - indexed for MEDLINE]
165: Curr Opin Rheumatol. 2001 Nov;13(6):469-75.
Inclusion body myositis: genetic factors, aberrant protein expression, and
autoimmunity.
Oldfors A, Fyhr IM.
Goteborg Neuromuscular Center, Department of Pathology, Sahlgrenska University
Hospital, Goteborg, Sweden. anders.oldfors@path.gu.se
Sporadic inclusion body myositis (s-IBM) is an inflammatory myopathy mainly
affecting elderly individuals. It has a chronic progressive course leading to
severe disability. Immunosuppressive treatment is in most instances ineffective.
S-IBM is morphologically characterized by mononuclear cell infiltrates and
vacuolated muscle fibers with pathologic accumulation of a large number of
different proteins. Recent research has focused on the expression of various
factors that may contribute to the inflammatory reaction and the typical
inclusions. This review summarizes the new information on genetic factors,
abnormal protein expression and inflammation, which provides a basis for linking
the different typical morphologic features of s-IBM to a cascade of pathogenic
events.
Publication Types:
Review
Review, Tutorial
PMID: 11698722 [PubMed - indexed for MEDLINE]
166: Acta Neuropathol (Berl). 2001 Oct;102(4):385-92.
CCR2A and CCR2B, the two isoforms of the monocyte chemoattractant protein-1
receptor are up-regulated and expressed by different cell subsets in idiopathic
inflammatory myopathies.
Bartoli C, Civatte M, Pellissier JF, Figarella-Branger D.
Laboratoire de Biopathologie Nerveuse et Musculaire, Faculte de medecine, IBDM
Marseille, France.
The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM),
polymyosititis (PM) and inclusion body myositis (IBM), are a group of autoimmune
diseases characterized by chronic lymphocytic and macrophagic infiltration in
muscle. The mechanism for recruitment of these cells probably involves
chemokines. We have previously reported that monocyte chemoattractant protein-1
(MCP-1), a beta chemokine, seems to play a major role in mononuclear cell
recruitment especially in DM. Here we have investigated the distribution of
the
main MCP-1 receptors CCR2A and CCR2B in IIM by polymerase chain reaction (PCR),
immunohistochemistry and in situ hybridization. We have shown by reverse
transcription-PCR that both CCR2A and CCR2B were expressed at low level in
normal muscle and that CCR2A was up-regulated in IIM (P=0.02) and was higher
in
PM and IBM than in DM (P=0.04). By immunohistochemistry and in situ
hybridization we have observed that CCR2 isoforms were expressed by different
cell subsets in both normal and IIM muscle. CCR2A was expressed in vessel walls
and by some mononuclear cells, especially in cells involved in partial invasion
in PM and IBM. CCR2B expression was observed in all satellite cells, in the
muscular domain of neuromuscular junctions and in some regenerative fibers of
IIM, but not in inflammatory exudates. In conclusion, the present study
highlights the major role played by MCP-1 and its counter-receptor CCR2 in the
pathophysiology of IIM, and shows that the CCR2 receptors are cell specific.
The
variation of the total amount of CCR2A and its local distribution according
to
the type of IIM might be a new path towards the understanding of the
constitution of mononuclear infiltrates in IIM.
PMID: 11603815 [PubMed - indexed for MEDLINE]
167: Liver. 2001 Oct;21(5):357-60.
Inclusion body myositis associated with hepatitis C virus infection.
Kase S, Shiota G, Fujii Y, Okamoto K, Oyama K, Nakano T, Nomura T, Suou T,
Nakashima K, Ito H, Kawasaki H.
Second Department of Internal Medicine, Faculty of Medicine, Tottori University,
Yonago, Japan. kaseron@grape.med.tottori-u.ac.jp
The case of a 77-year-old woman with hepatitis C virus infection with a 5-year
history of muscle weakness and mild disturbance of gait is reported. Steroid
therapy did not improve her symptoms. She developed HCV-related liver cirrhosis
and hepatocellular carcinoma, and muscle biopsy revealed inclusion body
myositis. Immunohistochemistry showed that the nonstructural region of HCV and
8-hydroxy-2'-deoxyguanosine, a marker of DNA damage by reactive oxygen species,
were present in striated muscle cells of this patient.
Publication Types:
Case Reports
PMID: 11589773 [PubMed - indexed for MEDLINE]
168: Intern Med. 2001 Sep;40(9):940-4.
Severe inclusion body myositis with interstitial pneumonia.
Mori S, Hamada H, Yokoyama A, Kohno N, Kondo K, Hara Y, Kawata H, Hiwada K.
Second Department of Internal Medicine, Ehime University School of Medicine,
Onsen-gun.
We report a patient with a severe inclusion body myositis (IBM). His illness
was
unusual in terms of a rapid progression, high creatine kinase levels, and
complication with interstitial pneumonia. He responded well to immunosuppressive
agents such as corticosteroids, cyclosporin A, cyclophosphamide, and
immunoglobulin. The present patient indicates the wide range of the disease,
and
that immunosuppressive agents may be useful for treatment of IBM.
Publication Types:
Case Reports
PMID: 11579961 [PubMed - indexed for MEDLINE]
169: Neuropediatrics. 2001 Aug;32(4):196-205.
Reducing body myopathy with cytoplasmic bodies and rigid spine syndrome: a
mixed
congenital myopathy.
Goebel HH, Halbig LE, Goldfarb L, Schober R, Albani M, Neuen-Jacob E, Voit T.
Department of Neuropathology, Medical Center, Johannes Gutenberg University,
Mainz, Germany. goebel@neuropatho.klinik.uni-mainz.de
At the age of five years a male child started to develop a progressive rigid
spine, torsion scoliosis, and flexion contractures of his elbows, knees, hips,
and ankles owing to severe proximal and distal muscle weakness. He had three
muscle biopsies from three different muscles at ages 7, 11, and 14 years,
respectively. Myopathologically, these muscle tissues contained numerous
inclusions which, at the ultrastructural level, turned out to be reducing bodies
and cytoplasmic bodies, often in close spatial proximity. Similar histological
inclusions, although not further identified by histochemistry and electron
microscopy, were seen in his maternal grandmother's biopsied muscle tissue who
had developed weakness of the legs and hands after the age of 50 years. The
patient's parents were healthy, but the mother's quadriceps muscle showed an
increased spectrum of muscle fibre diameters. Our patient, thus, had a
neuromuscular disorder, perhaps familial, presenting as a mixed congenital
myopathy, i.e., reducing body myopathy with cytoplasmic bodies, of which the
morphological lesions could be consistently documented over several years in
his
different limb muscles. While other mixed congenital myopathies had shown cores
and rods, both related to sarcomeres and thus possibly morphogenetically
related, cytoplasmic bodies thought to be related to Z-bands and reducing bodies
dissimilar to any muscle fibre constituent do not share any common denominator.
Therefore, we suggest that this neuromuscular disorder may be a unique mixed
congenital myopathy, either sporadic or genetic. In the latter case, the
transmission pattern suggested X-linked recessive inheritance, but an
autosomal-dominant transmission with variable penetrance could not be ruled
out.
Publication Types:
Case Reports
Review
Review of Reported Cases
PMID: 11571700 [PubMed - indexed for MEDLINE]
170: Arch Pathol Lab Med. 2001 Oct;125(10):1326-30.
Bcl-2, Bcl-x, and Bax expression by immunohistochemistry in inclusion body
myositis: a study of 27 cases.
Prayson RA, Yu AC.
Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio
44195, USA.
CONTEXT: Bcl-2, Bcl-x, and Bax are among the variety of proteins that have
been
described as being involved in the regulation of apoptotic cell death. Bcl-2
and
Bcl-x(L) inhibit apoptosis, and Bax is proapoptotic. OBJECTIVE: To evaluate
the
expression of Bcl-2, Bcl-x, and Bax in inclusion body myositis (IBM).Design.-We
examined muscle specimens from 27 patients (17 men, 10 women) with IBM to
evaluate Bcl-2, Bcl-x, and Bax expression by immunohistochemistry. RESULTS:
Patient ages ranged from 29 to 80 years (mean 62.2 years). All biopsies were
marked by endomysial chronic inflammation, muscle fiber necrosis, and
regeneration. Rimmed (autophagic) vacuoles were present in all cases. Ragged
red
fibers were noted in 4 biopsies (15%), and cytochrome oxidase-deficient fibers
were found in 10 biopsies (37%). Ultrastructural evidence of intranuclear or
cytoplasmic tubulofilamentous inclusions, confirming the diagnosis of IBM, were
noted in all cases. Paracrystalline mitochondrial inclusions were seen in 5
biopsies (18.5%). Inflammatory cells stained positively with Bcl-2 in all
biopsies, Bax in 26 biopsies (96%), and Bcl-x in 8 biopsies (30%). Degenerating
muscle fibers were highlighted with Bax in 24 biopsies (89%), Bcl-2 in 2
biopsies (7%), and Bcl-x in 3 biopsies (11%). Regenerative muscle fibers were
noted to stain with Bax in 24 muscles (89%), Bcl-2 in 21 muscles (78%), and
Bcl-x in 4 muscles (15%). Rimmed vacuoles were highlighted by Bax in 24 biopsies
(89%) and only rarely by Bcl-2 (n = 2, 7%) and Bcl-x (n = 3, 11%). A
subsarcolemmal staining pattern was observed in 21 biopsies (78%) with Bax,
6
biopsies (22%) with Bcl-2, and only 1 biopsy (4%) with Bcl-x. CONCLUSIONS: (1)
Bax (proapoptotic) immunostaining highlighted most autophagic vacuoles; (2)
subsarcolemmal Bax and Bcl-2 immunoreactivity may be associated with
mitochondrial defects that are commonly noted in IBM; (3) Bcl-2 and Bax
immunoreactivity were not confined to degenerating muscle fibers and in fact
appeared to be expressed more commonly in regenerating fibers, suggesting that
their expression may be independent of apoptosis in the setting of IBM.
PMID: 11570908 [PubMed - indexed for MEDLINE]
171: Curr Opin Neurol. 2001 Oct;14(5):591-6.
Inflammatory muscle diseases.
Hilton-Jones D.
Muscular Dystrophy Campaign Muscle and Nerve Centre, Department of Clinical
Neurology, Radcliffe infirmary, Oxford OX2 6HE, UK.
david.hilton-jones@cineuro.ox.ac.uk
Dermatomyositis and polymyositis are treatable disorders of skeletal muscle.
Despite their clinical similarities, they appear to have fundamentally different
autoimmune origins. Inclusion body myositis, from its origins 30 years ago,
has
emerged as the commonest acquired myopathy of the elderly. Despite inflammatory
changes, it is unclear whether it should be considered a primary inflammatory
myopathy, and it generally responds poorly to the same treatments that are
effective in other inflammatory myopathies.
Publication Types:
Review
PMID: 11562570 [PubMed - indexed for MEDLINE]
172: Medicine (Baltimore). 2001 Sep;80(5):320-7.
Inclusion body myositis in Connecticut: observations in 35 patients during
an
8-year period.
Felice KJ, North WA.
Department of Neurology, University of Connecticut School of Medicine,
Farmington, Connecticut 06030-1840, USA. felice@nso.uchc.edu
PMID: 11552086 [PubMed - indexed for MEDLINE]
173: Nat Genet. 2001 Sep;29(1):83-7.
The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is
mutated in recessive hereditary inclusion body myopathy.
Eisenberg I, Avidan N, Potikha T, Hochner H, Chen M, Olender T, Barash M,
Shemesh M, Sadeh M, Grabov-Nardini G, Shmilevich I, Friedmann A, Karpati G,
Bradley WG, Baumbach L, Lancet D, Asher EB, Beckmann JS, Argov Z,
Mitrani-Rosenbaum S.
Unit for Molecular Biology, Hadassah, Hospital, The Hebrew University-Hadassah
Medical School, Jerusalem, Israel.
Hereditary inclusion body myopathy (HIBM; OMIM 600737) is a unique group of
neuromuscular disorders characterized by adult onset, slowly progressive distal
and proximal weakness and a typical muscle pathology including rimmed vacuoles
and filamentous inclusions. The autosomal recessive form described in Jews of
Persian descent is the HIBM prototype. This myopathy affects mainly leg muscles,
but with an unusual distribution that spares the quadriceps. This particular
pattern of weakness distribution, termed quadriceps-sparing myopathy (QSM),
was
later found in Jews originating from other Middle Eastern countries as well
as
in non-Jews. We previously localized the gene causing HIBM in Middle Eastern
Jews on chromosome 9p12-13 (ref. 5) within a genomic interval of about 700 kb
(ref. 6). Haplotype analysis around the HIBM gene region of 104 affected people
from 47 Middle Eastern families indicates one unique ancestral founder
chromosome in this community. By contrast, single non-Jewish families from
India, Georgia (USA) and the Bahamas, with QSM and linkage to the same 9p12-13
region, show three distinct haplotypes. After excluding other potential
candidate genes, we eventually identified mutations in the
UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene in
the
HIBM families: all patients from Middle Eastern descent shared a single
homozygous missense mutation, whereas distinct compound heterozygotes were
identified in affected individuals of families of other ethnic origins. Our
findings indicate that GNE is the gene responsible for recessive HIBM.
PMID: 11528398 [PubMed - indexed for MEDLINE]
174: Arch Neurol. 2001 Aug;58(8):1253-6.
Inclusion body myositis mimicking motor neuron disease.
Dabby R, Lange DJ, Trojaborg W, Hays AP, Lovelace RE, Brannagan TH, Rowland LP.
Neurological Institute, Columbia-Presbyterian Medical Center, Box 150, 710
W
168th St, New York, NY 10032, USA.
OBJECTIVE: To describe the clinical and electrophysiologic features of patients
with inclusion body myositis that was misinterpreted as motor neuron disease.
PATIENTS AND METHODS: We retrospectively retrieved the medical records of 70
patients with a pathologic diagnosis of inclusion body myositis. From this
group, we selected those who had been first diagnosed as having motor neuron
disease or amyotrophic lateral sclerosis. We reviewed the clinical,
electrophysiologic, laboratory, and morphologic studies. RESULTS: Nine (13%)
of
70 patients with inclusion body myositis had been diagnosed as having motor
neuron disease. Six of the 9 patients had asymmetric weakness; in 4 the distal
arm muscles were affected. Eight patients had finger flexor weakness. Tendon
reflexes were preserved in weak limbs in 6, hyperactive in 2, and absent in
1.
Four patients had dysphagia. Fasciculation was seen in 2 patients. None had
definite upper motor neuron signs or muscle cramps. Routine electromyographic
studies showed fibrillation potentials and positive sharp waves in all 9.
Fasciculation potentials were seen in 7 and long-duration polyphasic motor unit
potentials were seen in 8. There was no evidence of a myogenic disorder in these
9 patients. Muscle biopsy was done because of slow progression or prominent
weakness of the finger flexors and was diagnostic of inclusion body myositis.
A
quantitative electromyogram was myopathic in 4 of the 5 patients studied.
CONCLUSIONS: Inclusion body myositis may mimic motor neuron disease. Muscle
biopsy and quantitative electromyographic analysis are indicated in patients
with atypical motor neuron disease, especially those with slow progression or
early and disproportionate weakness of the finger flexors.
PMID: 11493165 [PubMed - indexed for MEDLINE]
175: Acta Neuropathol (Berl). 2001 Jun;101(6):579-84.
Expression of the lysosome-associated membrane proteins in myopathies with
rimmed vacuoles.
Tsuruta Y, Furuta A, Furuta K, Yamada T, Kira J, Iwaki T.
Department of Neuropathology, Neurological Institute, Graduate School of Medical
Sciences, Kyushu University, Fukuoka, Japan.
Lysosome-associated membrane proteins (LAMPs) are structural glycoproteins
located on the lysosomal membrane and are thought to have an important role
in
protein degradation. Increased lysosomal activity is associated with the
formation of rimmed vacuoles, which are observed in various muscle disorders
such as inclusion body myositis (IBM) and distal myopathy with rimmed vacuole
(DMRV). In the present study, we examined LAMP-1 and LAMP-2 in biopsied muscle
specimens from four cases of sporadic IBM and two of DMRV, as well as six of
myopathies without rimmed vacuoles. In all cases of IBM and DMRV,
immunohistochemistry showed accumulation of LAMPs in the rimmed vacuoles and
the
subsarcolemmal portion of the vacuolated fibers. Immunoreactivities of LAMPs
in
the vacuolated fibers were often associated with those of cathepsin D; however,
cathepsin D was not expressed on some LAMP-positive fibers. Further, atrophic
muscle fibers were sometimes positive for LAMPs expression. These findings were
more prominent in LAMP-2 than in LAMP-1. Thus, LAMP-2 may play an important
role
in the increased protein degradation in diseased muscle fibers. The increased
expression of LAMPs in the vacuolated muscle fibers may be associated with the
formation of rimmed vacuoles in IBM and DMRV.
PMID: 11515786 [PubMed - indexed for MEDLINE]
176: Acta Neuropathol (Berl). 2001 Jun;101(6):572-8.
Immunolocalization of FAS and FAS ligand in inflammatory myopathies.
De Bleecker JL, Meire VI, Van Walleghem IE, Groessens IM, Schroder JM.
Ghent University Hospital, Department of Neurology, Belgium.
jan.debleecker@rug.ac.be
Fas/Fas ligand (FasL) interaction can induce apoptosis, have a costimulatory
role or act as a mechanism by which cytotoxic T cells produce target cell lysis.
We used several commercially available antibodies to study Fas and FasL
expression in polymyositis (PM), inclusion body myositis (IBM), dermatomyositis
(DM) and normal controls. A strong Fas signal occurred on the sarcolemma, and
to
a lesser extent in the sarcoplasm of neural cell adhesion molecule
(NCAM)-positive or developmental myosin heavy chain-positive regenerating muscle
fibers and of injured fibers with presumed abortive regenerative activity,
including some nonnecrotic invaded fibers in PM and IBM and some of the atrophic
perifascicular fibers in DM. Most fibers within groups of atrophic fibers in
IBM
were strongly Fas-positive, and statistically more muscle fibers were
Fas-positive in IBM compared to PM. A subset of the actively invading CD8+ T
cells in nonnecrotic muscle fibers in PM and IBM, and scattered CD4+ cells in
each inflammatory myopathy, had up-regulated Fas expression, probably reflecting
costimulation. No FasL antibody consistently labeled the positive control tissue
(testis) or intramuscular elements in control or inflammatory myopathy
specimens. Our study identifies regenerating muscle fibers as the main site
of
Fas immunoreactivity in inflammatory myopathies, and Fas expression may be part
of an activated or reactivated developmental program of new gene expression
in
regenerating or denervated muscle fibers. Our data plead against a specific
role
of Fas/FasL interaction in the immunopathogenesis of the inflammatory
myopathies.
PMID: 11515785 [PubMed - indexed for MEDLINE]
177: Neurology. 2001 Aug 14;57(3):548-50.
A prospective natural history study of inclusion body myositis: implications
for
clinical trials.
Rose MR, McDermott MP, Thornton CA, Palenski C, Martens WB, Griggs RC.
Department of Neurology, King's Neurosciences Centre, King's College Hospital,
London, UK. m.r.rose@kcl.ac.uk
Eleven patients with untreated inclusion body myositis (IBM) were prospectively
studied during a 6-month period that included muscle strength, lean body mass,
and muscle mass measurements. There was an overall quantifiable mean decline
in
percent of predicted normal muscle strength of 4% from baseline in a 6-month
period, but one third of patients showed no change or slight improvements in
strength. Short-term treatment trials in IBM will require large numbers of
patients to detect slowing, arrest, or even slight improvement in muscle
strength.
PMID: 11502935 [PubMed - indexed for MEDLINE]
178: Curr Rheumatol Rep. 2001 Aug;3(4):334-45.
Utility of magnetic resonance imaging in the evaluation of patients with
inflammatory myopathies.
Park JH, Olsen NJ.
Department of Radiology, Vanderbilt University Medical School, MCN-CCC-1121,
Nashville, TN 37232-2675, USA. Jane.Park@mcmail.vanderbilt.edu
Magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (P-31
MRS) provide unique, quantitative data that cannot be obtained from routine
laboratory tests. MRI is the method of choice for imaging of muscle
abnormalities. It is also a very sensitive technique for localizing
nonhomogeneous inflammation in inflammatory myopathies such as dermatomyositis,
juvenile dermatomyositis, amyopathic dermatomyositis, polymyositis, and
inclusion body myositis. During treatment of inflammatory myopathies, the extent
and severity of inflammation may decrease at varying rates, but weakness and
fatigue remain serious clinical problems. The metabolic abnormalities detected
with P-31 MRS are more persistent and can be used for objective patient
evaluation after the disappearance of inflammation and normalization of serum
levels of muscle enzymes. With P-31 MRS, biochemical defects are quantitated,
including low levels of ATP and phosphocreatine (PCr) and elevated
concentrations of ADP and inorganic phosphate (Pi), which may all be related
to
weakness and fatigue. Thus, MRI and P-31 MRS are useful in assessing the status
of patients with inflammatory myopathies during treatment with prednisone and
immunosuppressive drugs.
Publication Types:
Review
Review, Tutorial
PMID: 11470053 [PubMed - indexed for MEDLINE]
179: Curr Rheumatol Rep. 2001 Aug;3(4):317-24.
The benefits and limitations of a physical training program in patients with
inflammatory myositis.
Lawson Mahowald M.
Minneapolis VA Medical Center, Rheumatology Office (111R), One Veterans Drive,
Minneapolis, MN 55417, USA. Mahow001@umn.edu
The clinical features of inflammatory myositis are determined by the severity
and extent of muscle weakness and systemic manifestations. The benefits and
limitations of physical training programs and rehabilitation strategies depend
on the clinical phase of the disease and analysis of underlying impairments
responsible for functional limitations in the patient. Patients with early stage
disease and severe weakness will be treated differently than patients who have
responded to medication and are improving. Not all patients will respond to
medications; their therapy programs will have different requirements. This
article reviews available data on the physiologic responses to exercise in
patients with inflammatory muscle diseases. New data support more aggressive
approaches to progressive strengthening exercises for patients with inflammatory
myositis.
Publication Types:
Review
Review, Tutorial
PMID: 11470051 [PubMed - indexed for MEDLINE]
180: Neurology. 2001 Jul 24;57(2):368.
Comment on:
Neurology. 2000 Oct 24;55(8):1235.
Prion codon 129 homozygosity and sporadic inclusion body myositis.
Lampe J, Gossrau G, Reichmann H, Walter MC, Mendel B, Lochmuller H.
Publication Types:
Comment
Letter
PMID: 11468340 [PubMed - indexed for MEDLINE]
181: Eur J Hum Genet. 2001 Jul;9(7):501-9.
Physical and transcriptional map of the hereditary inclusion body myopathy
locus
on chromosome 9p12-p13.
Eisenberg I, Hochner H, Shemesh M, Levi T, Potikha T, Sadeh M, Argov Z, Jackson
CL, Mitrani-Rosenbaum S.
The Unit for Development of Molecular Biology and Genetic Engineering, Hadassah
Hospital, The Hebrew University-Hadassah Medical School, Jerusalem 91240,
Israel.
Hereditary inclusion body myopathy (HIBM) is a group of neuromuscular disorders
characterised by adult-onset, slowly progressive distal and proximal muscle
weakness and typical muscle pathology. Previously, we have mapped the gene
responsible for a recessive form of HIBM to chromosome 9p1 and narrowed the
interval to one single YAC clone of 1 Mb in size. As a further step towards
the
identification of the HIBM gene, we have constructed a detailed physical and
transcriptional map of this region. A high resolution BAC contig that includes
the HIBM critical region, flanked by marker 327GT4 and D9S1859, was constructed.
This contig allowed the precise localisation of 25 genes and ESTs to the
proximal region of chromosome 9. The expression pattern of those mapped genes
and ESTs was established by Northern blot analysis. In the process of refining
the HIBM interval, 13 new polymorphic markers were identified, of which 11 are
CA-repeats, and two are single nucleotide polymorphisms. Certainly, this map
provides an important integration of physical and transcriptional information
corresponding to chromosome 9p12-p13, which is expected to facilitate the
cloning and identification not only of the HIBM gene, but also other disease
genes which map to this region.
PMID: 11464241 [PubMed - indexed for MEDLINE]
182: Neuroreport. 2001 Jul 3;12(9):1809-14.
Novel cytoplasmic immunolocalization of RNA polymerase II in inclusion-body
myositis muscle.
Wilczynski GM, Engel WK, Askanas V.
USC Neuromuscular Center, Department of Neurology, University of Southern
California, Keck School of Medicine, Good Samaritan Hospital, 637 South Lucas
Ave, Los Angeles, CA 90017-1912, USA.
Sporadic inclusion-body myositis (IBM) is a progressive degenerative muscle
disease of older persons. Abnormalities of gene-expression and RNA metabolism
have recently been proposed to contribute to the IBM pathogenic cascade. We
now
demonstrate, using well characterized, epitope-specific antibodies, that the
largest subunit of RNA polymerase II is abnormally accumulated in the cytoplasm
of IBM muscle fibers, where it is co-localized with phosphorylated tau on IBM
paired helical filaments. Since RNA polymerase II is a crucial nuclear factor
involved in both transcription and mRNA processing, our results support the
hypothesis that abnormality of either or both of those processes might be
caused, in part, by pathological trafficking of RNA polymerase II, and that
abnormal trafficking might be an important factor in the IBM pathogenic cascade.
PMID: 11435903 [PubMed - indexed for MEDLINE]
183: Surg Today. 2001;31(6):553-6.
Fournier's gangrene: report of six cases.
Ochiai T, Ohta K, Takahashi M, Yamazaki S, Iwai T.
Department of Surgery, Ohta Nishinouchi General Hospital, Koriyama, Fukushima,
Japan.
Fournier's gangrene (FG) is a fatal infectious disease with necrotic fasciitis
of the external genitalia. This disease persists to this day in spite of recent
advances in antibiotics. Although fewer than 100 cases have been reported in
Japan, we have treated six cases in the last 4 years. The patients consisted
of
five men and one woman, with an average age of 47.5 years. All patients received
surgical treatment including incisions, aggressive debridement, drainage,
irrigation, and antibiotic therapy. Two patients, who suffered from underlying
diseases of diabetic nephropathy and inclusion body myositis, died. These
findings confirm the fact that FG requires a prompt diagnosis and immediate
surgical treatment.
Publication Types:
Case Reports
PMID: 11428614 [PubMed - indexed for MEDLINE]
184: Ann Intern Med. 2001 Jun 19;134(12):1156.
Long-lasting effectiveness of intravenous immunoglobulin in a patient with
inclusion-body myositis.
Mukunda BN, Dileep Kumar P, Smith HR.
Publication Types:
Case Reports
Letter
PMID: 11412071 [PubMed - indexed for MEDLINE]
185: Ann Intern Med. 2001 Jun 19;134(12):1087-95.
Incidence of malignant disease in biopsy-proven inflammatory myopathy. A
population-based cohort study.
Buchbinder R, Forbes A, Hall S, Dennett X, Giles G.
Department of Clinical Epidemiology, Suite 41, Cabrini Medical Centre, 183
Wattletree Road, Malvern, Victoria, Australia 3144.
rachelle.buchbinder@med.monash.edu.au
BACKGROUND: The validity and magnitude of an association between myositis and
malignant disease continue to be debated. Such issues as the legitimacy of a
myositis diagnosis and distinction among myositis subgroups in previous
population-based studies remain unresolved. OBJECTIVE: To determine the risk
for
malignant disease in patients with biopsy-proven inflammatory myopathies.
DESIGN: Population-based, retrospective cohort study. SETTING: Victoria,
Australia. PATIENTS: 537 patients in whom a biopsy-positive idiopathic
inflammatory myopathy was first diagnosed from 1981 through 1995. MEASUREMENTS:
Standardized incidence ratios were calculated to compare the incidence of
malignant disease in patients with inflammatory myopathy and the general
population. RESULTS: A total of 116 cases of malignant disease were found in
104
patients. Seventy-four cases were identified concurrently with (within 7 days)
or after diagnosis of myositis. The highest risk for malignant disease was
associated with dermatomyositis (standardized incidence ratio, 6.2 [95% CI,
3.9
to 10.0]). The risk was also increased in polymyositis (standardized incidence
ratio, 2.0 [CI, 1.4 to 2.7]), although the relative risk for malignant disease
in dermatomyositis compared with polymyositis was 2.4 (CI, 1.3 to 4.2). An
increased risk for malignant disease was also found in inclusion-body myositis
(standardized incidence ratio, 2.4 [CI, 1.2 to 4.9]). The excess risk for
malignant disease diminished with time (standardized incidence ratio, 4.4 [CI,
2.7 to 7.1] in the first year; 3.4 [CI, 2.3 to 5.1] between 1 and 3 years; 2.2
[CI, 1.3 to 3.9] between 3 and 5 years; and 1.6 [CI, 1.0 to 2.6] beyond 5 years
[ P for trend, 0.002]). CONCLUSION: The risk for malignant disease is increased
in biopsy-proven dermatomyositis and polymyositis and also appears to be
increased in inclusion-body myositis.
PMID: 11412048 [PubMed - indexed for MEDLINE]
186: Fukuoka Igaku Zasshi. 2001 Apr;92(4):99-104.
High-dose vitamin C therapy for inclusion body myositis.
Yamada T, Minohara M, Imaiso Y, Sakae N, Hara H, Tanaka K, Yamamoto T, Taniwaki
T, Furuya H, Kira J.
Department of Neurology, Neurological Institute, Graduate School of Medical
Sciences, Kyushu University, Fukuoka 812-8582, Japan.
yamada@neuro.med.kyushu-u.ac.jp
OBJECTIVES: The efficiency of high-dose vitamin C therapy for inclusion body
myositis (IBM) was assessed. SUBJECTS & METHODS: The subjects were five
patients
with IBM confirmed pathologically. After the intravenous administration of 40
mg/kg vitamin C five times/week for four weeks, muscle weakness was found to
improve in three cases. The average muscle score improved from 8.1 to 8.8, from
7.0 to 8.1 and from 6.2 to 6.8. Magnetic resonance imaging (MRI) demonstrated
a
reduction in the size of T2 high lesions and gadolinium enhancement in the thigh
muscles in one case. Based on our findings, high-dose vitamin C therapy is
considered to be effective in some cases of IBM.
Publication Types:
Evaluation Studies
PMID: 11411094 [PubMed - indexed for MEDLINE]
187: Neuromuscul Disord. 2001 Jul;11(5):452-7.
Macrophagic myofasciitis associated with inclusion body myositis: a report
of
three cases.
Cherin P, Menard D, Mouton P, Viallard JF, Le Hello C, Authier FJ, Gherardi
RK,
Coquet M, Herson S, Leroi JP.
Medecine Interne I, CHU Pitie-Salpetriere, 47 Boulevard de l'Hopital, 75013,
Paris, France. patrick.cherin@psl.ap-hop-paris.fr
We describe three patients with macrophagic myofasciitis and inclusion body
myositis. All patients fulfilled diagnostic criteria for inclusion body myositis
and myopathologic criteria for macrophagic myofasciitis. In the three cases
macrophagic myofasciitis complicated the evolution of a known and painless
inclusion body myositis and was diagnosed in a repeated deltoid biopsy because
of the appearance of myalgia during the course of inclusion body myositis in
all
cases. The unexpected appearance of myalgia during the course of painless
inclusion body myositis must arouse the suspicion of an association of another
inflammatory muscle disease, macrophagic myofasciitis.
Publication Types:
Case Reports
PMID: 11404116 [PubMed - indexed for MEDLINE]
188: Neuromuscul Disord. 2001 Jul;11(5):447-51.
Rimmed vacuoles and the added value of SMI-31 staining in diagnosing sporadic
inclusion body myositis.
van der Meulen MF, Hoogendijk JE, Moons KG, Veldman H, Badrising UA, Wokke JH.
Department of Neurology, G 03.228, Division of Neuromuscular Disorders,
University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX, The, Utrecht,
Netherlands. m.f.g.vdmeulen@neuro.azu.nl
Problems in diagnosing sporadic inclusion body myositis may arise if all
clinical features fit a diagnosis of polymyositis, but the muscle biopsy shows
some rimmed vacuoles. Recently, immunohistochemistry with an antibody directed
against phosphorylated neurofilament (SMI-31) has been advocated as a diagnostic
test for sporadic inclusion body myositis. The aims of the present study were
to
define a quantitative criterion to differentiate sporadic inclusion body
myositis from polymyositis based on the detection of rimmed vacuoles in the
haematoxylin-eosin staining and to evaluate the additional diagnostic value
of
the SMI-31 staining. Based on clinical criteria and creatine kinase levels in
patients with endomysial infiltrates, 18 patients complied with the diagnosis
of
sporadic inclusion body myositis, and 17 with the diagnosis of polymyositis.
A
blinded observer counted the abnormal fibres in haematoxylin-eosin-stained
sections and in SMI-31-stained sections. The optimal cut-off in the
haematoxylin-eosin test was 0.3% vacuolated fibres. Adding the SMI-31 staining
significantly increased the positive predictive value from 87 to 100%, but
increased the negative predictive value only to small extent. We conclude that
(1) patients with clinical and laboratory features of polymyositis, including
response to treatment, may show rimmed vacuoles in their muscle biopsy and that
(2) adding the SMI-31 stain can be helpful in differentiating patients who
respond to treatment from patients who do not.
PMID: 11404115 [PubMed - indexed for MEDLINE]
189: Adv Exp Med Biol. 2001;487:219-28.
Neurodegeneration-associated proteins and inflammation in sporadic
inclusion-body myositis.
Lampe JB, Walter MC, Reichmann H.
Department of Neurology, Technical University of Dresden, Germany.
PMID: 11403162 [PubMed - indexed for MEDLINE]
190: Mol Cell Neurosci. 2001 May;17(5):793-810.
Beta-amyloid peptide expression is sufficient for myotube death: implications
for human inclusion body myopathy.
Querfurth HW, Suhara T, Rosen KM, McPhie DL, Fujio Y, Tejada G, Neve RL, Adelman
LS, Walsh K.
Division of Neurology, St. Elizabeth's Medical Center, Boston, MA 02135, USA.
hquerfur@opal.tufts.edu
Inclusion body myositis (sIBM) is the most common disorder of skeletal muscle
in
aged humans. It shares biochemical features with Alzheimer's disease, including
congophilic deposits, which are immunoreactive for beta-amyloid peptide (Abeta)
and C'-terminal betaAPP epitopes. However, the etiology of myofiber loss and
the
role of intracellular Abeta in IBM is unknown. Here we report correlative
evidence for apoptotic cell death in myofibers of IBM patients that exhibit
pronounced Abeta deposition. HSV-1-mediated gene transfer of Abeta(42) into
cultured C2C12 myotubes resulted in a 12.6-fold increase in dUTP-labeled and
condensed nuclei over nonexpressing myotubes (P < 0.05). The C'-terminal
betaAPP
domain C99 also induced myotube apoptosis, but to a significantly lesser extent
than Abeta. Apoptosis specific to Abeta-expressing myotubes was also
demonstrated through DNA fragmentation, decreased mitochondrial function and
the
loss of membrane phospholipid polarity. Myotubes laden with Abeta(42), but not
other transgene products, developed cytoplasmic inclusions consisting of
fibrillar material. Furthermore, injection of normal mouse gastrocnemius muscle
with HSV-encoding Abeta cDNA resulted in TUNEL-positive myofibers with pyknotic
nuclei. We conclude that Abeta is sufficient to induce apoptosis in myofibers
both in vivo and in vitro and suggest it may contribute to myofiber loss and
muscle dysfunction in patients with IBM. Copyright 2001 Academic Press.
PMID: 11358479 [PubMed - indexed for MEDLINE]
191: J Neurol Neurosurg Psychiatry. 2001 May;70(5):706.
Anti-Jo-1 positive inclusion body myositis with a marked and sustained clinical
improvement after oral prednisone.
Hengstman GJ, Ter Laak HJ, van Engelen BG, van Venrooij BG.
Publication Types:
Case Reports
Letter
PMID: 11336039 [PubMed - indexed for MEDLINE]
192: J Neurol Sci. 2001 Apr 1;185(2):119-22.
Mycophenolate (CellCept) treatment of myasthenia gravis, chronic inflammatory
polyneuropathy and inclusion body myositis.
Mowzoon N, Sussman A, Bradley WG.
Department of Neurology, University of Miami School of Medicine (M712), PO
Box
016960, Miami, FL 33101, USA.
We report favorable results of the long term use of mycophenolate in the
treatment of three patients with myasthenia gravis (MG), two patients with
chronic inflammatory demyelinating polyneuropathy (CIDP), one patient with
secondary polymyositis (PM), and one patient with inclusion body myositis (IBM).
Side effects were mild. Mycophenolate appears to be a useful addition to the
armamentarium of immunosuppressants for treatment of chronic immunologically
mediated neuromuscular diseases.
Publication Types:
Clinical Trial
PMID: 11311292 [PubMed - indexed for MEDLINE]
193: Brain Pathol. 2001 Apr;11(2):182-9.
Increased expression of the normal cellular isoform of prion protein in
inclusion-body myositis, inflammatory myopathies and denervation atrophy.
Zanusso G, Vattemi G, Ferrari S, Tabaton M, Pecini E, Cavallaro T, Tomelleri
G,
Filosto M, Tonin P, Nardelli E, Rizzuto N, Monaco S.
Department of Neurological and Visual Sciences, University of Verona, Italy.
The cellular isoform of the prion protein (PrPc) is a
glycosylphosphatidylinositol-anchored glycoprotein, normally expressed in neural
and non-neural tissues, including skeletal muscle. In transmissible spongiform
encephalopathies, or prion diseases, PrPc, which is soluble in nondenaturing
detergent and sensitive to proteinase K (PK)-treatment, represents the molecular
substrate for the production of a detergent-insoluble and PK-resistant isoform,
termed PrP(Sc). In human prion diseases, PrP(Sc) accumulation occurs only in
brain tissues, with the exception of new variant Creutzfeldt-Jakob disease,
where PrP(Sc) is also detected in lymphoid tissues. Increased amounts of prion
protein expression and deposition have been described in pathological muscle
fibers of two human muscle disorders, called sporadic inclusion-body myositis
(s-IBM) and hereditary inclusion-body myopathy, but it is unknown whether
accumulated prion protein reflects normal PrPc or PrP(Sc). We investigated the
biochemical characteristics of prion protein in normal human muscle, s-IBM,
other inflammatory myopathies and denervation atrophy. We report that 1) both
the glycoform profile and size of the normal muscle PrPc are different from
those of human brain PrPc; 2) in addition to s-IBM, increased PrPc expression
is
seen in polymyositis, dermatomyositis and neurogenic muscle atrophy, but PrPc
glycoforms are unchanged; 3) only the normal PrPc isoform, and not PrP(Sc),
is
detected in s-IBM. The present results exclude that s-IBM is a prion disease.
PMID: 11303793 [PubMed - indexed for MEDLINE]
194: Acta Neurol Scand. 2001 Feb;103(2):131-5.
Report of a patient with inclusion body myositis and CD8+ chronic lymphocytic
leukaemia--post-mortem analysis of muscle and brain.
Arnardottir S, Ansved T, Nennesmo I, Borg K.
Department of Clinical Neuroscience, Karolinska Hospital, Karolinska Institutet,
Stockholm, Sweden.
We report a 73-year-old woman with sporadic inclusion body myositis (s-IBM)
and
a T-cell chronic lymphocytic leukaemia (T-CLL). The s-IBM diagnosis was based
on
clinical symptoms and muscle biopsy showing inflammatory infiltrates and rimmed
vacuoles with 15 18 nm diameter tubulofilamentous inclusions on ultrastructural
examination. The inflammatory infiltrates consisted of CD8+ T-lymphocytes and
macrophages. The diagnosis of a CD8+ T-CLL was based on peripheral blood samples
and bone marrow aspiration. The postmortem analysis of skeletal muscle showed
fascicular atrophy, which may support a neurogenic component in s-IBM and the
analysis of the brain showed only a few diffuse plaques in different cortical
regions and occasionally neuritic plaques. A pathophysiological analogy between
s-IBM and Alzheimer's has been suggested on the basis of similarities in protein
accumulation in muscle of s-IBM patients and brain of Alzheimer's patients.
However, we were unable to detect any changes suggestive of Alzheimer's disease
in the brain of the s-IBM patient presented here.
Publication Types:
Case Reports
PMID: 11227133 [PubMed - indexed for MEDLINE]
195: J Neuropathol Exp Neurol. 2001 Jan;60(1):1-14.
Inclusion-body myositis: newest concepts of pathogenesis and relation to aging
and Alzheimer disease.
Askanas V, Engel WK.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, Los Angeles
90017-1912, USA.
We review the newest advances related to seeking the pathogenic mechanism(s)
of
sporadic inclusion-body myositis (s-IBM) and present the pathologic diagnostic
criteria of s-IBM. We discuss the possible pathogenic role of several themes,
such as 1) increased amyloid-beta precursor protein (AbetaPP) and of its
fragment Abeta; 2) phosphorylation of tau protein; 3) oxidative stress; 4)
abnormal a) signal-transduction, b) transcription, and c) RNA accumulation;
5)
"junctionalization" and myogenous" denervation; and 6) lymphocytic
inflammation.
Evidence is provided supporting our hypothesis that overexpression of AbetaPP
within the aging muscle fibers is an early upstream event causing the subsequent
pathogenic cascade. The remarkable pathologic similarities between s-IBM muscle
and Alzheimer disease (AD) brain are discussed, and the possible cause and
significance are addressed.
Publication Types:
Review
Review, Tutorial
PMID: 11202170 [PubMed - indexed for MEDLINE]
196: Hosp Med. 2000 Nov;61(11):767-71.
Pitfalls in the diagnosis of motor neurone disease.
Hardiman O.
Department of Neurology, Beaumont Hospital, Dublin 9, Ireland.
Motor neurone disease is characterized by progressive degeneration of upper
and
lower motor neurones with preservation of cognition. Recognition of classical
motor neurone disease is not difficult, but during the early stages both false
positive and false negative diagnoses are common. Careful examination, frequent
follow-up and ancillary tests are necessary to avoid erroneous diagnoses.
Publication Types:
Review
Review, Tutorial
PMID: 11198744 [PubMed - indexed for MEDLINE]
197: Neurology. 2001 Feb 13;56(3):323-7.
A controlled study of intravenous immunoglobulin combined with prednisone in
the
treatment of IBM.
Dalakas MC, Koffman B, Fujii M, Spector S, Sivakumar K, Cupler E.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, MD, USA.
OBJECTIVE: To investigate whether the combination of intravenous immunoglobulin
(IVIg) with prednisone improves muscle strength and alters endomysial
inflammation in patients with sporadic inclusion body myositis (s-IBM).
BACKGROUND: In a previous controlled trial in s-IBM, IVIg did not significantly
improve strength in spite of modest benefits in some muscle groups. The
possibility that prednisone may have a synergistic effect with IVIg prompted
another controlled trial. METHODS: Thirty-six patients with biopsy-proven IBM
were randomized to receive IVIg or placebo monthly for 3 months. Before
infusions, all patients were started on high-dose prednisone for 3 months.
Primary outcome measures were differences in the 1) Quantitative Muscle Strength
(QMT) testing; and 2) modified Medical Research Council (MRC) scores, between
the patients randomized to IVIg + prednisone compared with those randomized
to
placebo + prednisone. Repeated open muscle biopsies were performed at random
in
24 patients to determine changes in the number of autoinvasive T cells and
necrotic muscle fibers. RESULTS: Nineteen patients were randomized to IVIg +
prednisone and 17 to placebo + prednisone. No significant change was noted in
muscle strength, assessed by QMT and MRC, from baseline to the 2nd, 3rd, or
4th
month after treatment between the two groups. The number of necrotic fibers
was
reduced in the IVIg randomized group (p < 0.01), and the mean number of CD2+
cells was significantly decreased in both groups (p < 0.0001), denoting a
steroid effect. CONCLUSION: IVIg combined with prednisone for a 3-month period
was not effective in IBM. Endomysial inflammation was significantly reduced
after treatment, but the reduction was not of clinical significance.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 11171896 [PubMed - indexed for MEDLINE]
198: Clin Infect Dis. 2001 Feb 1;32(3):510-4. Epub 2001 Jan 24.
Sporadic inclusion body myositis in a patient with human T cell leukemia virus
type 1-associated myelopathy.
Ozden S, Gessain A, Gout O, Mikol J.
Unite d'Oncologie Virale, Institut Pasteur, Paris, France.
Sporadic inclusion body myositis is a disease of unknown pathogenesis in which
a
viral etiology has long been suspected. We report a case that occurred in a
patient with human T cell leukemia virus type 1-associated myelopathy. The
diagnosis was confirmed by histopathological studies of the deltoid muscle.
Nucleic acids amplification and in situ hybridization indicated the presence
of
integrated proviral DNA and viral mRNA transcripts in the lesions.
Publication Types:
Case Reports
PMID: 11170963 [PubMed - indexed for MEDLINE]
199: Neuromuscul Disord. 2001 Jan;11(1):88-92.
64th ENMC International Workshop: therapeutic approaches to dermatomyositis,
polymyositis, and inclusion body myositis29-31 January 1999, Naarden, The
Netherlands.
Muller-Felber W, Pongratz D, Reimers C.
Friedrich-Baur-Institut, Ludwig Maximilians University, Munich, Germany.
Publication Types:
Congresses
PMID: 11166170 [PubMed - indexed for MEDLINE]
200: Brain. 2001 Feb;124(Pt 2):341-51.
Expression of specific matrix metalloproteinases in inflammatory myopathies.
Kieseier BC, Schneider C, Clements JM, Gearing AJ, Gold R, Toyka KV, Hartung HP.
Department of Neurology, Karl Franzens University, Graz, Austria.
bc.kieseier@kfunigraz.ac.at
The family of matrix metalloproteinases (MMPs) comprises endopeptidases that
are
capable of degrading all extracellular matrix components. Given these actions,
it is conceivable that MMPs may play a pathogenic role in inflammatory
myopathies. These immune-mediated disorders are characterized by the invasion
of
mononuclear phagocytes and T lymphocytes and the loss of muscle fibres. We
examined whether specific MMPs and their natural inhibitors (tissue inhibitors
of metalloproteinases; TIMPs) are expressed in muscle during acute inflammatory
attacks by studying muscle biopsies obtained from patients diagnosed as having
polymyositis, dermatomyositis, sporadic inclusion body myositis and, for
comparison, from cases of various muscular dystrophies. Quantitative polymerase
chain reaction analysis revealed significantly elevated mRNA expression of
interstitial collagenase (MMP-1) and gelatinase B (MMP-9) in polymyositis and
dermatomyositis and to a lesser extent in inclusion body myositis, whereas the
level of expression of TIMPs remained unchanged in comparison with controls.
Increased mRNA levels were associated with enhanced enzyme expression, as
determined by immunoblotting, gelatin zymography and in situ zymography.
Immunohistochemically, MMP-1 could be localized around the sarcolemma of
diseased muscle fibres and to cells resembling fibroblasts, whereas MMP-9 seemed
to be expressed primarily by invading T lymphocytes. Raised levels of MMPs could
not be detected in the sera of affected patients, emphasizing the crucial action
of MMPs in the inflamed muscle. Our results imply a pathogenic role for specific
MMPs in the genesis of inflammatory myopathies, and open new strategies for
therapeutic intervention.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 11157561 [PubMed - indexed for MEDLINE]
201: Ann Rheum Dis. 2001 Feb;60(2):116-23.
Comment in:
Ann Rheum Dis. 2001 Aug;60(8):810.
Autoantibody profiles in the sera of European patients with myositis.
Brouwer R, Hengstman GJ, Vree Egberts W, Ehrfeld H, Bozic B, Ghirardello A,
Grondal G, Hietarinta M, Isenberg D, Kalden JR, Lundberg I, Moutsopoulos H,
Roux-Lombard P, Vencovsky J, Wikman A, Seelig HP, van Engelen BG, van Venrooij
WJ.
Department of Biochemistry, University of Nijmegen, Nijmegen, The Netherlands.
OBJECTIVE: To determine the prevalence of myositis specific autoantibodies
(MSAs) and several myositis associated autoantibodies (MAAs) in a large group
of
patients with myositis. METHODS: A total of 417 patients with myositis from
11
European countries (198 patients with polymyositis (PM), 181 with
dermatomyositis (DM), and 38 with inclusion body myositis (IBM)) were
serologically analysed by immunoblot, enzyme linked immunosorbent assay (ELISA)
and/or immunoprecipitation. RESULTS: Autoantibodies were found in 232 sera
(56%), including 157 samples (38%) which contained MSAs. The most commonly
detected MSA was anti-Jo-1 (18%). Other anti-synthetase, anti-Mi-2, and anti-SRP
autoantibodies were found in 3%, 14%, and 5% of the sera, respectively. A
relatively high number of anti-Mi-2 positive PM sera were found (9% of PM sera).
The most commonly detected MAA was anti-Ro52 (25%). Anti-PM/Scl-100,
anti-PM/Scl-75, anti-Mas, anti-Ro60, anti-La, and anti-U1 snRNP autoantibodies
were present in 6%, 3%, 2%, 4%, 5%, and 6% of the sera, respectively. Remarkable
associations were noticed between anti-Ro52 and anti-Jo-1 autoantibodies and,
in
a few sera, also between anti-Jo-1 and anti-SRP or anti-Mi-2 autoantibodies.
CONCLUSIONS: The incidence of most of the tested autoantibody activities in
this
large group of European patients is in agreement with similar studies of
Japanese and American patients. The relatively high number of PM sera with
anti-Mi-2 reactivity may be explained by the use of multiple recombinant
fragments spanning the complete antigen. Furthermore, our data show that some
sera may contain more than one type of MSA and confirm the strong association
of
anti-Ro52 with anti-Jo-1 reactivity.
PMID: 11156543 [PubMed - indexed for MEDLINE]
202: J Neurol. 2000 Nov;247(11):882-4.
Familial inclusion body myositis with histologically confirmed sensorimotor
axonal neuropathy.
Hengstman GJ, van Engelen BG, ter Laak HJ, Gabreels-Festen AA.
Publication Types:
Case Reports
Letter
PMID: 11151424 [PubMed - indexed for MEDLINE]
203: Neurology. 2001 Jan 9;56(1):87-93.
Inclusion body myositis: expression of extracellular signal-regulated kinase
and
its substrate.
Nakano S, Shinde A, Kawashima S, Nakamura S, Akiguchi I, Kimura J.
Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto,
Japan. snakano@isola.kuhp.kyoto-u.ac.jp
OBJECTIVE: To assess abnormal intracellular signal transduction in inclusion
body myositis (IBM). BACKGROUND: Mitogen-activated protein kinases (MAPKs) play
pivotal roles in intracellular signal transduction and regulate cell growth
and
differentiation. Upon their activation, MAPKs translocate from the cytoplasm
into the nucleus. DESIGN/METHODS: The authors investigated the localization
of
several forms of the MAPK family-extracellular signal-regulated kinase (ERK),
c-Jun N-terminal protein kinase (JNK), and p38 MAPK (p38)-in 10 patients with
sporadic IBM and in 52 control subjects. The relationship between the
localization of immunopositive deposits and nuclei was tested with
bis-benzimide. RESULTS: Vacuolated fibers in IBM displayed very strong focal
immunoreactivity of ERK, but not of JNK or p38. The ERK-positive deposits in
these vacuolated fibers colocalized with the nuclear substrate of ERK, Elk-1.
ERK- and Elk-1-positive deposits were located frequently on the surface of the
nuclei in vacuolated fibers in IBM. Similar findings to those of sporadic IBM
were observed in three patients with distal myopathy with rimmed vacuoles, but
not in eight normal or the other 41 disease controls. CONCLUSION: There is
evidence for impaired molecular transport to the nucleus from the cytoplasm
in
the vacuolated fibers in IBM. This could be due to cytoplasmic aggregation of
ERK and Elk-1 or to abnormal nuclear pore machinery involved in the transport
of
ERK and its substrate upon ERK activation.
PMID: 11148241 [PubMed - indexed for MEDLINE]
204: Curr Rheumatol Rep. 2000 Jun;2(3):216-24.
The role of cytokines, chemokines, and adhesion molecules in the pathogenesis
of
idiopathic inflammatory myopathies.
Lundberg IE.
Department of Rheumatology, Karolinska Hospital, S-171 76 Stockholm, Sweden.
Ingrid.Lundberg@medks.ki.se
Cytokines, chemokines, and adhesion molecules are important mediators in chronic
inflammation and in immune regulation. In idiopathic inflammatory myopathies
(IIM), increased expression of proinflammatory cytokines particularly
interleukin (IL)-1alpha and IL-1beta, tumor necrosis factor (TNF)-alpha and
macrophage inflammatory proteins (MIP)-1alpha, as well as of the inhibitory
cytokines transforming growth factor (TGF)-beta was observed in muscle. There
was no difference in cytokine and chemokine pattern between polymyositis,
dermatomyositis, and inclusion body myositis, which could indicate that similar
pathogenetic mechanisms are involved in these subsets of myositis. A prominent
finding of IL-1alpha expression in endothelial cells, both in patients with
active inflammation and in patients with chronic persisting muscle weakness
without inflammation, makes this an interesting molecule in understanding the
mechanisms for the pathogenesis of muscle weakness. Involvement of the blood
vessels in the pathogenesis of myositis was further supported by increased
expression of adhesion molecules and by a phenotypical expression of endothelial
cells, resembling high endothelium venules in all three subsets of IIM. The
molecular studies to date indicate a role of the microvessels in the
pathogenesis of IIM not only in DM, as was previously suggested, but also in
PM
and IBM. The studies also indicate that IL-1alpha could be a target molecule
for
new therapeutical interventions.
Publication Types:
Review
Review, Tutorial
PMID: 11123062 [PubMed - indexed for MEDLINE]
205: Curr Treat Options Neurol. 2000 Jan;2(1):7-12.
Inclusion Body Myositis.
Barohn RJ, Amato AA.
Department of Neurology, University of Texas Southwestern Medical Center, 5323
Harry Hines Blvd., Dallas, TX 75235-8897, USA.
Inclusion body myositis (IBM) is usually refractory to immunosuppressive
therapy; however, a few reports suggest that a minority of patients with IBM
may
have a partial, transient response or that therapy may slow progression.
Therefore, although we generally discourage the use of immunosuppressive therapy
for IBM, if the patient is willing to accept the potential side effects of
therapy, a 3- to 6-month trial of oral prednisone can be attempted: 100 mg/d
for
2 to 4 weeks, then 100 mg every other day for 2 to 3 months. If prednisone alone
produces no improvement after 3 months, oral methotrexate can be added: 10 to
15
mg/wk for 6 to 12 months. If there is no objective clinical improvement in
strength after a trial of prednisone alone or prednisone plus methotrexate over
the course of 6 to 12 months, we discontinue pharmacologic therapy. Because
of
the great expense, relative lack of availability, and minimal evidence of
benefit of intravenous immunoglobulin (IVIG), we do not recommend this form
of
immunomodulating therapy for IBM.
PMID: 11096732 [PubMed - as supplied by publisher]
206: Curr Treat Options Neurol. 1999 Jul;1(3):263-272.
Inflammatory Myopathy.
Mastaglia FL, Phillips BA, Zilko PJ.
Departments of Medicine, Neurology, and Clinical Immunology, Australian
Neuromuscular Research Institute, 4th Floor, G Block, Queen Elizabeth II Medical
Centre, Perth, Australia 6009.
Patients with polymyositis or dermatomyositis should be treated with prednisone
(approximately 1 mg/kg/d) for an initial period of 4 to 6 weeks. Once
improvement occurs, the dose should be tapered and converted to an alternate-day
regimen, which should be continued for at least 12 months. Methotrexate or
azathioprine should be administered concomitantly to patients in whom there
is
inadequate control. The early introduction of one of these drugs allows more
rapid reduction in the dose of prednisone and helps to avert serious side
effects. Intravenous immunoglobulin therapy is indicated for patients who have
immunodeficiency, who are unable to tolerate immu-nosuppressive drugs, whose
conditions are deteriorating, or who have severe relapses. Cyclosporine or
cyclophosphamide may be effective for resistant disease. Patients with inclusion
body myositis should undergo a 3- to 6-month trial of prednisone, alone or in
combination with methotrexate or azathioprine. Maintenance doses of these drugs
should be continued if the patient's condition improves or stabilizes.
PMID: 11096714 [PubMed - as supplied by publisher]
207: Curr Opin Rheumatol. 2000 Nov;12(6):482-91.
Update on the genetics of the idiopathic inflammatory myopathies.
Shamim EA, Rider LG, Miller FW.
Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research,
Food and Drug Administration, Bethesda, Maryland 20892, USA. shamim@cber.fda.gov
A number of lines of investigation suggest that, as is likely the case for
other
autoimmune diseases, the idiopathic inflammatory myopathies (IIM) develop as
a
result of specific environmental exposures in genetically susceptible
individuals. Current data imply that multiple genes are involved in the etiology
of these complex disorders. Targeted gene studies and whole genome approaches
have begun to identify several genetic risk factors for autoimmune diseases,
but
the rarity and heterogeneity of the IIM have limited our knowledge of their
associated genes. Current findings suggest that human leukocyte antigen (HLA)
genes on chromosome 6, particularly HLA DRB1*0301 and the linked allele
DQA1*0501, have the strongest associations with all clinical forms of IIM in
white patients. Different HLA alleles, however, may confer risk or protection
for myositis in distinct ethnic, serologic, and environmental exposure groups.
Non-HLA genetic risk factors, which have been documented for other autoimmune
diseases, are now being identified for the IIM. These include polymorphic genes
encoding immunoglobulin heavy chains (defined by serologic markers known as
Gm
allotypes), cytokines and their receptors, and certain proteins that accumulate
in the myocyte vacuoles of inclusion body myositis patients. Selected allelic
polymorphisms of interleukin-1 receptor antagonist variable number tandem
repeats and genes for tumor necrosis factor alpha and interleukin-1 alpha also
have recently been associated with IIM. The pathogenic bases for the differences
among the many clinically, pathologically and immunologically defined syndromes
known as the IIM will be elucidated through a better understanding of the
multiple genes that define risks for their development, as well as through
investigations of gene-gene and gene-environment interactions.
Publication Types:
Review
Review, Tutorial
PMID: 11092196 [PubMed - indexed for MEDLINE]
208: Neurology. 2000 Nov 14;55(9):1385-7.
Epidemiology of inclusion body myositis in the Netherlands: a nationwide study.
Badrising UA, Maat-Schieman M, van Duinen SG, Breedveld F, van Doorn P, van
Engelen B, van den Hoogen F, Hoogendijk J, Howeler C, de Jager A, Jennekens
F,
Koehler P, van der Leeuw H, de Visser M, Verschuuren JJ, Wintzen AR.
Department of Neurology, Leiden University Medical Center, The Netherlands.
ubadrising@neurology.azl.nl
Epidemiologic data on inclusion body myositis (IBM) are scarce, and possibly
biased, because they are derived from larger neuromuscular centers. The present
nationwide collaborative cross-sectional study, which culminated on July 1,
1999, resulted in identification of 76 patients with IBM and the establishment
of a prevalence of 4.9 patients with IBM per million inhabitants in the
Netherlands. Several discrepancies suggest that this may be an underestimation.
The most frequently identified pitfall in diagnosing IBM was an erroneous
diagnosis of polymyositis or motor neuron disease.
PMID: 11087787 [PubMed - indexed for MEDLINE]
209: Arch Neurol. 2000 Nov;57(11):1561-5.
Apolipoprotein E and neuromuscular disease: a critical review of the literature.
Bedlack RS, Strittmatter WJ, Morgenlander JC.
PO Box 3403, Duke University Medical Center, Durham, NC 27710, USA.
bedla001@mc.duke.edu
Molecular mechanisms that alter the incidence and rate of neuromuscular disease
progression are, in many cases, only partially understood. Several recent
studies have asked whether apolipoprotein E (apoE for the protein, APOE for
the
gene) influences these aspects of specific neuromuscular disorders, as it does
in central nervous system disorders such as Alzheimer disease. Although these
studies are open to methodological criticism, several interesting trends have
emerged. First, the APOE4 allele seems to be associated with an increased risk
for developing certain neuromuscular diseases, including diabetic neuropathy
and
human immunodeficiency viral neuropathy. Second, this allele appears to be
associated with faster progression of some neuromuscular diseases, including
diabetic neuropathy and possibly motor neuron disease. Third, the APOE2 allele
seems to confer protection against developing certain neuromuscular diseases,
including the amyotrophic lateral sclerosis (ALS)/parkinsonism/dementia complex
of Guam. Finally, this allele is associated with a better prognosis in
neuromuscular diseases such as motor neuron disease. The effect of various APOE
alleles on neuromuscular diseases therefore parallels their influence on central
nervous system diseases. Arch Neurol. 2000;57:1561-1565
Publication Types:
Review
Review, Tutorial
PMID: 11074787 [PubMed - indexed for MEDLINE]
210: Neurology. 2000 Oct 24;55(8):1235.
Comment in:
Neurology. 2001 Jul 24;57(2):368.
Sporadic inclusion body myositis not linked to prion protein codon 129 methionine
homozygosity.
Orth M, Tabrizi SJ, Schapira AH.
University Department of Clinical Neurosciences, Royal Free and University
College Medical School, London, UK.
PMID: 11071511 [PubMed - indexed for MEDLINE]
211: Neurosci Lett. 2000 Oct 20;293(1):33-6.
Cyclin-dependent kinase 5 colocalizes with phosphorylated tau in human
inclusion-body myositis paired-helical filaments and may play a role in tau
phosphorylation.
Wilczynski GM, Engel WK, Askanas V.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, Los Angeles
90017-1912, USA.
To investigate the possible role of cyclin-dependent kinase 5 (cdk5) in the
formation of paired helical filaments (PHFs) in muscle of patients with
inclusion-body myositis (IBM), we immunolocalized cdk5, by light- and electron-
microscopy, in muscle biopsies of six IBM patients. Approximately 80-90% of
IBM
vacuolated muscle fibers, and 10-15% of nonvacuolated fibers, contained well
defined cdk5-immunoreactive inclusions that colocalized with phosphorylated
tau
in 70-80% of those fibers. Immunoelectronmicroscopy revealed the association
of
cdk5 with tau-immunoreactive PHFs. In all biopsies that contained them,
regenerating muscle fibers had diffuse, moderate to strong cdk5
immunoreactivity. At all neuromuscular junctions, there was strong cdk5
immunoreactivity postsynaptically. Our study suggests that cdk5: (1) plays a
role in IBM pathogenesis, possibly mediating phosphorylation of PHF-related
tau;
(2) is involved in muscle regeneration; and (3) has a novel function at normal
neuromuscular junctions.
PMID: 11065131 [PubMed - indexed for MEDLINE]
212: J Neuroimmunol. 2000 Nov 1;111(1-2):146-51.
T-cell anti-apoptotic mechanisms in inflammatory myopathies.
Vattemi G, Tonin P, Filosto M, Spagnolo M, Rizzuto N, Tomelleri G.
Department of Neurological Sciences and Vision, University of Verona, Verona,
Italy.
Recent studies have shown an up-regulation of the Fas/Fas ligand system in
inflammatory myopathies. In myositis, however, the major Fas-mediated
cytotoxicity which activates caspases bypasses apoptosis. We therefore evaluated
the expression of proteins promoting cell survival, such as bcl-2, bcl-x(l)
and
cyclin-dependent kinase inhibitors, on muscle biopsies from 14 patients with
polymyositis, dermatomyositis, inclusion body myositis and HIV-associated
myositis. Our data demonstrate that inflammatory cells are immunoreactive for
bcl-x(l), p16 and p57, three apoptosis-preventing proteins. Hence, we assume
that these proteins might protect T cells from apoptotic nuclear changes. Our
results could explain the non-self-limiting nature of inflammatory myopathies.
PMID: 11063832 [PubMed - indexed for MEDLINE]
213: J Neurol Sci. 2000 Oct 1;179(S 1-2):92-102.
Peripheral neuropathy associated with hereditary and sporadic inclusion body
myositis: confirmation by electron microscopy and morphometry.
Hermanns B, Molnar M, Schroder JM.
Institut fur Neuropathologie, Universitatsklinikum der Rheinisch-Westfalischen
Technischen Hochschule Aachen, Pauwelsstrasse 30, D-52074, Aachen, Germany.
Inclusion body myositis (IBM) is a disabling myopathy affecting proximal and
distal muscle groups. The involvement of peripheral nerves in IBM is still a
controversial matter. In a previous morphometric study at the light microscopic
level only, we described a peripheral neuropathy in sural nerve biopsies of
eight patients with sporadic IBM (s-IBM). Here we present a larger series of
14
cases in which a combined muscle and nerve biopsy was available for additional
electron microscopic investigation. In two of the new cases, the IBM had a
hereditary background (h-IBM). The presence of neuropathy was confirmed in all
14 cases studied. Morphometry using an optic-electronic, digital evaluation
system showed large variation of severity presumably due to age and coincidal
factors such as diabetes mellitus or lymphoma. Ultrastructural analysis revealed
a variety of changes considered to be non-specific. Signs of axonal damage
predominated. In addition, there were numerous changes in Schwann cells and
myelin sheaths. Neither inflammatory changes nor tubulofilamentous inclusions
were detectable in the sural nerves. Peripheral neuropathy, although
occasionally without apparent clinical manifestation, appears to be a common
and
aggravating feature in IBM; its pathogenesis, however, remains elusive.
PMID: 11054491 [PubMed - indexed for MEDLINE]
214: Neuromuscul Disord. 2000 Dec;10(8):604-11.
Mitochondrial DNA variants in inclusion body myositis.
Kok CC, Boyt A, Gaudieri S, Martins R, Askanas V, Dalakas M, Kiers L, Mastaglia
F, Garlepp M.
Australian Neuromuscular Research Institute, Queen Elizabeth II Medical Centre,
Nedlands, Western Australia, Australia.
Mitochondrial DNA variants have been shown to be associated with many diseases.
Mutations at mitochondrial DNA nucleotide positions 3192, 3196, 3397 and 4336
have been described in association with late-onset Alzheimer's disease. The
pathological similarities between inclusion body myositis and Alzheimer's
disease prompted an analysis of the relationship between the reported mutations
and sporadic inclusion body myositis. The 4336G variant was not significantly
increased in patients with inclusion body myositis or Alzheimer's disease when
compared to controls. None of the patients with inclusion body myositis carried
mutations at nucleotide positions 3192, 3196 and 3397. A transition at
nucleotide position 4580 was detected in some patients with inclusion body
myositis and Alzheimer's disease but was not significantly higher in frequency
when compared to controls. Phylogenetic analysis showed that the 4336G and 4580A
variants clustered together in their respective group. A group of patients with
inclusion body myositis also clustered together on a separate branch of the
phylogenetic tree. Closer investigation of this group revealed a common
polymorphism at nucleotide position 16311. The frequency of the 16311C variant
was higher in inclusion body myositis than in Alzheimer's disease and controls,
although when only caucasian patients were considered the increased frequency
was not statistically significant. Further studies will be required to determine
whether this variant plays a role in the pathogenesis of inclusion body
myositis.
PMID: 11053689 [PubMed - indexed for MEDLINE]
215: Brain. 2000 Oct;123 ( Pt 10):2030-9.
Clonal restriction of T-cell receptor expression by infiltrating lymphocytes
in
inclusion body myositis persists over time. Studies in repeated muscle biopsies.
Amemiya K, Granger RP, Dalakas MC.
Neuromuscular Disease Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, Maryland 20892-1382, USA.
Inclusion body myositis (IBM) is an inflammatory myopathy characterized
immunohistologically by prominent invasion of the non-necrotic, MHC-I class
antigen-expressing muscle fibres by CD8+ cytotoxic T cells. If the autoinvasive
CD8+ T cells are recruited specifically to the muscle and play a primary
pathogenetic role in the disease, a clonal restriction persisting over time
should be anticipated. In this study, we analysed the T-cell receptor (TCR)
gene
usage by endomysial T lymphocytes in three sequential muscle biopsies from three
different IBM patients over a 19-22 month period using immunohistochemistry,
reverse transcription-polymerase chain reaction (RT-PCR) and sequence analysis
of the complementarity determining region (CDR3) of the amplified TCRs. We found
that CD8+ T lymphocytes persist in the endomysial infiltrates in all biopsies
during a 19-22 month period. The most frequently detected TCRs were the V beta
3, V beta 5.1, V beta 6.7 and V beta 13 gene families, and several of the
autoinvasive CD8+ T cells expressed the TCRs V beta 6.7 and V beta 5.1. A
restricted usage of the examined V beta 6 gene family was found to persist in
the complementarity CDR3 determining region of the autoinvasive T cells over
the
22 month period. Identical V beta 6 CDR3 gene arrangements were also found in
the multiple muscle biopsies from two of the three IBM patients. The results
indicate that in IBM there is a restricted expression of the TCR gene families
among the autoinvasive T lymphocytes with homologies in the CDR3 region that
persist over the course of the disease. A continuous, antigen-driven T-cell
response is prominent in the muscle of patients with IBM.
PMID: 11004120 [PubMed - indexed for MEDLINE]
216: Immunobiology. 2000 Aug;202(2):199-203.
Common variable immunodeficiency (CVID) and inclusion body myositis (IBM).
Gause A, Inderrieden DC, Laas R, Arlt AC, Gross WL.
Poliklinik fur Rheumatologie, Universitatsklinikum Lubeck und
Krankenhausabteilung der Rheumaklinik Bad Bramstedt, Germany.
a.gause@rheuma-zentrum.de
A case of a 38-year old man with a common variable immunodeficiency syndrome
(CVID) is demonstrated who suffered at the same time from a histologically
proven inclusion body myositis (IBM). The myositis did not resolve after
institution of regular intravenous IgG infusions. This case demonstrates a very
long lasting benign course of IBM. The occurrence with CVID may be a clinical
hint for a viral pathogenesis of IBM. So far only two similar cases are reported
in the literature.
Publication Types:
Case Reports
PMID: 10993295 [PubMed - indexed for MEDLINE]
217: Int J Exp Pathol. 2000 Aug;81(4):231-9.
Accumulation of amyloid-beta protein in exocrine glands of transgenic mice
overexpressing a carboxyl terminal portion of amyloid protein precursor.
Fukuchi K, Li L, Hart M, Lindsey JR.
Departments of Comparative Medicine; Medicine, Schools of Medicine and
Dentistry, University of Alabama at Birmingham, Birmingham, Alabama, USA.
fukuchi@uab.edu
Amyloid-beta protein (Abeta) and its precursor (betaPP) play important roles
in
the pathogenesis of Alzheimer disease and inclusion-body myositis. In humans,
Abeta deposits are found in brain, skeletal muscle, and skin. Therefore, we
have
investigated possible Abeta deposits in multiple tissues of two transgenic mouse
lines overexpressing the signal plus Abeta-bearing 99-amino acid carboxyl
terminal sequences of betaPP under the control of a cytomegalovirus
enhancer/beta-actin promoter. One of the lines developed Abeta-immunoreactive
intracellular deposits consistently in the pancreas and lacrimal gland, and
occasionally in gastric, DeSteno's, and lingual glands. Although the Abeta
deposits increased during ageing and degenerative changes of the tissues were
observed, little or no extracellular Abeta deposits were observed up to the
age
of 25 months. These lines of transgenic mice are useful for studying the
molecular mechanisms of development and clearance of intracellular Abeta
deposits.
PMID: 10971744 [PubMed - indexed for MEDLINE]
218: Br J Dermatol. 2000 Sep;143(3):671.
Comment on:
Br J Dermatol. 1999 Nov;141(5):926-30.
Dermatomyositis with the features of inclusion body myositis associated with
carcinoma of the bladder: a true association?
Grau JM, Perea M.
Publication Types:
Comment
Letter
PMID: 10971365 [PubMed - indexed for MEDLINE]
219: Arch Phys Med Rehabil. 2000 Aug;81(8):1123-6.
Inclusion body myositis masquerading as polymyositis: a case study.
Boon AJ, Stolp-Smith KA.
Department of Physical Medicine and Rehabilitation, Mayo Clinic and Mayo
Foundation, Rochester, MN 55905, USA.
A case of inclusion body myositis masquerading as unresponsive polymyositis
is
presented. A 56-year-old woman diagnosed with "biopsy-proven" polymyositis
in
1991 was referred to our clinic in 1997 with progressive, painless weakness
that
was unresponsive to steroid therapy. Further evaluation, including
electromyography and review of the original muscle biopsy specimen, found a
diagnosis of inclusion body myositis, leading to a change in the patient's
prognosis and management. Inclusion body myositis is frequently mistaken for
polymyositis, despite the fact that it is now the most common inflammatory
myopathy affecting people older than 50 years. The purpose of this report is
to
increase awareness of this disease, to enhance early diagnosis, and to ensure
appropriate management. We discuss the clinical findings, pathogenesis, and
physiatric management, as well as compare this disease with other idiopathic
inflammatory myopathies.
Publication Types:
Case Reports
PMID: 10943766 [PubMed - indexed for MEDLINE]
220: Neurol Sci. 2000 Apr;21(2):99-102.
An Italian family with autosomal recessive quadriceps-sparing inclusion-body
myopathy (ARQS-IBM) linked to chromosome 9p1.
Mirabella M, Christodoulou K, Di Giovanni S, Ricci E, Tonali P, Servidei S.
Institute of Neurology, Catholic University, Policlinico Gemelli, Rome, Italy.
We report an Italian family with autosomal recessive quadriceps-sparing
inclusion-body myopathy (ARQS-IBM). The patients (two second cousins) developed
a slowly progressive distal and proximal myopathy with complete sparing of the
quadriceps. Muscle biopsy showed rimmed vacuoles in numerous muscle fibers,
and
electron microscopy documented accumulation of 15-21 nm filaments. DNA analysis
established linkage to 9p1 and haplotype analysis revealed that the patients
shared a recombined common haplotype. The gene locus of ARQS-IBM was initially
mapped to chromosome 9p1-q1 in families of Iranian-Jewish origin and later
confirmed in a few other ethnic groups. This is the first report of Italian
patients with ARQS-IBM showing positive linkage to chromosome 9p1. Our data
suggest that patients having distal and proximal myopathy with rimmed vacuoles
and possible recessive inheritance, often classified as distal myopathies,
should be thoroughly investigated according to the diagnostic criteria of h-IBM
and, when positive, studied for linkage to chromosome 9p1.
Publication Types:
Case Reports
PMID: 10938188 [PubMed - indexed for MEDLINE]
221: Ultrastruct Pathol. 2000 May-Jun;24(3):151-6.
Muscle involvement in rheumatoid arthritis: an ultrastructural study.
de Palma L, Chillemi C, Albanelli S, Rapali S, Bertoni-Freddari C.
Department of Orthopedics, University of Ancona, Italy.
An electron microscopic investigation has been carried out on muscle bioptic
samples from patients affected by rheumatoid arthritis (RA). This study was
undertaken to seek further ultrastructural alterations affecting striated
muscles in RA pathology. Bioptic samples were collected on a total of 30
surgical interventions of hip (10), knee (8), and foot (12). This yielded three
muscle types: gluteus maximus, vastus lateralis, and extensor digitorum
communis. Muscle samples from 12 patients with no RA stigmata, selected to match
RA patients by age and gender, constituted the control group. Tissue samples
were prepared both for conventional histochemical methods and according to
conventional electron microscopic procedures, including morphometric analysis.
Although to a different extent in each sample, in muscles from RA vs. controls
the authors observed the simultaneous presence of discrete muscular alterations
such as wider separation of myofibrils, myelin figures, dilated sarcotubular
system, pleomorphic mitochondria, myofibril flaking, and lipofuscin deposition
in the subsarcolemmal region. In addition to a progressive atrophy, the above
findings are suggestive of rheumatoid myositis and lend further support to the
still poorly documented presence of an idiopathic inflammatory myopathy and
inclusion body myositis associated with RA.
PMID: 10914426 [PubMed - indexed for MEDLINE]
222: Acta Neuropathol (Berl). 2000 Jul;100(1):23-8.
Multiple mitochondrial DNA deletions in hereditary inclusion body myopathy.
Jansson M, Darin N, Kyllerman M, Martinsson T, Wahlstrom J, Oldfors A.
Department of Pathology, Sahlgrenska University Hospital, Goteborg, Sweden.
We have recently described an autosomal dominant hereditary inclusion body
myopathy (h-IBM). Clinically it is is characterized by congenital joint
contractures and slowly progressive, proximal muscle weakness and
ophthalmoplegia. There is deterioration of muscle function between 30 and 50
years of age. While young patients show minor pathological changes in muscle,
the middle-aged and old patients show rimmed vacuoles and inclusions of
filaments measuring 15-18 nm in diameter. Except for the absence of significant
inflammation the histopathology is similar to that found in sporadic inclusion
body myositis (s-IBM). In s-IBM mitochondrial alterations including cytochrome
c
oxidase (COX) -deficient muscle fibers are common. These are due to multiple
mitochondrial DNA (mtDNA) deletions. In this study we investigated the
occurrence of mitochondrial alterations in autosomal dominant h-IBM. Young
affected individuals showed no mitochondrial changes but three patients aged
38,
51 and 59 years, respectively, showed ragged red fibers and COX-deficient muscle
fibers. Polymerase chain reaction analysis showed multiple mtDNA deletions.
By
in situ hybridization clonal expansions of mtDNA with deletions were
demonstrated in COX-deficient muscle fibers. Most of the analyzed deletion
breakpoints showed nucleotide repeats flanking the deletions. The results show
that COX-deficient muscle fibers and somatic mtDNA deletions are present in
this
family with h-IBM. The same factors may be involved in the development of mtDNA
deletions in s-IBM and this family with h-IBM.
PMID: 10912916 [PubMed - indexed for MEDLINE]
223: Neurology. 2000 Jul 25;55(2):296-8.
Disease progression in sporadic inclusion body myositis: observations in 78
patients.
Peng A, Koffman BM, Malley JD, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurologic Diseases and
Stroke, National Institutes of Health, Bethesda, MD, USA.
Functional decline for each decade at symptom onset and need for cane, walker,
or wheelchair were assessed in 78 biopsy-proved patients with sporadic inclusion
body myositis. Patients with disease onset between 40 and 59 years used a walker
after 10.2 +/- 5.8 years, whereas those with disease onset between 60 and 79
years used a walker after 5.7 +/- 5.0 years (p = 0.05). Because patients
progress faster to disability when symptoms begin after the age of 60, age at
disease onset may define patient subsets for stratification in clinical trials.
PMID: 10908910 [PubMed - indexed for MEDLINE]
224: J Neuropathol Exp Neurol. 2000 Jul;59(7):592-8.
Novel immunolocalization of alpha-synuclein in human muscle of inclusion-body
myositis, regenerating and necrotic muscle fibers, and at neuromuscular
junctions.
Askanas V, Engel WK, Alvarez RB, McFerrin J, Broccolini A.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, Los Angeles
90017-1912, USA.
Alpha-synuclein (alpha-syn) is an important component of neuronal and glial
inclusions in brains of patients with several neurodegenerative disorders.
Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle
disease of older patients. Its muscle phenotype shows several similarities with
Alzheimer disease brain. A distinct feature of s-IBM pathology is specific
vacuolar degeneration of muscle fibers characterized by intracellular amyloid
inclusions formed by both amyloid-beta (Abeta) and paired-helical filaments
composed of phosphorylated tau. We immunostained alpha-syn in muscle biopsies
of
s-IBM, disease-control, and normal patients. Approximately 60% of Abeta-positive
vacuolated muscle fibers (VMF) contained well-defined inclusions immunoreactive
with antibodies against alpha-syn. In those fibers. alpha-syn co-localized with
Abeta, both by light microscopy, and ultrastructurally. Paired-helical filaments
did not contain alpha-syn immunoreactivity. In all muscle biopsies, alpha-syn
was strongly immunoreactive at the postsynaptic region of the neuromuscular
junctions. alpha-syn immunoreactivity also occurred diffusely in regenerating
and necrotic muscle fibers. In cultured human muscle fibers, alpha-syn and its
mRNA were expressed by immunocytochemistry, immunoblots, and Northern blots.
Our
study provides the first demonstration that alpha-syn participates in normal
and
pathologic processes of human muscle. Therefore. its function is not exclusive
to the brain and neurodegenerative diseases.
PMID: 10901230 [PubMed - indexed for MEDLINE]
225: Baillieres Best Pract Res Clin Rheumatol. 2000 Mar;14(1):55-71.
Inflammatory muscle disease: therapeutic aspects.
Catoggio LJ, Soriano ER.
Rheumatology Section, Medical Services, Hospital Italiano de Buenos Aires,
Argentina. ljcatoggio@connmed.com.ar
The present treatment of the inflammatory myopathies remains unsatisfactory
in
several areas, perhaps due in part to our incomplete knowledge of their
aetiology. These conditions have been grouped together for practical purposes
and because of a similar approach to treatment. However, recent data regarding
pathological findings, serological patterns and different outcomes, suggest
that
some of these myopathies may be distinct, and perhaps approaches to treatment
should be tailored according to these findings. This chapter will attempt to
update our current management, offer an analysis of recent data regarding newer
treatment modalities and highlight areas lacking solid data that need to be
further addressed. Although corticosteroids are still considered to be the
mainstay of treatment, the earlier use of immunosuppressive therapy will be
discussed, as will the use of autoantibody profiles for tailoring treatment.
Newer modalities for the monitoring of therapeutic response and their current
place in clinical practice will be analysed. The management of refractory cases
will be addressed as will the current management of calcinosis, a problem more
frequently encountered in children.
PMID: 10882214 [PubMed - indexed for MEDLINE]
226: Am J Pathol. 2000 Jun;156(6):1835-40.
Association of active extracellular signal-regulated protein kinase with paired
helical filaments of inclusion-body myositis muscle suggests its role in
inclusion-body myositis tau phosphorylation.
Wilczynski GM, Engel WK, Askanas V.
Department of Neurology, University of Southern California Keck School of
Medicine, Good Samaritan Hospital, Los Angeles, CA 90017-1912, USA.
The possible role of extracellular signal-regulated kinase (ERK) in the
pathogenesis of inclusion-body myositis (IBM) was investigated by immunostaining
the active phosphorylated form of ERK in muscle biopsies of six IBM and 14
control patients. Between 80% and 90% of IBM vacuolated muscle fibers contained
well-defined ERK-immunoreactive inclusions, which were co-localized by light
microscopy, with phosphorylated tau in 70 to 80% of those fibers.
Immunoelectronmicroscopy colocalized ERK to small amorphous tufts adjacent to
the muscle fiber paired-helical filaments. Strong ERK immunoreactivity was also
present at the postsynaptic domain of all human neuromuscular junctions. Our
study suggests 1) that ERK, a signal transducer, might play a role in IBM
pathogenesis, including participation in the pathological phosphorylation of
IBM
tau; and 2) that signal transduction abnormalities may be a component of the
IBM
pathogenic cascade. Our novel immunolocalization of ERK at the postsynaptic
domain of human neuromuscular junctions supports a role in transcription of
junctional-protein genes. The ERK localized in nonjunctional regions of IBM
fibers may underlie the known pathological up-regulation of junctional proteins
there.
PMID: 10854206 [PubMed - indexed for MEDLINE]
227: Ann Neurol. 2000 Jun;47(6):811-6.
Partial laminin alpha2 chain deficiency in a patient with myopathy resembling
inclusion body myositis.
Di Blasi C, Mora M, Pareyson D, Farina L, Sghirlanzoni A, Vignier N, Blasevich
F, Cornelio F, Guicheney P, Morandi L.
Department of Neuromuscular Diseases, Istituto Nazionale Neurologico Carlo
Besta, Milano, Italy.
It is becoming evident that clinical phenotypes associated with partial laminin
alpha2 chain deficiency are variable. We recently observed a 29-year-old man
with leukoencephalopathy and vacuolar myopathy resembling inclusion body
myositis. Laminin alpha2 immunohistochemical analysis showed reduction of the
protein on muscle fiber surfaces. Molecular analysis revealed two novel compound
heterozygous mutations in the LAMA2 gene. This is the first report linking a
mutation in the LaMA2 gene with leukoencephalopathy and inclusion body-like
myositis.
Publication Types:
Case Reports
PMID: 10852549 [PubMed - indexed for MEDLINE]
228: Muscle Nerve. 2000 Jun;23(6):970-2.
Prevalence of sporadic inclusion body myositis in Western Australia.
Phillips BA, Zilko PJ, Mastaglia FL.
Centre for Neuromuscular and Neurological Disorders, Australian Neuromuscular
Research Institute, University of Western Australia, Australia.
A 10-year retrospective review was conducted to ascertain the prevalence of
inclusion body myositis (IBM) in Western Australia. Seventeen patients with
sporadic IBM aged 45-90 years were identified and the prevalence of IBM was
calculated to be 9.3 x 10(-6). The prevalence was higher in men (10.9 x 10(-6))
than in women (7.7 x 10(-6)). The mean age of onset of IBM was 56.6 years, and
the mean delay between onset of symptoms and diagnosis was 4.4 years. The
age-adjusted prevalence over the age of 50 years was 35.3 x 10(-6). The results
suggest a higher prevalence of IBM than has previously been reported. Copyright
2000 John Wiley & Sons, Inc.
PMID: 10842277 [PubMed - indexed for MEDLINE]
229: Neurosci Lett. 2000 Jun 16;287(1):1-4.
Redox factor-1 in muscle biopsies of patients with inclusion-body myositis.
Broccolini A, Engel WK, Alvarez RB, Askanas V.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA
90017-1912, USA.
To determine whether redox factor-1 (Ref-1) participates in the pathogenesis
of
inclusion-body myositis (IBM), we immunolocalized Ref-1 in muscle biopsies of
IBM patients by light- and electron-microscopy. Approximately 70-80% of the
IBM
vacuolated muscle fibers had focal inclusions strongly immunoreactive for Ref-1.
By immunoelectronmicroscopy, Ref-1 was localized to paired-helical filaments,
6-10 nm amyloid-like fibrils and amorphous material. Virtually all regenerating
and necrotic muscle fibers in various muscle biopsies had diffusely strong Ref-1
immunoreactivity. At all neuromuscular junctions, postsynaptically there was
strong Ref-1 immunoreactivity. Our study suggests that Ref-1 plays a role in
IBM
pathogenesis, and in other pathologic and normal processes of human muscle.
PMID: 10841976 [PubMed - indexed for MEDLINE]
230: Aust N Z J Med. 2000 Apr;30(2):275-6.
Inclusion body myositis associated with systemic lupus erythematosus (SLE)
Limaye V, Scott G, Kwiatek R, Pile K.
Publication Types:
Case Reports
Letter
PMID: 10833124 [PubMed - indexed for MEDLINE]
231: J Neuroimmunol. 2000 Jul 1;106(1-2):1-5.
Expression of human IAP-like protein in skeletal muscle: a possible explanation
for the rare incidence of muscle fiber apoptosis in T-cell mediated inflammatory
myopathies.
Li M, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Diseases
and
Stroke, National Institute of Health, Building 10, Room 4N248, 10 Center Drive,
MSC 1382, Bethesda, MD 20892-1382, USA.
In Polymyositis (PM) and sporadic Inclusion Body Myositis (s-IBM), the CD8(+)
cytotoxic T cells invade the muscle membrane and release perforin and granzyme
B
to induce cell death. Although granzyme B is a direct activator of executioner
caspases, there is no convincing evidence of apoptosis in the muscle fibers
of
these patients. To search for an explanation, we examined the muscle expression
of the human IAP-Like Protein (hILP), an evolutionarily conserved cell death
suppressor, that exerts major anti-apoptotic effects by inhibiting the
executioner caspases. Muscle biopsy specimens from patients with inflammatory
myopathies and controls were studied with: (a) immunocytochemistry using
antibodies against hILP and caspase-3 in single and double-labeled confocal
laser microscopy; (b) immunoblotting of muscle extracts immunoreacted with
anti-hILP antibodies; and (c) subcellular fractionation of muscle lysates
immunoreacted with antibodies against hILP. We found that hILP is expressed
on
the sarcolemmal region and co-localizes with dystrophin. Caspase-3 is
undetectable. Subcellular fractionation of the muscle specimens confirmed that
hILP is a membrane-associated protein. By immunoblotting, the 57 kD hILP was
abundantly expressed in the normal as well as the diseased muscles. We conclude
that in s-IBM and PM the expression of hILP, a major cell death suppressor,
on
the muscle membrane may prevent the induction of apoptosis by the autoinvasive
cytotoxic T cells on the cell surface, by inhibiting the caspase activation.
PMID: 10814776 [PubMed - indexed for MEDLINE]
232: Toxicol Pathol. 2000 Mar-Apr;28(2):363-6.
Recent developments in animal models of human neurodegenerative diseases.
Guyer C.
Department of Veterinary Pathobiology, University of Illinois, Urbana 61802,
USA.
Publication Types:
Congresses
PMID: 10805156 [PubMed - indexed for MEDLINE]
233: J Immunol. 2000 May 15;164(10):5459-65.
The inhibition of apoptosis in myositis and in normal muscle cells.
Nagaraju K, Casciola-Rosen L, Rosen A, Thompson C, Loeffler L, Parker T, Danning
C, Rochon PJ, Gillespie J, Plotz P.
Arthritis and Rheumatism Branch, National Institute of Arthritis and
Musculoskeletal and Skin Diseases, and National Cancer Institute, National
Institutes of Health, Bethesda, MD 20892, USA.
The mechanism of injury and death of muscle cells in the inflammatory myopathies
(dermatomyositis, polymyositis, and inclusion body myositis) remains obscure.
We
and others have not detected apoptosis in the muscle biopsies from patients
with
myositis despite clear evidence of cell damage and loss. We provide evidence
in
this study that Fas ligand (FasL) as well as Fas is present on muscle cells
and
inflammatory cells in myositis biopsies: Fas is present on most muscle cells
and
lymphocytes, and FasL is present on degenerating muscle cells and many
infiltrating mononuclear cells. The expression of both Fas and FasL in the
inflamed tissue makes the absence of apoptosis more striking. To address the
mechanisms of this resistance to classical apoptosis in muscle cells, we have
investigated the expression of the antiapoptotic molecule FLICE (Fas-associated
death domain-like IL-1-converting enzyme)-inhibitory protein (FLIP) in muscle
biopsies of myositis patients and in cultured human skeletal muscle cells. Using
laser capture microscopy, we have shown that FLIP is expressed in the muscle
fibers and on infiltrating lymphocytes of myositis biopsies. Furthermore, we
have shown that FLIP, but not Bcl-2, is expressed in cultured human skeletal
muscle cells stimulated with proinflammatory cytokines, and inhibition of FLIP
with antisense oligonucleotides promotes significant cleavage of
poly(ADP-ribose) polymerase autoantigen, a sensitive indicator of apoptosis.
These studies strongly suggest that the resistance of muscle to Fas-mediated
apoptosis is due to the expression of FLIP in muscle cells in the inflammatory
environment in myositis.
PMID: 10799913 [PubMed - indexed for MEDLINE]
234: Clin Neuropathol. 2000 Jan-Feb;19(1):13-20.
Inclusion body myositis (IBM).
Gayathri N, Anisya-Vasanth, Veerendra Kumar M, Das S, Santosh V, Yasha TC,
Ramamohan Y, Taly AB, Gourie-Devi M, Shankar SK.
Department of Neuropathology, National Institute of Mental Health and
Neurosciences, Bangalore, India.
Clinical, histological, immunohistochemical and ultrastructural features of
5
cases of inclusion body myositis -4 sporadic (s-IBM) and one hereditary (h-IBM)
form are described. These patients (3 men, 2 women) had chronic progressive
weakness of varying severity in all 4 extremities with sparing of cranial
muscles. Elevation of CPK was noted in 2 patients. Electromyography revealed
features of myopathy in 4 and additional neurogenic changes in 2 subjects.
Clinical diagnosis was often other than inclusion body myositis. Presence of
characteristic eosinophilic inclusions within the vacuoles established the
diagnosis. The inclusions were congophilic and showed positivity to ubiquitin,
beta-amyloid and SMI-31 in the sporadic cases while congophila was absent in
the
hereditary form. Immunostaining to hyperphosphorylated-tau was negative in both
s-IBM and h-IBM. Membraneous whorls were observed at ultrastructural level.
None
of the patients improved with steroids and trial with other immunosuppressants
was unsuccessful.
PMID: 10774946 [PubMed - indexed for MEDLINE]
235: Am J Med Sci. 2000 Apr;319(4):227-33.
Autoantibodies in inflammatory myopathies.
Garlepp MJ, Mastaglia FL.
School of Pharmacy, Curtin University of Technology, Western Australia, Perth.
tgarlepp@cc.curtin.edu.au
Publication Types:
Review
Review, Tutorial
PMID: 10768607 [PubMed - indexed for MEDLINE]
236: Neurology. 2000 Apr 25;54(8):1665-70.
The muscle mitogen-activated protein kinase is altered in sporadic inclusion
body myositis.
Li M, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institute of Health, Bethesda, MD 20892-1382, USA.
OBJECTIVE: To examine the origin of hyperphosphorylated proteins within the
vacuolated myofibers in sporadic inclusion body myositis (s-IBM) and search
for
dysregulated intracellular protein phosphorylation. BACKGROUND: s-IBM is
morphologically characterized by primary endomysial inflammation and vacuolated
myofibers containing tubulofilaments that originate from cytoskeletal proteins.
Mitogen-activated protein kinases (MAPKs) play a role in regulating
phosphorylation and maintaining the stability of the cytoskeletal architecture.
METHODS: Muscle biopsies from seven patients with s-IBM and 15 controls were
examined for the expression of the active components of the various MAPKs,
including p44/42MAPK, p38MAPK, p46JNK1, p54JNK2, and p54JNK3, using
immunocytochemistry and Western blot analysis. The expression of selected
phosphorylated components was also examined in the same specimens. RESULTS:
In
s-IBM, but not the disease controls, the vacuolated muscle fibers express active
p42MAPK but not JNK or p38MAPK. Western blots of cell lysates confirmed the
hyperexpression of p42MAPK and demonstrated a novel 35 kD phosphoprotein.
Antibodies against phosphoepitopes of the 35 kD protein preferentially
immunostained antigens within the vacuolated muscle fibers of s-IBM but not
disease controls. CONCLUSION: In s-IBM, there is increased p42MAPK activation
and abnormal intracellular protein phosphorylation with selective accumulation
of a 35 kD phosphoprotein within the vacuolated fibers. Although the
hyperexpression of 35kD protein may represent cytoskeletal by-products due to
heightened p42MAPK activation, its abundant expression only in s-IBM implies
that hyperphosphorylated myofibrillar proteins may be involved in the primary
disease process.
Publication Types:
Clinical Trial
Controlled Clinical Trial
PMID: 10762511 [PubMed - indexed for MEDLINE]
237: Ann Neurol. 2000 Apr;47(4):544-9.
Inclusion body myositis, muscle blood vessel and cardiac amyloidosis, and
transthyretin Val122Ile allele.
Askanas V, Engel WK, Alvarez RB, Frangione B, Ghiso J, Vidal R.
Department of Neurology, University of Southern California, Keck School of
Medicine, Good Samaritan Hospital, Los Angeles, CA, USA.
Typical of sporadic inclusion body myositis muscle biopsies are vacuolated
muscle fibers containing intracellular amyloid deposits and accumulations of
"Alzheimer-characteristic" proteins. There is no muscle blood vessel
or cardiac
amyloidosis. We report on a 70-year-old African-American man homozygous for
the
transthyretin Val122Ile allele who has both sporadic inclusion body myositis
and
cardiac amyloidosis. His unique pathological features included transthyretin
immunoreactivity in prominent muscle blood vessel amyloid and congophilic
amyloid deposits within vacuolated muscle fibers.
Publication Types:
Case Reports
PMID: 10762172 [PubMed - indexed for MEDLINE]
238: Am J Pathol. 2000 Apr;156(4):1151-5.
Paired helical filaments of inclusion-body myositis muscle contain RNA and
survival motor neuron protein.
Broccolini A, Engel WK, Alvarez RB, Askanas V.
University of Southern California Neuromuscular Center, Los Angeles, California
90017-1712, USA.
Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle
disease of older persons. Pathologically, the muscle biopsy manifests various
degrees of inflammation and specific vacuolar degeneration of muscle fibers
characterized by paired helical filaments (PHFs) composed of phosphorylated
tau.
IBM vacuolated fibers also contain accumulations of several other
Alzheimer-characteristic proteins. Molecular mechanisms leading to formation
of
the PHFs and accumulations of proteins in IBM muscle are not known. We report
that the abnormal muscle fibers of IBM contained (i) acridine-orange-positive
RNA inclusions that colocalized with the immunoreactivity of phosphorylated
tau
and (ii) survival motor neuron protein immunoreactive inclusions, which by
immuno-electron microscopy were confined to paired helical filaments. This study
demonstrates two novel components of the IBM paired helical filaments, which
may
lead to better understanding of their pathogenesis.
PMID: 10751338 [PubMed - indexed for MEDLINE]
239: J Neuropathol Exp Neurol. 2000 Feb;59(2):164-9.
Increased expression of beta-chemokines in muscle of patients with inflammatory
myopathies.
Confalonieri P, Bernasconi P, Megna P, Galbiati S, Cornelio F, Mantegazza R.
Divisione Malattie Neuromuscolari, Istituto Nazionale Neurologico Carlo Besta,
Milan, Italy.
Idiopathic inflammatory myopathies (IIM) are muscle diseases of autoimmune
pathogenesis characterized by mononuclear cell infiltration within muscle
tissue. Since immune cell homing and accumulation at the site of antigenic
challenge is usually mediated by chemokines, we evaluated the expression of
2
beta-chemokines--monocyte chemoattractant protein-1 (MCP-1) and macrophage
inflammatory protein-1alpha (MIP-1alpha)--by immunohistochemistry and polymerase
chain reaction in muscles of polymyositis, inclusion body myositis, and
dermatomyositis patients, and related their expression to immunopathological
alterations in muscle. MCP-1 and MIP-1alpha transcripts were detected by PCR
in
all IIM muscles, but not in controls. By immunohistochemistry, the chemokines
were found in all IIM muscle sections located in infiltrating inflammatory cells
and also in neighboring extracellular matrix. The extent to which extracellular
matrix was filled by each chemokine differed in each disease. In view of the
known ability of chemokines to bind extracellular matrix and their possible
synthesis by extracellular matrix components, we suggest that chemokine storage
in the extracellular matrix can act as a microenvironmental factor amplifying
lymphocyte activation and migration, thereby maintaining the autoimmune attack
against unknown muscle antigens.
PMID: 10749105 [PubMed - indexed for MEDLINE]
240: J Biol Chem. 2000 Mar 24;275(12):8703-10.
Sporadic inclusion body myositis correlates with increased expression and
cross-linking by transglutaminases 1 and 2.
Choi YC, Park GT, Kim TS, Sunwoo IN, Steinert PM, Kim SY.
Department of Neurology, College of Medicine, Yonsei University, Seoul 135-270,
Republic of Korea. ycchoi@yumc.yonsei.ac.kr
Sporadic inclusion body myositis (SIBM) is characterized by vacuolar
degeneration of muscle fibers and intrafiber clusters of paired helical
filaments with abnormal amyloid deposition. Because of their potential
involvement in other degenerative disorders, we have examined the expression
of
transglutaminases (TGases) in normal and SIBM tissues. We report that at least
two different enzymes, the ubiquitous TGase 2 as well as the TGase 1 enzyme,
are
present in muscle tissues. However, in comparison with normal tissue, the
expression of TGases 1 and 2 was increased 2.5- and 4-fold in SIBM, accompanied
by about a 20-fold higher total TGase activity. By immunohistochemical staining,
in normal muscle, TGase 2 expression was restricted to some endomysial
connective tissue elements, whereas TGase 1 and beta-amyloid proteins were not
detectable. In SIBM muscle, both TGases 1 and 2 as well as amyloid proteins
were
brightly expressed and co-localized in the vacuolated muscle fibers, but none
of
these proteins colocalized with inflammatory cell markers. Next, we isolated
high molecular weight insoluble proteins from SIBM muscle tissue and showed
that
they were cross-linked by about 6 residues/1000 residues of the isopeptide bond.
Furthermore, by amino acid sequencing of solubilized tryptic peptides, they
contain amyloid and skeletal muscle proteins. Together, these findings suggest
that elevated expression of TGases 1 and 2 participate in the formation of
insoluble amyloid deposits in SIBM tissue and in this way may contribute to
progressive and debilitating muscle disease.
PMID: 10722712 [PubMed - indexed for MEDLINE]
241: Neurology. 2000 Mar 14;54(5):1033-41.
Comment in:
Neurology. 2000 Mar 14;54(5):1020-1.
AlphaB-crystallin immunolocalization yields new insights into inclusion body
myositis.
Banwell BL, Engel AG.
Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic,
Rochester, MN 55905, USA.
OBJECTIVE: To study the expression of the small heat shock protein,
alphaB-crystallin (alphaBC), in inclusion body myositis (IBM). BACKGROUND: In
humans, alphaBC is constitutively expressed in the eye lens, muscle, and heart,
but not in lymphoid tissues. Induced expression of alphaBC occurs under
metabolic stress, in virus-infected lymphocytes, and in degenerative brain
lesions, including neurofibrillary tangles and senile plaques in AD. The
previously reported pathologic similarities between AD and IBM prompted us to
study alphaBC expression in IBM. METHODS: Immunolocalization of alphaBC in
muscle of 11 patients with IBM, 50 patients with other muscle diseases, and
4
controls; and quantitative analysis of the frequency of fibers with 1) increased
alphaBC expression in IBM and polymyositis and 2) structural abnormality
(vacuolated, non-necrotic and invaded by mononuclear cells, Congo red-positive,
SMI-31 positive, and ubiquitin positive) in IBM. RESULTS: We detected enhanced
expression of alphaBC not only in all structurally abnormal IBM fibers, but
also, and with severalfold higher frequency, in IBM fibers without significant
structural abnormality (X fibers) (p values in paired t-tests < 0.001). We
also
found enhanced alphaBC in abnormal fibers in other diseases; X fibers, however,
were extremely sparse or absent, except in two atypical cases of polymyositis
refractory to immunotherapy. CONCLUSION: That the X fibers are much more
frequent than the structurally abnormal fibers in IBM points to a pathogenic
stressor acting upstream to the development of structural abnormalities. The
identification of this stressor is now of paramount importance for deciphering
the enigma of IBM.
PMID: 10720271 [PubMed - indexed for MEDLINE]
242: Neurology. 2000 Mar 14;54(5):1020-1.
Comment on:
Neurology. 2000 Mar 14;54(5):1033-41.
Biologically stressed muscle fibers in sporadic IBM: a clue for the enigmatic
etiology?
Karpati G, Hohlfeld R.
Publication Types:
Comment
Editorial
PMID: 10720268 [PubMed - indexed for MEDLINE]
243: Am J Med. 2000 Mar 6;108 Suppl 4a:43S-46S.
Management of upper esophageal sphincter disorders: indications and
complications of myotomy.
Kelly JH.
Department of Otolaryngology, Head and Neck Surgery, Greater Baltimore Medical
Center, Maryland 21204, USA.
Since 1951, when it was first used as a treatment for post-poliomyelitis
dysphagia, cricopharyngeal myotomy (CPM) has been used in the treatment of
various neurogenic, myogenic, structural, and idiopathic disorders. Yet, the
efficacy of CPM in treating patients with upper esophageal sphincter (UES)
disorders remains controversial. Despite favorable reports regarding its
success, too few studies about indications, complications, and outcomes of CPM
have been conducted to quell the controversy. Swallowing is accomplished when
three primary conditions exist: (1) the cricopharyngeus muscle (CP)
relaxes--that is, it is not tonically contracted, (2) the laryngo-hyoid complex
elevates in an anterior-superior direction to open the sphincter, and (3)
pharyngeal pressure is sufficient to propel a bolus through the open sphincter.
CPM is indicated when the second and third conditions are "adequate"
but the
first is inadequate, thus resulting in pharyngeal dysphagia associated with
a
defective opening of the UES. UES dysfunction is determined most often through
patient history, physical examination, and testing. Patients with Zenker's
(pharyngoesophageal) diverticulum, oculopharyngeal dystrophy, or inclusion body
myositis are among those reported to have the most positive responses to CPM.
Modified barium swallow is the most common measurement of UES dysfunction;
manometry also is used, but to a lesser degree because of catheter motion during
swallowing. There are four approaches to CPM, including: (1) the external
technique, which is indicated when a muscle biopsy or neck exploration is
needed; (2) the endoscopic approach, which is reported to work best with
patients with Zenker's diverticulum and offers the choice of electrocautery,
laser, or the surgical stapler--the last option being the best choice for
high-risk patients; (3) balloon dilatation of the UES, a low-risk option that
reportedly works best in patients with fibrosis of the CP; and (4) botulinum
toxin injection of the CP transcervically or endoscopically, which offers low
risk and minimal or no anesthesia. This approach best serves cases of failed
relaxation of the CP. Each approach has potential complications, but reports
of
such are few and rarely severe. In all cases, massive reflux should be
controlled before CPM and the patient should be medically stable. Patient
selection for CPM remains inadequate. To assess the efficacy of CPM, more
multi-institutional outcome studies need to be conducted. In the meanwhile,
clinical judgment and selective testing via modified barium swallow are the
best
methods for identifying patients who may derive the most benefit from CPM.
Publication Types:
Review
Review, Tutorial
PMID: 10718451 [PubMed - indexed for MEDLINE]
244: J Neurol. 2000 Jan;247(1):22-8.
High-dose immunoglobulin therapy in sporadic inclusion body myositis: a
double-blind, placebo-controlled study.
Walter MC, Lochmuller H, Toepfer M, Schlotter B, Reilich P, Schroder M,
Muller-Felber W, Pongratz D.
Department of Neurology, Friedrich-Baur-Institut, Medizinische Klink, University
of Munich, Germany. Maggie.Walter@lrz.uni-muenchen.de
Sporadic inclusion body myositis (s-IBM) is an acquired inflammatory muscle
disease of unknown cause. In general, s-IBM presents with slowly progressive,
asymmetric weakness, and atrophy of skeletal muscle. There is a mild transitory
or nil responsiveness to standard immunosuppressive treatment. A controlled
cross-over study of 22 s-IBM patients over 3 months showed a partial improvement
in those treated with high-dose intravenous immunoglobulin therapy (IVIG) versus
placebo. The present study included 22 patients aged 32-75 years and with a
mean
duration of disease of 5.2+/-3.6 years. They were randomized by a double-blind,
placebo-controlled, cross-over design to monthly infusions of 2 g/kg bodyweight
IVIG or to placebo for 6 months each, followed by the alternative treatment.
After 6 and 12 months the response to treatment was evaluated, using a modified
Medical Research Council scale, Neuromuscular Symptom Score (NSS), the patient's
own assessment of improvement, arm outstretched time, and electromyography.
No
serious side effects were seen, in particular no viral infection and no major
cardiac or neurological complications. Overall there was no progression of the
disease in 90% of patients, unlike that which might have been expected in
untreated patients. A mild and significant improvement (11%) in clinical
symptoms was found using NSS, but not with other test procedures. There was
a
trend to mild improvement in treated patients when using other tests. Individual
responses to treatment was heterogeneous. The validity of this study may be
reduced by mismatch of groups with regard to age at onset and variability in
disease expression. The findings of this study largely confirm those of a
previous IVIG trial. Treatment with IVIG may be mildly effective in s-IBM by
preventing disease progression or inducing mild improvement. Long-term studies
are needed to evaluate further the benefit of IVIG therapy in s-IBM.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 10701893 [PubMed - indexed for MEDLINE]
245: J Neurosci Res. 2000 Feb 15;59(4):553-60.
Muscular dystrophy in adult and aged anti-NGF transgenic mice resembles an
inclusion body myopathy.
Capsoni S, Ruberti F, Di Daniel E, Cattaneo A.
Neuroscience Program, International School for Advanced Studies (SISSA),
Trieste, Italy.
The role of nerve growth factor (NGF) and its receptors in the physiology of
skeletal muscles has not been extensively studied in animal models. We describe
the production of transgenic lines of mice expressing a neutralizing antibody
against NGF (alphaD11) and the morphological and histochemical analysis of
skeletal muscles from adult and aged anti-NGF mice. This study reveals that
the
chronic deprivation of NGF results in a decreased size of myofibers of dorsal
and hindlimb muscles in adult but not in postnatal day (P)2 mice. In myofibers
from adult anti-NGF mice, the presence of central nuclei, vacuolization of the
cytoplasm, and inflammatory cell infiltration was observed. The
immunohistochemical analysis of these muscular fibers revealed an upregulation
of p75 expression, a decrease in adenosine triphosphatase (ATP)ase activity,
and
a subsarcolemmal Congo Red-positive staining. Immunostaining with an antibody
against amyloid precursor protein showed an increased labeling of the cytoplasm
of myofibers from adult and aged anti-NGF mice. These features are reminiscent
of human myopathies, such as inclusion body myositis. We conclude that NGF
deficits might be relevant for a class of human myopathies. Copyright 2000
Wiley-Liss, Inc.
PMID: 10679795 [PubMed - indexed for MEDLINE]
246: Brain. 2000 Feb;123 ( Pt 2):374-9.
Synergistic effect of beta-amyloid protein and interferon gamma on nitric oxide
production by C2C12 muscle cells.
Baron P, Galimberti D, Meda L, Prat E, Scarpini E, Conti G, Moggio M, Prelle
A,
Scarlato G.
Institute of Neurology, University of Milan, IRCCS Ospedale Maggiore
Policlinico, Milan, Italy.
Nitric oxide (NO) is an important mediator of diverse physiological and
pathological responses. NO-induced oxidative stress has been proposed in the
pathogenesis of muscle tissue damage in inclusion-body myositis (IBM), which
is
characterized by deposition of beta-amyloid protein (Abeta) in vacuolated muscle
fibres. To determine whether Abeta can induce NO production in skeletal muscle,
we stimulated C2C12 mouse skeletal muscle cells in vitro with Abeta[1-42] or
Abeta[25-35] peptides in the presence or absence of interferon gamma
(IFN-gamma). Neither Abeta peptides nor IFN-gamma were able to stimulate nitrite
(NO(2)(-)) production by C2C12 cells when given alone. However, combination
of
IFN-gamma with either Abeta[1-42] or Abeta[25-35] resulted in significant
NO(2)(-) release into cell-free supernatants. Northern blot analysis of RNA
obtained from Abeta/IFN-gamma-stimulated C2C12 cells revealed increased mRNA
accumulation of inducible nitric oxide synthase (iNOS). Moreover, approximately
4% of muscle cells incubated with Abeta peptides and IFN-gamma showed
ultrastructural features of DNA fragmentation. These findings, taken together,
indicate that the association of Abeta with IFN-gamma stimulates NO(2)(-)
production via induction of iNOS gene expression in skeletal muscle cells, with
occasional evidence for nuclear changes suggesting apoptotic morphology. These
data further support a role for Abeta deposition in the pathogenesis of
postulated oxidative damage in IBM.
PMID: 10648444 [PubMed - indexed for MEDLINE]
247: J Neurol Neurosurg Psychiatry. 2000 Feb;68(2):230-3.
A case of inclusion body myositis with benign monoclonal gammopathy successfully
responding to repeated immunoabsorption.
Nakayama T, Horiuchi E, Watanabe T, Murayama S, Nakase H.
Department of Neurology, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo
105-8470, Japan.
A 69 year old woman with inclusion body myositis is described. She presented
with benign monoclonal gammopathy. She was resistant to steroid therapy, but
responded to repeated immunoabsorption. Up to now, there has been no established
therapy for inclusion body myositis, including IVIg. It is suggested that
immunoabsorption could be an alternative therapy for inclusion body myositis,
when it was accompanied by immunological abnormality.
Publication Types:
Case Reports
PMID: 10644796 [PubMed - indexed for MEDLINE]
248: Clin Immunol. 2000 Feb;94(2):99-104.
Downregulation of TGF-beta1 mRNA and protein in the muscles of patients with
inflammatory myopathies after treatment with high-dose intravenous
immunoglobulin.
Amemiya K, Semino-Mora C, Granger RP, Dalakas MC.
Neuromuscular Diseases Section, National Institutes of Health, Bethesda,
Maryland 20892, USA.
We used reverse transcription-polymerase chain reaction to study the level
of
TGF-beta1 mRNA expression and immunocytochemistry to examine the immunoreactive
TGF-beta1 in muscle biopsy specimens from five patients with dermatomyositis
(DM) and five patients with inclusion body myositis (IBM) obtained before and
after 3 months treatment with intravenous immunoglobulin (IVIg). At baseline,
the mRNA expression of TGF-beta1 was increased up to fivefold in the muscles
of
DM patients compared to that of IBM patients. After IVIg, TGF-beta1 was
downregulated and the TGF-beta1 mRNA decreased twofold in the muscles of
patients with DM who had successfully responded to therapy, but remained
unchanged in the muscles of patients with IBM who did not respond. The
downregulation of TGF-beta1 in DM was associated with improvement of the muscle
cytoarchitecture and reduction of the endomysial inflammation and connective
tissue, suggesting that in DM the excess of TGF-beta1 may be involved in the
pathogenesis of chronic inflammation, fibrosis, and accumulation of
extracellular matrix proteins. Copyright 2000 Academic Press.
PMID: 10637094 [PubMed - indexed for MEDLINE]
249: Neurology. 2000 Jan 11;54(1):65-71.
Expression of matrix metalloproteinases in the muscle of patients with
inflammatory myopathies.
Choi YC, Dalakas MC.
Neuromuscular Disease Section, National Institute of Neurological Disorders
and
Stroke, National Institute of Health, Bethesda, MD 20892-1382, USA.
OBJECTIVE: To investigate the role of matrix metalloproteinases (MMPs) in the
pathogenesis of inflammatory myopathies and the amyloid formation in sporadic
inclusion body myositis (s-IBM). BACKGROUND: MMPs comprise a family of
calcium-dependent zinc endoproteinases induced by cytokines and secreted by
inflammatory cells. They enhance T-cell migration or adhesion and degrade
components of the extracellular matrix proteins. Some MMPs also have been
implicated in the formation of beta-amyloid. METHODS: We examined the expression
of MMPs with single and double immunocytochemistry using antibodies against
MMP-2, MMP-3, MMP-7, MMP-9, major histocompatibility complex (MHC) class I,
CD8+
cells, macrophage, and beta-amyloid precursor protein (beta-APP) on serial
muscle biopsy sections from patients with s-IBM, polymyositis (PM),
dermatomyositis (DM), and disease control specimens. The enzyme activity of
MMPs
was measured by gelatin substrate zymography. RESULTS: Only the gelatinases,
MMP-9 and MMP-2, were expressed in the muscle. In s-IBM and PM, but not the
control specimens, MMP-9 and MMP-2 immunostained the non-necrotic and MHC
class-I-expressing muscle fibers, and MMP-9, but not MMP-2, immunostained the
autoinvasive CD8+ cytotoxic T cells. Zymography in muscle homogenates confirmed
the increased MMP-2 and MMP-9 enzymatic activity. MMP-2, but not MMP-9,
immunostained the rimmed vacuoles in s-IBM and colocalized with beta-APP,
suggesting a possible involvement with the amyloid deposits. CONCLUSIONS:
Because collagen IV is prominent on the muscle membrane, the overexpression
of
matrix metalloproteinases (MMPs) 2 and 9 on the non-necrotic muscle fibers in
polymyositis (PM) and sporadic inclusion body myositis (s-IBM) may facilitate
lymphocyte adhesion and enhance T-cell-mediated cytotoxicity by degrading
extracellular matrix proteins. The findings may have practical implications
in
considering therapeutic trials with MMP inhibitors in patients with PM and
s-IBM.
PMID: 10636127 [PubMed - indexed for MEDLINE]
250: Curr Eye Res. 2000 Feb;20(2):137-43.
Prion protein expression in mammalian lenses.
Frederikse PH, Zigler SJ Jr, Farnsworth PN, Carper DA.
Department of Ophthalmology, Department of Pharmacology & Physiology, UMDNJ-New
Jersey Medical School, Newark, New Jersey 07103, USA. frederph@umdnj.edu
PURPOSE: Aging and oxidative stress resulting from over-expression of Alzheimer
precursor protein (betaAPP) have been studied as important factors contributing
to the major age-related (sporadic), and minor (hereditary) forms of Alzheimer's
disease (AD), and muscle inclusion body myositis, (IBM). AD and prion proteins
accumulate in plaques linked with AD and scrapie diseases, and in rimmed
vacuoles of IBM. Soluble beta-amyloid (Abeta) fibrillar forms are now thought
to
play a critical role in and outside of cells by producing oxidative stress.
In
lens, betaAPP and Abeta increase in cultured lenses exposed to oxidative stress,
and in areas of lens fiber cell degeneration in thiamine (vitamin B1) deprived
mice, a classic model of systemic oxidative stress. The purpose of the present
study is to extend our studies of amyloid disease-related protein expression
in
mammalian lenses. METHODS: Western blot, immunohistochemical detection, and
RT-PCR methods were used to identify and quantitate prion protein expression
in
human, monkey, and guinea pig lenses. RESULTS: We demonstrate for the first
time
that prion protein gene expression increases with oxidative stress in cultured
human lens epithelial cells. In addition, we detected greater prion protein
gene
expression in fiber cells than epithelial cells in vivo. This is consistent
with
increases in prion protein expression demonstrated in myoblasts and neuronal
cells induced to differentiate. Our initial investigations of prion protein
in
human lens cataracts identified increased prion protein immunoreactivity in
regions of lens fiber cell degeneration. CONCLUSIONS: The present data indicate
that prion protein expression increases during lens development, and is
substantially increased in cultured human lens epithelial cells exposed to
oxidative stress. We also provide evidence that prion protein immunoreactivity
can be increased in regions of fiber cell disorganization. These data suggest
a
potential role for prion protein as a marker for some types of lens pathology,
and in the mechanism of oxidative stress-related lens degeneration.
PMID: 10617916 [PubMed - indexed for MEDLINE]
251: Brain. 2000 Jan;123 ( Pt 1):93-104.
Apoptosis in mitochondrial encephalomyopathies with mitochondrial DNA mutations:
a potential pathogenic mechanism.
Mirabella M, Di Giovanni S, Silvestri G, Tonali P, Servidei S.
Institute of Neurology, Catholic University, Rome, Italy.
Mitochondrial encephalomyopathies caused by mitochondrial DNA (mtDNA) defects
are a genetically and phenotypically heterogeneous group of disorders. The site,
percentage and distribution of mutations do not explain the overall clinical
heterogeneity that is found. Apoptosis (programmed cell death) is an
evolutionarily conserved mechanism that is essential for tissue development
and
homeostasis. Dysregulation of apoptosis has been implicated in the pathogenesis
of various human diseases, such as cancer and autoimmune and neurodegenerative
disorders. Recent in vitro evidence has indicated the central role of
mitochondria in the apoptotic process. We investigated the occurrence of
apoptosis in muscle biopsies of 36 patients carrying different mtDNA mutations
and four patients with inclusion body myositis and mitochondrial abnormalities.
Apoptotic features, mainly localized in cytochrome c oxidase-negative fibres,
were observed in muscle fibres of patients carrying a high percentage of single
mtDNA deletions (>40%) and of tRNA point mutations (>70%). By contrast,
no
apoptotic changes were observed in inclusion body myositis and in patients
carrying mutations of mtDNA structural genes. Our study suggests that apoptosis
is not simply a means whereby cells with dysfunctional mitochondria are
eliminated, but that it seems to play a role in the pathogenesis of
mitochondrial disorders associated with mtDNA defects affecting mitochondrial
protein synthesis. The imbalance and relative abundances of nuclear-encoded
and
mtDNA-encoded subunits may favour cytochrome c inactivation and release.
Cytochrome c, together with respiratory chain dysfunction, could activate
apoptotic pathways that, in turn, inhibit the rate of mitochondrial translation
and the importation of nuclear-encoded mitochondrial protein precursors. This
vicious circle may amplify the biochemical defects and tissue damage and
contribute to the modulation of clinical features.
PMID: 10611124 [PubMed - indexed for MEDLINE]
252: Neurology. 1999 Dec 10;53(9):2184-7.
Cultured inclusion-body myositis muscle fibers do not accumulate beta-amyloid
precursor protein and can be innervated.
McFerrin J, Engel WK, Askanas V.
USC Neuromuscular Center, Department of Neurology, University of Southern
California Keck School of Medicine, Good Samaritan Hospital, Los Angeles
90017-1912, USA.
Cultured muscle fibers from patients with sporadic inclusion-body myositis
(s-IBM), similar to normal control muscle fibers, 1) did not have beta-amyloid
precursor protein (betaAPP) immunoreactivity; and 2) became normally innervated,
as evidenced by the following features: full cross-striation, continuous
contraction, and acetylcholinesterase and acetylcholine receptors accumulated
only at neuromuscular junctions. Thus, factors responsible for betaAPP
accumulation and denervation-like changes in s-IBM muscle biopsies are not
operative in the relatively short-term, non-aged, cultured s-IBM muscle fibers.
PMID: 10599804 [PubMed - indexed for MEDLINE]
253: Adv Exp Med Biol. 1999;455:187-91.
Dermatomyositis and drugs.
Dourmishev AL, Dourmishev LA.
Department of Dermatology, University of Medicine, Sofia, Bulgaria.
Dermatomyositis (DM) is an idiopathic inflammatory disorder consisting of skin
and skeletal muscle involvement. Patients with skeletal muscle involvement have
polymyositis (PM), and those unresponsive to therapy and with characteristic
findings on muscle biopsy have inclusion body myositis. Patients without muscle
damage and typical skin lesions have amyopathic dermatomyositis. Disease in
children (juvenile dermatomyositis) is not associated with malignancy as it
may
be in adults (paraneoplastic dermatomyositis). Overlap syndrome (OS) is mixed
connective tissue disease combining some features of DM, SS and LES.
Scleromyositis is overlap syndrome associated with anti-PM-Sci antibodies.
Patients with PM, DM or OS with "interstitial lung disease" and anti-synthetase
antibodies have an "anti-synthetase syndrome". Various drugs, including
d-penicillamine, NSAIDs, anti-infectious agents, as well as lipid lowering
drugs, the HMG-CoA reductase inhibitors may cause myopathy and skin lesions
(drug induced dermatomyositis). "Dermatomyositis" occurring as adverse
reactions
of drugs are rare, irregular and impossible to predict in individual patients.
They are very interesting in that they may be keys for explaining the pathogenic
mechanisms of the disease.
Publication Types:
Review
Review, Tutorial
PMID: 10599342 [PubMed - indexed for MEDLINE]
254: Adv Exp Med Biol. 1999;455:181-6.
Dermatomyositis. Diagnosis and evaluation of dermatomyositis, polymyositis,
and
inclusion-body myositis.
Krajnc I.
Department Of Internal Medicine, Rheumatology, Teaching Hospital Maribor,
Ljubljanska, Slovenia.
In diseases of an unknown etiology, such as the idiopathic inflammatory
myopathies, we must tackle first of all the question of classification and the
degree of disease activity before we can institute treatment. The majority of
idiopathic inflammatory myopathies are diagnosed clinically and confirmed by
biopsy. The presently applicable methods of diagnosis and evaluation of
idiopathic inflammatory myopathy have certain limitations, and hence it is
necessary to apply new methods of rating the disease activities. Magnetic
resonance imaging (MRI) and 99m-technetium muscle-scanning are the latest
noninvasive methods for evaluation of disease activities with myositis. Future
laboratory methods to determine the numerous myositis-specific autoantibodies
will probably enable identification of subsets of these diseases.
Publication Types:
Review
Review, Tutorial
PMID: 10599341 [PubMed - indexed for MEDLINE]
255: Curr Opin Neurol. 1999 Oct;12(5):527-33.
Inclusion body myositis.
Oldfors A, Lindberg C.
Department of Pathology, Goteborg Neuromuscular Center, Sahlgrenska University
Hospital, Sweden. anders.oldfors@ss.gu.se
Sporadic inclusion body myositis is a severely disabling muscle disease that
mainly affects elderly individuals. The typical distribution of muscle weakness,
poor response to immunosuppressive treatment, pathological accumulation of
various proteins in vacuolated muscle fibres, inflammatory reaction and
mitochondrial changes have all been subjects of recent research that has led
to
better understanding of the pathogenic events that leads to muscle degeneration
and weakness.
Publication Types:
Review
Review, Tutorial
PMID: 10590889 [PubMed - indexed for MEDLINE]
256: Eur Cytokine Netw. 1999 Dec;10(4):471-8.
Cytokines in the muscle tissue of idiopathic inflammatory myopathies:
implications for immunopathogenesis and therapy.
Megens-de Letter MA, Visser LH, van Doorn PA, Savelkoul HF.
Department of Neurology, St. Elisabeth Hospital Tilburg, PO Box 90151, 5000
LC
Tilburg, The Netherlands. megens-deletter@wxs.nl
The inflammatory myopathies (IM), dermatomyositis (DM), polymyositis (PM) and
idiopathic inclusion body myositis (IBM) are acquired immune-mediated
myopathies. About their pathogenesis and etiology no definitive insights are
available yet. Here we present a review of cytokine studies in IM. Combined
with
cellular immunohistochemical findings a model is presented describing a common
mechanism of immune activation in IM. This model is based on a "hit"
triggering
local cytokine production with dominance of pro-inflammatory cytokines, like
IFN-gamma and Th1-mediated activities. The altered Th1-Th2 balance necessitates
detection of the anti-inflammatory arm of immune activation, which includes
Th2-derived IL-4, IL-1, and Th3/Tr1 derived IL-10 and TGF-beta. Redirection
of
the ratio provides targets for novel immunotherapy by direct inhibition of the
IFN-gamma-mediated Th1 response, stimulation of Th3/Tr1, or IL-4-secreting
Th2-cells, negative feedback inhibition with IFN-beta and IFN-gamma and
inactivation of MHC molecules.
Publication Types:
Review
Review, Tutorial
PMID: 10586113 [PubMed - indexed for MEDLINE]
257: Br J Dermatol. 1999 Nov;141(5):926-30.
Comment in:
Br J Dermatol. 2000 Sep;143(3):671.
Dermatomyositis with the features of inclusion body myositis associated with
carcinoma of the bladder.
Talanin NY, Bushore D, Rasberry R, Rudolph T, Tuli M, Friedman-Musicante R.
Division of Dermatology, Department of Medicine, The University of Tennessee,
Memphis, TN 38163, USA.
Inclusion body myositis (IBM) is a unique category of inflammatory myopathy.
It
is characterized histologically by the presence of muscle fibres with rimmed
vacuoles and abnormal intracellular accumulations of proteins. We report here
a
62-year-old patient with bladder carcinoma, where the signs of IBM overlapped
with clinical features of dermatomyositis (DM). A combination of cutaneous
changes typical for DM with histological and other features of IBM is
exceedingly rare, and has not been previously addressed in dermatological
literature. To the best of our knowledge this is also the first description
of
the association of DM/IBM with internal malignancy.
Publication Types:
Case Reports
PMID: 10583182 [PubMed - indexed for MEDLINE]
258: Lancet. 1999 Nov 13;354(9191):1696.
Weak at the knees.
Webster G, Beynon H.
Royal Free Hospital, London, UK.
Publication Types:
Case Reports
PMID: 10568573 [PubMed - indexed for MEDLINE]
259: Neurology. 1999 Nov 10;53(8):1671-6.
Aberrant expression of cyclin-dependent kinase 5 in inclusion body myositis.
Nakano S, Akiguchi I, Nakamura S, Satoi H, Kawashima S, Kimura J.
Department of Neurology, Faculty of Medicine, Kyoto University, Japan.
snakano@isola.kuhp.kyoto-u.ac.jp
OBJECTIVE: To investigate abnormal protein expression in inclusion body myositis
(IBM). BACKGROUND: In IBM, ectopic deposition of beta-amyloid protein as well
as
several other proteins in some muscle fibers occurs. Some, but not all, of these
proteins are also expressed in myofibrillar myopathy (MFM). The authors recently
reported aberrant expressions of several cyclin-dependent kinases (CDKs)-enzymes
regulating the cell replication cycle-in MFM. They therefore tested the notion
that aberrant expression of CDKs also occurs in IBM. Among CDKs, CDK1, CDK2,
and
CDK5 have been demonstrated to phosphorylate tau, which is a component of
inclusions in IBM. CDK5 appears in a stage of myogenesis when CDK1 and CDK2
are
downregulated. METHODS: Cryostat sections of muscle specimens from 10 patients
with sporadic IBM were immunostained for CDK1, CDK2, and CDK5. Fourteen patients
with polymyositis and eight individuals with dermatomyositis served as disease
control subjects. RESULTS: In IBM, numerous CDK5-positive inclusions were
present in vacuolated fibers. CDK5 expression was not observed in any disease
control subject. Regenerating fibers expressed CDK1 and CDK2 in all diseases.
CONCLUSION: The results suggest that cyclin-dependent kinases (CDK)5, but no
other CDKs, is involved in the formation of inclusions in IBM.
PMID: 10563611 [PubMed - indexed for MEDLINE]
260: Curr Opin Rheumatol. 1999 Nov;11(6):456-61.
Treatment of inclusion body myositis.
Cherin P.
Service de Medecine Interne du Pr Herson, Paris, France.
patrick.cherin@psl.ap-hop-paris.fr
Sporadic inclusion body myositis (s-IBM) is considered the most common muscle
disease in patients older than 50 years, with a male predominance. Features
of
s-IBM include insidious onset, slowly and relentlessly progressive muscle
weakness, a characteristic distribution and atrophy of both the proximal and
distal muscle groups, and resistance to immunosuppressive drugs. The most
characteristic pathologic feature is vacuolar degeneration of muscle fibers
accompanied by intrafiber congophilia and clusters ("tangles") of
paired-helical
filaments, containing phosphorylated tau. The response of s-IBM to immunotherapy
remains controversial. Some reports emphasized partial improvement in early
stages of the disease. However, the lack of clear response to corticosteroids
and immunosuppressive therapies, the deterioration of clinical strength despite
suppression of inflammation but increasing number of fibers with vacuoles and
amyloid deposits under therapy, and the accumulation of
"Alzheimer-characteristic" proteins in vacuolated muscle fibers suggest
that
s-IBM may be a degenerative rather than an auto-immune inflammatory myopathy,
and a secondary inflammation response.
Publication Types:
Review
Review, Tutorial
PMID: 10551668 [PubMed - indexed for MEDLINE]
261: Muscle Nerve. 1999 Nov;22(11):1479-97.
Intravenous immunoglobulin in the treatment of autoimmune neuromuscular
diseases: present status and practical therapeutic guidelines.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Building 10, Room 4N248, 10 Center Drive
MSC 1382, Bethesda, Maryland 20892-1382, USA. dalakas@helix.nih.gov
This review summarizes the current status of intravenous immunoglobulin (IVIg)
in the treatment of autoimmune neuromuscular disorders and the possible
mechanisms of action of the drug based on work in vivo, in vitro, and in animal
models. Supply of idiotypic antibodies, suppression of antibody production,
or
acceleration of catabolism of immunoglobulin G (IgG) are relevant in explaining
the efficacy of IVIg in myasthenia gravis (MG), Lambert-Eaton myasthenic
syndrome (LEMS), and antibody-mediated neuropathies. Suppression of pathogenic
cytokines has putative relevance in inflammatory myopathies and demyelinating
neuropathies. Inhibition of complement binding and prevention of membranolytic
attack complex (MAC) formation are relevant in dermatomyositis (DM),
Guillain-Barre syndrome (GBS), and MG. Modulation of Fc receptors or T-cell
function is relevant in chronic inflammatory demyelinating polyneuropathy
(CIDP), GBS, and inflammatory myopathies. The clinical efficacy of IVIg, based
on controlled clinical trials conducted in patients with GBS, CIDP, multifocal
motor neuropathy (MMN), DM, MG, LEMS, paraproteinemic IgM anti-myelin-associated
glycoprotein (anti-MAG) demyelinating polyneuropathies, and inclusion body
myositis is summarized and practical issues related to each disorder are
addressed. The present role of IVIg therapy in other disorders based on small
controlled or uncontrolled trials is also summarized. Finally, safety issues,
risk factors, adverse reactions, spurious results or serological tests, and
practical guidelines associated with the administration of IVIg in the treatment
of neuromuscular disorders are presented. Copyright 1999 John Wiley & Sons,
Inc.
Publication Types:
Review
Review, Tutorial
PMID: 10514226 [PubMed - indexed for MEDLINE]
262: Dysphagia. 1999 Summer;14(3):187.
Dysphagia in patients with inclusion body myositis.
Buchholz DW, Neumann S.
PMID: 10507903 [PubMed - indexed for MEDLINE]
263: Neurology. 1999 Aug 11;53(3):659.
Comment on:
Neurology. 1998 Aug;51(2):598-600.
Inclusion body myositis in twins.
Naumann M, Toyka KV.
Publication Types:
Comment
Letter
PMID: 10449152 [PubMed - indexed for MEDLINE]
264: J Neurol Sci. 1999 Jun;165 Suppl 1:S14-20.
Problems and pitfalls in the diagnosis of ALS.
Ludolph AC, Knirsch U.
Department of Neurology, University of Ulm, Germany.
albert.ludolph@medizin.uni-ulm.de
Although misdiagnosis of amyotrophic lateral sclerosis (ALS) is rare, it may
be
more difficult to make a diagnosis in some groups of patients than in others.
If
a patient presents in the later stages of the disease, only a small number of
alternative diagnoses need to be considered. These include spinal muscular
atrophies of adult onset, inclusion body myositis and motor neuropathies with
conduction block. The latter group in particular may present a serious
diagnostic problem, as several groups have recently reported patients suffering
from lower motor neuron syndrome without detectable conduction block, who
responded unexpectedly to treatment with immunoglobulins. As recent laboratory
results suggest that a lengthy pre-clinical period may precede clinical ALS,
there is increased pressure for clinicians to make an early diagnosis so that
the maximum effect can be achieved from neuroprotective drugs. Thus, diseases
such as distal motor amyotrophies, pressure palsies of motor branches of hand
nerves, and cervical myelopathies, which can be differentiated mainly by their
time-course, may be relevant in the differential diagnosis of ALS in some
patients. During recent years, a few patients have been seen in our clinic who
presented with pure motor deficits but later developed a more complex pattern
of
vulnerability suggestive of multisystem degeneration. The existence of patients
with a disease that borders the spectrum of motor neuron diseases cannot be
disputed. These patients include those carrying the Huntington mutation and
those suffering from Guam and New Guinea disease ('ALS/PD'). From our
experience, however, these 'difficult' diagnoses represent less than 10% of
the
patients seen in our clinic.
Publication Types:
Case Reports
PMID: 10448976 [PubMed - indexed for MEDLINE]
265: Am J Pathol. 1999 Aug;155(2):453-60.
Expression of the costimulatory molecule BB-1, the ligands CTLA-4 and CD28,
and
their mRNA in inflammatory myopathies.
Murata K, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, Maryland, USA.
To examine if the muscle fibers in patients with inflammatory myopathies have
the potential to behave as antigen presenting cells (APCs), we investigated
the
expression of costimulatory molecules BB-1, B7-1 (CD80), and B7-2 (CD86), and
their counterreceptors, CD28 or CTLA-4 (CD152), in the muscle biopsies of
patients with polymyositis (PM), PM associated with human immunodeficiency virus
infection (HIV-PM), sporadic inclusion body myositis (s-IBM), dermatomyositis
(DM), and normal or disease controls. The expression of the B7 family of
molecules on the muscle fibers was limited to BB-1. In PM, HIV-PM, and s-IBM,
but not the disease controls, the nonnecrotic, MHC-class I-expressing muscle
fibers, invaded or not by CD8+ T cells, had prominent membrane expression of
BB-1. Several of the BB-1-positive fibers bound strongly in a cell-to-cell
contact with their CD28 or CTLA-4 ligands on the autoinvasive CD8+ T cells,
as
confirmed by confocal microscopy. By reverse transcription-polymerase chain
reaction, the expression of CD28 and CTLA-4 was up-regulated in PM, HIV-PM,
and
s-IBM, but not the controls. Because the BB-1-positive fibers expressed
MHC-class I antigen and bound to up-regulated counterreceptors CD28 and CTLA-4
on the autoinvasive CD8+ T cells only in PM, HIV-PM, and s-IBM, the BB-1
molecule in these diseases should have a functional role in antigen presentation
and T cell differentiation. These findings complement recent studies and suggest
that in PM, HIV-PM, and s-IBM the muscle fibers are not only targets of CD8+
cytotoxic T cells but may also behave as "professional" APC.
PMID: 10433938 [PubMed - indexed for MEDLINE]
266: Neuromuscul Disord. 1999 Jun;9(4):239-46.
Immunolocalization of tumor necrosis factor-alpha and its receptors in
inflammatory myopathies.
De Bleecker JL, Meire VI, Declercq W, Van Aken EH.
Neurology Department, University Hospital, Gent, Belgium.
jan.debleecker@rug.ac.be
Adhesion molecule upregulation occurs in inflammatory myopathies, and is one
of
the myriad functions of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha acts
via two different receptors of 55 (TNF-R55) and 75 kD (TNF-R75). We
immunolocalized TNF-alpha and its receptors in polymyositis, inclusion body
myositis and dermatomyositis. In each myopathy, TNF-alpha was detected in
macrophages, in myonuclei in regenerating muscle fibers, and freely dispersed
in
endomysial or perimysial connective tissue. Many endothelial cells in
dermatomyositis expressed TNF-alpha. TNF-R55 was strongly expressed on myonuclei
of regenerating muscle fibers. TNF-R75 was increased on endothelial cells in
the
midst of inflammatory infiltrates in each myopathy, and on perifascicular and
perimysial endothelia, remote from inflammatory foci in dermatomyositis.
Possible TNF-alpha-mediated effects include: increased transendothelial cell
trafficking, activation of T/B cells and macrophages, induction of MHC-I gene
products, and focal muscle fiber atrophy. In dermatomyositis, the upregulated
TNF-R75, via its consensus elements for transcription factors, may be involved
in endothelial cell degeneration. Strong TNF-R55 expression on regenerating
myonuclei is consistent with a role of TNF-alpha and TNF-R55 in muscle
regeneration.
PMID: 10399751 [PubMed - indexed for MEDLINE]
267: J Neurol Sci. 1999 Mar 15;164(1):76-81.
Bcl-2 and Bax protein expression in human myopathies.
Olive M, Ferrer I.
Servicio de Neurologia, Hospital Principes de Espana, Barcelona, Spain.
Expression of the apoptosis-related proteins Bcl-2 and Bax was analysed by
means
of immunohistochemistry in muscle biopsies from 13 patients suffering from
different muscular diseases (inclusion body myositis n=4, polymyositis n=3,
Becker muscular dystrophy n=4, necrotizing myopathy n=2, and controls n=4),
in
an attempt to learn about the role of these proteins in human muscle diseases
associated with muscle fiber necrosis and regeneration. Increased Bcl-2 and
Bax
immunoreactivity was observed as fine granular precipitates in the cytoplasm
or
as subsarcolemmal aggregates in pathological cases. Increased Bcl-2 and Bax
immunoreactivity was detected in some necrotic fibers, regenerating fibers,
ring
fibers and some apparently normal muscle fibers. In addition, increased Bcl-2
and Bax immunoreactivity was observed in the periphery of rimmed vacuoles and
in
muscle fibers with abnormal mitochondria in patients suffering from inclusion
body myositis. Double-labelling immunohistochemistry disclosed co-localization
of both proteins in about 50% of Bcl-2-immunoreactive fibers. Finally,
double-labelling immunohistochemistry using N-CAM antibodies revealed that some
Bax-positive fibers were regenerating fibers. Since increased Bax
immunoreactivity was not restricted to necrotic muscle fibers, the present
results suggest that over-expression of this protein in human myopathies is
probably independent of the process of cell death.
PMID: 10385052 [PubMed - indexed for MEDLINE]
268: Immunogenetics. 1999 Jun;49(6):508-16.
Mapping of a candidate region for susceptibility to inclusion body myositis
in
the human major histocompatibility complex.
Kok CC, Croager EJ, Witt CS, Kiers L, Mastaglia FL, Abraham LJ, Garlepp MJ.
Australian Neuromuscular Research Institute, Queen Elizabeth II Medical Centre,
Nedlands, Western Australia.
Inclusion body myositis (IBM) is a form of idiopathic inflammatory myopathy
of
unknown aetiology. A strong association with HLA class II (HLA-DR3) suggested
a
role for genes in the human major histocompatibility complex (MHC) in the
predisposition to this disease. In this study, we have taken advantage of the
ancestral haplotype (AH) concept and historical recombinations to map for a
possible susceptibility gene(s) in the MHC. We performed detailed typing of
three MHC-related HSP70 genes and defined allelic combinations in the context
of
MHC AH. We also modified existing methods to give a simple and accurate method
for typing two TNF microsatellites. Using the HSP70 and TNF markers and HLA-DR,
-B, and C4 typing of our patients with IBM, we defined a potential site for
the
MHC-associated susceptibility gene(s) in the region between HLA-DR and C4.
PMID: 10380695 [PubMed - indexed for MEDLINE]
269: Acta Neuropathol (Berl). 1999 Jun;97(6):642-8.
Local expression of monocyte chemoattractant protein-1 (MCP-1) in idiopathic
inflammatory myopathies.
Liprandi A, Bartoli C, Figarella-Branger D, Pellissier JF, Lepidi H.
Laboratoire de Biopathologie Nerveuse et Musculaire, Faculte de Medecine, JE
2053, IBDM Marseille, France.
The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM),
polymyositis (PM), and inclusion body myositis (IBM), are a group of autoimmune
diseases characterized by the recruitment of lymphocytes and monocytes to the
site of affection. The mechanism for recruitment of these cells likely involves
chemokines. The monocyte chemoattractant protein-1 (MCP-1), a chemoattractant
to
T lymphocytes and monocytes, may play an important role in the pathogenesis
of
IIM. Frozen muscular tissues were obtained from eight cases of DM, five PM,
and
four IBM. We investigated the MCP-1 expression by the reverse transcription-PCR
technique, immunohistochemistry and in situ hybridization. MCP-1 mRNA was
markedly expressed in all the IIM cases. Greater amounts of MCP-1 mRNA were
observed in DM, and in situ hybridization showed MCP-1 mRNA accumulation in
perivascular mononuclear cells. Immunohistochemistry showed MCP-1 expression
in
vessels (endothelial cells and walls of veins and arteries) in all IIM cases.
Very few mononuclear cells in DM perivascular infiltrates expressed MCP-1,
whereas in PM and IBM, it was strongly expressed by mononuclear cells partially
invading non-necrotic muscle fibers. These findings suggest that MCP-1 can
contribute to the inflammatory response by attracting monocytes and T
lymphocytes to sites of cell-mediated immune injury. The morphological
characteristics and distribution of positive cells indicate that macrophages,
lymphocytes, and endothelial cells previously reported to produce MCP-1,
contribute to its production in IIM lesions.
PMID: 10378384 [PubMed - indexed for MEDLINE]
270: Can J Neurol Sci. 1999 May;26(2):139-52.
IGIV in neurology--evidence and recommendations.
Bril V, Allenby K, Midroni G, O'Connor PW, Vajsar J.
Division of Neurology, Toronto Hospital, Ontario, Canada.
OBJECTIVE: To summarize the evidence for neurologic uses of immunoglobulin,
intravenous (IGIV) in light of present-day clinical usage. This summary guided
the development of practice recommendations for the effective and efficient
use
of IGIV in Neurology. METHODS: MEDLINE was searched to identify pertinent
English-language review articles and original reports (n = 231) on the use of
IGIV in neurology (excluding editorials, letters, and comments) published before
March 1998. Evidence on alternative therapies was only included as compared
to
IGIV. The relevant original reports and review articles and older classic
studies (n = 92) were synthesized into an information foundation. Extracted
data
included laboratory and clinical findings, objective measures, and clinical
impressions. Clinical recommendations were based on evidence quality, graded
by
study design, clinical experiences of IGIV in Neurology Advisory Board members,
and the conditions of IGIV use in therapy. RESULTS AND CONCLUSIONS: In
neurology, many disorders are poorly understood, and the mechanisms behind
beneficial regimens even less so. As a result, it is fairly common for
best-practice decisions to rest on weaker evidence. The usefulness of IGIV in
neurology can be described by a "combined score" based on evidence
quality and
strength of impact. Combined scores ranged from A+ (strongly recommended) to
C
(recommended as a last resort). The following clinical recommendations are made:
IGIV is: strongly recommended for the treatment of Guillain-Barre syndrome (A+);
favorably recommended for the treatment of chronic inflammatory demyelinating
polyradiculoneuropathy, dermatomyositis, and multifocal motor neuropathy (A);
recommended as a second resort for the treatment of multiple sclerosis and
myasthenia gravis (B); and recommended as a last resort for the treatment of
polymyositis, inclusion-body myositis, intractable epilepsies, and stiff-man
syndrome (C).
Publication Types:
Review
PMID: 10352875 [PubMed - indexed for MEDLINE]
271: Clin Exp Rheumatol. 1999 Mar-Apr;17(2):235-9.
Inclusion body myositis long after dermatomyositis: a report of two cases.
McCoy AL, Bubb MR, Plotz PH, Davis JC.
Arthritis and Rheumatism Branch, National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda,
Maryland, USA.
Dermatomyositis, polymyositis, and inclusion body myositis are rare illnesses
which appear to be distinct in clinical and pathologic features, pathogenesis,
natural history, and response to therapy. We report two patients who first
developed dermatomyositis, and then, after a disease-free interval of many
years, developed inclusion body myositis. This may have useful therapeutic
implications for patients with dermatomyositis whose illness bocomes refractory
to treatment.
Publication Types:
Case Reports
PMID: 10342053 [PubMed - indexed for MEDLINE]
272: Acta Neuropathol (Berl). 1999 May;97(5):509-14.
Familial inclusion body myopathy with desmin storage.
Fidzianska A, Drac H, Kaminska AM.
Department of Neurology, Warsaw Medical Academy, Poland.
We report two adult familial cases of inclusion body myopathy (IBM) with desmin
storage in skeletal muscle. Clinically, both patients presented late-onset,
progressive, symmetrical, both proximal and distal muscle weakness. Muscle
biopsy findings were identical in both cases and consisted of marked variability
in fiber size, increased number of central nuclei and vacuolation involving
10%
of fibers. Single or multiple vacuoles were located subsarcolemmally or in the
center, and were rimmed by basophilic material. At the ultrastructural level,
tubulofilamentous nuclear and cytoplasmic inclusions of 16-21 nm in diameter
were frequently observed. In addition, large subsarcolemmal and central deposits
composed of electron-dense granular material were present in many fibers.
Immunocytochemistry revealed staining for desmin, vimentin and ubiquitin within
both inclusions and vacuolated fibers. Possible structural and functional
associations between these two types of muscle changes remain unclear. They
may
either represent two coexistent disease processes or merely reflect an abnormal
form of muscle fiber degradation, with unidentifiable specificity.
Publication Types:
Case Reports
PMID: 10334489 [PubMed - indexed for MEDLINE]
273: Muscle Nerve. 1999 Apr;22(4):480-7.
Quantitative electrophysiologic studies in sporadic inclusion body myositis.
Barkhaus PE, Periquet MI, Nandedkar SD.
Department of Neurology, Medical College of Wisconsin, Milwaukee, USA.
Sporadic inclusion body myositis (S-IBM) is a progressive, acquired disease
of
unknown etiology. Prior studies have suggested neurogenic involvement based
on
electrophysiologic data, although the biopsy is compatible with a myopathic
process. Quantitative electrophysiologic studies were performed in the biceps
brachii of 17 subjects with biopsy-proven S-IBM. Quantitative motor unit action
potential (MUAP) analysis was compatible with myopathy in 16 subjects, with
the
remaining subject being within normal limits. Quantitative interference pattern
was myopathic in all 13 subjects studied. Macro-EMG MUAP amplitude was reduced
in 3 of 17 studies; the remainder were within normal range, and none was
increased as would be expected in neurogenic disease. Fiber density was normal
to borderline increased in all subjects. Possible reasons for encountering
neurogenic-appearing MUAPs may include choice of muscle studies, because some
patients have co-existing polyneuropathy and large-amplitude MUAPs from
hypertrophied muscle fibers. The data from this study indicate that S-IBM is
a
myopathic process.
Publication Types:
Clinical Trial
PMID: 10204783 [PubMed - indexed for MEDLINE]
274: Acta Neuropathol (Berl). 1999 Mar;97(3):267-74.
Study of some components of the cytoskeleton in muscular disorders with
nonspecific cytoplasmic bodies.
Caron A, Gohel C, Mollaret K, Morello R, Chapon F.
Laboratory of Neuropathology, CHU Cote de Nacre, Caen, France.
To gain a better understanding of the mechanisms involved in the formation
of
cytoplasmic bodies (CBs), the immunohistochemical and biochemical features of
muscle samples with nonspecific CBs were compared to those previously described
by our group in cytoplasmic body myopathy (CBM), a congenital disease in which
specific CBs are found. Accordingly, we studied nonspecific CBs found in the
muscle biopsies of 15 patients with the following diseases: peripheral
neuropathy (n = 5), polymyositis (n = 3), myotonic dystrophy (n = 2),
sarcoidosis (n = 1), inclusion body myositis (n = 1), hereditary inclusion body
myopathy (n = 1), hypothyroidism (n = 1), and muscle atrophy in a patient with
multiple brain infarctions (n = 1). Nonspecific inclusions were stained at their
periphery by anti-desmin but not by anti-dystrophin antibodies, except in the
case of hypothyroidism in which immunostaining was observed with both
antibodies. Biochemical studies showed normal amounts of desmin and
phosphorylation pattern (the latter data are available for only four patients)
as compared to control specimens. Our results differ from those previously
reported in CBM, in which CBs were stained by both antidesmin and
anti-dystrophin antibodies and in which a hyperphosphorylation of desmin was
found. Hypothyroidism is, thus, the only disease in which nonspecific CBs show
the same immunostaining pattern as specific CBs from CBM patients. These
findings indicate that CBs may result from different mechanisms, and that one
of
these mechanisms may be shared by CBM and hypothyroidism.
PMID: 10090674 [PubMed - indexed for MEDLINE]
275: Neurology. 1999 Feb;52(3):669-70.
Minimal expansion of the GCG repeat in the PABP2 gene does not predispose to
sporadic inclusion body myositis.
Mezei MM, Mankodi A, Brais B, Marineau C, Thornton CA, Rouleau GA, Karpati G.
Montreal Neurological Institute and Hospital, McGill University, Quebec, Canada.
PMID: 10025815 [PubMed - indexed for MEDLINE]
276: Lancet. 1999 Feb 6;353(9151):465-6.
Methionine homozygosity at prion gene codon 129 may predispose to sporadic
inclusion-body myositis.
Lampe J, Kitzler H, Walter MC, Lochmuller H, Reichmann H.
Publication Types:
Letter
PMID: 9989722 [PubMed - indexed for MEDLINE]
277: Genomics. 1999 Jan 1;55(1):43-8.
Fine-structure mapping of the hereditary inclusion body myopathy locus.
Eisenberg I, Thiel C, Levi T, Tiram E, Argov Z, Sadeh M, Jackson CL, Thierfelder
L, Mitrani-Rosenbaum S.
Unit for Development of Molecular Biology and Genetic Engineering, The Hebrew
University-Hadassah Medical School, Jerusalem, 91240, Israel.
The gene responsible for a recessive form of hereditary inclusion body myopathy
(HIBM) has previously been mapped to a 10-cM interval on chromosome 9p1-q1.
We
report the results of further mapping studies using two-point linkage analyses
and linkage disequilibrium analyses with 20 HIBM families. We demonstrate that
the HIBM gene (HGMW-approved symbol IBM2) lies between loci D9S1791 and D9S50,
which are about 1 Mb apart. Genetic analyses in 56 affected individuals of
Persian, Afghani, and Iraqi Jewish descent demonstrated a common haplotype at
these loci, indicating that a founding mutation accounts for disease in these
related ethnic groups. beta-Tropomyosin, an abundant skeletal muscle protein
that maps within 1 cM of D9S1791, was excluded as the disease gene because an
intragenic polymorphism did not exhibit linkage disequilibrium in HIBM probands.
We conclude that the disease gene resides in a 1-Mb interval on chromosome 9
and
speculate that a novel muscle protein encoded there is mutated in HIBM.
Copyright 1999 Academic Press.
PMID: 9888997 [PubMed - indexed for MEDLINE]
278: Adv Anat Pathol. 1998 May;5(3):164-9.
Inclusion body myositis--a review.
Vogel H.
Department of Pathology, Baylor College of Medicine, Houston, Texas, USA.
Inclusion body myositis (IBM), a sporadic inflammatory myopathy, is the most
frequently occurring progressive myopathy in adults older than 55 years. It
more
commonly affects men and usually is clinically and pathologically
distinguishable from dermatomyositis or polymyositis. Muscle biopsy specimens
will display inflammation in virtually all cases of sporadic IBM, along with
rimmed vacuoles accompanied by the accumulation of beta-amyloid and other
substances similar to those found in the degenerating neurons of Alzheimer's
disease. The similarities between IBM and other inflammatory myopathies may
contribute to its low level of diagnosis by pathologists. The proper recognition
of IBM is important because, unlike other inflammatory myopathies, IBM is
unresponsive to anti-inflammatory drugs.
Publication Types:
Review
Review, Tutorial
PMID: 9868522 [PubMed - indexed for MEDLINE]
279: Arch Neurol. 1998 Dec;55(12):1509-12.
Molecular immunology and genetics of inflammatory muscle diseases.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, MD 20892-1382, USA.
Polymyositis, dermatomyositis, and inclusion body myositis, although
immunopathologically distinct, share 3 dominant histological features:
inflammation, fibrosis, and loss of muscle fibers. Progress in molecular
immunology and immunogenetics has enhanced our understanding of these cellular
processes. Based on the T-cell receptor gene rearrangement, the autoinvasive
CD8+ T cells in polymyositis and inclusion body myositis, but not
dermatomyositis, are specifically selected and clonally expanded in situ by
heretofore unknown muscle-specific autoantigens. The messenger RNA of cytokines
is variably expressed, except for a persistent up-regulation of interleukin
1beta in inclusion body myositis and transforming growth factor beta in
dermatomyositis. In inclusion body myositis, the interleukin 1, secreted by
the
chronically activated endomysial inflammatory cells, may participate in the
formation of amyloid because it up-regulates beta-amyloid precursor protein
(beta-APP) gene expression and beta-APP promoter and colocalizes with beta-APP
within the vacuolated muscle fibers. In dermatomyositis, transforming growth
factor beta is overexpressed in the perimysial connective tissue but is
down-regulated after successful immunotherapy and reduction of inflammation
and
fibrosis. The degenerating muscle fibers express several antiapoptotic
molecules, such as Bcl-2, and resist apoptosis-mediated cell death. In myositis,
several of the identified molecules and adhesion receptors play a role in the
process of inflammation, fibrosis, and muscle fiber loss, and could be targets
for the design of semispecific therapeutic interventions.
Publication Types:
Review
Review, Tutorial
PMID: 9865793 [PubMed - indexed for MEDLINE]
280: Neurology. 1998 Dec;51(6):1742-5.
Inclusion body myositis: abnormal protein accumulation does not trigger
apoptosis.
Hutchinson DO.
Department of Neurology, Auckland Hospital, New Zealand.
To examine whether apoptosis may contribute to muscle fiber loss in inclusion
body myositis, we used the terminal deoxynucleotidyl transferase-mediated X-dUTP
nick-end labeling (TUNEL) assay to compare the occurrence of DNA fragmentation
in muscle samples from patients with inclusion body myositis and polymyositis.
TUNEL-positive nuclei in nonnecrotic muscle fibers were rare even in the
vicinity of amyloid-like material; significantly more frequent in polymyositis
than inclusion body myositis; and several times less frequent than necrotic
muscle fibers or mononuclear cell myocytotoxicity in both patient groups.
Apoptosis is unlikely to play a significant role in the pathogenesis of
inclusion body myositis.
PMID: 9855538 [PubMed - indexed for MEDLINE]
281: Scand J Rheumatol. 1998;27(6):389-405.
Sporadic inclusion-body myositis and its similarities to Alzheimer disease
brain. Recent approaches to diagnosis and pathogenesis, and relation to aging.
Askanas V, Engel WK.
Sporadic inclusion-body myositis (s-IBM) is the most common, debilitating and
progressive muscle disease beginning at the age 50 or later. The most
characteristic pathologic feature is vacuolar degeneration of muscle fibers
accompanied by intrafiber congophilia and clusters ("tangles") of
paired-helical
filaments, containing phosphorylated tau. An unusual feature of sporadic
inclusion-body myositis is accumulation within its abnormal muscle fibers of
several proteins that are characteristic of Alzheimer disease brain, including
epitopes of beta-amyloid precursor protein (betaAPP), phosphorylated tau,
alpha-1-antichymotrypsin, apolipoprotein E, and presenilin-1. Indicators of
oxidative stress are also present within abnormal s-IBM muscle fibers. In this
review, we describe new advances seeking the pathogenic mechanism of sporadic
inclusion-body myositis. We hypothesize on the possible pathogenic role of
abnormally accumulated proteins, and we propose that important contributory
factors leading to inclusion-body myositis are the milieu of muscle-fiber aging
and oxidative stress. In addition, we present evidence that overexpression of
adenovirus-transferred betaAPP gene in cultured human muscle fibers induces
aspects of the inclusion-body myositis phenotype, and suggest that
betaAPP-overexpression is an early event in the pathogenic cascade causing
inclusion-body myositis.
Publication Types:
Editorial
Review
PMID: 9855208 [PubMed - indexed for MEDLINE]
282: Neurology. 1998 Dec;51(6 Suppl 5):S37-45.
Controlled studies with high-dose intravenous immunoglobulin in the treatment
of
dermatomyositis, inclusion body myositis, and polymyositis.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health Bethesda, MD 20892-1382, USA.
There are three major subsets of the inflammatory myopathies: polymyositis
(PM),
dermatomyositis (DM), and inclusion-body myositis (IBM). High-dose intravenous
immunoglobulin (IVIg) has been tried in controlled clinical trials in patients
with DM and IBM but not with PM. In patients with DM that is resistant or
partially responsive to conventional therapies, IVIg was very effective. The
treated patients experienced dramatic improvement not only in muscle strength
but also of their skin rash. Repeated muscle biopsies with quantitative
histologic studies showed the IVIg-treated patients had a statistically
significant improvement of the muscle cytoarchitecture, with resolution of the
aberrant immunopathologic parameters. In two controlled clinical trials
conducted in IBM patients, IVIg showed marginal improvements in muscle strength
which were nonsignificant. However, a few IBM patients had a definite clinical
improvement with increased activities of daily living, but when analyzed within
the entire IVIg-treated group, their total gains in muscle strength did not
reach statistical significance compared to the placebo-treated group. Of
interest is that certain muscle groups in the IVIg-treated patients, such as
the
muscles of swallowing, showed significant improvement compared to those of the
placebo-treated patients, implying mild regional effects. In PM, uncontrolled
trials have shown improvements in muscle strength, but the controlled clinical
trial is still ongoing.
Publication Types:
Clinical Trial
Controlled Clinical Trial
Review
Review, Tutorial
PMID: 9851729 [PubMed - indexed for MEDLINE]
283: J Neurol Sci. 1998 Oct;160 Suppl 1:S6-24.
Diagnosis of amyotrophic lateral sclerosis.
Rowland LP.
Eleanor and Lou Gehrig MDA/ALS Center, Neurological Institute,
Columbia-Presbyterian Medical Center, New York, NY 10032, USA. lprl@columbia.edu
This review of the differential diagnosis of amyotrophic lateral sclerosis
focuses on two themes. The first is practical, how to establish the diagnosis
based primarily on clinical findings buttressed by electrodiagnosis. The main
considerations are multifocal motor neuropathy and cervical spondylotic
myelopathy. The second theme is the relationship of motor neuron disease to
other conditions, including benign fasciculation (Denny-Brown, Foley syndrome),
paraneoplastic syndromes, lymphoproliferative disease, radiation damage,
monomelic amyotrophy (Hirayama syndrome), as well as an association with
parkinsonism, dementia and multisystem disorders of the central nervous system.
Publication Types:
Review
PMID: 9851643 [PubMed - indexed for MEDLINE]
284: Curr Opin Neurol. 1998 Oct;11(5):453-9.
Hereditary inclusion body myopathies.
Tome FM, Fardeau M.
INSERM Unit. 153, Hopital de la Salpetriere, Paris, France.
Hereditary inclusion body myopathies comprise autosomal recessive and autosomal
dominant muscle disorders that have a variable clinical phenotype but share
similar morphological features. These include rimmed vacuoles within muscle
fibres and collections of intrasarcoplasmic and intranuclear tubulofilamentous
inclusions, 16-18 nm in external diameter. The resemblances and the differences
between the sporadic and the hereditary inclusion body myopathies are discussed.
Recent advances in the identification of various proteins involved in these
diseases are mentioned because they have provided better insight into their
underlying pathophysiological mechanisms. Linkage studies have allowed the
localization of the genetic defect of some hereditary inclusion body myopathies
and related disorders, contributing to their individualization.
Publication Types:
Review
Review, Tutorial
PMID: 9847994 [PubMed - indexed for MEDLINE]
285: J Neuroimmunol. 1998 Nov 2;91(1-2):129-34.
T cell receptor beta-chain repertoire in inclusion body myositis.
Fyhr IM, Moslemi AR, Lindberg C, Oldfors A.
Department of Pathology, Gothenburg University, Sweden.
Inclusion body myositis (IBM) is the most common muscle disease affecting
individuals over 50 years of age. The inflammatory reaction is characterized
by
cell infiltrates predominated by CD8+ cytotoxic T cells. To analyze clonality
of
muscle infiltrating lymphocytes, we studied the complementarity determining
region 3 (CDR3) length distribution of the T cell receptor (TCR). Muscle
infiltrating lymphocytes were studied in three IBM patients and compared with
peripheral blood lymphocytes (PBL) in two of these patients. The study was
performed by reverse transcription polymerase chain reaction (RT-PCR) of RNA
extracted from muscle tissue and PBL followed by analysis of fragment length
distribution of the CDR3 region in each of 24 different Vbeta families. There
was a restricted usage of TCR Vbeta gene families in muscle infiltrating T cells
in all three patients. Some of the TCR Vbeta gene families showed oligoclonal
expansions but polyclonal patterns were dominating. The CDR3 distribution of
most Vbeta families differed between muscle infiltrating lymphocytes and PBL
indicating that T cells have expanded locally or selectively accumulated in
muscle.
PMID: 9846829 [PubMed - indexed for MEDLINE]
286: Am J Pathol. 1998 Dec;153(6):1687-93.
Comment in:
Am J Pathol. 1998 Dec;153(6):1673-7.
Amyloid-beta deposition in skeletal muscle of transgenic mice: possible model
of
inclusion body myopathy.
Fukuchi K, Pham D, Hart M, Li L, Lindsey JR.
Department of Comparative Medicine, Schools of Medicine and Dentistry,
University of Alabama at Birmingham, 35294-0019, USA. cmed037@uabdpo.dpo.uab.edu
Inclusion body myopathy is a progressive muscle disorder characterized by
nuclear and cytoplasmic inclusions and vacuolation of muscle fibers. Affected
muscle fibers contain deposits of congophilic amyloid, amyloid-beta
immunoreactive filaments, and paired helical filaments, all of which are
pathological hallmarks of Alzheimer's disease in brain. Accumulations of
amyloid-beta and its precursor are thought to play important roles in the
pathogenesis of both inclusion body myopathy and Alzheimer's disease.
Overexpression of mutant forms of beta protein precursor in transgenic mice
by
neuron-specific promoters has been reported to cause amyloid deposits in the
brain. Here we report that overexpression in transgenic mice of the signal plus
99-amino acid carboxyl-terminal sequences of beta protein precursor, under the
control of a cytomegalovirus enhancer/beta-actin promoter, resulted in
vacuolation and increasing accumulation of the 4-kd amyloid-beta and the
carboxyl-terminus in skeletal muscle fibers during aging. These deposits in
transgenic muscle only rarely showed Congo red birefringence. Thus,
overexpression of part of beta protein precursor in transgenic mice led to
development of some of the characteristic features of inclusion body myopathy.
These mice may be a useful model of inclusion body myopathy, which shares a
number of pathological markers with Alzheimer's disease.
PMID: 9846958 [PubMed - indexed for MEDLINE]
287: Am J Pathol. 1998 Dec;153(6):1679-86.
Comment in:
Am J Pathol. 1998 Dec;153(6):1673-7.
Transgenic mice over-expressing the C-99 fragment of betaPP with an
alpha-secretase site mutation develop a myopathy similar to human inclusion
body
myositis.
Jin LW, Hearn MG, Ogburn CE, Dang N, Nochlin D, Ladiges WC, Martin GM.
Department of Pathology, University of Washington, Seattle 98195-6480, USA.
lwjin@u.washington.edu
Inclusion body myositis (IBM) is the most common muscle disease in the elderly.
Amyloid-beta protein (A beta) has been shown to accumulate abnormally in the
vacuolated fibers and to localize to amyloid-like fibrils in muscles from IBM
patients. We studied the skeletal muscles from a line of transgenic mice
over-expressing the carboxyl-terminal 99 amino acids (C99) of the beta-amyloid
precursor protein (betaPP) with a substitution of lysine-612 to valine (K612V),
intended to abolish alpha-secretase recognition and to preserve the A beta
domain of C99. The majority (87%) of the 24-month-old transgenic mice showed
myopathic changes, and approximately one-third of them had degenerating fibers
with sarcoplasmic vacuoles and thioflavin-S-positive deposits.
Ultrastructurally, the inclusions were aggregates of short thin amyloid-like
fibrils, 6 to 8 nm in diameter. These features are similar to those of human
IBM. Immunocytochemistry using an antibody against A beta showed membranous
staining in most muscle fibers of transgenic mice, as well as granular or
vacuolar cytoplasmic staining in the atrophic fibers. Western blots showed a
high level of accumulation of carboxyl-terminal fragments of betaPP in the
muscles of the transgenic mice with the most severe IBM-like lesions. The
expression of IBM-like lesions was age dependent. These transgenic mice provide
a model for the study of IBM and for the peripheral expression of a key element
in the pathogenesis of Alzheimer disease.
PMID: 9846957 [PubMed - indexed for MEDLINE]
288: Am J Pathol. 1998 Dec;153(6):1673-7.
Comment on:
Am J Pathol. 1998 Dec;153(6):1679-86.
Am J Pathol. 1998 Dec;153(6):1687-93.
Does overexpression of betaAPP in aging muscle have a pathogenic role and a
relevance to Alzheimer's disease? Clues from inclusion body myositis, cultured
human muscle, and transgenic mice.
Askanas V, Engel WK.
Neuromuscular Center, Department of Neurology, University of Southern California
School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912, USA.
askanas@hsc.usc.edu
Publication Types:
Comment
PMID: 9846956 [PubMed - indexed for MEDLINE]
289: Muscle Nerve. 1998 Dec;21(12):1724-8.
Inflammatory myopathy with cytochrome oxidase negative muscle fibers:
methotrexate treatment.
Levine TD, Pestronk A.
Department of Neurology, Washington University School of Medicine, St. Louis,
Missouri 63110, USA.
Inflammatory myopathy with cytochrome oxidase negative muscle fibers (IM/COX-)
is characterized by slowly progressive weakness, most prominent in the
quadriceps, muscle fibers with reduced COX staining and mitochondrial DNA
mutations, and a poor response to corticosteroid treatment. We reviewed records
of quantitative measurements of muscle strength in 7 IM/COX- patients to
evaluate the outcomes after treatment with oral, once weekly, methotrexate for
an average of 15 months. We compared the results to 6 patients with IM/COX-
who
received no long-term immunosuppression, and to 4 with inclusion body myositis
(IBM) who received methotrexate during the same period. Methotrexate treatment
of IM/ COX- was followed by improved muscle strength in 5 of 7 patients,
averaging 17+/-5%. In contrast, there was no improvement in the strength of
6
untreated IM/COX- patients (-6+/-4%; P=0.003), or 4 methotrexate-treated IBM
patients (1+/-2%; P=0.03). We conclude that, despite clinical similarities to
inclusion body myositis, which is usually refractory to immunosuppressive
therapy, strength in IM/COX- appears to improve with methotrexate treatment.
Biopsy studies of inflammatory myopathies with evaluation of muscle for
mitochondrial changes and vacuoles can help to direct the choice of appropriate
immunomodulating treatments.
PMID: 9843075 [PubMed - indexed for MEDLINE]
290: J Neurol. 1998 Dec;245(12):816-8.
Inclusion body myositis: immune globulins improve muscle strength, but not
abnormal postures.
Johannes S, Schubert M, Heidenreich F, Walter GF, Dengler R.
Publication Types:
Case Reports
Letter
PMID: 9840358 [PubMed - indexed for MEDLINE]
291: J Immunol. 1998 Dec 1;161(11):5943-51.
Erratum in:
J Immunol 2000 May 15;164(10):5330.
Human muscle cells express a functional costimulatory molecule distinct from
B7.1
(CD80) and B7.2 (CD86) in vitro and in inflammatory lesions.
Behrens L, Kerschensteiner M, Misgeld T, Goebels N, Wekerle H, Hohlfeld R.
Department of Neuroimmunology, Max-Planck Institute of Neurobiology,
Martinsried, Germany.
The B7 family of costimulatory molecules likely includes members distinct from
B7.1 (CD80) and B7.2 (CD86). After stimulation with IFN-gamma or TNF-alpha,
human myoblasts selectively express BB-1, but not B7.1 or B7.2. BB-1 is detected
by anti-BB-1, a mAb cross-reacting with B7.1 (but not B7.2) and an as yet
undefined costimulatory molecule. The absence of B7.1 and B7.2 in BB-1-positive
myoblasts was confirmed by RT-PCR. The molecule detected by anti-BB-1 is
functional, because anti-BB-1 mAb and CTLA4Ig (but not anti-B7.1- or
anti-B7.2-specific mAbs) completely inhibit Ag presentation by cytokine-induced
myoblasts to HLA-DR-matched Ag-specific CD4+ T cell lines. Stimulation of
myoblasts with IL-4 induces B7.1 and B7.2, as well as BB-1, but with different
time kinetics. Stimulation of CD40-positive myoblasts with anti-CD40 mAb
selectively induces BB-1, whereas stimulation with CD40L-transfected mouse L
cells induces BB-1 and B7.1, with different kinetics. To assess whether BB-1
is
expressed in muscle tissue, we investigated 23 muscle biopsy specimens from
patients with polymyositis, dermatomyositis, inclusion body myositis, Duchenne
muscular dystrophy, and nonmyopathic controls by immunohistochemistry and
confocal laser microscopy. We found that, in all inflammatory myopathy cases,
but not in normal muscle, many muscle fibers strongly react with anti-BB-1.
In
contrast, muscle fibers did not react with B7.1- or B7.2-monospecific mAbs in
any of the pathologic specimens or in normal muscle. Our results demonstrate
that human muscle cells can be induced to selectively express BB-1, a functional
costimulatory molecule distinct from B7.1 and B7.2. This molecule may play an
important role in the immunobiology of muscle.
PMID: 9834075 [PubMed - indexed for MEDLINE]
292: Neuroreport. 1998 Oct 5;9(14):3201-5.
Impaired innervation of cultured human muscle overexpressing betaAPP
experimentally and genetically: relevance to inclusion-body myopathies.
McFerrin J, Engel WK, Askanas V.
USC Neuromuscular Center, Department of Neurology, University of Southern
California School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912,
USA.
To investigate whether abnormally accumulated betaAPP may be responsible for
denervation of muscle fibers that are present in hereditary inclusion-body
myopathy (h-IBM) and sporadic inclusion-body myositis (s-IBM), we cultured five
h-IBM and eight normal muscle biopsies. In eight other experiments, a 3 kb human
751-betaAPP-cDNA was transferred, using adenovirus vector, into cultured normal
myotubes immediately after myoblast fusion. In all experiments, cultured muscle
fibers were co-cultured with fetal rat spinal cord. Controls had no detectable
betaAPP epitopes, whereas betaAPP epitopes were greatly increased in cultured
h-IBM muscle and in cultured normal muscle after betaAPP-gene transfer.
Innervated normal cultured muscle fibers were continuously contracting and fully
cross-striated, and they had acetylcholine receptors (AChRs) and
acetylcholinesterase (AChE) accumulated only at the neuromuscular junctions
(NMJs). By contrast, both groups of betaAPP-overexpressing cultured muscle
fibers were not contracting and not cross-striated; and did not have NJMs
containing AChRs and AChE. Our results suggest that over-expression of betaAPP
in cultured muscle fibers inhibits their innervation, and that the accumulation
of betaAPP in muscle fibers of both h- and s-IBM patients may be responsible
for
their not becoming or remaining properly innervated or reinnervated, i.e. a
'myogenous-dysinnervation' mechanism.
PMID: 9831451 [PubMed - indexed for MEDLINE]
293: Brain. 1998 Nov;121 ( Pt 11):2119-26.
Normal in vivo skeletal muscle oxidative metabolism in sporadic inclusion body
myositis assessed by 31P-magnetic resonance spectroscopy.
Lodi R, Taylor DJ, Tabrizi SJ, Hilton-Jones D, Squier MV, Seller A, Styles
P,
Schapira AH.
MRC Biochemical and Clinical Magnetic Resonance Unit, Oxford Radcliffe Hospital,
UK.
Sporadic inclusion body myositis (s-IBM) is a chronic inflammatory myopathy
of
unknown pathogenesis. The common findings of ragged red fibres, cytochrome c
oxidase-negative fibres and multiple mitochondrial DNA deletions in the muscle
of patients with s-IBM have suggested that a deficit of energy metabolism may
be
of pathogenic relevance. To test this hypothesis we used 31P magnetic resonance
spectroscopy to assess in vivo skeletal muscle mitochondrial function in the
calf muscles of 12 patients with definite s-IBM. Eleven patients showed multiple
mitochondrial DNA deletions in skeletal muscle and 67% showed ragged red fibres
and/or cytochrome c oxidase-negative fibres. T1-weighted MR images showed
increased signal intensity in the calf muscle of all patients except one. The
involvement of calf muscle was confirmed by 31P magnetic resonance spectroscopy
of resting muscle, which disclosed abnormalities in metabolite ratios in all
patients. However, muscle oxidative metabolism assessed during recovery from
exercise was normal in patients with s-IBM, as maximum rates of mitochondrial
ATP production and post-exercise ADP recovery rates were within the normal range
in all cases. We conclude that muscle mitochondrial abnormalities are a
secondary process and unlikely to play a significant role in the pathogenesis
of
s-IBM.
PMID: 9827771 [PubMed - indexed for MEDLINE]
294: Curr Opin Rheumatol. 1998 Nov;10(6):543-7.
Genetics of inclusion body myopathies.
Argov Z, Eisenberg I, Mitrani-Rosenbaum S.
Department of Neurology, Hadassah University Hospital, Jerusalem.
We review the current knowledge about the genetic susceptibility to develop
inflammatory inclusion body myositis, especially in relation to the increased
presence of the HLA DR3 allele in patients with familial and sporadic forms,
indicating an autoimmune predisposition. The main focus of the review is the
clinical and genetic presentations of the various hereditary inclusion body
myopathies. Criteria for diagnosis and classification of these myopathies are
presented. The spectrum of the recessive forms of hereditary inclusion body
myopathies currently linked to chromosome 9p1-q1 is described, with emphasis
on
the up-to-date status of the gene search for these forms.
Publication Types:
Review
Review, Tutorial
PMID: 9812214 [PubMed - indexed for MEDLINE]
295: Curr Opin Rheumatol. 1998 Nov;10(6):530-42.
Sporadic inclusion-body myositis and hereditary inclusion-body myopathies:
current concepts of diagnosis and pathogenesis.
Askanas V, Engel WK.
Department of Neurology, University of Southern California School of Medicine,
Good Samaritan Hospital, Los Angeles 90017-1912, USA.
We discuss the pathologic diagnostic criteria and review the major new advances
related to seeking the pathogenic mechanism of sporadic inclusion-body myositis
(s-IBM) and hereditary inclusion-body myopathy (h-IBM). A classification of
the
various h-IBM syndromes is also presented. The several forms of the h-IBMs have
different genetic transmissions and probably different genetic defects. In
neither s-IBM nor the h-IBMs are the sequential steps of the pathogenic cascade
understood. Because s-IBM and the h-IBMs have a number of characteristic
pathologic features in common, we postulate that their different causes trigger
the same upstream aberration leading to a similar downstream cascade of
pathologic events, which are ultimately responsible for the characteristic
muscle-fiber degeneration. Muscle-biopsy and experimental evidence is given
supporting our hypothesis that overexpression of beta-amyloid precursor protein
within abnormal muscle fibers is an early upstream event causing the pathogenic
cascade. We also present evidence supporting our concept that muscle aging and
oxidative stress are important factors contributing to the s-IBM-specific muscle
fiber destruction. Additionally, the intriguing parallels between the pathologic
phenotype of IBM muscle fibers and Alzheimer's disease brain are summarized.
Publication Types:
Review
PMID: 9812213 [PubMed - indexed for MEDLINE]
296: Curr Opin Rheumatol. 1998 Nov;10(6):521-9.
New developments in the role of cytokines and chemokines in inflammatory
myopathies.
Lundberg IE, Nyberg P.
Rheumatology Unit, Karolinska Hospital, Stockholm, Sweden.
Cytokines and chemokines are important molecules in the inflammatory response
and in immune regulation. Investigations of the production of these molecules
in
the target organ of inflammation is of particular interest to obtain increased
knowledge of the pathogenesis of chronic inflammatory disorders. By
investigations of muscle tissue from patients with polymyositis, inclusion-body
myositis (IBM), and dermatomyositis a predominance of the cytokines
interleukin-1 alpha and -1 beta and transforming growth factor beta was
observed. Among the chemokines investigated, macrophage inflammatory protein
1
alpha was the most commonly found molecule. A similar pattern of cytokines and
chemokines was present in polymyositis, IBM, and dermatomyositis. This was also
true for the pronounced interleukin-1 alpha expression in the endothelial cells
of capillaries and venules. The results of these studies suggest a major role
of
the proinflammatory cytokines interleukin-1 alpha and -1 beta and the importance
of the endothelial cells in the pathogenesis not only in dermatomyositis, as
previously suggested, but also in polymyositis and IBM. Furthermore, the
pronounced interleukin-1 expression in the inflammatory myopathies makes this
molecule an interesting potential target for development of future therapies
for
these disorders.
Publication Types:
Review
Review, Tutorial
PMID: 9812212 [PubMed - indexed for MEDLINE]
297: Compr Ther. 1998 Oct;24(10):494-502.
Inflammatory myopathies [polymyositis, dermatomyositis, inclusion body myositis]
Bertorini TE.
Department of Neurology, University of Tennessee, Memphis 38163, USA.
Inflammatory myopathies are common treatable diseases of muscle that should
be
differentiated from similar but incurable conditions. This article discusses
the
diagnosis, laboratory studies, pathology, pathogenesis, differential diagnosis,
and treatment of the different autoimmune myopathies.
Publication Types:
Review
Review, Tutorial
PMID: 9801848 [PubMed - indexed for MEDLINE]
298: Hum Pathol. 1998 Oct;29(10):1128-33.
Rimmed vacuoles with beta-amyloid and ubiquitinated filamentous deposits in
the
muscles of patients with long-standing denervation (postpoliomyelitis muscular
atrophy): similarities with inclusion body myositis.
Semino-Mora C, Dalakas MC.
Neuromuscular Diseases Section, Medical Neurology Branch, National Institute
of
Neurological Disorders and Stroke, National Institutes of Health, Bethesda,
MD
20892, USA.
In the chronically denervated muscles of patients with prior paralytic
poliomyelitis, there are secondary myopathic features, including endomysial
inflammation and rare vacuolated fibers. To assess the frequency and
characteristics of the vacuoles and their similarities with those seen in
inclusion body myositis (IBM), we examined 58 muscle biopsy specimens from
patients with prior paralytic poliomyelitis for (1) the presence of rimmed
vacuoles; (2) acid-phosphatase reactivity; (3) Congo-red-positive amyloid
deposits; (4) electron microscopy, searching for tubulofilaments; and (5)
immunoelectron microscopy, using antibodies against beta-amyloid and ubiquitin.
We found vacuolated muscle fibers in 18 of 58 (31%) biopsies, with a mean
frequency of 2.06 +/- 0.42 fibers per specimen. The vacuoles contained acid
phosphatase-positive material in 6 of the 18 (33.30%) specimens and stained
positive for Congo red in five (27.80%). By immunoelectron microscopy, the
vacuoles contained 5.17 +/- 0.13 nm fibrils and 14.9 +/- 0.31 nm filaments that
immunoreacted with antibodies to beta-amyloid and ubiquitin in a pattern
identical to the one seen in IBM. We conclude that vacuolated muscle fibers
containing filamentous inclusions positive for amyloid and ubiquitin are not
unique to IBM and the other vacuolar myopathies but can also occur in a chronic
neurogenic condition, such as postpoliomyelitis. The chronicity of the
underlying disease, rather than the cause, may lead to vacuolar formation,
amyloid deposition, and accumulation of ubiquitinated filaments.
PMID: 9781653 [PubMed - indexed for MEDLINE]
299: Neurosci Lett. 1998 Sep 25;254(2):77-80.
Immunolocalization of transcription factor NF-kappaB in inclusion-body myositis
muscle and at normal human neuromuscular junctions.
Yang CC, Askanas V, Engel WK, Alvarez RB.
USC Neuromuscular Center, Department of Neurology, University of Southern
California School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912,
USA.
To investigate whether nuclear factor kappaB (NF-kappaB) is involved in the
pathogenesis of inclusion-body myositis (IBM), we immunostained muscle biopsies
of eight patients with IBM with specific antibodies against its p50 and p65
subunits. Approximately 70% of IBM vacuolated muscle fibers had strong focal
accumulations of both NF-kappaB p50 and p65, which by immunoelectronmicroscopy,
localized mainly to clusters of paired-helical filaments (PHFs). Virtually all
necrotic fibers, in various muscle biopsies, had diffusely strong p50
immunoreactivity, whereas p65 immunoreactivity was present only in a small
subset of necrotic fibers. At all neuromuscular junctions, postsynaptically
there was strong p65 but no p50 immunoreactivity. Our data suggest that
NF-kappaB plays a role in IBM pathogenesis. Different distributions of NF-kappaB
subunits in necrotic fibers and at normal neuromuscular junctions (NMJs)
suggests different roles of each subunit in human muscle pathology and
physiology.
PMID: 9779924 [PubMed - indexed for MEDLINE]
300: Rev Neurol (Paris). 1998 Jan;154(1):13-6.
Dermatomyositis, polymyositis and inclusion body myositis: current concepts.
Illa I, Dalakas MC.
Publication Types:
Editorial
Review
Review, Tutorial
PMID: 9773019 [PubMed - indexed for MEDLINE]
301: Muscle Nerve. 1998 Nov;21(11):1523-5.
Intracellular phosphates in inclusion body myositis--a 31P magnetic resonance
spectroscopy study.
Argov Z, Taivassalo T, De Stefano N, Genge A, Karpati G, Arnold DL.
Department of Neurology, Hebrew University-Hadassah Medical School, Jerusalem,
Israel.
Muscle phosphorus magnetic resonance spectroscopy was used to study oxidative
metabolism at rest and during recovery from exercise in 7 patients with sporadic
inclusion body myositis (s-IBM), compared with normal controls (n=8) and
mitochondrial myopathies (n=20). At rest, 6/7 patients had elevated inorganic
phosphates. Recovery parameters were not different from controls, in contrast
with mitochondrial myopathies, who showed abnormal rest and recovery. The normal
recovery suggests that mitochondrial oxidative capacity is not impaired in
s-IBM.
PMID: 9771678 [PubMed - indexed for MEDLINE]
302: Ann Neurol. 1998 Sep;44(3):423.
Presence of the anti-Jo-1 autoantibody excludes inclusion body myositis.
Hengstman GJ, van Engelen BG, Badrising UA, van den Hoogen FH, van Venrooij WJ.
Publication Types:
Letter
PMID: 9749616 [PubMed - indexed for MEDLINE]
303: Neurology. 1998 Aug;51(2):598-600.
Comment in:
Neurology. 1999 Aug 11;53(3):659.
Inclusion body myositis in twins.
Amato AA, Shebert RT.
Department of Medicine/Neurology, University of Texas Health Science Center
at
San Antonio, 78284-7883, USA.
Sporadic inclusion body myositis (s-IBM) is characterized by late onset of
slowly progressive weakness that involves the quadriceps and volar forearm
muscles early in the course of the disease. There are hereditary forms of
inclusion body myopathy (h-IBM) that histologically resemble s-IBM. The lack
of
inflammation on biopsy and the different ages at onset and patterns of muscle
weakness distinguish s-IBM from h-IBM. We report twin brothers with the typical
clinical and histologic features of s-IBM. The occurrence of s-IBM in these
twins suggests the possibility of a genetic susceptibility to developing s-IBM.
Publication Types:
Case Reports
PMID: 9710045 [PubMed - indexed for MEDLINE]
304: Ann Neurol. 1998 Aug;44(2):242-8.
Autosomal dominant myopathy with congenital joint contractures, ophthalmoplegia,
and rimmed vacuoles.
Darin N, Kyllerman M, Wahlstrom J, Martinsson T, Oldfors A.
Department of Pediatrics, Sahlgrenska University Hospital, Goteborg, Sweden.
We describe a new myopathy in a large family with 19 affected cases. Inheritance
was autosomal dominant. Characteristic clinical features were congenital joint
contractures, which normalized during early childhood, external ophthalmoplegia,
and proximal muscle weakness. Muscle atrophy was most prominent in the
pectoralis and quadriceps muscles. The clinical course was nonprogressive in
childhood, but most adult cases experienced deterioration of muscle function,
starting from 30 to 50 years of age. The major histopathological change of
skeletal muscle in childhood was focal disorganization of myofilaments. In
adults with progressive muscle weakness, the muscle biopsies showed dystrophic
changes and rimmed vacuoles with cytoplasmic and intranuclear inclusions of
15-
to 21-nm filaments. These findings suggests that this new disease should be
classified as a variant of hereditary inclusion body myopathy.
PMID: 9708547 [PubMed - indexed for MEDLINE]
305: Neurosci Res. 1998 May;31(1):1-8.
Chloroquine myopathy suggests that tau is degraded in lysosomes: implication
for
the formation of paired helical filaments in Alzheimer's disease.
Oyama F, Murakami N, Ihara Y.
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
We have found that amorphous tau deposits in chloroquine myopathy (CM), a
vacuolar myopathy induced by the administration of chloroquine, a well-known
lysosomotropic agent. The dynamics of tau in CM and immunocytochemistry strongly
suggest that the accumulation of tau is due to defective tau degradation in
the
lysosomal compartment in the muscle. This observation may offer a new view on
the formation of paired helical filaments in Alzheimer's disease: this selective
protein degradation pathway may be defective and result in intracellular
accumulation of tau, thereby forming the unusual filaments.
Publication Types:
Review
Review, Tutorial
PMID: 9704973 [PubMed - indexed for MEDLINE]
306: Acta Neuropathol (Berl). 1998 Jul;96(1):41-51.
Pleomorphic mitochondrial and different filamentous inclusions in inflammatory
myopathies associated with mtDNA deletions.
Molnar M, Schroder JM.
Institut fur Neuropathologie, Universitatsklinikum der Rheinisch-Westfalischen
Technischen Hochschule Aachen, Germany. neupath@amsd.imib.rwth-aachen.de
Mitochondrial changes are frequently observed in muscle fibers of patients
with
inclusion body myositis (IBM) and polymyositis (PM), suggesting that
mitochondrial function may be especially impaired in these forms of inflammatory
myopathies. Intranuclear and cytoplasmic tubulofilamentous inclusions are
characteristic, although not totally specific for IBM. In the present cases,
the
inclusions were strikingly pleomorphic when chloroquine had been given for long
periods. The nuclear inclusions were always tubular, whereas the cytoplasmic
filaments had either a tubular, a helical, or a cross-striated structure with
different diameters and arrangements in association with myelin-like figures,
and vacuoles. Abnormal mitochondria containing paracrystalline, globoid, and
other inclusions, noted in IBM, were occasionally also seen in PM or vasculitis.
By contrast, in the latter, no intranuclear or cytoplasmic tubulofilamentous
inclusions were apparent in muscle fibers. This study reports for the first
time
the presence of membrane-bound crystalloid inclusions in a muscle fiber with
numerous abnormal mitochondria; similar structures have thus far only been
observed in macrophages. The identity and function of these inclusions remains
unknown. Using PCR analysis we detected different mtDNA deletions not only in
IBM, but also in PM and vasculitis, indicating at least some degree of
association between the structural mitochondrial abnormalities and the mtDNA
mutations. There was no topographical correlation between the presence of
tubular or helical filaments and the mitochondrial abnormalities. As already
noted by others, the mitochondrial changes in IBM were more frequent than
expected in this age group. It is suggested that the presence of the mtDNA
deletions in IBM and PM are not primary, but rather the result of the
underlying, presumably immunological disorder causing nuclear and secondary
or
simultaneous mitochondrial changes.
PMID: 9678512 [PubMed - indexed for MEDLINE]
307: Arch Neurol. 1998 Jul;55(7):915-20.
Sporadic inclusion-body myositis and hereditary inclusion-body myopathies:
diseases of oxidative stress and aging?
Askanas V, Engel WK.
Neuromuscular Center, Department of Neurology, University of Southern California
School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912, USA.
Publication Types:
Review
Review, Tutorial
PMID: 9678308 [PubMed - indexed for MEDLINE]
308: Ann N Y Acad Sci. 1998 May 13;841:28-56.
Fourteen newly recognized proteins at the human neuromuscular junctions--and
their nonjunctional accumulation in inclusion-body myositis.
Askanas V, Engel WK, Alvarez RB.
Department of Neurology, University of Southern California School of Medicine,
Good Samaritan Hospital, Los Angeles 90017-1912, USA.
Publication Types:
Review
Review, Tutorial
PMID: 9668220 [PubMed - indexed for MEDLINE]
309: J Neurol Neurosurg Psychiatry. 1998 Jul;65(1):107-10.
Immunoglobulin therapy in inflammatory myopathies.
Mastaglia FL, Phillips BA, Zilko PJ.
Australian Neuromuscular Research Institute, University Department of Medicine,
Queen Elizabeth II Medical Centre, Perth WA.
A prospective open label trial of add on therapy with intravenous immunoglobulin
(i.v.Ig) was carried out in 16 patients with inflammatory myopathy who had
continued to deteriorate or had relapsed on conventional therapy. The response
was assessed using isometric myometry, functional scales, MRC grading, and serum
creatine kinase concentrations with a three month run in period before
commencement of i.v.Ig. Five of seven patients with isolated dermatomyositis
or
polymyositis and all four patients with an overlap syndrome responded to i.v.Ig
with partial or complete remission of disease and normalisation of serum
creatine kinase concentrations. None of five patients with inclusion body
myositis showed any functional improvement although myometry scores improved
in
some muscles in one case. It is concluded that i.v.Ig is an effective
therapeutic option in patients with drug resistant polymyositis or
dermatomyositis. However, further controlled trials are required to confirm
the
efficacy of this form of treatment and to establish optimal doses and
administration regimes.
PMID: 9667570 [PubMed - indexed for MEDLINE]
310: Laryngoscope. 1998 Jul;108(7):1001-5.
Dysphagia in patients with inclusion body myositis.
Houser SM, Calabrese LH, Strome M.
Department of Otolaryngology and Communicative Disorders, Cleveland Clinic
Foundation, Ohio 44195, USA.
OBJECTIVES: Inclusion body myositis (IBM) is an inflammatory myopathy with
a 40%
reported incidence of dysphagia. A protracted course, refractory to medical
therapy, frequently leads to consultation with an otolaryngologist for dysphagia
management. We studied the incidence, symptoms, and mechanisms of dysphagia
in
patients with IBM. STUDY DESIGN: Retrospective study of medical records and
self-reported follow-up survey; dysphagia is defined as difficulty in
swallowing. MATERIALS: Twenty-two patients with biopsy-proven IBM. RESULTS:
The
rate of dysphagia was more than 80% (16 of 19), twice as high as previously
reported. Progressive dysphagia was associated with a significantly worse
functional class. Relevant management guidelines are established, including
the
timing for appropriate surgical intervention. CONCLUSION: Progressive dysphagia
may signify more aggressive IBM or an episodic worsening in status. Recognition
of the disease manifestations will afford proper patient management. Informed
otolaryngologists can have a favorable impact on the dysphagia associated with
IBM.
Publication Types:
Case Reports
PMID: 9665246 [PubMed - indexed for MEDLINE]
311: Brain. 1998 Jun;121 ( Pt 6):1089-97.
Nitric oxide-induced oxidative stress in autosomal recessive and dominant
inclusion-body myopathies.
Yang CC, Alvarez RB, Engel WK, Heller SL, Askanas V.
USC Neuromuscular Center, Good Samaritan Hospital, University of Southern
California School of Medicine, Los Angeles, USA.
Autosomal-recessive and autosomal-dominant hereditary inclusion-body myopathies
are severe, progressive muscle diseases, characterized pathologically by
vacuolated muscle fibres containing paired helical filaments. We immunostained
muscle biopsy specimens from quadriceps-sparing autosomal-recessive and
autosomal-dominant inclusion-body myopathy subjects, disease-control subjects
and normal patients, utilizing isoform-specific antibodies against the neuronal
and inducible forms of nitric oxide synthase, and antibodies against
nitrotyrosine. Approximately 75% of the vacuolated muscle fibres in all
recessive and dominant inclusion-body myopathy patients contained inclusions
strongly immunoreactive with antibodies against neuronal and inducible nitric
oxide synthase which, by immunoelectron microscopy, were colocalized to clusters
of tubulofilaments (previously shown, by us, to be paired helical filaments).
Strong nitrotyrosine immunoreactivity was in the form of multiple dots and large
granular patches, which ultrastructurally did not immunolocalize to
tubulofilaments. Excess intracellular nitric oxide can combine with superoxide
to produce highly toxic peroxynitrite, which can nitrate tyrosines of proteins.
The presence of nitrotyrosine is indicative of nitric oxide-induced oxidative
stress. Our data suggest that oxidative stress plays a role in the pathogenic
cascade of hereditary inclusion-body myopathies.
PMID: 9648544 [PubMed - indexed for MEDLINE]
312: Clin Immunol Immunopathol. 1998 Jun;87(3):240-7.
Cell death and oxidative damage in inflammatory myopathies.
Tews DS, Goebel HH.
Division of Neuropathology, Johannes Gutenberg-University, Mainz, Germany.
There is evidence that muscle fibers in denervating disorders and muscular
dystrophies undergo apoptosis. In 21 patients with autoimmune inflammatory
myopathies, we found no features of muscle fiber apoptosis such as DNA
fragmentation or expression of apoptosis-related proteins. However, muscle
fibers in myositis displayed distinct up-regulation of inducible and neuronal
nitric oxide synthase (NOS). While inducible NOS was distinctly up-regulated
on
the sarcolemma of all kinds of muscle fibers neuronal NOS displayed increased
expression in the sarcoplasm of damaged as well as atrophic muscle fibers. There
were no disease-specific patterns in the different myositis subtypes. Enhanced
expression of NOS with production of nitric oxide may contribute to oxidative
stress mediating muscle fiber damage and muscle fiber necrosis representing
the
predominant cell death mechanism in myositis. Nevertheless, inflammatory cells
displayed numerous DNA-fragmentation-positive nuclei and expression of
apoptosis-related proteins indicating that apoptosis plays a role in the
regulation of the inflammatory cellular response.
PMID: 9646833 [PubMed - indexed for MEDLINE]
313: J Neuroimmunol. 1998 Apr 15;84(2):139-42.
HLA allele distribution distinguishes sporadic inclusion body myositis from
hereditary inclusion body myopathies.
Koffman BM, Sivakumar K, Simonis T, Stroncek D, Dalakas MC.
We studied the HLA class II associations in patients with sporadic inclusion
body myositis (s-IBM) and hereditary inclusion body myopathies (h-IBM) and
attempted to distinguish these myopathies on the basis of HLA allele
assignments. Forty-five patients, 30 with s-IBM and 15 with h-IBM, underwent
HLA
class II allele-specific typing using polymerase chain reaction
sequence-specific primers for 71 alleles contained in the DRbeta1, DRbeta3-5,
and DQbeta1 loci. In s-IBM, we found a high (up to 77%) frequency of
DRbeta1*0301, DRbeta3*0101 (or DRbeta3*0202) and DQbeta1*0201 alleles. No
significant association with alleles in the DR and DQ haplotypes was found among
the 15 h-IBM patients. The strong association of prominent alleles with s-IBM,
but not h-IBM, suggests that s-IBM is a distinct disorder with an immunogenetic
background that differs from h-IBM.
PMID: 9628455 [PubMed - indexed for MEDLINE]
314: J Neuroimmunol. 1998 May 1;85(1):52-8.
The expression of co-stimulatory and accessory molecules on cultured human
muscle cells is not dependent on stimulus by pro-inflammatory cytokines:
relevance for the pathogenesis of inflammatory myopathy.
Bernasconi P, Confalonieri P, Andreetta F, Baggi F, Cornelio F, Mantegazza R.
Divisione Malattie Neuromuscolari, Instituto Nazionale Neurologico Carlo Besta,
Milan, Italy. mantega@imiucca.csi.unimi.it
Specific activation of naive T cells requires TCR engagement plus interaction
of
CD28 on T cells with co-stimulatory B7-1/B7-2 on APCs. Since muscle cells may
be
directly involved in activating muscle-infiltrating T lymphocytes in
polymyositis and inclusion body myositis, we analyzed B7 expression on myoblasts
before and after treatment with pro-inflammatory cytokines. We found no
expression of B7-1/B7-2, either constitutively or after stimulus with cytokines.
Furthermore, myoblasts failed to stimulate alloreactive peripheral blood
lymphocytes in mixed lymphocyte reactions. Lack of B7 expression was confirmed
by immunostaining of polymyositis patients' muscle: only T and the few B
lymphocytes present in inflammation areas expressed B7-1.
PMID: 9626997 [PubMed - indexed for MEDLINE]
315: Neuromuscul Disord. 1998 Apr;8(2):115-8.
Welander distal myopathy--an overview.
Borg K, Ahlberg G, Anvret M, Edstrom L.
Department of Neurology, Karolinska Hospital, Stockholm, Sweden.
Welander distal myopathy has an autosomal dominant inheritance and a late onset.
The onset of symptoms is in the hands and gradually distal muscles of the lower
extremities are involved. The most-affected muscles are the long extensors of
the hands and feet. CK-values are normal or slightly elevated. There is never
any cardiac involvement in Welander distal myopathy. Neurophysiological findings
are of both myopathic and neuropathic character. Histopathological findings
in
muscle biopsies are mainly of myopathic type and include rimmed vacuoles which
correspond to autophagic vacuoles on the ultrastructural level.
Tubulo-filamentous inclusions with a diameter of 16-21 nm, i.e. of the same
type
as found in patients with Inclusion Body Myositis, are found in the sarcoplasm
and in myofibre nuclei. A neurogenic component in Welander distal myopathy has
been suggested, on the grounds of a sensory dysfunction, neuropathic findings
on
neurophysiology and muscle biopsy and a decrease of A-delta nerve fibres on
sural nerve biopsy. Genetic analysis has excluded linkage to other defined
distal myopathies and hereditary Inclusion Body Myopathy loci.
Publication Types:
Review
Review, Tutorial
PMID: 9608565 [PubMed - indexed for MEDLINE]
316: J Neuroimmunol. 1998 Apr 1;84(1):86-91.
T-cell heterogeneity in muscle lesions of inclusion body myositis.
Bender A, Behrens L, Engel AG, Hohlfeld R.
Department of Neuroimmunology, Max Planck Institute, Martinsried, Germany.
In the muscle lesions of inclusion body myositis (IBM), two populations of
T
cells can morphologically be distinguished, T cells that invade muscle fibers
and T cells that remain in interstitial areas. Using combined
immunohistochemistry and RT-PCR, we analysed the TCR expressed by these distinct
T cell populations. In three of eight IBM muscle specimens, the autoinvasive
T
cells were stained with one of the available mAbs: anti-Vbeta5.3 in patient
1,
anti-Vbeta5.2 in patient 2, and anti-Vbeta3 in patient 3. The corresponding
TCR
Vbeta mRNAs were amplified by RT-PCR and the PCR products were cloned and
sequenced. In all three specimens, the TCRs expressed by the autoinvasive T
cells were clonally restricted. Furthermore, in patient 1 two different mAbs
labelled two distinct populations of T cells: an autoaggressive population of
CD8 + Vbeta5.3 + cells that invaded muscle fibers and a noninvasive interstitial
population of CD8 - Vbeta5.1 + cells. TCR sequence analysis revealed that the
noninvasive Vbeta5.1 + T cells were clonally diverse, whereas the autoinvasive
Vbeta5.3 + T cells were clonally restricted.
PMID: 9600712 [PubMed - indexed for MEDLINE]
317: J Neuropathol Exp Neurol. 1998 May;57(5):396-403.
Characterization of the mitochondrial DNA abnormalities in the skeletal muscle
of patients with inclusion body myositis.
Horvath R, Fu K, Johns T, Genge A, Karpati G, Shoubridge EA.
Montreal Neurological Institute, McGill University, Quebec, Canada.
Inclusion body myositis (IBM) is a late-onset inflammatory myopathy with
distinctive clinical and histopathological features. The molecular basis for
the
disease remains unknown, but abnormal nuclear morphology and the accumulation
of
a protein that binds single-stranded DNA in a sequence-independent fashion
suggest a nuclear defect. Evidence of mitochondrial respiratory chain
dysfunction (ragged-red fibers, multiple mtDNA deletions) has been reported
in
IBM muscle. Here we have investigated the relationship of the mtDNA
abnormalities in sporadic and familial IBM patients to the pathogenesis of the
disease. In situ hybridization analysis with mtDNA probes revealed several
different mtDNA abnormalities in cytochrome c oxidase-negative muscle fibers
including large-scale mtDNA deletions and mtDNA depletion, but no evidence for
nonspecific DNA binding. Contrary to previous reports, we did not observe mtDNA
deletions on Southern blot analysis, consistent with the presence of multiple
different deleted mtDNA species demonstrated by single fiber PCR. There was
no
consistent correlation between the mitochondrial abnormalities and markers of
muscle regeneration, inflammation, or microscopically detectable pathological
alterations of myonuclei in the same fibers. Thus, early molecular abnormalities
in IBM may simply accelerate the accumulation of mtDNA abnormalities that occurs
with natural aging.
PMID: 9596410 [PubMed - indexed for MEDLINE]
318: Int Immunol. 1998 Mar;10(3):267-73.
Myoblasts produce IL-6 in response to inflammatory stimuli.
Gallucci S, Provenzano C, Mazzarelli P, Scuderi F, Bartoccioni E.
Institute of General Pathology, Catholic University, Rome, Italy.
Muscle fibers are the target of T cell-mediated cytotoxic reactions in
polymyositis and inclusion body myositis, while the success of myoblast
transplantation depends on the absence of an immune rejection against the
myofibers. In order to study the behaviour of muscle cells in an inflammatory
milieu, we investigated the production of IL-6 and its modulation, including
the
second messenger pathways controlling it, in in vitro highly purified human
myoblast cultures. We found that IL-1beta, tumor necrosis factor (TNF)-alpha
and
lipopolysaccharide (LPS) stimulated myoblast IL-6 secretion in a dose- and
time-dependent manner, whereas forskolin and cholera toxin did not. HA1004 at
10
microM did not significantly affect the IL-1beta- and TNF-alpha-induced IL-6
secretion, suggesting that cAMP and protein kinase A are not sufficient to
stimulate this process. To investigate the role of protein kinase C (PKC) in
this signal transduction, we employed the inhibitor calphostin C, and the
activators phorbol-12-myristate-13-acetate (PMA) and calcium ionophore A23187.
Calphostin C blocked IL-6 secretion, PMA had a small stimulatory effect and
A23187 had no effect; moreover, PKC down-regulation by PMA did not inhibit
IL-1beta stimulation, while it reduced TNF-alpha stimulation. These data
indicate that different PKC isoforms may be involved in TNF-alpha and IL-1beta
signal transduction. Such a difference can distinguish the action of two
traditionally 'overlapping' inflammatory cytokines. Our data suggest that muscle
cells, like myoblasts, satellite cells and in vivo regenerating myofibers, may
discriminate between different stimuli and produce IL-6 when activated in
response to muscle injury.
PMID: 9576614 [PubMed - indexed for MEDLINE]
319: Muscle Nerve. 1998 May;21(5):659-61.
Further observations on forearm flexor weakness in inclusion body myositis.
Felice KJ, Relva GM, Conway SR.
Department of Neurology, University of Connecticut Health Center, Farmington
06030-1840, USA.
In order to further characterize and provide a possible mechanism for the
asymmetrical involvement of forearm muscles in inclusion body myositis (IBM),
we
measured isometric hand and pinch grip strength, and forearm muscle girth on
15
IBM patients. Forearm muscle strength and girth were significantly greater on
the dominant versus nondominant side: mean grip strength, 173.9 vs. 98.8 N;
mean
pinch strength, 47.6 vs. 29.7 N; and mean forearm girth, 22.5 vs. 19.9 cm. This
observation may suggest a role for exercise in delaying the disease progression
in IBM.
PMID: 9572250 [PubMed - indexed for MEDLINE]
320: Arthritis Rheum. 1998 Apr;41(4):710-9.
Clinical, serologic, and immunogenetic features of familial idiopathic
inflammatory myopathy.
Rider LG, Gurley RC, Pandey JP, Garcia de la Torre I, Kalovidouris AE, O'Hanlon
TP, Love LA, Hennekam RC, Baumbach LL, Neville HE, Garcia CA, Klingman J, Gibbs
M, Weisman MH, Targoff IN, Miller FW.
Center for Biologics Evaluation and Research, FDA, and the National Institute
of
Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892,
USA.
OBJECTIVE: To describe the clinical, serologic, and immunogenetic features
of
familial idiopathic inflammatory myopathy (IIM) and to compare these with the
features of sporadic IIM. METHODS: Clinical signs and symptoms, autoantibodies,
HLA-DRB1 and DQA1 alleles, and GM/KM phenotypes were compared among 36 affected
and 28 unaffected members of 16 unrelated families in which 2 or more blood
relatives developed an IIM. In addition, findings in patients with familial
IIM
were compared with those in 181 patients with sporadic IIM. The families
included 3 pairs of monozygotic twins with juvenile dermatomyositis, 11 families
with other siblings or relatives with polymyositis or dermatomyositis, and 2
families with inclusion body myositis. RESULTS: The clinical features of
familial IIM were similar to those of sporadic IIM, although the frequency of
myositis-specific autoantibodies was lower in familial than in sporadic IIM.
DRB1*0301 was a common genetic risk factor for familial and sporadic IIM, but
contributed less to the genetic risk of familial IIM (etiologic fraction 0.35
versus 0.51 in sporadic IIM). Homozygosity at the HLA-DQA1 locus was found to
be
a genetic risk factor unique to familial IIM (57% versus 24% of controls; odds
ratio 4.2, corrected P = 0.002). CONCLUSION: These findings emphasize that 1)
familial muscle weakness is not always due to inherited metabolic defects or
dystrophies, but may be the result of the development of IIM in several members
of the same family, and 2) multiple genetic factors are likely important in
the
etiology and disease expression of familial IIM, as is also the case for
sporadic myositis, but DQA1 homozygosity is a distinct risk factor for familial
IIM.
PMID: 9550481 [PubMed - indexed for MEDLINE]
321: Neuropathol Appl Neurobiol. 1998 Feb;24(1):73-9.
Local expression of cytokines in idiopathic inflammatory myopathies.
Lepidi H, Frances V, Figarella-Branger D, Bartoli C, Machado-Baeta A, Pellissier
JF.
Laboratoire de Biopathologie Nerveuse et Musculaire, Faculte de Medecine, IBDM
Marseille, France.
The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM),
polymyositis (PM), and inclusion body myositis (IBM), are regarded as autoimmune
diseases. They are characterized by chronic lymphocytic and macrophagic
infiltration in muscle tissue. Of particular importance in understanding the
immune response to IIM is the specific pattern of locally produced cytokines.
Frozen muscle tissues from IIM (5 DM, 3 PM, and 1 IBM) were used to investigate
the cytokine responses. The RT-PCR technique was instrumental to determine the
pattern of expression of pro-inflammatory (IL-1 beta, IL-6, TNF-alpha), Th1
(IFN-gamma IL-2), and Th2 (IL-4) cytokines. Immunohistochemistry was also used
to localize morphologically IFN-gamma and IL-4. Our results show that
pro-inflammatory cytokines and Th1 cytokines are mainly expressed in IIM. The
accumulation of mononuclear inflammatory cells and the inflammatory syndrome
in
IIM are probably related in part to the production of pro-inflammatory
cytokines. Moreover, the pattern of local cytokine expression is consistent
with
a Th1 immune response related to autoimmune diseases.
PMID: 9549732 [PubMed - indexed for MEDLINE]
322: Am J Pathol. 1998 Apr;152(4):889-95.
Light and electron microscopic immunolocalization of presenilin 1 in abnormal
muscle fibers of patients with sporadic inclusion-body myositis and
autosomal-recessive inclusion-body myopathy.
Askanas V, Engel WK, Yang CC, Alvarez RB, Lee VM, Wisniewski T.
USC Neuromuscular Center, Los Angeles, California 90017-1912, USA.
Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle
disease of older persons. The muscle biopsy demonstrates mononuclear cell
inflammation and vacuolated muscle fibers containing paired helical filaments
and 6- to 10-nm fibrils, both resembling those of Alzheimer disease brain and
Congo red positivity. The term hereditary inclusion-body myopathies (h-IBMs)
designates autosomal-recessive or autosomal-dominant disorders with muscle
biopsies cytopathologically similar to s-IBM but without inflammation.
Vacuolated muscle fibers of both s-IBM and the h-IBMs contain accumulations
of
several "Alzheimer-characteristic proteins" including beta-amyloid
protein and
beta-amyloid precursor protein, and their paired helical filaments are composed
of phosphorylated tau. We used six well characterized antibodies against several
residues of presenilin 1 (PS1) to immunostain muscle biopsies of 12 patients
with s-IBM, 5 patients with autosomal-recessive inclusion-body myopathy, and
16
normal and disease controls. Seventy to eighty percent of the vacuolated muscle
fibers of both s-IBM and autosomal-recessive inclusion-body myopathy had
inclusions that were strongly PS1-immunoreactive, which by immunoelectron
microscopy localized mainly to paired helical filaments and 6- to 10-nm
filaments. None of the control biopsies had PS1-positive inclusions
characteristic of the s- and h-IBM abnormal muscle fibers. Mutations of the
newly discovered PS1 gene are responsible for early-onset familial Alzheimer
disease (AD), and PS1 is abnormally accumulated in sporadic and familial AD
brain. Our study provides the first demonstration of PS1 abnormality in
non-neural tissue and in diseases other than AD and suggests that the
cytopathogenesis in AD brain and IBM muscle may share similarities.
PMID: 9546349 [PubMed - indexed for MEDLINE]
323: J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):396-8.
Absence of characteristic features in two patients with inclusion body myositis.
van der Meulen MF, Hoogendijk JE, Jansen GH, Veldman H, Wokke JH.
Department of Neurology, University Hospital Utrecht, The Netherlands.
mmeulen@neuro.azu.nl
According to recently published criteria a diagnosis of definite sporadic
inclusion body myositis is made if the typical histopathological abnormalities
(rimmed vacuoles and abnormal accumulations of proteins, in addition to
mononuclear cell infiltrates) are present. The two women described here
presented with myositis which was unresponsive to treatment. Patient 1 had
features of non-progressive sporadic inclusion body myositis clinically, whereas
patient 2 had a very slowly progressive limb girdle syndrome. The cryostat
sections of the first biopsies did not show rimmed vacuoles, even in retrospect.
Only a repeated biopsy, 12 years after presentation in one patient and 18 years
after presentation in the other, disclosed the typical features of sporadic
inclusion body myositis. The initial absence of abnormal fibres probably
represents a real absence or scarcity rather then a sampling error due to a
multifocal nature of the histological abnormalities. It is of importance for
the
clinician to realise that some patients with myositis unresponsive to treatment,
even if both clinical and histological features do not suggest sporadic
inclusion body myositis, may prove to have the disease on repeated
histopathological examination.
Publication Types:
Case Reports
PMID: 9527159 [PubMed - indexed for MEDLINE]
324: Curr Opin Rheumatol. 1997 Nov;9(6):520-6.
Cellular immune mechanisms in inflammatory myopathies.
Hohlfeld R, Engel AG, Goebels N, Behrens L.
Department of Neurology, Klinikum Grosshadern, University of Munich, Germany.
The inflammatory myopathies include dermatomyositis, polymyositis, and inclusion
body myositis. In dermatomyositis, muscle fiber injury is secondary to an
antibody- or immune-complex-mediated immune response against a
vascular-endothelial component. In polymyositis and inclusion body myositis,
CD8+ T cells and macrophages invade and eventually destroy initially nonnecrotic
muscle fibers. The autoaggressive T cells have the phenotype of activated
(HLA-DR+) memory (CD45RO+) cells. T-cell receptor analyses indicate that the
autoaggressive T cells are oligoclonal. In inflammatory lesions, muscle fibers
express various cytoplasmic and surface molecules that are not detectable in
normal fibers. These molecules, which include HLA class I antigens, heat-shock
proteins, adhesion molecules, and Fas, are probably induced by locally secreted
cytokines. The autoaggressive CD8+ T cells harbor granules containing perforin
that aggregate near the contact zone with the target muscle fiber. This is
consistent with a perforin- and secretion-dependent mechanism of muscle fiber
injury. Many invaded muscle fibers also express the Fas "death receptor,"
but
signs of apoptosis are absent.
Publication Types:
Review
Review, Tutorial
PMID: 9375281 [PubMed - indexed for MEDLINE]
325: Ann Neurol. 1998 Jan;43(1):127-30.
Upregulation of Fas/Fas ligand in inclusion body myositis.
Fyhr IM, Oldfors A.
Department of Pathology, Goteborg University, Gothenburg, Sweden.
In inclusion body myositis, T cells invade and destroy nonnecrotic muscle
fibers. The mechanism by which T cells damage muscle fibers in inflammatory
myopathies is not known. In this study we have investigated the expression of
Fas and Fas ligand in muscle in five patients with inclusion body myositis.
Reverse transcription polymerase chain reaction showed upregulation of both
Fas
and Fas ligand in all inclusion body myositis patients. Immunohistochemical
investigation showed expression of Fas ligand in many of the muscle infiltrating
mononuclear cells. Fas was expressed both in mononuclear cells and on the
surface of muscle fibers in inclusion body myositis patients and in patients
with polymyositis but not in patients with Duchenne muscular dystrophy or
denervation. The results indicate that the Fas/Fas ligand system may be of
importance for the inflammatory reaction and T-cell-mediated muscle cell injury.
PMID: 9450780 [PubMed - indexed for MEDLINE]
326: Muscle Nerve. 1998 Jan;21(1):115-7.
Immune-mediated conditions and antibodies associated with sporadic inclusion
body myositis.
Koffman BM, Rugiero M, Dalakas MC.
Neuromuscular Diseases Section, NINDS/NIH, Bethesda, MD 20892-1382, USA.
We reviewed 99 patients with sporadic inclusion body myositis (IBM), searching
for a coexisting autoimmune disease, other conditions with altered immune
function, or the presence of autoantibodies. Thirteen patients had one or more
of 11 diseases with altered immune function. Forty-three patients had elevated
titers of one or more of nine different, albeit nondisease-specific,
autoantibodies. Twenty-five patients had dysproteinemia or dysproteinuria. We
conclude that IBM is frequently associated with systemic immune disorders or
nonspecific autoantibodies. Although aging may explain some of these phenomena,
an altered immune function need to be considered in the pathogenesis of IBM.
PMID: 9427231 [PubMed - indexed for MEDLINE]
327: J Neurol Neurosurg Psychiatry. 1997 Dec;63(6):776-9.
The role of quantitative electromyography in inclusion body myositis.
Brannagan TH, Hays AP, Lange DJ, Trojaborg W.
Department of Neurology, Columbia-Presbyterian Medical Center New York, NY, USA.
OBJECTIVE AND METHODS: Inclusion body myositis is said to have both myopathic
and neurogenic features on electrophysiological tests. Twenty one studies from
20 patients with biopsy defined inclusion body myosis, 13 of whom had
quantitative electromyography (qEMG), were reviewed to determine if this
technique added diagnostic specificity (one patient had both needle EMG and
a
later study with qEMG before muscle biopsy). RESULTS: Excessive numbers of
polyphasic motor unit potentials (MUPs) (> 12% per muscle) were seen in 11
of
the 13 patients. In 10 of 13 patients, mean MUP duration was abnormally reduced
(26% to 48%). In three patients, mean MUP duration was abnormally reduced only
after polyphasic MUPs were excluded. In all 13 patients, the simple MUP duration
was reduced. Myopathy was unequivocally diagnosed in all 13 studies that
included qEMG; of the remaining eight patients, the conclusions of the
electrophysiological studies without qEMG was myopathy (one), neurogenic (four)
or non-diagnostic (three). CONCLUSIONS: There is no evidence of a neurogenic
component in inclusion body myosis if qEMG is used. Quantitative EMG is often
necessary to make an electrophysiological diagnosis of a myogenic disorder in
patients with inclusion body myosis.
PMID: 9416815 [PubMed - indexed for MEDLINE]
328: J Neurol Neurosurg Psychiatry. 1997 Dec;63(6):770-5.
Neuromuscular disorder as a presenting feature of coeliac disease.
Hadjivassiliou M, Chattopadhyay AK, Davies-Jones GA, Gibson A, Grunewald RA,
Lobo AJ.
Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK.
OBJECTIVES: To describe the range of neuromuscular disorders which may be
associated with cryptic coeliac disease. METHODS: Nine patients were described
with neuromuscular disorders associated with circulating antigliadin antibodies,
whose duodenal biopsies later confirmed the diagnosis of coeliac disease.
Neurological symptoms antedated the diagnosis of coeliac disease in all, and
most had minimal or no gastrointestinal symptoms at the onset of the
neuromuscular disorder. RESULTS: Three patients had sensorimotor axonal
peripheral neuropathy, one had axonal motor peripheral neuropathy, one had
probable inclusion body myositis and axonal motor peripheral neuropathy, one
had
polymyositis and sensorimotor peripheral neuropathy, one had mononeuropathy
multiplex, one had neuromyotonia, and one had polyneuropathy. CONCLUSION: A
wide
range of neuromuscular disease may be the presenting feature of coeliac disease.
This represents the first report of inclusion body myositis and neuromyotonia
associated with coeliac disease. Estimation of circulating antigliadin
antibodies should be considered in all patients with neuromuscular disease of
otherwise obscure aetiology.
Publication Types:
Case Reports
PMID: 9416814 [PubMed - indexed for MEDLINE]
329: Hum Mutat. 1997;10(5):381-6.
Analysis of multiple mitochondrial DNA deletions in inclusion body myositis.
Moslemi AR, Lindberg C, Oldfors A.
Department of Pathology, Sahlgrenska University Hospital, Goteborg, Sweden.
Inclusion body myositis (IBM) is a sporadic progressive myopathy, which is
morphologically characterized by inflammatory cell infiltrates and rimmed
vacuoles in muscle fibers. Mitochondrial changes are regularly present with
ragged-red fibers showing deficiency of cytochrome c oxidase. In these muscle
fiber segments, there is accumulation of mitochondria with mitochondrial DNA
(mtDNA) deletions. There are different deletions in different muscle fibers.
In
this study, we have sequenced for the first time the multiple mtDNA deletions
in
muscle from four patients with IBM. The deletion breakpoints were sequenced
from
cloned polymerase chain reaction (PCR)-amplified mtDNA fragments. The sequencing
was performed directly from the bacterial colonies used for cloning. Of 122
analyzed clones, 33 different deletions were identified. The majority of these
have not previously been described. There was a marked predominance of deletion
breakpoints in certain regions of mtDNA. These predominant breakpoint regions
are similar to those described in other conditions with multiple deletions,
such
as autosomal dominant progressive external ophthalmoplegia (adPEO) and normal
aging, but different from those described in diseases due to single deletions
such as Kearns-Sayre syndrome and sporadic PEO. These findings indicate that
common factors are involved in the development of multiple mtDNA deletions in
IBM, adPEO, and aging.
PMID: 9375854 [PubMed - indexed for MEDLINE]
330: J Neuroimmunol. 1997 Nov;79(2):185-9.
Oligoclonal expansion of muscle infiltrating T cells in inclusion body myositis.
Fyhr IM, Moslemi AR, Mosavi AA, Lindberg C, Tarkowski A, Oldfors A.
Department of Pathology, Sahlgrenska Hospital, Gothenburg University, Sweden.
Inclusion body myositis (IBM) is the most common muscle disease affecting
individuals over 50 years of age. An important feature of IBM is invasion of
muscle fibers by T cells. The muscle infiltrating T cells show a restricted
usage of variable (V) alpha/beta gene families. In this study we have
investigated the clonality of T cells using two of the predominant V beta
families i.e. V beta 3 and V beta 8 in three patients with IBM. The study was
performed by reverse transcription and polymerase chain reaction (RT-PCR)
analysis, followed by cloning and sequencing of the T cell receptor
complementarity determining region 3. We found oligoclonal expansion of V beta
3
bearing muscle infiltrating T cells in two patients and of V beta 8 in one
patient, supporting the concept that antigen stimulated T cells are important
in
the pathogenesis of IBM. Results of HLA typing indicated a genetic
predisposition for the disease by the presence of DR3, DR52 and DQB1*0201/0202
in all three patients.
PMID: 9394791 [PubMed - indexed for MEDLINE]
331: Ann Neurol. 1997 Nov;42(5):815.
Comment on:
Ann Neurol. 1996 Mar;39(3):389-91.
SMI-31 immunoreactivity in inclusion body myositis.
Spuler S, Engel AG.
Publication Types:
Comment
Letter
PMID: 9392584 [PubMed - indexed for MEDLINE]
332: J Neurochem. 1997 Oct;69(4):1580-91.
Caffeine stimulates amyloid beta-peptide release from beta-amyloid precursor
protein-transfected HEK293 cells.
Querfurth HW, Jiang J, Geiger JD, Selkoe DJ.
Department of Biomedical Research, St. Elizabeth's Hospital, Boston,
Massachusetts 02115, U.S.A.
Extracellular amyloid beta-peptide (A beta) deposition is a pathological feature
of Alzheimer's disease and the aging brain. Intracellular A beta accumulation
is
observed in the human muscle disease, inclusion body myositis. A beta has been
reported to be toxic to neurons through disruption of normal calcium
homeostasis. The pathogenic role of A beta in inclusion body myositis is not
as
clear. Elevation of intracellular calcium following application of calcium
ionophore increases the generation of A beta from its precursor protein
(betaAPP). A receptor-based mechanism for the increase in A beta production
has
not been reported to our knowledge. Here, we use caffeine to stimulate ryanodine
receptor (RYR)-regulated intracellular calcium release channels and show that
internal calcium stores also participate in the genesis of A beta. In cultured
HEK293 cells transfected with betaAPP cDNA, caffeine (5-10 mM) significantly
increased the release of A beta fourfold compared with control. These actions
of
caffeine were saturable, modulated by ryanodine, and inhibited by the RYR
antagonists ruthenium red and procaine. The calcium reuptake inhibitors
thapsigargin and cyclopiazonic acid potentiated caffeine-stimulated A beta
release. NH4Cl and monensin, agents that alter acidic gradients in intracellular
vesicles, abolished both the caffeine and ionophore effects. Immunocytochemical
studies showed some correspondence between the distribution patterns of RYR
and
cellular betaAPP immunoreactivities. The relevance of these findings to
Alzheimer's disease and inclusion body myositis is discussed.
PMID: 9326287 [PubMed - indexed for MEDLINE]
333: Muscle Nerve. 1997 Oct;20(10):1242-8.
Safety and efficacy of strength training in patients with sporadic inclusion
body myositis.
Spector SA, Lemmer JT, Koffman BM, Fleisher TA, Feuerstein IM, Hurley BF,
Dalakas MC.
Neuromuscular Diseases Section, NINDS, National Institutes of Health, Bethesda,
MD 20892, USA.
We studied the effects of a 12-week progressive resistance strength training
program in weakened muscles of 5 patients with sporadic inclusion body myositis
(IBM). Strength was evaluated with Medical Research Council (MRC) scale ratings
and quantitative isometric and dynamic tests. Changes in serum creatine kinase
(CK), lymphocyte subpopulations, muscle size (determined by magnetic resonance
imaging), and histology in repeated muscle biopsies were examined before and
after training. After 12 weeks, the values of repetition maximum improved in
the
least weakened muscles, 25-120% from baseline. This dynamic effect was not
captured by MRC or isometric muscle strength measurements. Serum CK, B cells,
T-cell subsets, and NK cells remained unchanged. Repeat muscle biopsies did
not
reveal changes in the number and degree of degenerating fibers or inflammation.
The size of the trained muscles did not change. We conclude that a supervised
progressive resistance training program in IBM patients can lead to gains in
dynamic strength of the least weak muscles without causing muscle fatigue and
muscle injury or serological, histological, and immunological abnormalities.
Even though the functional significance of these gains is unclear, this
treatment modality is a safe and perhaps overlooked means of rehabilitation
of
IBM patients.
PMID: 9324080 [PubMed - indexed for MEDLINE]
334: Curr Opin Neurol. 1997 Oct;10(5):413-20.
Inclusion body myositis and myopathies.
Sivakumar K, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, Maryland 20892-1382, USA.
Sporadic inclusion body myositis is a frequent, acquired, adult-onset vacuolar
myopathy affecting proximal and distal muscles with a distinct, easily
identifiable clinical pattern. Although its primary cause is still unknown,
autoimmune, viral, and degenerative processes, alone or in combination, are
being considered. A uniform and sustained therapeutic response using the
currently available immunomodulatory agents has not yet been achieved.
Hereditary, inherited noninflammatory rimmed vacuolar myopathies with similar
histologic features, collectively called hereditary inclusion body myopathies,
are being redefined with the use of molecular genetics. The implications of
the
recent advances in clinical and basic sciences are discussed in the present
review.
Publication Types:
Review
Review, Tutorial
PMID: 9330888 [PubMed - indexed for MEDLINE]
335: Mol Cell Biochem. 1997 Sep;174(1-2):277-81.
Mitochondrial abnormalities and peripheral neuropathy in inflammatory myopathy,
especially inclusion body myositis.
Schroder JM, Molnar M.
Institut fur Neuropathologie, Universitatsklinikum der RWTH Aachen, Germany.
Computer retrieval in a database, comprising 7,225 muscle cases, revealed that
mitochondrial myopathies do not occur more frequently in inflammatory myopathies
(3.74%) than in the whole series (3.69%). A more detailed study of inclusion
body myositis (IBM), however, showed that severe mitochondrial alterations were
apparent in about twice as many IBM cases as expected. This confirms recent
studies of others although a causal relationship has thus far not been
established. Identification of mitochondrial deletions by Southern blotting
corresponded to the presence of severe structural abnormalities of mitochondria.
Peripheral neuropathy of variable severity was noted in all cases of IBM and
mitochondrial myopathy. By contrast, the association of severe mitochondrial
abnormalities with polymyositis, systemic scleroderma, and vasculitis observed
in some cases of the present series may be incidental or age dependent.
PMID: 9309700 [PubMed - indexed for MEDLINE]
336: J Neurol. 1997 Aug;244(8):489-92.
Specific binding of Ulex europaeus agglutinin I lectin to sarcolemma of distal
myopathy with rimmed vacuole formation.
Yatabe K, Kawai M.
Department of Neurology, Tokyo Women's Medical College, Japan.
Ulex europaeus agglutinin I (UEA I) binding was studied in 83 patients with
various neuromuscular disorders. UEA I labelled endomysial capillaries and
endothelial cells of perimysial blood vessels in all the examined muscles. There
was no UEA I binding to muscle fibres except for all (9) cases of distal
myopathy with rimmed vacuole formation (DMRV), 1 of 5 cases of inclusion body
myositis and 1 of 36 cases of inflammatory myopathies. The UEA I binding was
completely eliminated by preincubation of UEA I solution with L-fucose. Using
electron microscopy, the UEA I binding was localized to sarcolemma and
intrasarco-plasmic membranous organelles other than mitochondria. Myosatellite
cells were not labelled. These findings revealed the existence of fucosylated
proteins or lipids in a subset of skeletal muscles suffering from DMRV.
Biochemical identification of the fucosylated substance and further detailed
study on subcellular localization of UEA I binding may yield important clues
to
the unknown pathogenesis of DMRV.
PMID: 9309554 [PubMed - indexed for MEDLINE]
337: Hum Pathol. 1997 Aug;28(8):887-92.
Ubiquitin immunostaining and inclusion body myositis: study of 30 patients
with
inclusion body myositis.
Prayson RA, Cohen ML.
Department of Pathology, Cleveland Clinic Foundation, and Case Western Reserve
University, OH 44195, USA.
Distinction of inclusion body myositis (IBM) from other forms of inflammatory
myopathy is significant from prognostic and therapeutic standpoints. This study
retrospectively examines ubiquitin expression by paraffin immunohistochemistry
in muscle biopsy material from 30 patients with IBM. Patients included 19 men
and 11 women (ages 29 to 80 years; mean, 64 years). All biopsies were
characterized by endomysial chronic inflammation, muscle fiber degeneration
and
regeneration, rimmed vacuoles, and angular atrophic esterase-positive muscle
fibers. Ragged red fibers were identified in biopsies of five patients and a
partial cytochrome C-oxidase deficiency by enzyme histochemistry in biopsies
of
10 patients. Evidence of intranuclear or cytoplasmic tubulofilamentous
structures confirming a diagnosis of IBM was observed in all 30 cases.
Paracrystalline mitochondrial inclusions were noted in five patients. Discrete
myocyte intranuclear ubiquitin-positive inclusions were noted in 14 patients
(47%). Discrete intracytoplasmic ubiquitin-positive inclusions were noted in
24
(80%) patients. Positive staining of rimmed vacuoles by ubiquitin was observed
in 25 (83%) patients. Diffuse staining of scattered muscle fibers was observed
in 21 (70%) patients. In a control group including patients with polymyositis
(n
= 3), dermatomyositis (n = 3), necrotizing vasculitis (n = 1), and granulomatous
myositis (n = 1), discrete intranuclear or cytoplasmic ubiquitin-positive
inclusions were not observed. Rimmed vacuoles were not seen either by light
microscopy or ubiquitin immunostaining in any of the eight cases. Occasional
myofibers from all eight cases showed diffuse, positive muscle fiber staining.
Although not present in all cases, evidence of ubiquitin-positive myocytic
intranuclear or cytoplasmic inclusions or positive-staining rimmed vacuoles
in
the setting of an inflammatory myopathy may be suggestive of a diagnosis of
inclusion body myositis. Use of ubiquitin immunohistochemistry may be useful
in
cases in which frozen tissue or tissue processed for electron microscopy is
not
available, and IBM is suspected. Light or electron microscopic evidence of
mitochondrial abnormalities were noted in a significant subset of patients (13
of 30; 43%) of patients with IBM.
PMID: 9269823 [PubMed - indexed for MEDLINE]
338: Neurol Clin. 1997 Aug;15(3):615-48.
Idiopathic inflammatory myopathies.
Amato AA, Barohn RJ.
Department of Neurology, University of Texas Health Science Center at San
Antonio, San Antonio, Texas 78284-7883, USA.
Dermatomyositis, polymyositis, and inclusion body myositis are the major
categories of idiopathic inflammatory myopathy. These inflammatory myopathies
are distinct clinically, histologically, and pathogenically. Features of
dermatomyositis and polymyositis can overlap with those of other autoimmune
connective tissue diseases. In this article, the authors review the
characteristic features of these myopathies, update the recent developments
in
this area, and provide a framework for treatment.
Publication Types:
Review
Review, Tutorial
PMID: 9227956 [PubMed - indexed for MEDLINE]
339: Neuroreport. 1997 Jul 7;8(9-10):2155-8.
Beta APP gene transfer into cultured human muscle induces inclusion-body
myositis aspects.
Askanas V, McFerrin J, Alvarez RB, Baque S, Engel WK.
Department of Neurology, University of Southern California, School of Medicine,
Good Samaritan Hospital, Los Angeles 90017-1912, USA.
Direct transfer of the beta-amyloid precursor protein (beta APP) gene into
cultured normal human muscle, using recombinant adenovirus vector, was
sufficient to induce several of the typical light microscopic, electron
microscopic (EM), and EM-immunochemical aspects of the inclusion-body myositis
(IBM) phenotype, including congophilia, clusters of amyloid-beta-positive 6-10
nm filaments, and 15-21 nm tubulofilamentous inclusions in the nuclei. Our
results suggest that excessive production of intracellular beta APP may play
an
important role in the pathogenic cascade leading to the IBM phenotype.
PMID: 9243602 [PubMed - indexed for MEDLINE]
340: Brain. 1997 Jun;120 ( Pt 6):929-38.
Cytotoxic mechanisms in inflammatory myopathies. Co-expression of Fas and
protective Bcl-2 in muscle fibres and inflammatory cells.
Behrens L, Bender A, Johnson MA, Hohlfeld R.
Department of Neuroimmunology, Max-Planck Institute, Martinsried, Germany.
Expression of the Fas 'death receptor', Fas (CD95/APO-1) renders cells
susceptible to programmed cell death ('apoptosis'), whereas Bcl-2 protects cells
from apoptosis. Using fluorescence immunohistochemistry, we analysed Fas and
Bcl-2 expression in muscle from five patients with polymyositis (PM), four
patients with inclusion body myositis (IBM), three patients with dermatomyositis
(DM), three patients with Duchenne muscular dystrophy (DMD) and three
nonmyopathic controls. Fas (CD95) and Bcl-2 were not detected in control muscle,
but expressed in muscle fibres and inflammatory cells in PM, IBM, DM and DMD.
The proportion of Fas+ muscle fibres ranged from < 1 to 50%, and was higher
in
PM and IBM than in DM and DMD. On average, the Fas+ muscle fibres were smaller
(median diameter, 10 microns; range, 7-32 microns) than the Fas- fibres (median,
36 microns; range, 10-60 microns). Less than 10% of the Fas+ muscle fibres
co-expressed the regeneration marker CD56 (neural cell adhesion molecule N-CAM).
In PM and IBM, the proportion of Fas+ muscle fibres was higher among fibres
invaded or contacted by T cells than among fibres not contacted by T cells (P
<
0.01). The proportion of Fas+ fibres co-expressing Bcl-2 was 76 +/- 16% in PM,
100% in IBM and 63 +/- 23% in DM. Fas and Bcl-2 expression was also noted in
inflammatory cells in PM, IBM, DM and DMD. Using the terminal
deoxytransferase-catalysed DNA nick end labelling technique for detection of
nuclear DNA fragmentation, none of myonuclei, and < 0.1% of inflammatory
cell
nuclei, showed signs of apoptosis. Our results suggest that, although Fas
expression confers susceptibility to Fas-mediated apoptosis, Fas-expressing
muscle fibres and inflammatory cells are protected by the anti-apoptotic protein
Bcl-2.
PMID: 9217678 [PubMed - indexed for MEDLINE]
341: Muscle Nerve. 1997 Jun;20(6):651-64.
Treatment of inflammatory myopathies.
Mastaglia FL, Phillips BA, Zilko P.
Australian Neuromuscular Research Institute and Department of Medicine, Queen
Elizabeth II Medical Centre, Perth, Australia.
The treatment of the immune-mediated inflammatory myopathies remains largely
empirical. Corticosteroids are usually effective in polymyositis and
dermatomyositis but may need to be combined with methotrexate or azathioprine
in
some patients. Intravenous immunoglobulin (IVIg) is effective as add-on therapy
in some patients not adequately controlled with steroids or immunosuppressive
agents, but further controlled trials of IVIg are necessary to define the
indications and optimal dose regimens. Cyclophosphamide, cyclosporin, or
chlorambucil may be effective in patients with refractory polymyositis or
dermatomyositis. Low-dose whole body or lymphoid irradiation is a last option
in
severely disabled patients resistant to all other treatments. As a small
proportion of patients with inclusion body myositis respond to corticosteroid
or
immunosuppressive therapy, a 3-6-month trial of such therapy is justified in
this condition. More specific immunotherapy for these disorders awaits
identification of the target antigens and further clarification of the
immunopathogenetic mechanisms.
Publication Types:
Review
PMID: 9149071 [PubMed - indexed for MEDLINE]
342: J Neurol. 1997 May;244(5):277-87.
Inflammatory myopathies and systemic disorders: a review of immunopathogenetic
mechanisms and clinical features.
Mantegazza R, Bernasconi P, Confalonieri P, Cornelio F.
Department of Neuromuscular Diseases, C. Besta National Neurological Institute,
Milan, Italy. mantega@imiucca.csi.unimi.it
The inflammatory myopathies are a heterogeneous group of muscle diseases
characterized by muscle degeneration mediated by inflammatory processes. They
may be idiopathic, as in polymyositis, dermatomyositis and inclusion body
myositis, or associated with systemic disorders such as malignancies, overlap
syndromes, and retroviral infection. The pathogenesis of each disease is
discussed together with more recent molecular and cellular immunology findings.
Salient diagnostic, clinical and pharmacological features are also reviewed.
Publication Types:
Review
Review, Tutorial
PMID: 9178151 [PubMed - indexed for MEDLINE]
343: Arthritis Rheum. 1997 May;40(5):865-74.
Cytokine production in muscle tissue of patients with idiopathic inflammatory
myopathies.
Lundberg I, Ulfgren AK, Nyberg P, Andersson U, Klareskog L.
Karolinska Hospital, Stockholm, Sweden.
OBJECTIVE: To study cytokine expression in muscle tissues of patients with
inflammatory myopathies and to compare the profiles of patients with
polymyositis (PM), inclusion body myositis (IBM), and dermatomyositis (DM).
METHODS: We performed indirect immunohistochemistry studies of muscle tissue
sections with a panel of 16 different cytokine-specific monoclonal antibodies,
directed against interleukin-1alpha, (IL-1alpha), IL-1beta, IL-1 receptor
antagonist (IL-1Ra), IL-2, IL-3, IL-4, IL-6, IL-8, IL-10, IL-13,
interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha),
granulocyte-macrophage colony-stimulating factor (GM-CSF), transforming growth
factor beta1 (TGF beta1), TGF beta2, and TGF beta3 in 5 untreated patients each
with PM, DM, and IBM and in 4 normal controls. Fresh frozen muscle tissue
sections were fixed in formaldehyde before the procedure. The use of saponin
as
a detergent to permeabilize the cell membranes enabled identification of
intracellular cytokine production. RESULTS: The most prominent finding was the
expression of IL-1alpha observed in all patients but in none of the normal
controls. In all patients with PM, DM, and IBM, IL-1alpha was expressed in
endothelial cells of capillaries, arterioles, and venules in areas surrounded
by
inflammatory cells, and also in areas with no or scarce inflammatory cells in
both endomysium and perimysium. Furthermore, IL-1alpha was also expressed in
mononuclear inflammatory cells in all 15 cases. IL-1beta was observed in
inflammatory cells in 10 of the 15 patients but, in contrast to IL-1alpha, it
was not expressed in blood vessel walls. TGF beta1, TGF beta2, and TGF beta3
were strongly positive in all 15 patients, but only scattered cells were
positive in the normal controls. The remaining cytokines were observed only
in
relatively few cells and only in occasional patients (although the patients
were
selected for the presence of large infiltrates), and in none of the controls.
The patterns were similar in PM, DM, and IBM. CONCLUSION: Cytokine expression
in
muscle tissue of patients with inflammatory myopathy is dominated by IL-1alpha,
IL-1beta, and TGF beta1-3. The predominant IL-1alpha expression in the blood
vessels indicates an importance of the endothelial cells in the inflammatory
process in PM, IBM, and DM. A sustained, local release of T cell-derived
cytokines may not be a requirement for tissue injury in the inflammatory
myopathies. There does not appear to be a qualitative difference in cytokine
expression patterns in PM, IBM, and DM.
PMID: 9153548 [PubMed - indexed for MEDLINE]
344: Ann Intern Med. 1997 May 1;126(9):721-30.
Comment in:
Ann Intern Med. 1997 Dec 15;127(12):1130.
Ann Intern Med. 1997 Dec 15;127(12):1130.
Intravenous immune globulin therapy for neurologic diseases.
Dalakas MC.
National Institute of Neurological Disorders and Stroke, National Institutes
of
Health, Bethesda, MD 20892-1382, USA.
High-dose intravenous immune globulin (IVIg) has emerged as an important therapy
for various neurologic diseases. Different interpretations of clinical trial
results; the expected benefit of IVIg compared with that of alternate therapies;
and issues about IVIg's safety, cost, and mechanisms of action have raised
concern and uncertainty among practitioners. To clarify these areas, this paper
examines the clinical, serologic, and immunologic data on more than 110 patients
with various autoimmune neurologic diseases who received IVIg during the past
6
years at the National Institute of Neurological Disorders and Stroke. It also
reviews work by other investigators on the efficacy, risks, benefits, and
mechanisms of the action of IVIg in these diseases. In controlled clinical
trials, IVIg has been effective in treating the Guillain-Barre syndrome,
multifocal motor neuropathy, chronic inflammatory demyelinating polyneuropathy,
and dermatomyositis. In other controlled or open-label trials and case reports,
IVIg produced improvement in several patients with the Lambert-Eaton myasthenic
syndrome and myasthenia gravis but had a variable, mild, or unsubstantiated
benefit in some patients with inclusion-body myositis, paraproteinemic IgM
demyelinating polyneuropathy, certain intractable childhood epilepsies,
polymyositis, multiple sclerosis, optic neuritis, and the stiff-man syndrome.
The primary adverse reaction was headache; aseptic meningitis, skin reactions,
thromboembolic events, and renal tubular necrosis occurred rarely. The most
relevant immunomodulatory actions of IVIg, operating alone or in combination,
are inhibition of complement deposition, neutralization of cytokines, modulation
of Fc-receptor-mediated phagocytosis, and down-regulation of autoantibody
production. Therapy with IVIg is effective for certain autoimmune neurologic
diseases, but its spectrum of efficacy has not been fully established.
Additional controlled clinical trials are needed.
Publication Types:
Review
PMID: 9139559 [PubMed - indexed for MEDLINE]
345: Neuropathol Appl Neurobiol. 1997 Apr;23(2):132-40.
Interleukin-1 expression in inflammatory myopathies: evidence of marked
immunoreactivity in sarcoid granulomas and muscle fibres showing ischaemic and
regenerative changes.
Authier FJ, Mhiri C, Chazaud B, Christov C, Cherin P, Barlovatz-Meimon G,
Gherardi RK.
Groupe d'Etude et de Recherche sur le Muscle et le Nerf (GERMEN), Universite
Paris XII-Val de Marne, Creteil, France.
The most frequent autoimmune adult inflammatory myopathies are dermatomyositis,
polymyositis, inclusion body myositis, and sarcoid myopathy. Interleukin-1
(IL-1) is a pleiotropic molecule, implicated in the inflammatory process, but
also in tissue protection and remodelling. We evaluated the immunocytochemical
expression of [L,-1alpha and beta in frozen muscle biopsy specimens from
patients with dermatomyositis (15 cases), polymyositis (five cases), inclusion
body myositis (five cases) and sarcoid myopathy (five cases). Positive
immunoreactivities, were observed in both inflammatory cells and muscle fibres.
Specificity of the immunostaining was assessed by Western blot experiments.
IL-1
positive inflammatory cells were rare in polymyositis and inclusion body
myositis, moderately abundant in dermatomyositis, and prominent in sarcoid
myopathy granulomas. In sarcoid myopathy, 24.6 +/- 4.1% inflammatory cells were
IL-1alpha-positive and 45.2 +/- 2.6% were IL-1beta-positive. IL-1 positive
muscle fibres were mainly observed in dermatomyositis, usually remote from
inflammatory infiltrates. Positive immunostaining for IL-1 was observed in
fibres showing ischaemic punched-out vacuoles, that correspond to areas of
myosinolysis, in atrophic perifascicular fibres, and in fibres located within
healing microinfarcts. All NCAM-positive regenerating fibres were IL-1 positive.
We conclude that: (i) IL-1 is expressed in granulomas of sarcoid myopathy, which
is in keeping with the role ascribed to IL-1 in the formation of granulomas:
(ii) IL-1 is expressed by muscle fibres undergoing ischaemic damage: and (iii)
IL-1 expression by muscle fibres is associated with myofibrillar protein
breakdown and regeneration.
PMID: 9160898 [PubMed - indexed for MEDLINE]
346: Brain. 1997 Apr;120 ( Pt 4):653-61.
An inflammatory, familial, inclusion body myositis with autoimmune features
and
a phenotype identical to sporadic inclusion body myositis. Studies in three
families.
Sivakumar K, Semino-Mora C, Dalakas MC.
Neuromuscular Diseases Section, National Institutes for Neurological Disorders
and Stroke, National Institute of Health, Bethesda, Maryland 20892, USA.
We describe the occurrence of an inflammatory inclusion body myositis in
siblings of a single generation in three separate families. The disease in this
total of seven patients was characterized by selective and early involvement
of
forearm and finger flexors, confirmed by MRI, and weakness of the quadriceps,
triceps and foot extensors. Muscle biopsies in at least two members from each
family showed endomysial inflammation, red-rimmed vacuoles, intracellular
amyloid deposition and 15-18-nm tubulo-filaments within the vacuolated muscle
fibres. Immunocytochemistry on serial muscle biopsy sections demonstrated an
abundance of CD8+ cells invading non-necrotic, MHC-1-expressing muscle fibres.
Immunogenetic studies showed the presence of the DR3 allele (DRB1*0301/0302)
in
all seven patients. The combination of the clinical, histological,
immunopathological and immunogenetic features indicate that these patients have
a disease identical to sporadic inclusion body myositis (s-IBM). We conclude
that the classic, inflammatory, s-IBM can also occur in families (familial
inclusion body myositis), in a pattern analogous to the familial occurrence
of
other autoimmune neurological diseases such as myasthenia gravis and multiple
sclerosis. These observations strengthen the view that s-IBM behaves like other
autoimmune diseases and has disease susceptibility linked to the DR3 allele.
PMID: 9153127 [PubMed - indexed for MEDLINE]
347: Ann Neurol. 1997 Apr;41(4):548-51.
Comment in:
Ann Neurol. 1997 Apr;41(4):421-2.
Various types of hereditary inclusion body myopathies map to chromosome 9p1-q1.
Argov Z, Tiram E, Eisenberg I, Sadeh M, Seidman CE, Seidman JG, Karpati G,
Mitrani-Rosenbaum S.
Department of Neurology, Hadassah University Hospital, The Hebrew
University-Hadassah Medical School, Jerusalem, Israel.
Hereditary inclusion body myopathies are a clinically heterogeneous group of
disorders characterized by adult-onset, slowly progressive muscle weakness and
typical histopathology: rimmed vacuoles and filamentous inclusions. The
disorders are usually inherited as an autosomal recessive trait. The gene
responsible for the disease found in Iranian Jews, who present with
quadriceps-sparing myopathy, maps to chromosome 9p1-q1. We address the question
of whether hereditary inclusion myopathies are genetically as well as clinically
heterogeneous disorders. We mapped the disease gene segregating in two families
of Afghani-Jewish and one family of Iraqi-Jewish descent to the chromosome 9
locus. Similarly, the disease gene segregating in a non-Jewish family from India
mapped to the same locus. By contrast, the disease gene segregating in a
French-Canadian family in which affected individuals had central nervous system
involvement as well as hereditary inclusion body myopathy, did not map to this
locus. We conclude that many but not all forms of autosomal recessive hereditary
inclusion body myopathy are caused by a gene defect that maps to chromosome
9p1-q1.
PMID: 9124813 [PubMed - indexed for MEDLINE]
348: Ann Neurol. 1997 Apr;41(4):421-2.
Comment on:
Ann Neurol. 1997 Apr;41(4):548-51.
New developments in hereditary inclusion body myopathies.
Askanas V.
Publication Types:
Comment
Editorial
PMID: 9124797 [PubMed - indexed for MEDLINE]
349: Neurology. 1997 Apr;48(4):863-6.
Magnetic resonance imaging of the forearm as a diagnostic aid in patients with
sporadic inclusion body myositis.
Sekul EA, Chow C, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, MD 20892-1382, USA.
Because weakness of finger flexors and atrophy of the forearms are frequent
findings in inclusion body myositis (IBM) patients, we examined the forearm
muscles by MRI to determine if involvement of the distal musculature has a
characteristic diagnostic pattern. We performed MRI of the forearms in 21
randomly selected patients with histologically confirmed IBM and in 9 patients
with other, age-matched, neuromuscular diseases who served as controls. In
addition, we analyzed axial images of 10 individual forearm muscles blindly
without knowledge of the clinical status or diagnosis of the patients.
T1-weighted MR images showed marbled brightness of the flexor digitorum
profundus (FDP) in 20 of 21 IBM patients, of the flexor carpi ulnaris in 7,
the
flexor digitorum superficialis (FDS) in 6, the flexor carpi radialis in 4, the
supinator in 3, and the brachioradialis in 1. The extensors were normal. The
abnormalities of the FDP correlated with the severity but not the duration of
the disease and in some patients preceded overt clinical signs of FDP weakness.
In contrast, the FDS was spared even late in the disease. We conclude that
selective involvement of the FDP may occur early in the course of IBM and can
be
easily demonstrated by MRI in up to 95% of patients. Because selective FDP
involvement appears to be a very frequent and characteristic finding in patients
with IBM, MRI of the forearm is a useful noninvasive test in supporting the
diagnosis of sporadic IBM.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 9109868 [PubMed - indexed for MEDLINE]
350: Arch Phys Med Rehabil. 1997 Mar;78(3):327-9.
Inclusion body myositis and transitional cell carcinoma of the bladder:
significant resolution of symptoms after tumor excision.
Jensen ML, Wieting JM, Andary MT, Fankhauser MJ, Jones MJ.
Department of Physical Medicine and Rehabilitation, Michigan Slato University,
East Lansing 48224-1316, USA.
Inclusion body myositis (IBM) is a separate class of the inflammatory myopathies
with recently proposed clinical and pathological diagnostic criteria. An
association between inflammatory myopathies and malignancy has been questioned
in the literature. Recent reviews of the inflammatory myopathies suggest that
only dermatomyositis is associated with malignancy. The largest study to date
of
patients with IBM found that 15% had a malignancy (6 of 40). We report the first
documented case of IBM and concurrent transitional cell carcinoma of the
bladder. We suggest that a causal relationship between IBM and malignancy may
exist because of significantly improved functional strength gained after tumor
removal.
Publication Types:
Case Reports
Review
Review of Reported Cases
PMID: 9084359 [PubMed - indexed for MEDLINE]
351: Neurology. 1997 Mar;48(3):712-6.
Comment in:
Neurology. 1997 Mar;48(3):567-8.
Treatment of inclusion-body myositis with IVIg: a double-blind,
placebo-controlled study.
Dalakas MC, Sonies B, Dambrosia J, Sekul E, Cupler E, Sivakumar K.
Neuromuscular Diseases Section, Medical Neurology Branch, NINDS, National
Institutes of Health, Bethesda, MD 20892-1382, USA.
We randomized 19 patients with inclusion-body myositis (IBM) to a double-blind,
placebo-controlled, crossover study using monthly infusions of 2 g/kg
intravenous immunoglobulin (IVIg) or placebo for 3 months. Patients crossed
over
to the alternate treatment after a washout period. We evaluated responses at
baseline and at the end of each treatment period using expanded (0-10) MRC
scales, the Maximum Voluntary Isometric Contraction (MVIC) method, symptom and
disability scores, and quantitative swallowing studies. We calculated the
differences in scores between IVIg and placebo from baseline to end of
treatment. Of the 19 patients, 9 (mean age, 61.2 years; mean disease duration,
5.6 years) were randomized to IVIg and 10 (mean age, 66.1 years; mean disease
duration, 7.4 years) to placebo. During IVIg the patients gained a mean of 4.2
(-16 to +39.8) MRC points, and during placebo lost 2.7 (-10 to +8) points (p
<
0.1). These gains were not significant. Similar results were obtained with the
MRC and MVIC scores when the patients crossed to the alternate treatment. Six
patients had a functionally important improvement by more than 10 MRC points
that declined when crossed over to placebo. Limb-by-limb analysis demonstrated
that during IVIg the muscle strength in 39% of the lower extremity limbs
significantly increased compared with placebo (p < 0.05), while a simultaneous
decrease in 28% of other limbs was detected. The clinical importance of these
minor gains is unclear. The duration of swallowing functions measured in seconds
with ultrasound improved statistically in the IVIg-randomized patients (p <
0.05) compared with placebo. Although the study did not establish efficacy of
IVIg, possibly because of the small sample size, the drug induced functionally
important improvement in 6 (28%) of the 19 patients. Whether the modest gains
noted in certain muscle groups justify the high cost of trying IVIg in IBM
patients at a given stage of the disease remains unclear.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 9065553 [PubMed - indexed for MEDLINE]
352: Neurology. 1997 Mar;48(3):567-8.
Comment on:
Neurology. 1997 Mar;48(3):712-6.
The therapeutic dilemma of inclusion body myositis.
Barohn RJ.
Publication Types:
Comment
Editorial
PMID: 9065526 [PubMed - indexed for MEDLINE]
353: Scand J Rheumatol. 1997;26(2):104-6.
Occurrence of polymyositis in the county of Gavleborg, Sweden.
Weitoft T.
Department of Internal Medicine, Lanssjukhuset Gavle, Sweden.
Through register research 21 new cases (10 male, 11 female) of
polymyositis/dermatomyositis during the period 1984-1993 in the county of
Gavleborg, Sweden, were identified. The case records were studied
retrospectively. Inclusion body myositis was found in three cases and overlap
syndrome in seven cases. Three patients had associated malignant disease. The
annual incidence was estimated to 7.6 cases/million people. The clinical
features are described. 19 patients were given steroid treatment, and
azathioprin was the most used additive immunosuppressive drug. All patients
could be followed for at least two years, and during this period three patients
died (all of cancer disease). Remission and withdrawal of medication were
achieved in five cases. The results of the study corresponds to previous
investigations with similar design.
PMID: 9137324 [PubMed - indexed for MEDLINE]
354: Brain. 1997 Jan;120 ( Pt 1):39-45.
Polymyositis with cytochrome oxidase negative muscle fibres. Early quadriceps
weakness and poor response to immunosuppressive therapy.
Blume G, Pestronk A, Frank B, Johns DR.
Department of Neurology, Washington University School of Medicine, St. Louis,
MO, USA.
We evaluated 10 patients with histologically typical polymyositis except for
an
excess of muscle fibres with absent cytochrome oxidase (COX) staining. No
biopsies had vacuoles or congophilic material in muscle fibres. All patients
presented with a history of slowly progressive weakness. The average age of
onset was 9 years older than a group of polymyositis patients with normal COX
staining of muscle fibres. Selective weakness of knee extension was a prominent
and disabling feature in most patients. Serum creatine kinase was usually mildly
elevated (363 +/- 115 U/l) but at levels lower than those in other patients
with
polymyositis. Mitochondrial DNA analysis showed multiple deletions in 90% of
muscles from patients with excessive numbers of COX-negative muscle fibres,
a
prevalence significantly greater than the 22% figure for controls (P = 0.005).
As a group, the patients responded poorly to immunosuppressive therapy. We
conclude that patients with polymyositis and an excess of COX-negative muscle
fibres, but no inclusion bodies, have common features including selective
quadriceps weakness, mitochondrial pathology by histochemical and DNA analysis
and a poor response to immunosuppressive therapy. Some of these features are
shared with inclusion body myositis (IBM) and this entity cannot be entirely
excluded as vacuoles may not be present in all muscle tissue in IBM patients.
Evaluation of the COX activity in muscle fibres of patients with inflammatory
myopathies provides useful prognostic information regarding the likelihood of
improved strength after immunosuppressive treatment.
Publication Types:
Case Reports
PMID: 9055796 [PubMed - indexed for MEDLINE]
355: Neurology. 1997 Jan;48(1):29-33.
Inclusion body myositis: no evidence for a neurogenic component.
Luciano CA, Dalakas MC.
Electromyography Section, National Institute of Neurological Disorders and
Stroke, National Institutes of Health, Bethesda, MD 20892-1382, USA.
Because electrophysiologic, clinical, and histopathologic observations have
suggested that inclusion body myositis (IBM) may have a coexistent neurogenic
component, we used macro-electromyography (macro-EMG) to search for changes
in
the motor unit territory and signs of reinnervation. We studied 11 patients,
aged 53 to 77 years (mean, 65.2 years), with typical, nonfamilial IBM lasting
a
mean of 8.5 years, and eight healthy volunteers aged 54 to 70 years (mean, 64.6
years), as control subjects. Nerve conduction studies showed focal abnormalities
in 5 of the patients, but no evidence of a polyneuropathy. Concentric needle
EMG
in various proximal and distal muscles of the upper and lower limbs revealed
short- or long-duration complex motor unit potentials (MUPs) or a mixture of
both types of MUPs. Macro-EMG studies in the tibialis anterior muscle showed
smaller macro-MUP amplitudes and areas in patients than in normal subjects.
Four
patients had abnormal macro-EMG studies with an increased number of small
macro-MUPs, 1 patient had an equivocal study with large-amplitude but
normal-area macro-MUPs, and the remaining 6 patients had normal studies. These
findings are consistent with a primary muscle disorder similar to those seen
in
other myopathies. We conclude that macro-EMG does not support a coexistent
neurogenic component in patients with IBM compared with normal subjects of
similar age.
PMID: 9008489 [PubMed - indexed for MEDLINE]
356: Ann Neurol. 1997 Jan;41(1):100-4.
Inclusion body myositis and paraproteinemia: incidence and immunopathologic
correlations.
Dalakas MC, Illa I, Gallardo E, Juarez C.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, Bethesda, MD 20892-1382, USA.
Serum from 70 patients with sporadic inclusion body myositis (IBM) was subjected
to agarose gel immunofixation electrophoresis. The IgG extracted from 9 patients
with monoclonal proteins, 3 without, and 2 control subjects and was purified,
biotinylated, and applied to muscle biopsy sections for immunocytochemistry
and
to purified muscle protein fractions for immunoblots. Sixteen of 70 (22.8%)
patients with IBM, compared with 2% of age-matched controls, had a monoclonal
gammopathy characterized as IgG lambda in 9 patients, IgG kappa in 4, IgM kappa
in 2, and IgA lambda in 1. The mean age of IBM patients with gammopathy was
60.6
years (range, 35-77 years), compared with 66.1 years (range, 42-80 years) of
the
IBM patients without gammopathy. The IgG of the patients, more often than that
of the control subjects, immunostained myonuclei and recognized various muscle
proteins of 35 to 145 kd. We conclude that IBM, regardless of age, is frequently
associated with monoclonal gammopathies, which often recognize various muscle
components, especially myonuclei, suggesting disturbed immunoregulation.
PMID: 9005871 [PubMed - indexed for MEDLINE]
357: Neuroreport. 1996 Dec 20;8(1):153-8.
Increase of nitric oxide synthases and nitrotyrosine in inclusion-body myositis.
Yang CC, Alvarez RB, Engel WK, Askanas V.
Department of Neurology, University of Southern California School of Medicine,
Good Samaritan Hospital, Los Angeles 90017-1912, USA.
To investigate the possible role of nitric oxide (NO)-induced 'oxidative stress'
in the pathogenesis of inclusion-body myositis (IBM), we immunostained muscle
biopsies of 12 patients with IBM with isoform-specific antibodies against the
neuronal and inducible forms of nitric oxide synthase and with antibodies
against nitrotyrosine. Between 70 and 80% of IBM vacuolated muscle fibers
contained inclusions strongly immunoreactive with all three antibodies, which
by
immuno-electronmicroscopy co-localized mainly to cytoplasmic paired-helical
filaments, and also to amorphous structures and floccular material. Excess
intracellular NO can combine with superoxide to produce highly reactive
peroxynitrite which can nitrate tyrosines of proteins. The presence of
nitrotyrosine is indicative of NO-induced "oxidative stress'. Our data
suggest
that this mechanism may play a pathogenic role in IBM.
PMID: 9051771 [PubMed - indexed for MEDLINE]
358: Rev Rhum Engl Ed. 1996 Dec;63(11):797-800.
The three groups of polymyositis.
Serratrice G.
Publication Types:
Editorial
PMID: 9010966 [PubMed - indexed for MEDLINE]
359: Brain. 1996 Dec;119 ( Pt 6):1887-93.
Inclusion body myositis in HIV-1 and HTLV-1 infected patients.
Cupler EJ, Leon-Monzon M, Miller J, Semino-Mora C, Anderson TL, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurologic Disorders
and
Stroke, NIH, Bethesda, Maryland 20892-1382, USA.
Sporadic inclusion body myositis (IBM) is the most common inflammatory myopathy
affecting patients over the age of 50 years. Dysimmune and degenerative
aetiologies have been postulated, but viral infections have not been associated
with the disease. Two HIV-I (human immunodeficiency virus type 1) infected men
and one woman infected with HTLV-1 (human T cell leukaemia virus type 1)
developed progressive proximal muscle weakness unrelated to antiretroviral
therapy. Their muscle biopsies were studied by light and electron microscopy,
by
immunocytochemistry to determine the expression of major histocompatibility
complex (MHC) molecules and identify the type of infiltrating cells and T cell
receptor (TCR) subunits, and by reverse transcription-polymerase chain reaction
(RT-PCR) and single or double immunocytochemistry to search for retrovirally
infected endomysial cells. The clinical features were consistent with sporadic
IBM. The muscle biopsies showed primary endomysial inflammation, red-rimmed
vacuoles, amyloid deposits, eosinophilic inclusions, and small round fibres
in
groups, all diagnostic of IBM. The muscle fibres expressed MHC class-1 antigens
and were invaded primarily by CD8+ T-lymphocytes preferentially bearing TCR
V
beta 5.1 and V beta 13 chains. The HIV-1 or HTLV-1 antigens were detected only
on endomysial macrophages on or around muscle fibres, but not within the muscle
fibres. We conclude that IBM occurs in HIV-1 and HTLV-1 infected individuals
and
has a clinical, histological and immunological pattern identical to sporadic
IBM
in the non-retrovirally infected patients. Retroviruses do not directly infect
the muscle, but persistent retroviral infections may provide superantigenic
stimulation and trigger an endomysial inflammatory response identical to that
occurring in sporadic IBM.
Publication Types:
Case Reports
PMID: 9009995 [PubMed - indexed for MEDLINE]
360: Ann Neurol. 1996 Dec;40(6):864-72.
Apolipoprotein E and apolipoprotein E messenger RNA in muscle of inclusion
body
myositis and myopathies.
Mirabella M, Alvarez RB, Engel WK, Weisgraber KH, Askanas V.
University of Southern California Neuromuscular Center, Department of Neurology,
University of Southern California School of Medicine, Good Samaritan Hospital,
Los Angeles 90017-1912, USA.
Sporadic inclusion body myositis and the hereditary inclusion body myopathies
are severe, progressive muscle diseases, characterized pathologically by
vacuolated muscle fibers containing paired helical filaments. We immunostained
muscle biopsy specimens from sporadic inclusion body myositis, hereditary
inclusion body myopathy, disease control, and normal patients with several
antibodies against apolipoprotein E (ApoE). Approximately 80 to 90% of the
vacuolated muscle fibers of sporadic inclusion body myositis contained
well-defined, strongly immunoreactive ApoE inclusions. In hereditary inclusion
body myopathy, only rare vacuolated fibers had immunoreactive inclusions,
whereas most had diffuse cytoplasmic ApoE immunoreactivity. Ultrastructurally,
ApoE immunoreactivity in sporadic myositis was localized mainly to the paired
helical filaments. By contrast, in the hereditary form, ApoE immunoreactivity
occurred on material in close proximity to the paired helical filaments, but
never was on the paired helical filaments. In both muscle diseases, ApoE was
also on the 6- to 10-nm filaments and amorphous material. In the sporadic form,
ApoE-immunoreactive deposits colocalized with Congo red-positive deposits;
however, in muscle fibers from patients with hereditary disease there was no
congophilia. ApoE messenger RNA was not detectable in muscle fibers from
patients with hereditary or sporadic disease but was expressed abundantly in
muscle macrophages. In all control and inclusion body myositis or myopathy
biopsy specimens, ApoE immunoreactivity was strong at the postsynaptic domain
of
neuromuscular junctions; nonjunctional regions of normal fibers were negative
for ApoE. ApoE immunoreactivity occurred diffusely in regenerating muscle
fibers, a subset of which had detectable ApoE messenger RNA.
PMID: 9007091 [PubMed - indexed for MEDLINE]
361: Ann Neurol. 1996 Dec;40(6):826-8.
Apolipoprotein E and inclusion body myositis.
Garlepp MJ, Mastaglia FL.
Publication Types:
Editorial
PMID: 9007086 [PubMed - indexed for MEDLINE]
362: J Neuroimmunol. 1996 Dec;71(1-2):227-9.
Increased in vitro uptake of the complement C3b in the serum of patients with
Guillain-Barre syndrome, myasthenia gravis and dermatomyositis.
Basta M, Illa I, Dalakas MC.
Neuromuscular Disease Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
To examine the role of complement in certain autoimmune neuromuscular diseases,
we used an in-vitro quantitative complement uptake assay that allows measurement
of the capacity of patients' sera to deposit fragments of the third complement
component onto sensitized targets. C3 uptake was significantly higher in
patients with active dermatomyositis, Guillain-Barre syndrome and myasthenia
gravis, compared to inclusion body myositis and controls. The in-vitro C3 uptake
assay supports the role of C3b neoantigen and Membranolytic Attack Complex
deposition in the target tissues and may be a useful tool to monitor disease
activity in patients with complement-mediated neurological disorders.
PMID: 8982124 [PubMed - indexed for MEDLINE]
363: J Neuropathol Exp Neurol. 1996 Dec;55(12):1205-9.
MHC class I-mediated cytotoxicity does not induce apoptosis in muscle fibers
nor
in inflammatory T cells: studies in patients with polymyositis, dermatomyositis,
and inclusion body myositis.
Schneider C, Gold R, Dalakas MC, Schmied M, Lassmann H, Toyka KV, Hartung HP.
Department of Neurology, Julius-Maximilians-Universitat Wurzburg.
Apoptosis plays a crucial role in natural recovery from T cell-mediated
autoimmune disorders of the nervous system. Whether apoptosis also occurs in
human inflammatory myopathies is unclear. In this study we examined muscle
biopsy specimens from untreated patients with polymyositis (n = 12),
dermatomyositis (n = 12), and inclusion body myositis (n = 12) for the presence
of apoptosis using morphological criteria and DNA fragmentation by in situ
tailing. In all these disorders, only rare T cells exhibited signs of apoptosis
by nuclear morphology and in situ labeling techniques. Although Fas-expression
was upregulated in a few inflammatory cells, increased apoptosis of the
surrounding T cells was not observed. Further, nuclei of degenerating muscle
fibers did not show morphological signs of apoptosis and were not labeled by
the
tailing reaction. We conclude that in the inflammatory myopathies, T cell
inflammation is not cleared by apoptosis and affected muscle fibers do not die
by apoptosis. The observations are consistent with the non-self-limited nature
of these disorders and suggest that, in contrast to the nervous system, the
local microenvironment in muscle does not deliver pro-apoptotic stimuli.
PMID: 8957443 [PubMed - indexed for MEDLINE]
364: Muscle Nerve. 1996 Dec;19(12):1605-7.
Apolipoprotein E allele frequencies in sporadic inclusion body myositis.
Love S, Nicoll JA, Lowe J, Sherriff F.
Department of Neuropathology, Frenchay Hospital, Bristol, United Kingdom.
PMID: 8941276 [PubMed - indexed for MEDLINE]
365: Curr Opin Rheumatol. 1996 Nov;8(6):514-20.
Genetics of the idiopathic inflammatory myopathies.
Garlepp MJ.
Australian Neuromuscular Research Institute, Queen Elizabeth II Medical Centre,
Nedlands, Western Australia, Australia.
Genetic predisposition to development of the idiopathic inflammatory myopathies
is probably multifactorial. Major histocompatibility complex associations with
these diseases provide the strongest evidence for a genetic component. In
Caucasoids, haplotypes marked by B8/DR3 are associated with each of the clinical
subgroups, except mixed connective tissue disease (DR4). The strongest
associations are with inclusion body myositis, polymyositis in the presence
of
anti-Jo-1, and with antibodies to PM-Scl in overlap syndromes. The underlying
mechanisms of these associations are probably different. Unique major
histocompatibility complex associations are seen with other myositis-associated
autoantibodies. The association can vary between racial groups as can the type
of autoantibody produced within a disease subgroup, perhaps reflecting different
T cell receptor repertoires or different inducing agents. The mapping of a gene
for one form of hereditary inclusion body myositis to chromosome 9p1-q1 provides
a lead for the investigation of sporadic inclusion body myositis, as does the
expanding knowledge of genetic factors in Alzheimer's disease. The demonstration
of deletions of mitochondrial DNA in the muscle of patients with inclusion body
myositis raises the question of their role in the pathogenesis of the disease.
Publication Types:
Review
Review, Tutorial
PMID: 9018454 [PubMed - indexed for MEDLINE]
366: J Neurol Sci. 1996 Nov;143(1-2):46-56.
Calf enlargement in neuromuscular diseases: a quantitative ultrasound study
in
350 patients and review of the literature.
Reimers CD, Schlotter B, Eicke BM, Witt TN.
Friedrich-Baur-Institute, Department of Internal Medicine and Neurology,
Ludwig-Maximilians-University, Munich, Germany.
Calf hypertrophy is a typical clinical feature in neuromuscular diseases such
as
X-linked muscular dystrophies of Duchenne and Becker type and can be seen as
an
atypical feature in numerous other diseases. The diagnosis of calf hypertrophy
usually is based on subjective visual assessment. The aim of this prospective
study was to examine the prevalence of calf hypertrophy in a large number of
patients with various neuromuscular diseases based on quantitative ultrasound
measurement of calf muscle thickness. Additionally, true and pseudohypertrophy
should be distinguished according to the absence or presence of abnormal muscle
echointensities caused by infiltration of fat tissue. Fifty adult normal
controls and 350 patients with various neuromuscular diseases were investigated.
Absolute calf hypertrophy was diagnosed if the combined thickness of the
gastrocnemius and soleus muscles exceeded the mean value of the control persons
by at least 3.0 standard deviations (SD). Relative calf hypertrophy was
diagnosed when the ratio of the combined thicknesses of the gastrocnemius and
soleus muscles divided by the combined thicknesses of the rectus femoris and
vastus intermedius muscles lay at least 3.0 SD below the mean value of the
controls. Pseudohypertrophy was present if the echointensities of the
gastrocnemius and soleus muscles reached or exceeded 3.0 SD above the mean value
of the controls. An absolute hypertrophy of the calves was detected in 80
patients (= 22,9%; 64 true and 16 pseudohypertrophies), 16 patients exhibited
a
relative hypertrophy of the calves (= 4.6%; 12 true and 4 pseudohypertrophies).
A significantly increased portion of both absolute calf hypertrophies and
pseudohypertrophies as compared to the control group were found in juvenile
proximal spinal muscular atrophy type 3, central core disease, centronuclear
myopathy, benign X-linked muscular dystrophy of Becker type, autosomal recessive
limb girdle muscular dystrophy, acid maltase deficiency, polymyositis, and
granulomatous myositis. A significantly increased number of relative calf
hypertrophies was present in juvenile proximal spinal muscular atrophy type
3,
facioscapulohumeral muscular dystrophy, and inclusion body myositis. In the
majority of the diseases included in the study, calf hypertrophy occurred in
at
least some patients. In conclusion, calf hypertrophy is a frequent and
unspecific clinical feature in many neuromuscular diseases. Ultrasound is a
convenient method for the exact definition of calf hypertrophy.
Publication Types:
Review
PMID: 8981297 [PubMed - indexed for MEDLINE]
367: J Neuropathol Exp Neurol. 1996 Nov;55(11):1179-80.
Comment on:
J Neuropathol Exp Neurol. 1996 Jul;55(7):774-86.
Two distinct forms of hyperphosphorylated tau in sporatic versus hereditary
inclusion myopathy.
Rosenblum WI.
Publication Types:
Comment
Letter
PMID: 8939201 [PubMed - indexed for MEDLINE]
368: J Neuropathol Exp Neurol. 1996 Nov;55(11):1105-14.
Inclusion body myositis, a review.
Carpenter S.
Division of Neuropathology, Toronto Hospital Western Division, Ontario, Canada.
Publication Types:
Historical Article
Review
Review, Tutorial
PMID: 8939193 [PubMed - indexed for MEDLINE]
369: Bull Rheum Dis. 1996 Oct;45(6):1-4.
New developments in the myositis syndromes.
Kagen LJ.
Hospital for Special Surgery, New York, NY, USA.
Publication Types:
Review
PMID: 8885477 [PubMed - indexed for MEDLINE]
370: Ann Neurol. 1996 Oct;40(4):581-6.
Inclusion body myositis: clinical and pathological boundaries.
Amato AA, Gronseth GS, Jackson CE, Wolfe GI, Katz JS, Bryan WW, Barohn RJ.
Department of Neurology, Wilford Hall Medical Center, San Antonio, TX, USA.
Inclusion body myositis, polymyositis, and dermatomyositis are three distinct
categories of inflammatory myopathy. Some authorities commented on the selective
early weakness of the volar forearm muscles, quadriceps, and ankle dorsiflexors
in inclusion body myositis. The most important feature distinguishing inclusion
body myositis from the other two inflammatory myopathies is the lack of
responsiveness to immunosuppressive treatment. Although most patients with
inclusion body myositis have characteristic muscle biopsy findings, some cannot
be distinguished histologically early from polymyositis. Predicting
responsiveness to immunosuppressive medications, independent of muscle
histology, would be valuable to clinicians. We retrospectively reviewed the
pattern of weakness and other clinical features of 46 patients newly diagnosed
with either inclusion body myositis, polymyositis, or dermatomyositis.
Asymmetrical muscle weakness with prominent wrist flexor, finger flexor, and
knee extensor involvement was specific for inclusion body myositis and
unresponsive polymyositis. Male sex, lower creatine kinase levels, slower rate
of progression, and peripheral neuropathy were also more common in inclusion
body myositis and unresponsive polymyositis than in responsive polymyositis
and
dermatomyositis patients. Repeat muscle biopsy in 2 patients in the unresponsive
polymyositis group demonstrated histological features of inclusion body
myositis. We suspect that patients with clinical features of inclusion body
myositis but lacking histological confirmation may nonetheless have inclusion
body myositis. Our study supports the recently proposed criteria for definite
and possible inclusion body myositis.
PMID: 8871577 [PubMed - indexed for MEDLINE]
371: Neurology. 1996 Oct;47(4):977-84.
The spectrum of familial inclusion body myopathies in 13 families and a
description of a quadriceps-sparing phenotype in non-Iranian Jews.
Sivakumar K, Dalakas MC.
Neuromuscular Diseases Section, National Institutes for Neurological Disorders
and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
The frequency, patterns of inheritance and clinical phenotypes of inherited
myopathies with histologic features of rimmed vacuoles, tubulofilamentous
inclusions and absence of inflammation (familial and hereditary inclusion body
myopathy [f-IBM]) are poorly defined. Quadriceps sparing is a characteristic
of
f-IBM seen in the Iranian Jewish population. Among 101 patients with the feature
of a red-rimmed vacuolar myopathy, characterized as inclusion body myopathy,
seen during the last 4 years, we identified 13 families with f-IBM (12.8%
frequency when one member per family was considered). Five families had an
autosomal dominant and eight had an autosomal recessive form of inheritance.
Among the latter group, five patients with early-onset disease (two Caucasian
Americans, an Asian Indian, and two unrelated Iranian Jews) had the distinct
feature of quadriceps sparing, which was confirmed by MRI of the thighs. Their
disease began with weakness and strophy of the foot extensors, forearm flexors,
and first dorsal interossei muscles and progressed to the forearm flexors,
girdle, and axial muscles, but spared the quadriceps. Serum CK was normal.
Muscle biopsies showed rimmed vacuoles, small fibers in groups, amyloid
deposition (in one patient), tubulofilaments, and no inflammation.
Immunocytochemistry did not reveal abnormalities of various membrane or
cytoskeletal proteins. Major histocompatibility complex (MHC) class I antigen
was expressed only in a few degenerating fibers invaded by macrophages. T-cell
infiltrates were not present. We conclude that in a large referral population,
dominant and recessive hereditary and familial forms of IBM are not rare.
Quadriceps-sparing myopathy appears to be a clinically distinct, autosomal
recessive, nonimmune, distal vacuolar myopathy that is not limited to
Iranian-Jewish ethnic groups.
PMID: 8857730 [PubMed - indexed for MEDLINE]
372: Am J Gastroenterol. 1996 Sep;91(9):1845-7.
Hepatitis C and inclusion body myositis.
Alexander JA, Huebner CJ.
Department of Medicine, Burns Clinic Medical Center, Petoskey, Michigan, USA.
Hepatitis C is known to be associated with a myriad of autoimmune diseases.
Inclusion body myositis is an inflammatory myopathy of unknown etiology. We
report the first case of chronic hepatitis C with inclusion body myositis.
Publication Types:
Case Reports
PMID: 8792712 [PubMed - indexed for MEDLINE]
373: Acta Neurol Scand. 1996 Aug;94(2):110-4.
Clinicopathologic characteristics of polymyositis patients with numerous tissue
eosinophils.
Kumamoto T, Ueyama H, Fujimoto S, Nagao S, Tsuda T.
Third Department of Internal Medicine, Oita Medical University, Japan.
INTRODUCTION: We evaluated associated clinicopathologic features of polymyositis
(PM) patients with numerous tissue eosinophils. MATERIALS AND METHODS: 680
muscle biopsies were examined in our institution and eight were identified with
greater than 0.3 eosinophils per square millimeter in the inflammatory
infiltrate without concomitant peripheral eosinophilia. RESULTS: All eight
patients had typical PM, but neither dermatomyositis nor inclusion body myositis
was identified. Clinically, a large number of PM patients with eosinophils
manifested an acute- or subacute-onset of symptoms, myoglobinuria, a marked
elevation of serum creatine kinase, a good response to steroid therapy, and
a
relatively benign course compared with 26 PM patients without eosinophils.
Muscle biopsies demonstrated necrotic fibers more frequently in PM patients
with
eosinophils than in PM patients without eosinophils. Hypertrophic fibers, fiber
splitting, basophilic fibers, and lobulated fibers were less frequently observed
in PM patients with eosinophils. CONCLUSION: These results suggest that the
majority of PM patients with eosinophils may be steroid-responsive and suffer
an
acute or subacute onset of PM.
PMID: 8891055 [PubMed - indexed for MEDLINE]
374: Neuromuscul Disord. 1996 Aug;6(4):255-60.
Peripheral lymphoid tissue-like adhesion molecule expression in nodular
infiltrates in inflammatory myopathies.
De Bleecker JL, Engel AG, Butcher EC.
University Hospital, Department of Neurology, Gent, Belgium.
Non-granulomatous nodular accumulations of inflammatory cells in inflammatory
myopathies were studied to characterize adhesion mechanisms used for leukocyte
recruitment. The nodules had a B-cell-rich center surrounded by a helper
T-cell-rich peripheral zone, resembling lymph nodes. The T-cell-rich zones
harbored high-walled venules resembling high endothelial venules (HEV), whose
endothelia frequently expressed ICAM-1, VCAM-1, and less constantly E-selectin.
This endothelial adhesion molecule profile differs from that found in
polymyositis, inclusion body myositis, or dermatomyositis, but resembles that
in
lymphoid tissues. Also, the peripheral lymph node addressin, a vascular
addressin specific for peripheral lymphoid tissue HEV, was present on many HEV.
This adhesion system is probably responsible for the excessive lymphocyte
recruitment. The similar cellular organization and lymphocyte recirculation
mechanisms of the nodular infiltrates in muscle and of lymph nodes suggest that
the former may also produce antibodies.
PMID: 8887954 [PubMed - indexed for MEDLINE]
375: J Korean Med Sci. 1996 Aug;11(4):358-63.
Inclusion body myositis--a case report.
Park SH, Park HR.
Department of Pathology, Chung Ang Gil Hospital, Inchon, Korea.
Inclusion body myositis is a rare myopathy that clinically resembles a chronic
polymyositis and histopathologically is characterized by the presence of rimmed
vacuoles containing ultrastructural cytoplasmic degradation products with
filamentous intranuclear and cytoplasmic inclusions. Since clinical features
are
not uniform, histopathologic and ultrastructural studies are necessary to
confirm the diagnosis. We report a typical case of inclusion body myositis with
histopathologic and ultrastructural study. The patient was a 31 year old male
who presented with progressive weakness of both forearms, hands and lower
extremities for 10 years.
Publication Types:
Case Reports
PMID: 8878808 [PubMed - indexed for MEDLINE]
376: J Intern Med. 1996 Aug;240(2):81-4.
Incidence of rare systemic rheumatic and connective tissue diseases in Finland.
Kaipiainen-Seppanen O, Aho K.
Department of Medicine, Kuopio University Hospital, Finland.
OBJECTIVE: To obtain information on the incidence of rare systemic rheumatic
and
connective tissue diseases in Finland. DESIGN: Population-based epidemiological
study. SETTING: Five out of 21 central hospital districts in Finland
(population: about 1 million adults > or = 16 years of age). SUBJECTS: Subjects
entitled under the nationwide sickness insurance scheme to receive specially
reimbursed medication for rare systemic rheumatic or connective tissue diseases
in 1990. MAIN OUTCOME MEASURE: Incidence. RESULTS: A total of 30 incident cases
occurred. Nine patients had mixed connective tissue disease, four had systemic
sclerosis, four had dermato/polymyositis and one patient had inclusion body
myositis; the corresponding annual incidence rates were 8, 4, 4 and 1/million
of
the adult population. Only one patient had adult Still's disease. The overall
annual incidence rate of systemic vasculitides was 9/million of the adult
population. CONCLUSION: This study provides population-based figures on the
incidence of rare systemic rheumatic and connective tissue diseases in Finland.
PMID: 8810933 [PubMed - indexed for MEDLINE]
377: Ann Neurol. 1996 Aug;40(2):264-5.
Apolipoprotein E alleles in sporadic inclusion-body myositis and hereditary
inclusion-body myopathy.
Askanas V, Engel WK, Mirabella M, Weisgraber KH, Saunders AM, Roses AD, McFerrin
J.
Publication Types:
Letter
PMID: 8773613 [PubMed - indexed for MEDLINE]
378: J Neuropathol Exp Neurol. 1996 Jul;55(7):774-86.
Comment in:
J Neuropathol Exp Neurol. 1996 Nov;55(11):1179-80.
Difference in expression of phosphorylated tau epitopes between sporadic
inclusion-body myositis and hereditary inclusion-body myopathies.
Mirabella M, Alvarez RB, Bilak M, Engel WK, Askanas V.
USC Neuromuscular Center, University of Southern California School of Medicine,
Good Samaritan Hospital, Los Angeles 90017-1912, USA.
Sporadic inclusion-body myositis (s-IBM) and the hereditary inclusion-body
myopathies (h-IBMs) are severe and progressive muscle diseases, characterized
pathologically by vacuolated muscle fibers containing paired-helical filaments
(PHFs). An interesting feature of the s- and h-IBM muscle phenotype is its
striking similarity to Alzheimer-disease (AD) brain. We immunostained muscle
biopsies of 9 s-IBM patients, 9 autosomal-recessive h-IBM patients, 1
autosomal-dominant h-IBM patients, and 18 normal and disease-controls with
several antibodies known to react with the hyperphosphorylated tau of AD-PHFs.
Those included SMI-31, SMI-310, PHF-1, and AT8. In both s- and h-IBM, virtually
all vacuolated muscle fibers had strongly immunoreactive inclusions with SMI-31,
and by immuno-electronmicroscopy SMI-31 was exclusively localized to PHFs.
Approximately 40 to 50% of both s- and h-IBM vacuolated muscle fibers were also
immunoreactive with AT8 antibody. To the contrary, in h-IBM, there was no
immunoreactivity with SMI-310 and PHF-1 antibodies, whereas in s-IBM the
vacuolated muscle fibers had strong immunoreactivity with those two antibodies.
By immunoelectronmicorscopy, SMI-310 and PHF-1 also were localized to PHFs.
Within s-IBM muscle fibers, the structures immunoreactive with SMI-310 were
congophilic, whereas h-IBM muscle fibers did not have congophilia. Our studies:
(a) demonstrate a distinct difference between s-IBM and the h-IBMs in regard
to
expression of immunoreactive phosphorylated tau and congophilia; (b) demonstrate
a new "diagnostic duo" combination of SMI-31 and SMI-310 antibodies
for
identifying and distinguishing s-IBM and the h-IBMs; and (c) provide another
close similarity of pathologic phenotypes between s-IBM muscle and AD brain,
suggesting that similar cellular pathogenic mechanisms may be active in both
diseases.
PMID: 8965093 [PubMed - indexed for MEDLINE]
379: Clin Exp Immunol. 1996 Jun;104(3):467-73.
Leucocyte/endothelial cell adhesion receptors in muscle biopsies from patients
with idiopathic inflammatory myopathies (IIM).
Cid MC, Grau JM, Casademont J, Tobias E, Picazo A, Coll-Vinent B, Esparza J,
Pedrol E, Urbano-Marquez A.
Department of Internal Medicine, Hospital Clinic i Provincial, Barcelona, Spain.
Interactions between leucocytes and endothelial cells through specific adhesion
receptors play an increasingly recognized crucial role in the development of
inflammatory infiltrates in chronic inflammatory diseases. In this study we
investigated adhesion molecule expression in muscle biopsies from 18
dermatomyositis, six polymyositis, five inclusion-body myositis patients and
from eight normal controls. Immunohistochemical detection of leucocyte integrins
LFA-1 and VLA-4, their endothelial counter-receptors intercellular adhesion
molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and the
endothelial cell markers CD31 and von Willebrand factor-related antigen (vWFAg)
was performed using specific MoAbs and an alkaline phosphatase anti-alkaline
phosphatase technique. ICAM-1 expression was up-regulated and VCAM-1 induced
in
muscle capillaries of dermatomyositis samples. In both dermatomyositis and
polymyositis, endothelial cells from vessels surrounded by inflammatory
infiltrates strongly expressed ICAM-1 and VCAM-1. Infiltrating leucocytes were
intensively LFA-1- and VLA-4-positive. These data suggest that
leucocyte/endothelial cell interactions mediated by the receptor/ligand pairs
LFA-1/ICAM-1 and VLA-4/VCAM-1 actively participate in the development of muscle
inflammatory infiltrates in the major inflammatory myopathies. In addition,
ICAM-1 and VCAM-1 over-expression by capillary endothelial cells in
dermatomyositis supports the hypothesis that capillary activation and/or injury
is a major feature in this disease.
PMID: 9099932 [PubMed - indexed for MEDLINE]
380: Curr Opin Neurol. 1996 Jun;9(3):B65-76.
Inflammatory disease.
[No authors listed]
Publication Types:
Bibliography
PMID: 8839622 [PubMed - indexed for MEDLINE]
381: Curr Opin Neurol. 1996 Jun;9(3):235-9.
The immunopathologic and inflammatory differences between dermatomyositis,
polymyositis and sporadic inclusion body myositis.
Dalakas MC, Sivakumar K.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institute of Health, Bethesda, Maryland 20892, USA.
In polymyositis and sporadic inclusion body myositis, clonal expansion of CD8+
cells which are primed to recognize previously unknown muscle antigens occurs.
Compared with sporadic inclusion body myositis, however, in which the T-cell
response may not be antigen driven, there is in polymyositis an overexpression
of certain T-cell receptor gene families among the autoinvasive T-cells.
Although studies on the endomysial expression of cytokines and cell adhesion
molecules have provided additional support for the concept of an ongoing immune
process, the site of sensitization and the mechanism by which the autoimmune
process is triggered remains to be established. In dermatomyositis, a multiorgan
disease, evidence exists that the complement-mediated microvascular injury by
the putative antibody may not be limited to the endomysial vessels but may also
involve the blood vessels in the dermis. The antigenic target on the endothelial
cell in dermatomyositis patients and the pathogenic role of the recently studied
anti-Mi-2 antibody directed against a helicase are still to be determined.
Publication Types:
Review
Review, Tutorial
PMID: 8839618 [PubMed - indexed for MEDLINE]
382: Ann Neurol. 1996 Jun;39(6):789-95.
Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: a
study of 56 patients.
Santorelli FM, Sciacco M, Tanji K, Shanske S, Vu TH, Golzi V, Griggs RC, Mendell
JR, Hays AP, Bertorini TE, Pestronk A, Bonilla E, DiMauro S.
H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related
Diseases--Department of Neurology, Columbia University, New York, NY, USA.
Inclusion body myositis, a chronic inflammatory disorder, is the most common
cause of myopathy in adults over the age of 50. Diagnosis is based on clinical
features and distinctive morphological findings by both light and electron
microscopy. The causes of inclusion body myositis are still unknown.
Ultrastructural mitochondrial changes and ragged-red fibers are common in
patients with sporadic inclusion body myositis, and multiple [correction of
mutiple] mitochondrial DNA (mtDNA) deletions have been reported in 3 such
patients, suggesting that mtDNA mutations may have a pathogenetic role. We
studied 56 patients with sporadic inclusion body myositis, using a combination
of clinical, morphological, biochemical, and molecular genetic analyses to
determine the frequency and the distribution of mtDNA deletions. Using the
polymerase chain reaction, we found multiple mtDNA deletions in 73% of patients,
compared to 40% of normal age-matched control subjects and 47% of disease
control subjects. The presence of deletions correlated with morphological
evidence of ragged-red, cytochrome c oxidase-negative fibers, and with defects
of complexes I and IV of the electron transport chain. Although aging may
account for a proportion of mtDNA deletions in patients with sporadic inclusion
body myositis and control subjects, mtDNA alterations may be accelerated in
sporadic inclusion body myositis.
PMID: 8651651 [PubMed - indexed for MEDLINE]
383: Muscle Nerve. 1996 Jun;19(6):787-9.
Inclusion body myositis associated with a severe unilateral levodopa-responsive
upper extremity tremor.
Felice KJ, Grunnet ML.
Department of Neurology, University of Connecticut School of Medicine,
Farmington 06030-1845, USA.
Publication Types:
Case Reports
PMID: 8609934 [PubMed - indexed for MEDLINE]
384: Ann Otol Rhinol Laryngol. 1996 May;105(5):331-5.
Comment in:
Ann Otol Rhinol Laryngol. 1997 Apr;106(4):357.
Inflammatory myopathy causing pharyngeal dysphagia: a new entity.
Shapiro J, Martin S, DeGirolami U, Goyal R.
Department of Otology and Laryngology, Harvard Medical School, Beth Israel
Hospital, Boston, Massachusetts, USA.
Seven patients presented to our swallowing center with solid food dysphagia.
The
age range at presentation was 69 to 90 years. All patients had normal findings
on neurologic evaluation, and in those patients undergoing electromyography
and
nerve conduction studies, results of all such tests were also normal. Pooling
of
saliva in the pharyngeal recesses was noted on fiberoptic laryngoscopy in most
cases. The swallowing videofluoroscopy findings were strikingly similar. All
patients had a prominent cricopharyngeus muscle, and some had a prominence in
a
more proximal portion of the inferior constrictor muscle. All patients had
decreased epiglottic tilt and moderate or severe residue in the pharyngeal
recesses. Three patients underwent pharyngoesophageal sphincter myotomy.
Biopsies of the omohyoid and cricopharyngeus muscles showed inflammatory
myopathy with no evidence of inclusion bodies. This is a distinct clinical
entity defined by isolated pharyngeal dysphagia in elderly patients with a
unique videofluoroscopic appearance and pharyngeal myopathy.
PMID: 8651624 [PubMed - indexed for MEDLINE]
385: Clin Exp Immunol. 1996 May;104 Suppl 1:55-60.
Clinical benefits and immunopathological correlates of intravenous immune
globulin in the treatment of inflammatory myopathies.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, Bethesda, MD 20892-1382, USA.
High-dose intravenous immune globulin (IVIG) is emerging as a promising therapy
for patients with inflammatory myopathies who have become unresponsive to, or
cannot tolerate, conventional therapies. In a double-blind, placebo-controlled
study, using objective criteria for improvement, IVIG demonstrated moderate
to
dramatic improvement in 75% of the patients with dermatomyositis. Preliminary
results from a controlled study in inclusion-body myositis show that IVIG may
also exert a mild benefit, but only in a small number of patients and in certain
muscle groups. In some patients with polymyositis, IVIG is reported to be of
benefit but controlled studies have not yet been completed. Immunocytochemical,
immunological and in vitro studies on the patients' repeated muscle biopsies
and
follow-up sera showed that IVIG exerts its action in inflammatory myopathies
by:
(i) inhibiting myotoxic cytokines, such as TNF-alpha and IL-1; (ii) blockade
of
Fc receptors on endomysial macrophages interfering with Fc receptor-mediated
phagocytosis; and (iii) inhibiting the uptake of C3 and intercepting the
formation and deposition of membranolytic attack complex on the endomysial
capillaries.
Publication Types:
Review
Review, Tutorial
PMID: 8625545 [PubMed - indexed for MEDLINE]
386: J Neurol Neurosurg Psychiatry. 1996 Mar;60(3):251-5.
Inclusion body myositis.
Garlepp MJ, Mastaglia FL.
Publication Types:
Editorial
Review
Review, Tutorial
PMID: 8609499 [PubMed - indexed for MEDLINE]
387: Ann Neurol. 1996 Mar;39(3):389-91.
Comment in:
Ann Neurol. 1997 Nov;42(5):815.
Use of anti-neurofilament antibody to identify paired-helical filaments in
inclusion-body myositis.
Askanas V, Alvarez RB, Mirabella M, Engel WK.
USC Neuromuscular Center, Department of Neurology, University of Southern
California School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912,
USA.
Paired-helical filaments (PHFs) are an important diagnostic criterion of the
inclusion-body myositis (IBM) muscle biopsy; but, until now, their presence
could be identified only by electronmicroscopy. In this report, we describe
an
easy immunocytochemical procedure, utilizing commercially available antibody,
that enables reliable identification of muscle PHFs by light microscopy. This
procedure greatly facilitates diagnosis of IBM.
PMID: 8602760 [PubMed - indexed for MEDLINE]
388: Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1314-9.
Transfer of beta-amyloid precursor protein gene using adenovirus vector causes
mitochondrial abnormalities in cultured normal human muscle.
Askanas V, McFerrin J, Baque S, Alvarez RB, Sarkozi E, Engel WK.
Department of Neurology, University of Southern California School of Medicine,
Good Samaritan Hospital, Los Angeles 90017, USA.
As in Alzheimer-disease (AD) brain, vacuolated muscle fibers of inclusion-body
myositis (IBM) contain abnormally accumulated beta-amyloid precursor protein
(beta APP), including its beta-amyloid protein epitope, and increased beta
APP-751 mRNA. Other similarities between IBM muscle and AD brain phenotypes
include paired helical filaments, hyperphosphorylated tau protein,
apolipoprotein E, and mitochondrial abnormalities, including decreased
cytochrome-c oxidase (COX) activity. The pathogenesis of these abnormalities
in
IBM muscle and AD brain is not known. We now report that direct transfer of
the
beta APP gene, using adenovirus vector, into cultured normal human muscle fibers
causes structural abnormalities of mitochondria and decreased COX activity.
In
this adenovirus-mediated beta APP gene transfer, we demonstrated that beta APP
overproduction can induce mitochondrial abnormalities. The data suggest that
excessive beta APP may be responsible for mitochondrial and COX abnormalities
in
IBM muscle and perhaps AD brain.
PMID: 8577761 [PubMed - indexed for MEDLINE]
389: J Neurol. 1996 Feb;243(2):126-30.
Glucocorticoid-sensitive hereditary inclusion body myositis.
Naumann M, Reichmann H, Goebel HH, Moll C, Toyka KV.
Department of Neurology, University of Wurzburg, Germany.
We report a hereditary muscle disorder with features of inclusion body myositis
(IBM) in two adult sisters with slowly progressive asymmetrical muscle weakness.
The findings of light microscopic and ultrastructural investigations of muscle
biopsy specimens were consistent with a diagnosis of IBM. Both patients improved
and stabilized on immunosuppressive treatment with corticosteroids and
azathioprine. This differentiates our patients from other sporadic and familial
cases of IBM. Clinical and histological features are described and compared
with
those of other previously reported families with IBM.
Publication Types:
Case Reports
PMID: 8750548 [PubMed - indexed for MEDLINE]
390: J Neurol. 1996 Jan;243(1):79-85.
Automatic decomposition electromyography in idiopathic inflammatory myopathies.
Jongen PJ, Vingerhoets HM, Roeleveld K, Stegeman DF.
Department of Neurology, University Hospital, Nijmegen, Netherlands.
Automatic decomposition electromyography (ADEMG) is a commercially available
software package with installed reference values that enables the objective
measurement of motor unit action potentials (MUAPs). To assess the diagnostic
yield of this package in idiopathic inflammatory myopathies (IIM) we performed
bicepts brachii ADEMG in 17 patients with polymyositis, dermatomyositis and
inclusion body myositis. Results were compared with those in 12 controls, and
with the results of conventional EMG of the biceps and other muscles. Decreased
mean values for MUAP duration occurred significantly more frequently in IIM
patients than in controls; other MUAP characteristics did not differ. In IIM
patients, decreased mean amplitude and increased mean number of turns occurred
significantly less frequently on ADEMG than did corresponding abnormalities
on
conventional biceps EMG. Decreased mean values for duration and amplitude, and
increased mean values for number of turns were seen significantly less often
on
ADEMG than corresponding abnormalities on conventional EMG of four different,
individually chosen muscles. Overall evaluation of ADEMG resulted in a diagnosis
of "possible myopathy" in 1 and "probable myopathy" in 8
patients, whereas
overall evaluation of conventional EMG led to a diagnosis "suggestive of
IIM" in
13 patients. We conclude that, although measurement of mean MUAP duration might
be valuable in IIM diagnosis, our results do not favour the use of biceps
brachii ADEMG and the installed reference values for the diagnosis of IIM. We
suggest modifications to improve ADEMG's applicability.
PMID: 8869392 [PubMed - indexed for MEDLINE]
391: Acta Neuropathol (Berl). 1996;91(5):530-6.
Cytochrome c oxidase deficiencies in the muscle of patients with inflammatory
myopathies.
Chariot P, Ruet E, Authier FJ, Labes D, Poron F, Gherardi R.
Department of Pathology, Hopital Henri Mondor, Creteil, France.
We studied mitochondrial function in inflammatory myopathies, using cytochrome
c
oxidase (COX) reaction on muscle biopsy samples from 30 patients (15 with
dermatomyositis, 12 with polymyositis, and 3 with inclusion body myositis) and
30 age-matched controls. We also performed immunocytochemistry for COX II and
COX IV subunits in 7 of these patients who had COX deficiency. COX-deficient
fibers were a constant finding in patients or controls older than 65 years and
the percentage of COX-deficient fibers correlated with age in both patients
and
controls. Focal COX deficiency was found in 24 patients (13 of 15 with
dermatomyositis, 8 of 12 with polymyositis, and 3 of 3 with inclusion body
myositis) and 18 controls. The percentages of COX-deficient fibers were higher
in patients with inflammatory myopathies (range: 0-4.7%; mean: 1.2%) than in
age-matched controls (range: 0-1.9%; mean: 0.4%) (P < 0.01). In the subgroup
of
patients under age 65, COX-deficient fibers were more frequent in
dermatomyositis than in polymyositis (mean: 0.8% vs 0.2%, P = 0.02). In patients
with dermatomyositis, capillary loss correlated positively with COX deficiency
(P < 0.02). Immunocytochemistry for COX II and IV showed that 82% of
COX-negative fibers were COX II-negative and 26% were COX IV-negative,
suggesting that proteins encoded by mitochondrial DNA are predominantly, but
not
exclusively, involved in COX deficiency. We conclude that mitochondrial
dysfunction and COX deficiency can occur in inflammatory myopathies. Such a
mitochondrial dysfunction is not solely related to the aging process. We suggest
that muscle ischemia contributes to mitochondrial dysfunction in
dermatomyositis.
PMID: 8740235 [PubMed - indexed for MEDLINE]
392: Eur Neurol. 1996;36(2):89-93.
Inclusion body myositis: atypical clinical presentations.
Schlesinger I, Soffer D, Lossos A, Meiner Z, Argov Z.
Department of Neurology, University Hospital, Hebrew University-Hadassah Medical
School, Jerusalem, Israel.
Inclusion body myositis affects primarily the proximal muscles but distal limb
muscles are involved too in this chronic myopathy. Characteristic
histopathologic findings include "rimmed vacuoles', inflammation and typical
cytoplasmic and nuclear filamentous inclusions. The patients are usually
unresponsive to steroids. We present four inclusion body myositis patients with
atypical clinical presentations: one with scapuloperoneal syndrome, one with
post-polio-like syndrome and two with associated immune-mediated diseases (one
with undefined autoimmune disorder and the second with scleroderma). Two
patients responded to high-dose steroid therapy. We suggest that the clinical
spectrum of inclusion body myositis is wider than previously appreciated.
Publication Types:
Case Reports
PMID: 8654492 [PubMed - indexed for MEDLINE]
393: Ann Neurol. 1996 Jan;39(1):139-43.
Sporadic inclusion body myositis: counts of different types of abnormal fibers.
Pruitt JN 2nd, Showalter CJ, Engel AG.
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Invasion of nonnecrotic muscle fibers by cytotoxic T cells, accumulation of
congophilic amyloid inclusions in muscle fibers, and fiber necrosis are
consistent histologic findings in sporadic inclusion body myositis (IBM). To
evaluate the relative significance of these alterations, we quantitatively
analyzed the frequency of these abnormalities in 31 electron microscopy proven
cases of IBM (20 untreated and 11 immunosuppressed). Nonnecrotic muscle fibers
invaded by T cells were severalfold more frequent than fibers displaying the
other pathologic alterations. Comparison of muscle samples from treated and
untreated patients revealed no significant differences in the respective
frequencies of the three species of abnormal fibers. Moreover, there was no
correlation of the frequency of any abnormality either with disease duration
or
length of treatment. The much higher frequency of the invaded than Congo
red-positive fibers points to the importance of an immune-mediated mechanism
in
the disease; but the basic cause of the disease remains undefined.
PMID: 8572661 [PubMed - indexed for MEDLINE]
394: Scand J Immunol. 1996 Jan;43(1):109-14.
Limited T-cell receptor V gene usage in inclusion body myositis.
Fyhr IM, Moslemi AR, Tarkowski A, Lindberg C, Oldfors A.
Department of Pathology, Goteborg University, Sahlgrenska Hospital, Gothenburg,
Sweden.
Inclusion body myositis (IBM) is a chronic, progressive inflammatory myopathy.
The inflammatory infiltrates are dominated by T cells, which frequently invade
muscle fibres. The present study was performed to characterize the usage of
the
variable (V) segment of the T-cell receptor of muscle infiltrating cells in
IBM.
Using the reverse transcriptase polymerase chain reaction (RT-PCR) technique
the
authors analysed the expression of 22 V alpha and 24 V beta families in muscle
tissue from six patients with IBM displaying intense inflammatory cell
infiltration. The following V alpha/V beta families appeared in at least 50%
of
the patients: V alpha 1, 5, 7, 15, 16, 17, 20, 21, 22 and V beta 3, 5.2, 8,
12,
14, 22. In all patients V alpha 7, 16 and V beta 8 were expressed in muscle
tissue. Furthermore, in two of the patients peripheral blood lymphocytes (PBL)
were investigated in parallel. There was a restricted usage of V alpha and V
beta families in muscle in comparison to PBL, indicating a selective homing
or
local proliferation of T lymphocytes in the inflammatory lesions in IBM.
PMID: 8560189 [PubMed - indexed for MEDLINE]
395: Muscle Nerve. 1996 Jan;19(1):23-8.
Inclusion body myositis: investigation of the mumps virus hypothesis by
polymerase chain reaction.
Fox SA, Ward BK, Robbins PD, Mastaglia FL, Swanson NR.
University Department of Medicine, Queen Elizabeth II Medical Centre, Perth,
Australia.
Inclusion body myositis (IBM) is a distinctive form of chronic inflammatory
myopathy characterized pathologically by the finding of rimmed vacuoles and
15-18nm microtubular filamentous inclusions in muscle fiber nuclei and
cytoplasm. The observation that these filaments resembled nucleocapsids of the
paramyxovirus group and showed immunoreactivity with mumps virus (MV) antibodies
has led to a long-standing postulate that IBM may be a "slow" mumps
infection.
We searched for the presence of MV RNA in 34 muscle biopsies (17 frozen and
17
paraffin-embedded) from 18 patients with IBM and 43 control biopsies (mainly
from patients with other forms of inflammatory myopathy) using a polymerase
chain reaction (PCR). The MV PCR was shown to be sensitive and specific for
MV
strains (including J-L) and the integrity of muscle RNA extracts was confirmed
by PCR detection of constitutive Ableson tyrosine kinase mRNA. MV RNA was not
found in any biopsy from the IBM group nor any of the control cases. Our results
therefore do not support the mumps hypothesis for IBM.
PMID: 8538666 [PubMed - indexed for MEDLINE]
396: Zhonghua Yi Xue Za Zhi (Taipei). 1995 Dec;56(6):386-92.
Vacuolar changes in neuromuscular disorders: a morphometric study.
Lee CC, Huang CC, Chen SS.
Department of Neurology, China Medical College Hospital, Taichung, Taiwan,
R.O.C.
BACKGROUND: Vacuoles in muscle represent a nonspecific alternation and are
found
in a variety of neuromuscular disorders. To understand their significance, a
morphometric study of the vacuolar formation in muscle biopsies from 340
patients was reviewed. METHODS: Vacuolar changes in muscles were found in 24
out
of 340 patients with muscle biopsies. The specimens were prepared for
histopathological, histochemical and electron microscopic examinations. The
location, size, shape, number and content of the vacuoles were recorded. The
number of fibers containing vacuoles was also assessed. RESULTS: Observed after
modified Gomori trichrome stain, there were rimmed and non-rimmed vacuoles.
Rimmed vacuoles were found in limb-girdle myopathy with rimmed vacuoles (5),
oculopharyngeal muscular dystrophy (1). inclusion body myositis (2) and
neurogenic disorder (1). These vacuoles were usually cleft-like in shape in
5-16% of muscle fibers with a diameter of 3-20 microns. An elevation of acid
phosphatase activities and the presence of cytoplasmic debris suggested an
autophagic process. In 15 patients with non-rimmed vacuoles, round and oval
shapes with variable sizes and numbers were noted. Four with acid maltase
deficiency (AMD) had numerous vacuoles containing glycogen, while three with
lipid storage disease contained lipid. Interestingly, in AMD the size of the
vacuoles was usually more than 10 microns in diameter, but less than 5 microns
in lipid storage disease. In other diseases including polymyositis (5), Duchenne
muscular dystrophy (2) and hypokalemic periodic paralysis (1), the numbers of
vacuoles were usually fewer than three in each fiber. CONCLUSIONS: Vacuolar
changes were not specific, but morphometric analysis of the vacuoles may provide
some clues in differential diagnosis. The vacuoles were usually numerous in
glycogen and lipid storage diseases, while rimmed vacuoles may be found in
limb-girdle myopathy with rimmed vacuoles, oculopharyngeal muscular dystrophy,
and inclusion body myositis.
PMID: 8851479 [PubMed - indexed for MEDLINE]
397: J Neuroimmunol. 1995 Dec;63(1):9-16.
Analysis of cytokine expression in muscle in inflammatory myopathies, Duchenne
dystrophy, and non-weak controls.
Lundberg I, Brengman JM, Engel AG.
Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden.
We investigated the profiles of cytokine mRNA expression in muscle in 15 cases
of inflammatory myopathy (IM) (5 each of polymyositis, inclusion body myositis,
and dermatomyositis) and in 10 controls (5 of Duchenne dystrophy and 5 non-weak
subjects). Expressions of the predominantly T cell-derived cytokines
(interleukin (IL)-2, IL-4, IL-5, and interferon-gamma (IFN-gamma), of the
predominantly macrophage-derived cytokines (IL-1, IL-6, and tumor necrosis
factor-alpha (TNF-alpha)), as well as cytokines that can be of either T cell
or
macrophage origin (granulocyte-macrophage colony stimulating factor (GM-CSF)
and
transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 2), were monitored
by the reverse transcriptase-PCR method. The expression of T cell cytokine mRNAs
for IL-2, IL-5, and IFN-gamma was generally weak or inconsistent. IL-4 mRNA
expression was consistently moderate to strong in polymyositis but generally
weak or absent in the other IMs. The expression of macrophage cytokine mRNAs
for
IL-1 alpha and IL-1 beta was weak or absent in all cases. Variable TNF-alpha
mRNA expression was observed in 12 of 15 IM cases and faint or weak expression
in 5 of 10 controls. Very strong GM-CSF expression was detected, but only on
boosted PCR, in 12 of 15 cases of IM but in none of the controls. IL-6 was
expressed only weakly or inconsistently. In contrast to the variable expression
of several of the above mentioned cytokine mRNAs, all IM specimens strongly
expressed TGF-beta 1 mRNA and 12 of 15 strongly expressed TGF-beta 2 mRNA. Thus,
with the exception of IL-4 expression in polymyositis, a similar pattern of
cytokine mRNA expression exists in the different types of IMs. Moreover, this
pattern resembles that detected in non-weak and DD controls, although expression
is generally weaker in the non-weak controls. The findings suggest that in IM
muscle a sustained secretion of cytokines by T cells or of IL-1 by macrophages
is not a prerequisite for operation of the immune effector response and that
muscle may not be the site of ongoing sensitization.
PMID: 8557829 [PubMed - indexed for MEDLINE]
398: Ann Neurol. 1995 Dec;38(6):957-9.
Apolipoprotein E epsilon 4 in inclusion body myositis.
Garlepp MJ, Tabarias H, van Bockxmeer FM, Zilko PJ, Laing B, Mastaglia FL.
Australian Neuromuscular Research Institute, Australia.
The genetic predisposition to inclusion body myositis (IBM) is probably
multifactorial. The deposition of the beta-amyloid protein is a characteristic
histological feature of both IBM and Alzheimer's disease (AD). The epsilon 4
allele of apolipoprotein E (APO E) has been strongly associated with familial
and late-onset AD. We therefore compared the APO E allele frequencies in a group
of 14 patients with IBM with those in a group of patients with other
inflammatory muscle diseases and in the general population. The frequency of
the
epsilon 4 allele in IBM was increased (0.29) compared with that in patients
with
other inflammatory muscle diseases (0.15) and the general population (0.13)
(p <
0.05). These data suggest that APO E genotype may be one of the factors involved
in determining the predisposition to the development of IBM.
PMID: 8526471 [PubMed - indexed for MEDLINE]
399: J Clin Immunol. 1995 Nov;15(6 Suppl):70S-75S.
Update on the use of intravenous immune globulin in the treatment of patients
with inflammatory muscle disease.
Dalakas MC.
Department of Health & Human Services, National Institute of Neurological
Disorders & Stroke, National Institutes of Health, Bethesda, Maryland, 20892,
USA.
The inflammatory myopathies consist of three distinct groups: dermatomyositis,
polymyositis, and inclusion body myositis. Dermatomyositis is distinguished
by
its characteristic rash, while polymyositis is a diagnosis of exclusion.
Inclusion body myositis is characterized by early involvement of distal muscle
groups and the quadriceps. Definitive diagnosis is made by muscle biopsy, which
demonstrates histological features characteristic for each disorder. Immune
mechanisms play a role in the pathogenesis of the inflammatory myopathies. A
complement-mediated microangiopathy is seen in dermatomyositis, while there
is
evidence for a T cell-mediated process in polymyositis and inclusion body
myositis. Treatment with prednisone is helpful to a majority of patients for
a
period of time. Immunosuppressive drugs have met with limited success. We
describe a group of patients with dermatomyositis, resistant to available
therapies, whose muscle strength, skin changes, and muscle biopsies improved
significantly during treatment with intravenous immune globulin. The treatment
of polymyositis and inclusion body myositis with intravenous immune globulin
is
currently under study.
PMID: 8613495 [PubMed - indexed for MEDLINE]
400: Curr Opin Rheumatol. 1995 Nov;7(6):510-5.
Treatment of inflammatory myopathy with intravenous gamma globulin.
Sussman GL, Pruzanski W.
Wellesley Hospital Research Institute, University of Toronto, Ontario, Canada.
Intravenous immunoglobulin (IVIg) is a new modality used to help treat
conditions associated with immune dysregulation. The inflammatory myopathies
are
a group of complex diseases including dermatomyositis, polymyositis, and
inclusion-body myositis. Overall evaluation of IVIg in myopathy has been
hampered by difficulty in accurately diagnosing and assessing disease activity.
The lack of large, well controlled, double-blind trials has precluded clear
evaluation of the effectiveness of IVIg in these diseases. However, from the
data presented in published reports, it appears that IVIg may be useful in the
treatment of inflammatory myopathies, particularly dermatomyositis.
Publication Types:
Review
Review, Tutorial
PMID: 8579971 [PubMed - indexed for MEDLINE]
401: Curr Opin Rheumatol. 1995 Nov;7(6):486-96.
New advances in the understanding of sporadic inclusion-body myositis and
hereditary inclusion-body myopathies.
Askanas V, Engel WK.
Neuromuscular Center, University of Southern California School of Medicine,
Hospital of the Good Samaritan, Los Angeles 90017-1912, USA.
This review emphasizes new advances in seeking the pathogenic mechanisms of
sporadic inclusion-body myositis and hereditary inclusion-body myopathy
syndromes. Clinical and pathologic similarities and differences between sporadic
and hereditary forms are described. Hypotheses are presented regarding the
possible causes and consequences of abnormally accumulated intramyofiber
beta-amyloid precursor protein (beta APP) (including beta-amyloid protein and
C-
and N-terminal epitopes), hyperphosphorylated tau, alpha 1-antichymotrypsin,
apolipoprotein E, prion protein, ubiquitin, nicotinic acetylcholine receptor
and
its 43-kD associated protein, fibroblast growth factor, and transforming growth
factor-beta. Also increased are beta APP mRNA and prion protein mRNA. Striking
similarities between the pathology of muscle specimens from sporadic
inclusion-body myositis and samples from the brains of patients with Alzheimer's
disease in regard to Congo red positivity and accumulations of several proteins
are discussed. Because most of the proteins that pathologically accumulate
throughout the abnormal muscle fibers also accumulate focally at normal human
neuromuscular junctions, the possible "junctionalization" of nonjunctional
nuclei as a pathogenic mechanism in the muscle fiber is discussed.
Publication Types:
Review
Review, Tutorial
PMID: 8579968 [PubMed - indexed for MEDLINE]
402: Ann Neurol. 1995 Nov;38(5):705-13.
Inclusion body myositis and myopathies.
Griggs RC, Askanas V, DiMauro S, Engel A, Karpati G, Mendell JR, Rowland LP.
University of Rochester, School of Medicine and Dentistry, Department of
Neurology, NY 14642, USA.
Publication Types:
Review
Review, Tutorial
PMID: 7486861 [PubMed - indexed for MEDLINE]
403: Rev Rhum Engl Ed. 1995 Oct;62(9):598-601.
Isokinetic strength testing for evaluating the efficacy of intravenous immune
globulin therapy for inclusion body myositis.
Dasque F, Laroche M, Marque P, Le Vourc'h P, Moulinier L, Mazieres B, Roques CF.
Rehabilitation Unit, Rangueil Hospital, Toulouse, France.
Inclusion body myositis is a disease of striated skeletal muscle of unclear
etiopathogenesis. Its diagnosis is difficult. Corticosteroids and
immunosuppressants are of limited efficacy. Positive responses to intravenous
immune globulins have recently been reported in a few patients. We used a CYBEX
6000 isokinetic dynamometer to evaluate the efficacy of intravenous immune
globulin therapy in a patient with inclusion body myositis. Measurements were
done at the flexors and extensors of the knee, at baseline and four and eight
months after treatment initiation. A course of intravenous immune globulins
(2 g
per course) was given every month for five months then every two months.
Isokinetic muscle strength measured at an angular speed of 180 degrees/second
increased by more than 41% at both knees. As compared with muscle imaging
studies (computed tomography, X-ray absorptiometry, ultrasonography, magnetic
resonance imaging), isokinetic strength testing has the advantage of providing
data on functional improvements under treatment.
Publication Types:
Case Reports
PMID: 8574634 [PubMed - indexed for MEDLINE]
404: Muscle Nerve. 1995 Sep;18(9):1016-8.
Amyloidosis causing a progressive myopathy.
Nadkarni N, Freimer M, Mendell JR.
Department of Neurology, College of Medicine, Ohio State University, Columbus
43210, USA.
A 62-year-old woman developed profound weakness secondary to a progressive
myopathy associated with primary systemic amyloidosis. The characteristic
apple-green birefringent amyloid deposits were demonstrated surrounding
individual muscle fibers in Congo red stained sections. Electron microscopy
demonstrated amyloid filaments in close apposition to muscle fibers exhibiting
excessive corrugations of the sarcolemmal membrane. The pathological features
of
progressive amyloid myopathy associated with primary systemic amyloidosis are
distinct from the intracellular amyloid deposits characteristic of sporadic
inclusion body myositis and inherited inclusion body myopathy.
Publication Types:
Case Reports
PMID: 7643863 [PubMed - indexed for MEDLINE]
405: Baillieres Clin Rheumatol. 1995 Aug;9(3):497-514.
Inflammatory myopathies.
Oddis CV, Medsger TA Jr.
Department of Medicine, University of Pittsburgh School of Medicine, PA 15261,
USA.
New information regarding myositis specific autoantibodies, histopathologic
analysis of muscle biopsy specimens, and immunogenetic features of the different
serologic subsets of disease has greatly increased our understanding of the
pathogenesis of the inflammatory myopathies. The clinical descriptions of
inclusion body myositis and 'amyopathic dermatomyositis' (Euwer and Sontheimer,
1993) are examples of our expanded descriptive capabilities in the evaluation
of
patients with myopathy. Finally, newer techniques such as cytokine analysis
and
magnetic resonance imaging may help in the ongoing assessment of disease
activity in patients with myositis. The combination of these recently described
clinical and laboratory parameters are enough to force a reconsideration of
the
previously described classification and diagnostic criteria in the inflammatory
myopathies.
Publication Types:
Review
Review, Tutorial
PMID: 7497535 [PubMed - indexed for MEDLINE]
406: Neurosci Lett. 1995 Jul 14;194(1-2):37-40.
Ubiquitinated inclusions in inclusion-body myositis patients are immunoreactive
for cathepsin D but not beta-amyloid.
Sherriff FE, Joachim CL, Squier MV, Esiri MM.
Department of Clinical Neurology (Neuropathology), University of Oxford,
Radcliffe Infirmary, UK.
The nature of the inclusions in the human muscle disease inclusion-body myositis
(IBM) has been the subject of debate. Parallels with Alzheimer's disease have
been drawn after these inclusions were found to be ubiquitinated, and
immunoreactive with antibodies to beta-amyloid (A beta) and certain
amyloid-associated proteins. We have used a battery of antibodies against A
beta
and associated proteins to immunostain muscle biopsies from patients with IBM.
Although the inclusions are ubiquitinated, we could not show immunoreactivity
for A beta or the associated proteins investigated. We did, however, find that
the ubiquitinated inclusions colocalised with the lysosomal marker, cathepsin
D.
PMID: 7478207 [PubMed - indexed for MEDLINE]
407: Neurology. 1995 Jul;45(7):1302-4.
Erratum in:
Neurology 1995 Dec;45(12):2304.
Inclusion body myositis: explanation for poor response to immunosuppressive
therapy.
Barohn RJ, Amato AA, Sahenk Z, Kissel JT, Mendell JR.
Department of Neurology, University of Texas Southwestern Medical Center, Dallas
75235-8897, USA.
We treated eight patients who had inclusion body myositis (IBM) with oral
prednisone therapy, and we performed muscle biopsies before and after treatment.
We documented the patients' clinical response to therapy and changes in serum
CK. Although the serum CK level fell, muscle strength worsened after prednisone
treatment. In addition, while inflammation decreased in the muscle biopsy
specimens, the number of vacuolated and amyloid-positive fibers increased after
oral prednisone therapy. These observations indicate that the inflammatory
response in IBM may play a secondary role in the pathogenesis of IBM. The unique
findings of intracellular amyloid deposits and rimmed vacuoles distinguishing
IBM from other inflammatory myopathies, and recognition that suppression of
inflammation has no effect on the clinical course, suggest that IBM may
represent a degenerative muscle disorder.
PMID: 7617187 [PubMed - indexed for MEDLINE]
408: J Neuropathol Exp Neurol. 1995 Jul;54(4):581-7.
Mitochondrial DNA deletions in muscle fibers in inclusion body myositis.
Oldfors A, Moslemi AR, Fyhr IM, Holme E, Larsson NG, Lindberg C.
Department of Pathology, Goteborg University, Sweden.
Inclusion body myositis (IBM) is an autoimmune, inflammatory myopathy where
morphological changes of muscle, including ragged red fibers, have indicated
mitochondrial dysfunction in some muscle fibers. In this study enzyme
histochemical analysis showed that cytochrome c oxidase (COX)-deficient muscle
fibers were present at a frequency ranging from 0.5 to 5% of the muscle fibers
in a series of 20 IBM patients. In age-matched controls, only occasional
COX-deficient muscle fibers were present. Polymerase chain reaction (PCR)
analysis of DNA extracted from muscle tissue of the IBM patients showed multiple
mtDNA deletions. PCR analysis of isolated, single muscle fibers showed presence
of mtDNA with only one type of deletion and deficiency of wild-type mtDNA in
each COX-deficient muscle fiber. This finding was supported by results from
in
situ hybridization using different mtDNA probes on consecutive sections. A 5
kb
deletion was identified in all 20 IBM patients. DNA sequencing of the breakpoint
region showed that this deletion was the so-called "common deletion."
Most but
not all of the investigated deletion breakpoints were flanked by direct repeats.
COX-deficient fibers were more frequent among fibers with positive
immunostaining with antibodies directed toward a regeneration marker, the Leu-19
antigen, than in the entire fiber population. These results show that COX
deficiency in muscle fiber segments in IBM is associated with deletions of
mtDNA. Clonal expansion of mtDNA with deletions may take place in regenerating
muscle fibers following segmental necrosis.
PMID: 7602331 [PubMed - indexed for MEDLINE]
409: Ann Neurol. 1995 Jun;37(6):806-10.
Common variable immunodeficiency and inclusion body myositis: a distinct
myopathy mediated by natural killer cells.
Dalakas MC, Illa I.
Medical Neurology Branch, National Institute of Neurological Disorders and
Stroke, National Institutes of Health, Bethesda, MD 20892-1382, USA.
Inclusion body myositis developed in two men, 36 and 48 years old with
long-standing common variable immunodeficiency. Immunophenotypic analysis of
the
endomysial cells showed an increased number of natural killer (NK) cells
(defined as CD57+, CD56+, CD3-, CD8-, CD68-) accounting for 8.5 to 9.5% of the
total cells, compared with a mean of 1% in sporadic inclusion body myositis.
The
remaining cells were CD8+, macrophages, and CD4+ T cells. NK cells were positive
for intercellular cell adhesion molecule-1 and invaded muscle fibers negative
for major histocompatibility complex (MHC) class I. In contrast to ubiquitous
endomysial expression of MHC class I antigen in sporadic inclusion body
myositis, the MHC class I in common variable immunodeficiency and inclusion
body
myositis was absent or weakly expressed in only some of the muscle fibers
surrounded by CD8+ cells. Enteroviral or retroviral RNA sequences were not
amplified. Treatment with intravenous immunoglobulin improved strength in 1
patient whose repeated muscle biopsy specimen showed normal NK cells. We
conclude that inclusion body myositis can develop in patients with common
variable immunodeficiency. Common variable immunodeficiency with inclusion body
myositis is an immune myopathy mediated by NK cells in a non-MHC class
I-restricted cytotoxicity, and by CD8+ cells in an MHC class I-restricted
process. This is the first description of an inflammatory myopathy in which
NK
cells participate in the myocytotoxic process.
Publication Types:
Case Reports
PMID: 7778855 [PubMed - indexed for MEDLINE]
410: Clin Exp Immunol. 1995 Jun;100(3):519-28.
Gamma delta T cell receptor gene expression by muscle-infiltrating lymphocytes
in the idiopathic inflammatory myopathies.
O'Hanlon TP, Messersmith WA, Dalakas MC, Plotz PH, Miller FW.
Molecular Immunology Laboratory, Food and Drug Administration, Bethesda, MD
20892, USA.
Autoreactive alpha beta T cells have been implicated as playing a primary
pathogenic role in a group of diseases characterized by chronic muscle
inflammation known as the idiopathic inflammatory myopathies (IIM). gamma delta
T cells, a distinct and enigmatic class of T cells, play a less certain role
in
a variety of human autoimmune diseases including the IIM. In an attempt to
understand the significance of gamma delta T cells in the IIM, we utilized a
sensitive polymerase chain reaction (PCR) technique to evaluate gamma delta
T
cell receptor (TCR) gene expression in 45 muscle biopsies obtained from 42 IIM
patients (17 polymyositis, 12 dermatomyositis, and 13 inclusion body myositis).
gamma delta TCR gene expression was not detected in 36 specimens, the majority
of muscle biopsies surveyed. gamma delta TCR gene expression by
muscle-infiltrating lymphocytes was detected among nine clinically heterogeneous
patients. We further analysed the junctional sequence composition of the V gamma
3 and V delta 1 transcripts, whose expression was prominent among gamma delta
positive patients. DNA sequence analysis of V gamma 3 amplification products
from two patients revealed the presence of several productively rearranged
transcripts with amino acid sequence similarities within the V gamma 3-N-J gamma
junctional domain. No amino acid sequence similarities were evident within the
V
delta-N-D delta-N-J delta region of V delta 1 transcripts amplified from four
patients, although a distinct and dominant clonotype was detected from each
patient. Our cumulative data suggest that unlike alpha beta T cells, gamma delta
T cells do not play a prominent pathologic role in the IIM. In fact, the
sporadic nature of gamma delta TCR gene expression detected among these patients
implies that gamma delta T cell infiltration, when it occurs, is a secondary
event perhaps resulting from non-specific inflammatory processes.
PMID: 7774065 [PubMed - indexed for MEDLINE]
411: Am J Pathol. 1995 May;146(5):1178-87.
Immunocytochemical study of CD45 T cell isoforms in inflammatory myopathies.
De Bleecker JL, Engel AG.
Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA.
The CD45RO and CD45RA antigens subdivide the CD8+ and the CD4+ T cells into
primed memory cells and unprimed virgin T cells, respectively. To assess the
relative abundance of the CD8+ and the CD4+ T cells expressing the two CD45
isoforms in the major inflammatory myopathies, we immunophenotyped T cells in
muscle specimens from patients with inclusion body myositis, polymyositis (PM),
and dermatomyositis. The analysis was according to diagnosis and sites of cell
accumulation: endomysial inflammatory cells focally surrounding and invading
nonnecrotic fibers were analyzed in inclusion body myositis and PM and
perivascular infiltrates in PM and dermatomyositis. In all diseases and at all
sites of accumulation, the CD45RO+ memory T cells were predominant and the
CD45RO/CD45RA ratio exceeded that in normal blood. In PM and inclusion body
myositis, the marked enrichment of endomysial T cells in memory cells implicates
these cells in the pathogenesis. The enrichment of perivascular T cells in
dermatomyositis and PM in memory cells may be a result of enhanced
transendothelial migratory capacity of these cells; alternatively, the
virgin-to-memory cell conversion may occur after diapedesis.
PMID: 7747812 [PubMed - indexed for MEDLINE]
412: Neurology. 1995 May;45(5):993-4.
Inclusion body myositis presenting with isolated erector spinae paresis.
Hund E, Heckl R, Goebel HH, Meinck HM.
Department of Neurology, University of Heidelberg, Germany.
We report a 70-year-old patient who presented with a 4-year history of weakness
of paravertebral muscles. Electrodiagnostic studies revealed a mixed
neurogenic-myopathic pattern. Light microscopic examination revealed atrophic
fibers with rimmed vacuoles; electron microscopy demonstrated cytoplasmic and
intranuclear filaments measuring about 16 nm in width, consistent with the
diagnosis of inclusion body myositis. Therapy with corticosteroids provided
only
a mild and transient benefit. Ten months after the initial evaluation, clinical
and electrodiagnostic examination demonstrated mild progression of the disease.
Publication Types:
Case Reports
PMID: 7746422 [PubMed - indexed for MEDLINE]
413: Scand J Immunol. 1995 May;41(5):421-6.
Local T-cell proliferation and differentiation in inflammatory myopathies.
Lindberg C, Oldfors A, Tarkowski A.
Department of Clinical Neuroscience, Sahlgrenska Hospital, University of
Goteborg, Sweden.
Our objective was to investigate the patterns of proliferation and
differentiation of infiltrating cells in inflammatory myopathies.
Immunohistochemical staining was performed on muscle biopsy specimens from 18
patients with inclusion body myositis, polymyositis and dermatomyositis using
monoclonal and polyclonal antibodies. An abundance of cells were TNF-alpha+
(4-8%), ICAM-1+ (7-65%), IFN-gamma+ (3-6%), and Ki-67+ (4-8%). It was shown
that
70% of the Ki-67+ cells were Ki-67+CD3+ cells. Very few mononuclear cells were
IL-2R+. MHC-I expression was found on nearly all muscle fibres in all cases,
while MHC-II expression was found on occasional muscle fibres in 1/3 of cases.
Analysis of repeated biopsies from four IBM patients after prednisolone
treatment showed no change in the proportions of TNF-alpha, ICAM-1, IFN-gamma
or
Ki-67 positive cells. In inflammatory myopathies there is an intense
proliferation and differentiation of inflammatory cells in situ, indicating
a
local stimulation of the inflammatory process.
PMID: 7725060 [PubMed - indexed for MEDLINE]
414: J Rheumatol. 1995 Mar;22(3):576-8.
Inclusion body myositis responding to longterm chlorambucil treatment.
Jongen PJ, ter Laak HJ, Van de Putte LB.
Publication Types:
Case Reports
Letter
PMID: 7783093 [PubMed - indexed for MEDLINE]
415: Rheum Dis Clin North Am. 1995 Feb;21(1):179-202.
The treatment of myositis. How to approach resistant disease.
Adams EM, Plotz PH.
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health, Bethesda, Maryland, USA.
Idiopathic inflammatory myopathies, polymyositis, dermatomyositis, and inclusion
body myositis, are increasingly recognized to cause long-term disability in
certain subsets of patients. Because these diseases are infrequent, only
retrospective analysis of most treatments are available. In this article,
identification of subsets of patients with different prognoses and discussion
of
confounding factors for increasing weakness are emphasized. The advantages and
disadvantages of different therapies for myositis and for extraskeletal muscle
features are also discussed.
Publication Types:
Review
Review, Tutorial
PMID: 7732167 [PubMed - indexed for MEDLINE]
416: Neurosci Lett. 1995 Jan 2;183(1-2):35-8.
Apolipoprotein E type epsilon 4 allele frequency is not increased in patients
with sporadic inclusion-body myositis.
Harrington CR, Anderson JR, Chan KK.
Cambridge Brain Bank Laboratory, Department of Psychiatry, University of
Cambridge Clinical School, UK.
The apolipoprotein E genotype was determined for 11 patients with sporadic
inclusion-body myositis. Seven cases had the genotype epsilon 3/epsilon 3, the
other four cases, epsilon 3/epsilon 4. The frequency of the epsilon 4 allele
in
this group of patients (0.182) was not significantly increased compared with
elderly controls (0.147; n = 58), in contrast to Alzheimer's disease in which
there was a significant increase (0.328; n = 67). The epsilon 2 allele was not
found in any of the 11 sporadic inclusion-body myositis patients and its
frequency was decreased in Alzheimer's disease. Despite certain pathological
similarities that exist between inclusion body myositis and Alzheimer's disease,
their association with particular apolipoprotein E genotypes is distinct.
PMID: 7746481 [PubMed - indexed for MEDLINE]
417: Acta Neuropathol (Berl). 1995;90(5):467-71.
Tau protein immunoreactivity in muscle fibers with rimmed vacuoles differs
from
that in regenerating muscle fibers.
Murakami N, Ishiguro K, Ihara Y, Nonaka I, Sugita H, Imahori K.
Department of Ultrastructural Research, National Center of Neurology and
Psychiatry, Tokyo, Japan.
To determine whether tau protein found in muscle fibers with rimmed vacuoles
and
in regenerating fibers was phosphorylated, we examined eight muscle biopsy
samples containing rimmed vacuoles (from five patients with distal myopathy
with
rimmed vacuole formation and three patients with inclusion body myositis) and
three muscle biopsy samples from patients with Duchenne muscular dystrophy
containing numerous regenerating fibers. Although both rimmed vacuolated and
regenerating fibers had increased immunoreactivity against tubulin and tau
protein, tau protein in the former was more highly phosphorylated than that
in
the latter. While very few microtubules in muscle fibers with rimmed vacuoles
were recognizable by electron microscopy, regenerating fibers, especially
immature ones, contained numerous microtubules. Since tau protein found in
vacuolated fibers is hyperphosphorylated, it can be considered to have reduced
ability to bind tubulin molecules. Thus, the tau protein cannot stabilize
microtubules, resulting in their depolymerization even in the presence of
tubulin molecules.
PMID: 8560979 [PubMed - indexed for MEDLINE]
418: Ann Neurol. 1995 Jan;37(1):24-9.
Comment in:
Ann Neurol. 1995 Aug;38(2):273-4.
Ragged red fibers in normal aging and inflammatory myopathy.
Rifai Z, Welle S, Kamp C, Thornton CA.
Department of Neurology, University of Rochester, NY 14642.
Ragged red fibers are an important marker for mitochondrial disease. To evaluate
the hypothesis that mitochondrial dysfunction may play a role in the
pathogenesis of aging and inclusion body myositis, we studied the frequency
of
ragged red fibers in muscle biopsy specimens from 15 young and 13 old normal
adults, and from 27 patients with inclusion body myositis, polymyositis, or
dermatomyositis. Serial transverse cryostat sections were stained with modified
Gomori trichrome, modified succinic dehydrogenase, and cytochrome c oxidase.
The
frequency of ragged red fibers, determined by measuring the percent number of
succinic dehydrogenase-positive ragged red fiber equivalents, was significantly
higher in old compared to young normal subjects (0.33 vs. 0.02%, p < 0.0001).
With the exception of a single polymyositis biopsy specimen showing a large
number of ragged red fibers, the frequency of ragged red fibers in patients
with
polymyositis or dermatomyositis was similar to that of age-matched normal
control subjects. The frequency of ragged red fibers was more than 1% in 7 of
8
patients with inclusion body myositis (maximum, 15%). The modified succinic
dehydrogenase stain was more sensitive than the modified Gomori trichrome in
detecting accumulation of mitochondria in muscle fibers. Cytochrome c oxidase
activity was deficient in most ragged red fibers. We conclude that the number
of
ragged red fibers increases with normal aging and may reflect an age-related
decline in muscle mitochondrial oxidative metabolism. The frequent occurrence
of
ragged red fibers in inclusion body myositis suggests that mitochondrial
function may be impaired in this disease.
PMID: 7818253 [PubMed - indexed for MEDLINE]
419: Neuromuscul Disord. 1995 Jan;5(1):31-8.
Rimmed basophilic vacuoles and filamentous inclusions in neuromuscular
disorders.
Jongen PJ, Ter Laak HJ, Stadhouders AM.
Department of Neurology, University Hospital Nijmegen, The Netherlands.
To study the incidence of rimmed basophilic vacuoles (RBV) and 15-21 nm
filamentous inclusions in neuromuscular disorders, other than inclusion body
myositis (IBM) and to determine the diagnostic value of RBV quantitation in
the
differential diagnosis of IBM, we reviewed 1600 muscle biopsies for RBV and
750
biopsies for filamentous inclusions. The number of RBV-positive fibers per 10
mm2--the RBV-fiber density--was determined. The incidence of RBV in non-IBM
biopsies was 8.8 per 1000. Major diagnostic categories were neurogenic disorders
(n = 7) and limb girdle muscular dystrophies (LGMD) (n = 3). In IBM (n = 7)
the
RBV-fiber density ranged from 10.4 to 63.1 and was significantly higher than
in
neurogenic disorders (0.9-4.4) and LGMD (1.1-2.7). The highest value was found
in rigid spine syndrome (205.8). Filamentous inclusions were seen in 2.7 per
1000 non-IBM biopsies, including familial oculopharyngeal muscular dystrophy
with distal myopathy (OPMD-DM), rigid spine syndrome, acid maltase deficiency
and amyloid neuropathy. RBV and filamentous inclusions coexisted in rigid spine
syndrome and in familial OPMD-DM. RBV, as well as filamentous inclusions, has
a
very low incidence in non-IBM neuromuscular disorders; the RBV-fiber density
may
help to discriminate neurogenic disorders and LGMD from IBM.
PMID: 7719139 [PubMed - indexed for MEDLINE]
420: Acta Neuropathol (Berl). 1995;89(1):29-34.
Muscle fiber degeneration in distal myopathy with rimmed vacuole formation.
Murakami N, Ihara Y, Nonaka I.
Department of Ultrastructural Research, National Center of Neurology and
Psychiatry (NCNP), Tokyo, Japan.
In 11 patients with distal myopathy with rimmed vacuole formation (DMRV), a
well-known autosomal recessively inherited disorder, the rimmed vacuole
formation appears to be the main pathological change accounting for the
progressive muscle fiber degeneration. To gain a better understanding of the
pathophysiology of the vacuole formation, we applied Congo red and
immunohistochemical stains to muscle biopsies from these patients and the
results were compared with those of patients with inclusion body myositis (IBM).
The vacuoles in DMRV contained Congophilic amyloid material and deposits
immunoreactive for beta-amyloid protein, both the NH2 and COOH termini of
beta-amyloid protein precursor, ubiquitin, and tau protein. These results were
similar to those seen in our present cases of IBM as well as in previously
reported cases. Therefore, there may be no pathogenetic differences in the
formation of rimmed vacuoles in DMRV and IBM. Nevertheless, the degenerative
process involved in rimmed vacuole formation in various diseases may share a
common pathogenetic mechanism with that in amyloid-plaque formation in
Alzheimer's disease brain as has been proposed previously.
PMID: 7709728 [PubMed - indexed for MEDLINE]
421: Am J Pathol. 1994 Dec;145(6):1280-4.
Comment in:
Am J Pathol. 1994 Dec;145(6):1261-4.
Abnormal accumulation of prion protein mRNA in muscle fibers of patients with
sporadic inclusion-body myositis and hereditary inclusion-body myopathy.
Sarkozi E, Askanas V, Engel WK.
Department of Neurology, University of Southern California School of Medicine,
Los Angeles.
Sporadic inclusion-body myositis is the most common progressive muscle disease
of older patients. The muscle biopsy demonstrates mononuclear cell inflammation
and vacuolated muscle fibers containing paired helical filaments and 6 to 10-nm
fibrils, both resembling those of Alzheimer brain, and Congo-red positivity.
Hereditary inclusion-body myopathy designates patients cytopathologically
similar but without inflammation. In both muscle diseases, prion, and several
proteins characteristic of Alzheimer brain--eg, beta-amyloid protein and
hyperphosphorylated tau (which normally are expressed mainly in neurons), and
apolipoprotein E--are abnormally accumulated in vacuolated muscle fibers, by
unknown mechanisms. We now demonstrate in both muscle diseases that prion mRNA
is strongly expressed in the vacuolated muscle fibers, which suggests that their
accumulated prion protein results, at least partly, from increased gene
expression. This, to our knowledge, is the first demonstration of abnormally
increased prion mRNA in human disease. Another novel finding is the increased
prion mRNA in human muscle macrophages, and both increased prion protein and
prion mRNA in regenerating muscle fibers. The latter indicates that prion may
play a role in human muscle development.
PMID: 7992832 [PubMed - indexed for MEDLINE]
422: Eur J Immunol. 1994 Nov;24(11):2659-63.
Restricted use of T cell receptor V genes in endomysial infiltrates of patients
with inflammatory myopathies.
Lindberg C, Oldfors A, Tarkowski A.
Department of Clinical Neuroscience, Sahlgrenska Hospital, University of
Gothenburg, Goteborg, Sweden.
Inclusion body myositis (IBM), polymyositis (PM) and dermatomyositis (DM) are
diseases characterized clinically by progressive muscle weakness and
histologically by T lymphocyte infiltrates in striated muscle. The pathogenetic
role of these cells is proposed to be cell-mediated cytotoxicity in PM and IBM,
but the exact mechanisms of their action are poorly understood. Characterization
of the variable regions of T cell receptors (TcR) on the infiltrating
lymphocytes may be expected to provide insights into the mechanisms of local
activation of the immune system in inflammatory myopathies. Immunohistochemical
analysis using a panel of monoclonal antibodies specific for 11 V alpha/beta
TcR
was performed on cryosectioned muscle biopsy specimens from eight patients with
IBM, eight with PM and three with DM. In addition, TcR expression was studied
in
inflammatory infiltrates in skin biopsies obtained from some of the IBM patients
challenged locally with tuberculin. Flow cytometry was used to assess expression
of TcR on peripheral blood lymphocytes. All the patients displayed a clear
restriction of TcR usage, preferentially limited to V alpha 2 and V beta 3 TcR
families in the endomysial, but not in perivascular infiltrates, even within
the
same muscle specimen. Such a restriction was not found in skin punch biopsies
or
PBL from the same subjects. Our results suggest that T cells extravasate
non-selectively to the skeletal muscle, but once there, only certain TcR
families proliferate, presumably after encounter with a locally exposed
superantigen.
PMID: 7957558 [PubMed - indexed for MEDLINE]
423: Curr Opin Rheumatol. 1994 Nov;6(6):595-601.
Current treatment of the inflammatory myopathies.
Dalakas MC.
Medical Neurology Branch, National Institute of Neurological Disorders and
Stroke, National Institutes of Health, Bethesda, MD 20892-1382.
Among the main concerns regarding the current therapy for the inflammatory
myopathies are a lack of adequate controlled trials, a lack of objective means
to reliably measure muscle strength, lack of natural history data, consideration
of polymyositis, dermatomyositis, and inclusion-body myositis as a homogeneous
group of inflammatory myopathies, and reliance on nonspecific markers for
determining prognosis and assessing response to therapies. Prednisone remains
the drug of choice in treating these disorders, although a controlled trial
has
never been undertaken to study its efficacy. Among the steroid-sparing agents,
azathioprine, methotrexate, cyclosporine, and chlorambucil are used with
invariably low to moderate success. There are no results of controlled trials
to
indicate whether one of these drugs is superior to another. Intravenous
immunoglobulin, which is very expensive, was shown in a controlled trial to
be
effective in steroid-resistant dermatomyositis not only in dramatically
improving muscle strength and skin rash but also in resolving the underlying
immunopathology. Controlled trials of intravenous immunoglobulin in patients
with polymyositis and inclusion-body myositis are under way. Inclusion-body
myositis has emerged as a common inflammatory myopathy that is predictably
disabling and resistant to most therapies.
Publication Types:
Review
Review, Tutorial
PMID: 7865379 [PubMed - indexed for MEDLINE]
424: Curr Opin Rheumatol. 1994 Nov;6(6):568-74.
Cellular aspects of myositis.
Mantegazza R, Bernasconi P.
Department of Neuromuscular Diseases, National Neurological Institute C. Besta,
Milan, Italy.
Polymyositis, dermatomyositis, and inclusion-body myositis are characterized
by
muscle cell infiltration and specific alterations on or within muscle fibers.
Infiltrating immune cells (ie, T or B lymphocytes, macrophages, and natural
killer cells) have distinctive distributions in these conditions: increased
presence of CD8+/MHC I-restricted T lymphocytes at endomysial sites in
polymyositis and more B than T lymphocytes perivascularly in muscles of
dermatomyositis patients. Muscle-infiltrating T lymphocytes mainly express alpha
beta T cell receptors (TCRs) in polymyositis; they also express TCRs
characterized by oligoclonal V beta repertoire, with a consensus motif
indicating a conventional antigen as target of the immune attack. In
inclusion-body myositis, TCRs with oligoclonal V beta also are found, but no
consensus motif has been identified, suggesting possible superantigen
involvement in lymphocyte recruitment. Sequence analysis of TCRs in these
lymphocytes has provided insight into the probable nature of the antigenic
stimulus and into recruitment of these cells to the inflammation sites. T cell-
or natural killer cell-mediated cytotoxic agents have been characterized by
messenger RNA or protein expression in these inflammatory myopathies, and the
roles of other cytokines in the inflammation processes have been determined.
In
vivo and in vitro studies on muscle cells have assessed their functions as
target cells or antigen-presenting cells. Combined molecular and cellular
immunology studies on effector and target cells are expected to clarify the
pathogenetic mechanisms underlying these inflammatory myopathies in the near
future.
Publication Types:
Review
Review, Tutorial
PMID: 7865375 [PubMed - indexed for MEDLINE]
425: Rheum Dis Clin North Am. 1994 Nov;20(4):955-72.
Inclusion body myositis.
Calabrese LH, Chou SM.
Cleveland Clinic Foundation, Ohio.
IBM remains a poorly understood form of idiopathic inflammatory myopathy,
although great progress in the areas of clinical recognition and pathophysiology
have been made recently. The question of whether therapy can favorably influence
short- and/or long-term outcome is still unanswered. Several recent reports
suggest some possibility of at least slowing progression with immunosuppressive
therapy. Long-term therapeutic trials with goals that include stabilization,
rather than improvements in strength, are urgently needed.
Publication Types:
Review
PMID: 7855331 [PubMed - indexed for MEDLINE]
426: Rheum Dis Clin North Am. 1994 Nov;20(4):943-53.
Relationship of cancer to inflammatory muscle diseases. Dermatomyositis,
polymyositis, and inclusion body myositis.
Callen JP.
University of Louisville School of Medicine, Kentucky.
Dermatomyositis (DM) is probably associated with a greater frequency of
malignancy than expected in the general population. For polymyositis (PM), there
does not appear to be greatly increased risks. Ovarian cancer may be
over-represented in women with DM. A paraneoplastic course occurs in some
patients with DM, but is unusual. Even young patients with DM should be
evaluated. The malignancy evaluation should be directed by symptoms, findings
on
physical examination or laboratory testing, or be age-appropriate.
Publication Types:
Review
PMID: 7855330 [PubMed - indexed for MEDLINE]
427: Rheum Dis Clin North Am. 1994 Nov;20(4):811-26.
Classification and prognosis of inflammatory muscle disease.
Miller FW.
Center for Biologics Evaluation and Research, Food and Drug Administration,
Bethesda, Maryland.
Although our understanding of the inflammatory myopathies is still evolving,
it
is becoming increasingly clear that these syndromes are composed of many
separate and distinct disorders with widely divergent clinical signs, symptoms,
laboratory abnormalities, and prognoses. Their classification remains
controversial, but three approaches of dividing the myositis syndromes appear
useful in helping to group disorders with similar features together. The three
approaches divide these syndromes on the basis of clinical and histopathologic
findings, by serology, and by exposures to known environmental agents. Studies
of the prognosis of these disorders are limited by the rarity and heterogeneity
of the myositis syndromes. Taken together, however, they suggest that a variety
of demographic, clinical, and serologic features are associated with a poor
outcome. These include older age at myositis onset, severe myositis, delay to
diagnosis and therapy, significant cardiac, pulmonary or gastrointestinal
involvement, and the presence of cancer, inclusion body myositis, or
antisynthetase or anti-SRP auto-antibodies. It is hoped that our understanding
of the classification and prognosis of the inflammatory myopathies will become
more complete as we perceive more fully the interrelationships between the
genetic and environmental risk factors necessary for the induction of myositis
and develop more rational ways of dividing and treating these increasingly
recognized syndromes.
Publication Types:
Review
Review, Tutorial
PMID: 7855323 [PubMed - indexed for MEDLINE]
428: Clin Exp Immunol. 1994 Oct;98(1):40-5.
HLA associations with inclusion body myositis.
Garlepp MJ, Laing B, Zilko PJ, Ollier W, Mastaglia FL.
Australian Neuromuscular Research Institute, Queen Elizabeth II Medical Centre,
Nedlands.
Inclusion body myositis (IBM) is defined clinically by a characteristic pattern
of progressive proximal and distal limb muscle weakness and resistance to
steroid therapy, and histologically by the presence of distinctive rimmed
vacuoles and filamentous inclusions as well as a mononuclear infiltrate in which
CD8+ T cells are predominant. Muscle damage is believed to be mediated by
autoimmune mechanisms, but very little information is available on the
immunogenic features of IBM. MHC class I and DR antigens were typed on 13
caucasoid patients with IBM using standard serological techniques or by
allele-specific oligonucleotide typing. Complement components C4 and properdin
factor B (Bf) were typed by immunofixation after electrophoresis. Restriction
fragment length polymorphisms (RFLP) in the class III region were analysed using
cDNA probes for C4 and 21-hydroxylase (CYP21) after Taq 1 digestion. IBM was
associated with DR3 (92%), DR52 (100%) and HLA B8 (75%). The phenotype data
were
examined for likely haplotypes by considering together the alleles at the class
I, DR and complement loci along with the C4 and CYP21 RFLP. Ten of the DR3+
subjects had a 6.4-kb C4-hybridizing fragment characteristic of a deletion of
C4A and CYP21-A. These patients probably carried all, or at least the class
II
and III regions, of the extended haplotype marked by
B8/C4A*Q0/C4B1/BfS/DR3/DR52, which has been associated with several autoimmune
diseases and is present in 11% of the healthy caucasoid population. Of the
remaining subjects, two had evidence of the extended haplotype marked by
B18/C4A3/C4BW*0/BfF1/DR3, which is present in less than 5% of the healthy
population and has been associated with insulin-dependent diabetes mellitus.
These data provide support for an autoimmune etiology for, and genetic
predisposition to, IBM.
PMID: 7923882 [PubMed - indexed for MEDLINE]
429: Curr Opin Neurol. 1994 Oct;7(5):448-56.
Idiopathic inflammatory myopathies: inclusion-body myositis, polymyositis,
and
dermatomyositis.
Askanas V, Engel WK, Mirabella M.
University of Southern California School of Medicine, Department of Neurology,
Los Angeles 90017-1912.
In this review, the main emphasis is on new advances concerning sporadic
inclusion-body myositis and hereditary inclusion-body myopathy. Polymyositis
and
dermatomyositis are reviewed briefly. Hypotheses are presented regarding the
possible cause and significance of abnormally accumulated beta-amyloid protein,
two other epitopes of beta-amyloid precursor protein, hyperphosphorylated tau,
alpha 1-antichymotrypsin, ubiquitin, and prion protein in sporadic
inclusion-body myositis and hereditary inclusion-body myopathy. Because most
of
those proteins are also accumulated at the neuromuscular junction,
"junctionalization" of other muscle fiber nuclei is a possibility.
Attention is
given to the fact that vacuolated muscle fibers in hereditary inclusion-body
myopathy may represent early changes because they are virtually free of
congophilic amyloid deposit but, like sporadic inclusion-body myositis, contain
large accumulations of beta-amyloid protein and prion.
Publication Types:
Review
Review, Tutorial
PMID: 7804466 [PubMed - indexed for MEDLINE]
430: Neurology. 1994 Aug;44(8):1516-8.
Inclusion body myositis: treatment with intravenous immunoglobulin.
Amato AA, Barohn RJ, Jackson CE, Pappert EJ, Sahenk Z, Kissel JT.
Department of Neurology, Wilford Hall Medical Center, Lackland Air Force Base,
TX.
We report the results of nine patients with inclusion body myositis treated
with
intravenous immunoglobulin in an open-label uncontrolled study. None of our
patients improved on objective manual muscle testing or functional disability
scores. One patient developed mild neutropenia, complicating the intravenous
immunoglobulin treatment. Our results do not exclude the possibility that
intravenous immunoglobulin could be beneficial in some patients by slowing the
rate of deterioration or perhaps stabilizing the disease. However, given the
lack of objective improvement and high cost of treatment, we would not recommend
intravenous immunoglobulin in the treatment of inclusion body myositis unless
a
blinded, controlled trial demonstrates clear benefit.
PMID: 8058161 [PubMed - indexed for MEDLINE]
431: J Neuropathol Exp Neurol. 1994 Jul;53(4):369-76.
Expression of cell adhesion molecules in inflammatory myopathies and Duchenne
dystrophy.
De Bleecker JL, Engel AG.
Neuromuscular Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905.
Cell adhesion molecules participate in target-effector cell interactions in
cell-mediated cytotoxicity and in leukodiapedesis in inflammatory diseases.
Two
ligand-receptor pairs may play a role in the adhesion of cytotoxic T cells to
their targets: 1) intercellular adhesion molecule-1 (ICAM-1) and lymphocyte
function-associated antigen-1 (LFA-1), and 2) LFA-3 and CD2. We therefore
immunolocalized these molecules in myopathies where there is evidence for T
cell-mediated myocytotoxicity, namely inclusion body myositis, polymyositis,
and
Duchenne dystrophy. Autoaggressive inflammatory cells close to invaded muscle
fibers showed an increased expression of ICAM-1 and LFA-1. The nonnecrotic
muscle fibers invaded by autoaggressive cells expressed ICAM-1 where their
surfaces faced the invading cells. That immunoreactivity for ICAM-1 on the
invading cells was distinct from that on the opposite muscle fiber surface was
established by colocalization of ICAM-1 with the sarcolemmal marker dystrophin
(or beta-spectrin) and was also confirmed by confocal microscopy.
Leukodiapedesis in inflamed tissues is mediated by ICAM-1, LFA-3, vascular cell
adhesion molecule-1 (VCAM-1), and E-selectin associated with endothelial cells.
In dermatomyositis ICAM-1 was strongly expressed on endothelial cells of
perimysial arterioles and venules and on some perifascicular capillaries. In
all
the other myopathies ICAM-1 and LFA-3 expressions were increased on endothelia
of capillaries surrounded by inflammatory cells. VCAM-1 was detected in few
arterioles in all diseases. E-selectin was not detected at any site in any
disorder.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 8021710 [PubMed - indexed for MEDLINE]
432: Neuropathol Appl Neurobiol. 1994 Jun;20(3):238-42.
Absence of Coxsackie viruses in idiopathic inflammatory muscle disease by in
situ hybridization.
Hilton DA, Fletcher A, Pringle JH.
Department of Neuropathology, Frenchay Hospital, Bristol, UK.
The role of coxsackie virus infection in the pathogenesis of idiopathic
inflammatory muscle disease (IIMD) has been investigated by many workers with
conflicting results. This study uses in situ hybridization, with
digoxigenin-labelled oligonucleotide probes complementary to the coxsackie B
virus genome, to investigate the presence of virus RNA in muscle biopsies from
26 patients with IIMD. In the five cases of inclusion body myositis studied,
there was focal probe-binding to nuclei and cytoplasm, and in nine cases
probe-binding to mast cells was seen. In both of these instances probe-binding
was non-specific and not due to hybridization. None of the cases showed the
presence of coxsackie virus RNA within muscle and it is concluded that lytic
infection of myocytes by coxsackie virus does not occur in IIMD.
PMID: 7936073 [PubMed - indexed for MEDLINE]
433: J Autoimmun. 1994 Jun;7(3):321-33.
The alpha beta T-cell receptor repertoire in inclusion body myositis: diverse
patterns of gene expression by muscle-infiltrating lymphocytes.
O'Hanlon TP, Dalakas MC, Plotz PH, Miller FW.
Laboratory of Molecular Immunology, National Institute of Neurological Disorders
and Stroke, National Institutes of Health, Bethesda, MD 20892.
Inclusion body myositis (IBM) is one member of a group of disorders known as
idiopathic inflammatory myopathies (IIM) in which autoreactive T cells directed
against muscle are thought to play a primary role in disease pathogenesis. We
have utilized the polymerase chain reaction to determine the pattern of alpha
beta T-cell receptor (TCR) variable (V) gene expression in muscle biopsies from
13 IBM patients. In the majority of biopsies, we detected oligoclonal patterns
of TCR V gene expression by muscle-infiltrating lymphocytes; an average of six
out of the 22 TCR V alpha gene families surveyed and seven out of 24 TCR V beta
gene families surveyed were detected per biopsy. While no TCR V alpha gene
families were over-represented in our survey, TCR V beta 3 and V beta 6 gene
usage was a prominent feature of IBM muscle biopsies. TCR gene expression was
characterized further by analysing the junctional sequence composition of both
V
beta 3 and V beta 6 clones from muscle biopsies of the IBM patients. A large
number of structurally diverse V beta 3 and V beta 6 clonotypes were identified
from these patients demonstrating a polyclonal pattern of T cell infiltration.
These data, while describing prominent TCR V beta 3 and V beta 6 gene detection,
do not suggest that a common antigen-driven T-cell response promotes chronic
inflammation in muscle of IBM patients.
PMID: 7916906 [PubMed - indexed for MEDLINE]
434: Am J Pathol. 1994 May;144(5):874-82.
Conspicuous accumulation of a single-stranded DNA binding protein in skeletal
muscle fibers in inclusion body myositis.
Nalbantoglu J, Karpati G, Carpenter S.
Department of Neurology-Neurosurgery, McGill University, Montreal, Quebec,
Canada.
In muscle biopsies from patients with inclusion body myositis (IBM), multiple
sites were found in many muscle fibers that bound single-stranded but not
double-stranded DNA without sequence specificity, as exemplified by several
different cDNA probes. This activity was attributable to a protein, because
it
was abolished by proteases but not by RNAse. Most of the sites of binding were
myonuclei, whereas some were rimmed vacuoles, which probably result from nuclear
breakdown. No comparable binding was seen in 27 control biopsies. A number of
human and viral single-stranded DNA binding proteins exist but our data does
not
identify the protein responsible for DNA binding in IBM. Our findings reinforce
the supposition that nuclear damage plays a basic role in the pathogenesis of
IBM.
PMID: 8178939 [PubMed - indexed for MEDLINE]
435: Neuromuscul Disord. 1994 May;4(3):219-26.
Immunohistochemical analysis of perforin and granzyme A in inflammatory
myopathies.
Orimo S, Koga R, Goto K, Nakamura K, Arai M, Tamaki M, Sugita H, Nonaka I,
Arahata K.
National Institute of Neuroscience, National Center of Neurology and Psychiatry
(NCNP), Tokyo, Japan.
Perforin (PF) and granzyme A (GA) are candidates suspected of being cytolytic
proteins of the granules of cytotoxic T lymphocytes (CTLs) and natural killer
(NK) cells. We analysed PF and GA in muscles from patients with inflammatory
myopathies. Five cases of polymyositis (PM), two cases of inclusion body
myositis (IBM), and five cases of dermatomyositis (DM) were studied
immunohistochemically using anti-PF and GA antibodies raised against each
synthetic peptide of human PF and mouse GA, together with a panel of monoclonal
antibodies reactive for lymphocyte subsets. In PM and IBM, PF positive cells
were colocalized with GA positive cells and occasionally invaded into the
non-necrotic muscle fibres. The percentage of PF positive cells among the
endomysial CD8 positive cell population was 9.9% (PM) and 12.5% (IBM), and the
majority of the endomysial CD8 positive cells were alpha/beta T cells. In
contrast, in DM, both PF and GA positive cells were very few in all cases. Only
few inflammatory cells were CD16+ or CD57+ NK cells among these diseases. Our
results suggest that PF and GA are secreted mainly from alpha/beta T cells,
and
may play a key role in muscle fibre damage in at least some PM and IBM, but
not
in DM.
PMID: 7919969 [PubMed - indexed for MEDLINE]
436: Acta Neurol Scand. 1994 Feb;89(2):123-31.
Inclusion body myositis: clinical, morphological, physiological and laboratory
findings in 18 cases.
Lindberg C, Persson LI, Bjorkander J, Oldfors A.
Department of Neurology, Sahlgrenska Hospital, University of Gothenburg, Sweden.
Eighteen consecutive patients with inclusion body myositis (IBM) were studied.
The mean age of onset of symptoms was 60 years. A typical clinical pattern with
insidious onset of muscle weakness in knee extensors and finger flexors combined
with dysphagia was observed. Serial measurements of the maximal voluntary muscle
strength revealed a mean loss of muscle strength of 1.4% per month. Two of the
cases had common variable immunodeficiency, and three cases had reduced levels
of the IgG3 subclass. Treatment with prednisone resulted in a temporary
improvement of muscle function in three patients. No positive effect of
azathioprine or cyclosporine A could be documented. The results show that IBM
may be associated with immunodeficiency, and that prednisone treatment may
temporarily improve the clinical signs. The results from our studies on the
progression of the muscle weakness may provide basis for future studies on
treatment of IBM.
PMID: 8191875 [PubMed - indexed for MEDLINE]
437: J Rheumatol. 1994 Feb;21(2):344-6.
Inclusion body myositis in association with rheumatoid arthritis.
Soden M, Boundy K, Burrow D, Blumbergs P, Ahern M.
Rheumatology Unit, Repatriation General Hospital, Daw Park, South Australia.
We describe 2 patients with rheumatoid arthritis (RA) and inclusion body
myositis (IBM). Examination and laboratory tests including muscle biopsy with
frozen section and electron microscopy were performed. Both patients fulfilled
diagnostic criteria for IBM, which is increasingly recognized in association
with autoimmune disease. A high index of suspicion and early thorough
investigation are required to diagnose IBM in patients with RA.
Publication Types:
Case Reports
PMID: 8182647 [PubMed - indexed for MEDLINE]
438: Am J Pathol. 1994 Jan;144(1):177-87.
Twisted tubulofilaments of inclusion body myositis muscle resemble paired
helical filaments of Alzheimer brain and contain hyperphosphorylated tau.
Askanas V, Engel WK, Bilak M, Alvarez RB, Selkoe DJ.
Department of Neurology, University of Southern California School of Medicine,
Los Angeles.
We immunostained muscle biopsies of 8 patients with sporadic inclusion body
myositis (S-IBM), 7 patients with autosomal recessive hereditary inclusion body
myopathy (H-IBM) (both diseases being characterized by similar muscle fiber
vacuoles containing inclusions), and 11 normal and disease controls. We used
the
following well-characterized antibodies against tau protein: Tau-1, Alz-50,
and
anti-paired helical filament (PHF) antiserum. By light microscopy, in all S-IBM
muscle biopsies virtually all vacuoles immunoreactive for ubiquitin and
beta-amyloid protein also contained inclusions immunoreactive with Alz-50 and
anti-PHF antiserum. With tau-1 antibody, strong immunoreactivity in the vacuoles
was obtained only after dephosphorylation of muscle sections. By
electronmicroscopy, all three antibodies immunodecorated exclusively cytoplasmic
twisted tubulofilaments (TTFs). In H-IBM, virtually all ubiquitin and
beta-amyloid-positive muscle fiber vacuoles contained inclusions immunoreactive
with anti-PHF antiserum, but in only 40% of those fibers were the inclusions
immunoreactive with Alz-50. In six H-IBM patients there were no tau-1
immunoreactive inclusions in any of their vacuolated muscle fibers; in one
patient, 24% of the vacuolated fibers had tau-1 immunoreactivity. By
demonstrating that hyperphosphorylated tau, which is characteristic of Alzheimer
brain PHFs, is a component of S-IBM-muscle TTFs (which are also
ultrastructurally similar to PHFs), our study: 1) provides the first
demonstration of abnormally accumulated tau in nonneural tissue and 2) suggests
that the cytopathogenesis in Alzheimer brain and S-IBM muscle may share some
similar mechanisms. Whether the difference in tau immunoreactivity between S-IBM
and most of the H-IBM patients reflects a difference in genetically determined
transcriptional or posttranslational modifications of tau protein or other
factors remains to be determined.
PMID: 8291607 [PubMed - indexed for MEDLINE]
439: Curr Opin Rheumatol. 1994 Jan;6(1):68-77.
Clinical aspects of amyloidosis, including related proteins and central nervous
system amyloid.
Cohen AS.
Arthritis and Amyloid Center, Boston University School of Medicine, MA 02118.
In the beta/A4 protein of Alzheimer's disease, on chromosome 21, three mutations
at the same locus have been described (Val 717 Ile, Val 171 Phe, and Val 171
Gly). The heterogeneity of the disease was indicated in individuals with
mutations involving chromosomes 19 and 14 as well. beta Protein has also been
demonstrated in the rimmed vacuoles of inclusion-body myositis. Therapeutic
advances include orthotopic liver transplantation to remove the site of
synthesis of the mutant transthyretin molecule. Clinical manifestations of the
various forms of amyloidosis involve virtually every system in the body; the
breadth of the curious series of proteins called amyloid has been extended
considerably in the past year.
Publication Types:
Review
PMID: 7913335 [PubMed - indexed for MEDLINE]
440: Clin Exp Immunol. 1994 Jan;95(1):166-72.
MHC class I, MHC class II and intercellular adhesion molecule-1 (ICAM-1)
expression in inflammatory myopathies.
Bartoccioni E, Gallucci S, Scuderi F, Ricci E, Servidei S, Broccolini A, Tonali
P.
Institute of General Pathology, Catholic University, Rome, Italy.
We investigated the relationship between the MHC-I, MHC-II and intercellular
adhesion molecule-1 (ICAM-1) expression on myofibres and the presence of
inflammatory cells in muscle specimens of 18 patients with inflammatory
myopathies (nine polymyositis, seven dermatomyositis, two inclusion body
myositis). We observed MHC-I expression in muscle fibres, infiltrating
mononuclear cells and endothelial cells in every specimen. In seven patients,
some muscle fibres were MHC-II-positive for the DR antigen, while the DP and
DQ
antigens were absent. ICAM-1 expression, detected in seven patients, was found
in clusters of myofibres, associated with a marked MHC-I positivity and a
widespread mononuclear infiltration. Most of the ICAM-1-positive fibres were
regenerating fibres. Furthermore, some fibres expressed both ICAM-1 and DR
antigens near infiltrating cells. This finding could support the hypothesis
that
myofibres may themselves be the site of autosensitization.
PMID: 7507012 [PubMed - indexed for MEDLINE]
441: Curr Opin Neurol. 1993 Dec;6(6):872-81.
Alzheimer's disease and Creutzfeldt-Jakob disease: overlap of pathogenic
mechanisms.
DeArmond SJ.
Department of Pathology, University of California, San Francisco 94143-0506.
This article compares beta-amyloid precursor protein (beta-APP) disorders
exemplified by Alzheimer's disease (AD), with prion protein (PrP) disorders,
exemplified by Creutzfeldt-Jakob disease (CJD) in humans and scrapie in animals.
Although there are obvious differences in the etiology and pathogenesis of both
sets of disorders, a remarkable number of similarities exist. Both sets of
disorders are characterized clinically by age-related sporadic and familial
diseases. In both, an abnormal form of a neuronal membrane protein appears to
play a key role in the pathogenesis: beta-A4 peptide in AD and PrPCJD in CJD.
Both beta-A4 and PrPCJD are amyloidogenic. Neuritic plaques characteristic of
AD
were once thought to be exclusively associated with beta-A4 amyloid; however,
some pedigrees with familial prion disease produced neuritic plaques with PrP
amyloid cores. Finally, beta-APP accumulation in skeletal muscle has been
implicated in the age-related muscle disorder, inclusion body myositis. A
similar myopathy has recently been discovered in transgenic mice expressing
high
levels of normal PrP. These similarities suggest that what is learned about
one
set of disorders may be applicable to the other.
Publication Types:
Review
Review, Tutorial
PMID: 7904883 [PubMed - indexed for MEDLINE]
442: Baillieres Clin Neurol. 1993 Nov;2(3):717-40.
Treatment of inflammatory myopathies.
Mastaglia FL, Laing BA, Zilko P.
University of Western Australia, Perth.
Although there have been considerable advances in our understanding of the
immunopathogenesis of the different forms of autoimmune inflammatory myopathy,
the treatment of these conditions remains largely empirical, being based upon
the use of immunosuppressive and immunomodulatory therapies which, for the most
part, are non-selective in their actions. Corticosteroids are usually effective
in adult and childhood cases of polymyositis and dermatomyositis, but are only
rarely helpful in inclusion body myositis, which is usually also unresponsive
to
other forms of immunosuppressive therapy. Alternate-day corticosteroid therapy
has a role in patients with mild disease and as a means of minimizing the
side-effects of steroids. This may also be achieved by the early introduction
of
a second-line agent such as methotrexate or azathioprine, which will allow more
rapid steroid withdrawal and may also improve the chances of inducing a
remission in more severe cases. In patients who fail to respond adequately to
oral corticosteroids, or who relapse after an initial response, intravenous
immunoglobulin therapy or pulse therapy with intravenous methylprednisolone
are
promising approaches which appeal as safer alternatives to cytotoxic drugs.
However these forms of treatment will require further evaluation in prospective
clinical trials. The same applies to cyclosporin, which has a more selective
action on T cells, and which has been reported to be effective in resistant
cases of adult and juvenile polymyositis and dermatomyositis. In the longer
term, the development of more specific forms of immunotherapy for these
myopathies, aimed at blocking autoantigen presentation or its interaction with
T
cells, awaits the identification of the target antigens and T cells which
initiate the autoimmune process.
Publication Types:
Review
Review, Tutorial
PMID: 8156149 [PubMed - indexed for MEDLINE]
443: Baillieres Clin Neurol. 1993 Nov;2(3):617-35.
Cellular mechanisms in inflammatory myopathies.
Hohlfeld R, Goebels N, Engel AG.
Department of Neurology, Ludwig-Maximilians University, Munich, Germany.
Cell-mediated immune mechanisms play a prominent role in inclusion body myositis
(IBM) and polymyositis (PM). In both IBM and PM, CD8+ cytotoxic T cells
expressing the alpha/beta receptor surround and focally invade non-necrotic
muscle fibres. This lesion can be considered the hallmark of cell-mediated
myocytotoxicity. Essentially the same type of lesion is observed in a variant
form of PM, in which CD4-CD8- T cells bearing the gamma/delta receptor surround
and invade non-necrotic muscle fibres. In both IBM and PM, all of the invaded
and some of the non-invaded muscle fibres strongly express HLA class I
molecules. This is consistent with the hypothesis that the CD8+ autoinvasive
cytotoxic T cells recognize antigenic peptide(s) bound to HLA class I molecules
on the muscle fibre surface. According to the rules of antigen processing, these
peptides derive from proteins synthesized in the muscle fibre. Theoretically,
the proteins could be viral components or self proteins that resemble viral
components. Most attempts to demonstrate viral antigens or genome in muscle
fibres have failed. On the other hand, the majority of HLA class I molecules
expressed on the surface of any cell are loaded with endogenous self peptides.
It seems plausible that muscle-specific autoantigen(s) could be recognized by
autoaggressive T cells in the inflammatory myopathies, but the precise reasons
for the recognition event remains elusive. Recently, it has become possible
to
study the interactions of muscle cells and cytotoxic effector cells in vitro.
Myoblasts and myotubes can be induced to express a variety of immunologically
relevant histocompatibility and cell adhesion molecules. Myotubes are highly
susceptible to lysis by allogeneic CD8+ cytotoxic T cells sensitized against
HLA
class I alloantigens. Interestingly, cultured myotubes are also susceptible
to
lysis by antigen-nonspecific natural killer cells. Further, myoblasts stimulated
by IFN gamma express HLA class II and acquire the full potential to process
and
present complex protein antigens to CD4+ T cells. This may indicate that
myoblasts can actively participate in local immune reactions by presenting
(auto) antigens to helper/inducer T cells. In different inflammatory myopathies,
CD8+ T cells have been expanded directly from muscle and their interactions
with
autologous myotubes have been investigated in vitro. In several cases, a low
but
significant autoreactive cytotoxic effect was observed. This is consistent with
the hypothesis that some cytotoxic effector T cells recognize an autoantigen
on
myotubes. One of the major goals for future studies is to define the
autoantigens that are relevant in the pathogenesis of the inflammatory
myopathies.
Publication Types:
Review
Review, Tutorial
PMID: 8156145 [PubMed - indexed for MEDLINE]
444: Baillieres Clin Neurol. 1993 Nov;2(3):579-97.
Immunogenetics of inflammatory myopathies.
Garlepp MJ.
Australian Neuromuscular Research Institute, Queen Elizabeth II Medical Center,
Nedlands.
The genes most commonly considered when investigating immunogenetic associations
with autoimmune diseases, including inflammatory muscle disease (IMD), are those
encoded in the major histocompatibility complex (MHC), the T-cell receptor (TCR)
genes and the immunoglobulin genes. In caucasoids HLA DR3 is associated with
adult polymyositis (PM) and juvenile dermatomyositis (JDM) and is probably
increased in frequency in adult DM. In inclusion body myositis (IBM) DR3 and
DR1
have been separately reported to be increased but few patients have been
analysed. The DR3 in IMD is almost always present on the ancestral haplotype
marked by HLA-B8, C4A*Q0 and DR3 and presumably accounts for the association
with C4A*Q0 which has been reported in some subgroups of IMD. In other races
the
associations are less clear although DR6 may be increased in blacks with PM.
In
PM, DR3 is strongly associated with the presence of antibodies to histidyl tRNA
synthetase (Jo-1). DR52 is even more strongly associated with the presence of
this autoantibody and this association can be demonstrated in black and white
patients. It is unlikely that DR3 is associated with autoantibodies to other
aminoacyl-tRNA synthetases or signal recognition proteins although fewer cases
have been reported and racial differences may exist. Antibodies to the Pm-Scl
antigen are also associated with DR3 while autoantibodies to Mi-2 may be
associated with DR53. In caucasoids DR4 was increased in D-penicillamine induced
IMD but again there may be inter-racial differences. Amongst caucasoids with
mixed connective tissue disease (MCTD) there is an increased frequency of DR4
and this allele is associated with the development of antibodies to
ribonucleoprotein (RNP). In other races the data are minimal. Very few
investigations of associations between TCR polymorphisms or immunoglobulin
allotypes and IMD have been reported. The phenotype Gm 3;5 has been associated
with PM in caucasoids and may interact with DR3 in predisposing to disease.
The
Gm phenotype 1,3;5,21 has been associated with MCTD and with the development
of
anti-RNP, with or without MCTD, in caucasoids. Multiple genetic factors are
likely to determine the development of IMD and the particular combination of
alleles at predisposing loci may differ between races and according to the
inducing agent. Furthermore, the predisposing genetic factors may vary between
subgroups of IMD.
Publication Types:
Review
Review, Tutorial
PMID: 8156144 [PubMed - indexed for MEDLINE]
445: Baillieres Clin Neurol. 1993 Nov;2(3):557-77.
Inclusion body myositis.
Chou SM.
ALS and Neuromuscular Research Foundation, San Francisco, CA 94115.
IBM has emerged as a clinicopathological entity during the past 25 years but
with increasing complexity. It occurs primarily in elderly persons (over the
sixth decade of life, with 3:1 male preponderance), but young adults or children
may also be affected in some families. FIBM is by and large non-inflammatory
though some autosomal dominant FIBM cases have inflammatory cell infiltrates.
In
IBM, slowly progressive weakness of proximal as well as distal muscle groups
occurs and is usually not associated with skin rash or malignancy. The incidence
of associated collagen-vascular disease is thought to be lower than in DM or
PM
but is reported to be as high as 15%. It is generally refractory to treatment
with corticosteroids or other immunosuppressants. Muscle biopsy and
electromyography may suggest a neurogenic process mixed with myopathic features.
None of the histopathological features is specific enough to be a diagnostic
criterion. The diagnostic criteria have to be collective, encompassing both
clinical and pathological criteria in different combinations. The presence of
eosinophilic intranuclear or cytoplasmic inclusions immunoreactive for both
beta-amyloid and ubiquitin in affected myofibres may facilitate the diagnosis
of
IBM. The diagnosis no longer depends on the ultrastructural demonstration of
characteristic microtubular filaments as previously thought. The identification
of both beta-amyloid and ubiquitin may provide a new concept for the disease
process in IBM. A chronic persistent intracytoplasmic synthesis of abnormal
amyloid protein in IBM is suspected to be similar to that in Alzheimer's
disease. IBM is considered to be intimately related to a heterogenous group
of
non-inflammatory IBMD, including DMY, OPMD, and both autosomal recessive and
dominant FIBM. An inflammatory response has been seen, however, in muscles of
both OPMD and autosomal dominant FIBM. The pathogenesis in IBM and in IBMD may
not be the same. Unlike IBM, there is no abnormal sarcolemmal expression of
MHC-I antigen in IBMD as a sign of T-cell-mediated cytotoxicity causing myofibre
destruction. The prion theory derived from identification of amyloidogenic
protein in the filament inclusions in the rimmed vacuoles is provocative. If
one
believes in the contention that the amyloidogenic filaments are the primary
pathogen of either IBM or IBMD, one must account for the fact that these
filaments are originally derived from sarcolemmal nuclei and not from autophagic
vacuoles. Until this is clarified, the possibility that the filaments represent
either abnormal or defective 'slow' virus nucleocapsids cannot be completely
ruled out.
Publication Types:
Review
Review, Tutorial
PMID: 8156143 [PubMed - indexed for MEDLINE]
446: Curr Opin Rheumatol. 1993 Nov;5(6):732-41.
New advances in inclusion-body myositis.
Askanas V, Engel WK.
University of Southern California School of Medicine, Los Angeles.
The major new advances in seeking the pathogenic mechanisms of sporadic
inclusion-body myositis and hereditary inclusion-body myopathy are discussed.
Hypotheses are presented regarding the possible causes and significance of
amyloid deposits in sporadic inclusion-body myositis and the roles of abnormally
accumulated ubiquitin, beta-amyloid protein, beta-amyloid precursor protein,
alpha 1-antichymotrypsin, hyperphosphorylated tau, and prion protein in the
vacuolated muscle fibers in both sporadic inclusion-body myositis and hereditary
inclusion-body myopathy. Because hereditary inclusion-body myopathy is virtually
free of Congophilic amyloid deposits but, like sporadic inclusion-body myositis,
contains large accumulations of beta-amyloid protein, it is possible that the
lesions in hereditary inclusion-body myopathy may represent "early"
changes.
There are striking similarities between the pathology of inclusion-body myositis
muscle and brains affected by Alzheimer's disease in regard to accumulation
of
ubiquitin, beta-amyloid protein and its precursor protein, alpha
1-antichymotrypsin, and hyperphosphorylated tau.
Publication Types:
Review
Review, Tutorial
PMID: 8117535 [PubMed - indexed for MEDLINE]
447: Neuroreport. 1993 Oct 25;5(1):25-8.
Prion protein is abnormally accumulated in inclusion-body myositis.
Askanas V, Bilak M, Engel WK, Alvarez RB, Tome F, Leclerc A.
Department of Neurology, University of Southern California School of Medicine,
Los Angeles 90017.
In muscle biopsies of 8 sporadic inclusion-body myositis (S-IBM) and 4
hereditary inclusion-body myopathy (H-IBM) patients, vacuolated muscle fibers
contained within their vacuoles strongly immunoreactive inclusions with 2
polyclonal and 1 monoclonal antibodies against prion protein (PrP). By
light-microscopy, PrP deposits co-localized with beta-amyloid protein (A beta)
and ubiquitin (Ub). By immuno-electronmicroscopy, both PrP and A beta were
present on amorphous material and on 6-10 nm amyloid-like fibrils; and PrP and
Ub co-localized on cytoplasmic twisted tubulofilaments (TTFs) and on amorphous
material. Our study provides the first demonstration of abnormally accumulated
PrP in pathological tissue other than brain, and it suggests that PrP may play
a
role in the pathogenesis of IBM.
PMID: 8280854 [PubMed - indexed for MEDLINE]
448: Ann Neurol. 1993 Oct;34(4):551-60.
beta-Amyloid precursor epitopes in muscle fibers of inclusion body myositis.
Askanas V, Alvarez RB, Engel WK.
Department of Neurology University of Southern California School of Medicine,
Los Angeles 90017-1912.
Sporadic inclusion body myositis (IBM) and hereditary inclusion body myopathy
(hIBM) are severe and progressive muscle diseases, characterized pathologically
by vacuolated muscle fibers that contain 15- to 21-nm cytoplasmic
tubulofilaments (CTFs). Those vacuolated muscle fibers also contain abnormally
accumulated ubiquitin and beta-amyloid protein (A beta), and they contain
amyloid in beta-pleated sheets as indicated by Congo red and crystal violet
positivity. Using several well-characterized antibodies, we have now
demonstrated that, in addition to A beta, two other epitopes, N-terminal and
C-terminal, of the beta-amyloid precursor protein (beta PP) are abnormally
accumulated in IBM vacuolated muscle fibers and similarly in hIBM. At the light
microscopy level, immunoreactivities of N- and C-epitopes of beta PP closely
colocalized with A beta and ubiquitin immunoreactivities. However, by immunogold
electronmicroscopy, even though N-, C-, and A beta epitopes of beta PP and
ubiquitin colocalized at the amorphous and dense floccular structures, only
A
beta was localized to the 6- to 10-nm amyloid-like fibrils and only ubiquitin
was localized to CTFs. beta PP immunoreactive structures were often in proximity
to CTFs, but CTFs themselves never contained beta PP immunoreactivities. The
fact that A beta but not C- or N-terminal epitopes of beta PP localized to the
6- to 10-nm amyloid-like fibrils suggests that free A beta might be generated
during beta PP processing and, after aggregation, may be responsible for the
amyloid present within IBM muscle fibers. Our study demonstrates that three
epitopes of beta PP accumulate abnormally in diseased human muscle, and
therefore this phenomenon is not unique to Alzheimer's disease, Down's syndrome
brain, and Dutch-type cerebrovascular amyloidosis.
PMID: 7692809 [PubMed - indexed for MEDLINE]
449: Chest. 1993 Sep;104(3):975-7.
Inclusion body myositis as a cause of respiratory failure.
Cohen R, Lipper S, Dantzker DR.
Long Island Jewish Medical Center, New Hyde Park, New York 11040.
Inclusion body myositis (IBM) is a slowly progressive myopathy that has not
been
reported to affect respiratory muscles. It is often refractory to treatment
and
a muscle biopsy specimen is necessary for the diagnosis. This is a report of
a
patient with IBM who quickly progressed to respiratory muscle failure requiring
intubation.
Publication Types:
Case Reports
PMID: 8396004 [PubMed - indexed for MEDLINE]
450: Semin Neurol. 1993 Sep;13(3):256-63.
Inclusion body myositis: new concepts.
Sekul EA, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, MD 20892.
Publication Types:
Review
Review, Tutorial
PMID: 8272596 [PubMed - indexed for MEDLINE]
451: Z Rheumatol. 1993 Sep-Oct;52(5):307-11.
Interstitial alveolitis as early manifestation of anti-Jo-1 positive
polymyositis.
Lohr HF, Bocher WO, Hermann E, Muller-Quernheim J, Schwickert H, Meyer zum
Buschenfelde KH, Gerken G.
I Department of Internal Medicine, Johannes-Gutenberg-University, Mainz, FRG.
Polymyositis (PM), dermatomyositis (DM) and inclusion-body myositis belong
to a
heterogenous group of inflammatory myopathies. Pulmonary manifestations occur
in
a minority of PM patients due to infiltration of diaphragmatic and thoracic
muscles or more rarely due to interstitial lung disease. Here, we report on
the
case of a 67-year-old patient who developed an interstitial idiopathic
alveolitis as an early and rare manifestation of anti-Jo-1-positive
polymyositis. Clinical and pathogenetical features of the PM associated
interstitial alveolitis are discussed.
Publication Types:
Case Reports
PMID: 8259723 [PubMed - indexed for MEDLINE]
452: Arch Pathol Lab Med. 1993 Aug;117(8):789-93.
Ubiquitin expression in inclusion body myositis. An immunohistochemical study.
Albrecht S, Bilbao JM.
Department of Pathology, Baylor College of Medicine, Houston, Tex.
Ubiquitin has been shown by immunohistochemical studies to be a component of
many of the filamentous inclusion bodies that are known in neuropathology. In
the current study, we examined the expression of ubiquitin in 14 cases of
typical inclusion body myositis, in skeletal muscle specimens from four cases
of
typical amyotrophic lateral sclerosis, and in muscle specimens from three normal
controls. In the cases of inclusion body myositis, rimmed vacuoles were
ubiquitin immunoreactive in all cases. Intrasarcoplasmic inclusions were
positive in the nine cases that had them. In four cases, there were positive
intranuclear inclusions, and in seven, there was homogeneous staining of nuclei.
Atrophic fibers and necrotic fibers were positive in 11 and nine cases,
respectively. In the cases of amyotrophic lateral sclerosis, atrophic fibers
were positive in three cases, and focal nuclear staining was seen in two. In
one
of the three control cases, a few atrophic fibers had faint sarcoplasmic
positivity; no other staining was seen. We conclude that ubiquitin is a
component of the inclusions that characterize inclusion body myositis. However,
ubiquitin expression in skeletal muscle disease is not pathognomonic of
inclusion body myositis.
PMID: 8393651 [PubMed - indexed for MEDLINE]
453: J Rheumatol. 1993 Aug;20(8):1455-6.
High dose immunoglobulin therapy in a case of inclusion body myositis: clinical
and immunologic aspects.
Salvarani C, Boiardi L, Maldini MC, Mancini R, Rinaldi M, Macchioni P, Portioli
I.
Publication Types:
Case Reports
Letter
PMID: 8230050 [PubMed - indexed for MEDLINE]
454: Medicine (Baltimore). 1993 Jul;72(4):225-35.
The treatment of inclusion body myositis: a retrospective review and a
randomized, prospective trial of immunosuppressive therapy.
Leff RL, Miller FW, Hicks J, Fraser DD, Plotz PH.
Arthritis and Rheumatism Branch, National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda,
Maryland.
We have sought to examine the response to immunosuppressive therapeutic
intervention in inclusion body myositis (IBM) in a retrospective review of prior
responses to therapy and in an open, randomized crossover trial. We collected
information on the response to prior therapy on 25 patients, and for prospective
therapy on 11 of these patients. All met criteria for a definite idiopathic
inflammatory myopathy and had biopsy-proven IBM. Clinical and laboratory results
were assessed by interviews of patients and by chart review in the retrospective
trial. Manual muscle strength was assessed by a single trained observer; the
patients' activities of daily living were assessed by questionnaire; and serum
tests of muscle-associated enzymes were measured in the prospective trial. In
the retrospective review, prednisone appeared to have been of some, albeit
modest, clinical benefit in 10 of 25 (40%) patients. Other therapies, primarily
azathioprine and methotrexate, also appeared to have halted the progression
of
weakness in 8 of 35 trials (23%). In the prospective study, combination therapy
of oral azathioprine and methotrexate and a biweekly infusion of high-dose
intravenous methotrexate with leucovorin rescue were given for 3 to 6 months
in
an open, crossover design. Both the oral and the intravenous regimens were
clinically effective in some patients. There was clinical improvement in 3
trials, stabilization in 11 trials, and worsening in 5 trials, out of a total
of
19 completed (22 intended) trials. The presence of active inflammation at entry
into the prospective therapeutic protocol, either directly observed on muscle
biopsy or indirectly indicated by serum creatine kinase level, may have been
associated with clinical improvement. A complete laboratory response with
normalization of creatine kinase and other muscle-associated enzymes did not,
however, significantly predict clinical responsiveness in the prospective trial.
In this first report, to our knowledge, of a prospective trial of
immunosuppressive therapy for this disease, stabilization and even slight
improvement of strength and functional abilities appeared to be achieved in
some
patients. We believe that prednisone and other immunosuppressive therapies were
of modest benefit in about half of patients with inclusion body myositis,
especially those with some evidence of active inflammation. Stabilization of
an
otherwise inexorably deteriorating course appears, therefore, to be an
attainable goal in some patients with IBM.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 8393509 [PubMed - indexed for MEDLINE]
455: Neuromuscul Disord. 1993 Jul;3(4):283-91.
Ubiquitin and beta-amyloid-protein in inclusion body myositis (IBM), familial
IBM-like disorder and oculopharyngeal muscular dystrophy: an immunocytochemical
study.
Leclerc A, Tome FM, Fardeau M.
INSERM U. 153, Paris, France.
We used immunocytochemistry to identify ubiquitin and beta-amyloid-protein
in
muscle biopsies from patients with three neuromuscular disorders characterized
by the presence of rimmed vacuoles in muscle fibres: inclusion body myositis
(IBM), familial IBM-like disorder and oculopharyngeal muscular dystrophy (OPMD).
Labelling with anti-ubiquitin antibodies was observed in all three diseases,
but
it was frequent in IBM, less common in familial IBM-like disorder and rare in
OPMD. This labelling is thought to correspond to the presence of IBM-type
filaments (16-18 nm in external diameter) which are characteristic but not
specific for IBM or familial IBM-like disorder, as they may also occur in other
diseases including OPMD. Labelling with anti-beta-amyloid-protein antibody was
seen in a few fibres in IBM but not in the other two conditions. The structures
labelled with this antibody have yet to be determined. Labelling with
anti-ubiquitin or anti-beta-amyloid-protein antibodies was not correlated with
the presence of acid phosphatase activity.
PMID: 8268725 [PubMed - indexed for MEDLINE]
456: Neuroreport. 1993 Jun;4(6):815-8.
beta-Amyloid precursor protein mRNA is increased in inclusion-body myositis
muscle.
Sarkozi E, Askanas V, Johnson SA, Engel WK, Alvarez RB.
Department of Neurology, University of Southern California, School of Medicine,
Los Angeles 90017.
Vacuolated muscle fibers in muscle biopsies of 8 out of 8 inclusion body
myositis (IBM) patients, including 2 hereditary patients, manifested increased
mRNA for the beta-amyloid precursor protein (beta APP) that contains Kunitz-type
protease inhibitor motif. In affected fibers, increased beta APP-mRNA correspond
to abnormally accumulated beta APP immunoreactivity (including beta-amyloid
protein epitope). In normal human muscle fibers increased beta APP-mRNA was
present only at the neuromuscular junctions. Our study (a) suggests that
abnormally accumulated beta APP in IBM vacuolated fibers results, at least
partly, from increased beta APP generation, and (b) provides the first
demonstration of up-regulated beta APP-mRNA in pathologic human tissue other
than brain of Alzheimer's disease and Down's syndrome.
PMID: 8394158 [PubMed - indexed for MEDLINE]
457: Neurology. 1993 Jun;43(6):1265-7.
Enhanced detection of congo-red-positive amyloid deposits in muscle fibers
of
inclusion body myositis and brain of Alzheimer's disease using fluorescence
technique.
Askanas V, Engel WK, Alvarez RB.
USC Neuromuscular Center, Department of Neurology, University of Southern
California School of Medicine, Los Angeles 90017.
PMID: 8170582 [PubMed - indexed for MEDLINE]
458: Neurology. 1993 Jun;43(6):1241-3.
Inclusion body myositis presenting solely as dysphagia.
Riminton DS, Chambers ST, Parkin PJ, Pollock M, Donaldson IM.
Department of Medicine, Christchurch Hospital, New Zealand.
Two patients presenting with dysphagia due to cricopharyngeal muscle dysfunction
developed limb weakness 2 to 3 years later. Cricopharyngeal and limb muscle
biopsies demonstrated changes typical of inclusion body myositis (IBM). Both
patients improved following cricopharyngeal myotomy. IBM should be considered
in
patients presenting with dysphagia.
Publication Types:
Case Reports
PMID: 8170574 [PubMed - indexed for MEDLINE]
459: J Neurol Sci. 1993 May;116(1):82-92.
Muscular ultrasound in idiopathic inflammatory myopathies of adults.
Reimers CD, Fleckenstein JL, Witt TN, Muller-Felber W, Pongratz DE.
Friedrich Baur-Institut bei der Medizinischen, Ludwig-Maximilians-Universitat,
Munchen, Germany.
To evaluate the value of myosonography in inflammatory myopathies ultrasound
of
skeletal muscles was performed in 70 patients, aged 21-82 years, suffering from
histologically proven polymyositis (n = 30), dermatomyositis (n = 18),
granulomatous myositis (n = 9), inclusion body myositis (n = 13), and in 102
control persons. The sensitivity of muscle ultrasound in detecting
histopathologically proven disease (82.9%) was not significantly different from
electromyography (92.4%) or serum creatine kinase activity (68.7%). The positive
predictive value of ultrasound was 95.1%, the negative predictive value 89.2%,
and the accuracy 91.3%. The different types of inflammatory myopathies presented
with typical, but not specific ultrasound features. Polymyositis showed atrophy
and increased echointensity predominantly of lower extremity muscles, whereas
in
dermatomyositis clear muscle atrophy was rare and echointensities were highest
in forearm muscles. Echointensities were lower in dermatomyositis compared to
poly- and granulomatous myositis. Granulomatous myositis was characterized by
the highest echointensities and a tendency towards muscle hypertrophy. Severe
muscle atrophy was the most impressive feature in the majority of patients with
inclusion body myositis. Comparison of ultrasound and histopathological findings
indicates that muscle lipomatosis has a much greater impact on muscular
echointensity than does muscle fibrosis. Ultrasound of myositis improved
clinical assessment of patients by supplying differential diagnostic clues based
on precise muscle size measurements and identification of mesenchymal
abnormalities, particularly muscle lipomatosis.
PMID: 8509807 [PubMed - indexed for MEDLINE]
460: Neurology. 1993 May;43(5):876-9.
Treatment of inclusion-body myositis with high-dose intravenous immunoglobulin.
Soueidan SA, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, MD 28092.
We report the treatment of four patients with inclusion-body myositis (IBM)
and
severe slowly progressive weakness using high-dose intravenous immunoglobulin
(IVIg). After two monthly infusions, the strength of the proximal and less
atrophic muscle groups improved or normalized in three of the four patients.
The
improvement lasted from 2 to 4 months. Intravenous immunoglobulin is the first
treatment modality to improve the strength of some muscles in patients with
this
disabling inflammatory myopathy. In view of the high cost of IVIg, the
unexpected but encouraging results from this pilot study warrant a controlled
trial.
Publication Types:
Case Reports
PMID: 8492940 [PubMed - indexed for MEDLINE]
461: Clin Investig. 1993 May;71(5):351-61.
Inclusion body myositis: clinical and histopathological features of 36 patients.
Beyenburg S, Zierz S, Jerusalem F.
Neurologische Universitatsklinik Bonn.
Thirty-six patients (15 females, 21 males) with inclusion body myositis (IBM)
were studied. The diagnosis was established according to clinical and
histopathological criteria. Clinical features were insidious onset of slowly
progressive muscle weakness and wasting with depressed or absent tendon reflexes
especially in the lower limbs. The pattern of muscle weakness was variable.
The
majority of patients (58%) showed proximal and symmetrical weakness usually
most
prominent in the legs. Isolated distal (6%) and asymmetrical weakness (19%)
was
less frequently observed. Myalgia occurred in 42% of the patients. The age at
onset of symptoms ranged from 20 to 73 years (mean 47 years). Serum creatine
kinase levels were normal (11%) or mildly elevated (89%). Needle
electromyography revealed myopathic features in about 80% of the patients, and
results of nerve conduction studies were normal in most of the cases. The
predominant histopathological findings were numerous muscle fibers with rimmed
vacuoles (100% of the patients), groups of atrophic fibers (92%), and
inflammatory infiltrates (89%). The inflammatory infiltrates were located
predominantly at endomysial sites and were composed mainly of T8 cells. Electron
microscopy showed characteristic intracytoplasmic filamentous inclusions in
all
36 cases. Immunosuppressive treatment in 16 patients failed to prevent disease
progression in all but one patient with an associated Sjogren's syndrome. It
is
concluded that the consistent combination of typical histopathological findings
and characteristic clinical features offers a firm basis for the diagnosis of
IBM. IBM should be suspected in any adult patient presenting with clinical signs
of a chronic polymyositis unresponsive to immunosuppressive therapy. The
etiology and pathogenesis of IBM remain to be established.
PMID: 8389626 [PubMed - indexed for MEDLINE]
462: Am J Med. 1993 Apr;94(4):379-87.
Drug therapy of the idiopathic inflammatory myopathies: predictors of response
to prednisone, azathioprine, and methotrexate and a comparison of their
efficacy.
Joffe MM, Love LA, Leff RL, Fraser DD, Targoff IN, Hicks JE, Plotz PH, Miller
FW.
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health, Bethesda, Maryland.
PURPOSE: To identify factors associated with responses to treatment with
prednisone, methotrexate, or azathioprine in patients with idiopathic
inflammatory myopathy, and to compare the efficacy of these drugs. PATIENTS
AND
METHODS: Data were collected on 113 adult patients meeting criteria for definite
idiopathic inflammatory myopathy in this retrospective cohort study. Patients
were categorized as responding completely, partially, or not at all to each
therapeutic trial based upon clinical and laboratory criteria. RESULTS: Clinical
group, presence of certain myositis-specific autoantibodies, and time from
disease onset to diagnosis influenced rates of complete clinical response to
these therapeutic agents. Patients with inclusion body myositis responded
comparatively poorly to prednisone and the other drugs: 43% had no clinical
response to prednisone and none responded completely to any medication. Patients
with autoantibodies to aminoacyl-tRNA synthetases or to signal recognition
particle proteins were likely to respond partially, but not completely, to
prednisone. No patient with a long delay to diagnosis (greater than 18 months)
responded completely, compared with 34% of those with a short delay (less than
3
months). A patient's response to the first course of prednisone predicted
subsequent responses to prednisone and to azathioprine better than response
to
methotrexate. Men responded to methotrexate better than women. Among certain
subgroups of patients, responses to methotrexate were better than to either
azathioprine or retreatment with prednisone. CONCLUSION: Determining the
clinical group, autoantibody status, and time from disease onset to diagnosis
of
patients with myositis provides useful information in predicting clinical
responses to therapy, and these factors should be considered in designing future
therapeutic trials. Methotrexate therapy may be superior to either azathioprine
or further steroid treatment alone in certain patients who do not respond
completely to an initial adequate course of prednisone.
PMID: 8386437 [PubMed - indexed for MEDLINE]
463: Brain. 1993 Apr;116 ( Pt 2):325-36.
Mitochondrial DNA deletions in inclusion body myositis.
Oldfors A, Larsson NG, Lindberg C, Holme E.
Department of Pathology, Gothenburg University, Sweden.
Skeletal muscle specimens from three patients with inclusion body myositis,
aged
39, 60 and 71 years, respectively, were investigated. Enzyme histochemical
staining of cytochrome c oxidase (COX), succinate dehydrogenase and myofibrillar
ATPase, and in situ hybridization of transcripts of mitochondrial DNA (mtDNA)
were performed on consecutive sections. In all three cases a proportion of
muscle fibres (2-5%) showed low or absent COX activity in spite of medium or
high succinate dehydrogenase activity (COX deficient muscle fibres). Two probes
detecting transcripts of different segments of mtDNA were used for the in situ
hybridization. One of the probes (ND4 probe) detected transcripts of a segment
of the NADH dehydrogenase subunit 4 gene, which is known to be affected in most
cases of mitochondrial myopathy with large deletions of mtDNA. There was reduced
hybridization of the ND4 probe in many COX deficient muscle fibres compared
with
adjacent normal fibres. The other probe (ND2 probe) detected transcripts of
a
segment of the NADH dehydrogenase subunit 2 gene, which usually is not included
in mtDNA deletions. There was accumulation of transcripts corresponding to the
ND2 probe in COX deficient fibres in all three cases. These findings demonstrate
that deleted mtDNA had accumulated in COX deficient muscle fibres in patients
with inclusion body myositis. Southern blot analysis of mtDNA in muscle revealed
a 16.6 kb fragment corresponding to normal mtDNA in all three cases. In one
case
two additional less abundant fragments of smaller size, corresponding to deleted
mtDNA, were detected. Ultrastructural investigation showed abnormal mitochondria
in all three cases. Control muscle specimens were obtained from nine patients,
aged 63-71 years, with muscle pain but without morphological evidence of muscle
disease. Occasional COX deficient fibres (< 1%) were found in three of the
control cases. The other six control cases showed no COX deficient fibres. Our
results show that mtDNA deletions may be involved in the pathogenesis of
inclusion body myositis and cause respiratory chain dysfunction in muscle fibre
segments.
Publication Types:
Case Reports
PMID: 8384916 [PubMed - indexed for MEDLINE]
464: Arthritis Rheum. 1993 Mar;36(3):416-21.
Inclusion body myositis and renal cell carcinoma. Report of two cases and review
of the literature.
Ytterberg SR, Roelofs RI, Mahowald ML.
Research Service, Department of Veterans Affairs Medical Center, Minneapolis,
MN
55417.
OBJECTIVE. To describe the clinical course of 2 patients with concurrent
inclusion body myositis and renal cell carcinoma and review published reports
of
inclusion body myositis associated with malignancy. METHODS. Prospective
followup of 2 patients. Review of published case reports and series of patients
with inclusion body myositis. RESULTS. Our 2 patients with inclusion body
myositis and renal cell carcinoma had no improvement of strength following
nephrectomy. Seven previously reported cases of inclusion body myositis and
malignancy were identified and are discussed. CONCLUSION. Findings in our 2
patients suggest that there is no etiopathologic relationship between inclusion
body myositis and malignancy.
Publication Types:
Case Reports
Review
Review of Reported Cases
PMID: 8383972 [PubMed - indexed for MEDLINE]
465: Neuromuscul Disord. 1993 Mar;3(2):149-55.
Muscle fibre degeneration in distal myopathy (Welander)--ultrastructure related
to immunohistochemical observations on cytoskeletal proteins and Leu-19 antigen.
Borg K, Ahlberg G, Hedberg B, Edstrom L.
Department of Neurology, Karolinska Hospital, Stockholm, Sweden.
In seven patients with long-standing and six patients with early symptoms of
Welander distal myopathy (WDM), monoclonal antibodies directed against such
cytoskeletal proteins as dystrophin, spectrin and desmin and against Leu-19,
a
myoblast and satellite cell related antigen, were applied to muscle biopsies
from the anterior tibial and soleus muscles. In addition, ultrastructural
studies were carried out on biopsies from the soleus muscle. In muscle fibres
from patients with early symptoms there was normal immunostaining for
dystrophin, spectrin, desmin and Leu-19. In the patients with long-standing
symptoms, there was also a normal expression of dystrophin, and a normal
staining for spectrin and desmin was found in normal sized muscle fibres.
Occasionally normal sized muscle fibres showed staining for Leu-19. Increased
staining for spectrin and desmin and a strong Leu-19 staining was seen in normal
sized muscle fibres with rimmed vacuoles and in atrophic fibres. Increased
staining for spectrin, desmin and Leu-19 has been described in denervated muscle
fibres and, thus, the present findings may support earlier findings of a
neurogenic component in Welander distal myopathy. In the soleus muscle,
ultrastructural muscle fibre abnormalities conformed to those in the anterior
tibial muscle. Many rimmed vacuoles were observed which corresponded, at the
ultrastructural level, to autophagic vacuoles. Intranuclear and cytoplasmic
filamentous inclusions of the same shape and diameter as in inclusion body
myositis were observed.
PMID: 7689381 [PubMed - indexed for MEDLINE]
466: Brain Res. 1993 Feb 19;603(2):343-7.
Rimmed vacuoles of inclusion body myositis and oculopharyngeal muscular
dystrophy contain amyloid precursor protein and lysosomal markers.
Villanova M, Kawai M, Lubke U, Oh SJ, Perry G, Six J, Ceuterick C, Martin JJ,
Cras P.
Laboratory of Neuropathology, Born-Bunge Foundation, University of Antwerp,
Wilrijk, Belgium.
Rimmed vacuoles are small areas of focal destruction of muscle fibres, found
in
inclusion body myositis, oculopharyngeal muscular dystrophy and other muscle
disorders. They are known to contain amyloid proteins, probably of beta-amyloid
type. We examined rimmed vacuoles immunohistochemically in 12 patients with
inclusion body myositis and two patients with oculopharyngeal muscular dystrophy
with antibodies to beta-amyloid precursor protein and cathepsin B and D. We
found evidence for the presence of all these markers in rimmed vacuoles. These
results confirm the presence of beta-amyloid in rimmed vacuoles, and provide
additional support for the hypotheses that rimmed vacuoles are of lysosomal
origin and that lysosomes are probably important in the metabolism of amyloid
precursor protein.
PMID: 8461987 [PubMed - indexed for MEDLINE]
467: Ann Rheum Dis. 1993 Feb;52(2):147-51.
Inclusion body myositis: an underdiagnosed condition?
Hopkinson ND, Hunt C, Powell RJ, Lowe J.
Department of Immunology, University Hospital, Queen's Medical Centre,
Nottingham, United Kingdom.
Inclusion body myositis is an increasingly recognised form of inflammatory
myopathy with characteristic clinical and histopathological features which has
seldom been reported in the United Kingdom. This paper presents the
clinicopathological features of a series of patients diagnosed in Nottingham
from 1986 to 1990. During this period, 1319 muscle biopsy samples were processed
by this laboratory and rimmed vacuoles were seen in 17 patients. Eleven patients
had definite or probable inclusion body myositis according to published
criteria. The mean age of the group was 69.4 years with a male to female ratio
of 8:3. Typical clinical features were a slowly progressive painless, proximal
lower limb weakness, with muscle wasting and early loss of reflexes. The median
duration of illness from first symptom to presentation was five years (range
2-18 years). Falls were a prominent symptom in six patients and distal weakness
occurred in nine patients. Creatine kinase was increased in 10 patients but
only
one had a level > 1000 IU/l; the erythrocyte sedimentation rate was normal
in
five patients. Treatment with steroids or cytotoxic drugs, or both, did not
prevent disease progression. It is confirmed that inclusion body myositis is
a
distinct cause of inflammatory myopathy which is probably underdiagnosed in
the
United Kingdom. Clinically, it should be suspected in older patients presenting
with muscle weakness of insidious onset. Pathologically, a careful search should
be made for rimmed vacuoles and inflammation; ultrastructurally, the presence
of
inclusions will confirm the diagnosis.
PMID: 8383483 [PubMed - indexed for MEDLINE]
468: Acta Neuropathol (Berl). 1993;85(4):378-82.
Strong immunoreactivity of alpha 1-antichymotrypsin co-localizes with
beta-amyloid protein and ubiquitin in vacuolated muscle fibers of inclusion-body
myositis.
Bilak M, Askanas V, Engel WK.
Department of Neurology, University of Southern California School of Medicine,
Los Angeles 90017.
In 10 of 10 inclusion-body myositis (IBM) patients, including 1 hereditary
case,
vacuolated muscle fibers contained large or small cytoplasmic inclusions
immunoreactive for alpha 1-antichymotrypsin (alpha 1-ACT). All IBM muscle
biopsies had characteristic cytoplasmic tubulo-filaments by electron microscopy.
None of 17 control muscle biopsies contained the alpha 1-ACT immunoreactive
inclusions characteristic of IBM. In vacuolated muscle fibers, alpha 1-ACT
immunoreactive inclusions colocalized with beta-amyloid protein and ubiquitin
immunoreactivities. Our study provides the first demonstration of alpha 1-ACT
accumulations in abnormal human muscle, and it suggest that, as in Alzheimer's
disease and Down's syndrome, alpha 1-ACT may be involved in the pathogenesis
of
IBM.
PMID: 8386897 [PubMed - indexed for MEDLINE]
469: Curr Opin Rheumatol. 1992 Dec;4(6):809-14.
Immune aspects of myositis.
Kalovidouris AE.
Indiana University School of Medicine, Richard L. Roudebush Veterans Affairs
Medical Center, Indianapolis 46202.
Myositis describes a heterogeneous group of disorders whose main pathologic
feature is chronic inflammation of the affected muscles. The association of
myositis with other autoimmune diseases, the response to corticosteroid and
immunosuppressive therapy, the frequent occurrence of autoantibodies, and the
presence of chronic inflammatory cells in the affected muscles of patients with
myositis indicate that the myositis syndromes are autoimmune diseases. This
review summarizes recent observations on the role of humoral and cellular
mechanisms in myositis. During the past year, the most notable contributions
included studies on the relationship among autoantibodies and various clinical
and epidemiologic features of patients with myositis; further evidence for
T-cell involvement in the pathogenesis of myositis; demonstration of amyloid
proteins in muscle fibers of patients with inclusion body myositis; and a
controlled trial of plasma exchange and leukapheresis in myositis.
Publication Types:
Review
Review, Tutorial
PMID: 1333783 [PubMed - indexed for MEDLINE]
470: Arch Neurol. 1992 Dec;49(12):1292-5.
Neurologic manifestations of progressive systemic sclerosis.
Averbuch-Heller L, Steiner I, Abramsky O.
Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
Neurologic involvement in progressive systemic sclerosis is considered uncommon.
We retrospectively examined the prevalence and nature of neurologic
complications in 50 patients with progressive systemic sclerosis. In 20 (40%),
neurologic abnormalities were detected, with a total of 28 neurologic
manifestations. All levels of the central and peripheral nervous system were
affected: muscle (22%), peripheral nerve (18%), spinal cord (8%), and brain
(6%). Of note were the presence of myelopathy in four patients and
inclusion-body myositis in two. In 10 patients (20%), no definable cause of
the
neurologic dysfunction could be identified, apart from progressive systemic
sclerosis. Thus, neurologic presentations of progressive systemic sclerosis
are
much more common than previously reported and may be due to direct involvement
of the nervous system by a primary pathologic process in a significant number
of
patients.
Publication Types:
Case Reports
PMID: 1333182 [PubMed - indexed for MEDLINE]
471: Neurology. 1992 Nov;42(11):2231-2.
Comment on:
Neurology. 1992 Apr;42(4):897-902.
Inclusion body myositis.
Mendell JR, Sahenk Z.
Publication Types:
Comment
Letter
PMID: 1279467 [PubMed - indexed for MEDLINE]
472: Clin Neuropharmacol. 1992 Oct;15(5):327-51.
Clinical, immunopathologic, and therapeutic considerations of inflammatory
myopathies.
Dalakas MC.
Neuromuscular Diseases Section, NINDS, National Institutes of Health, Bethesda,
MD 20892.
The inflammatory myopathies encompass a group of heterogenous muscle diseases
which have in common an acquired myopathy with histological signs of endomysial
inflammation. We present evidence based on recently emerged clinical,
histologic, immunopathologic, demographic and therapeutic observations that
these myopathies comprise three major and distinct groups: polymyositis (PM),
dermatomyositis (DM), and inclusion-body myositis (IBM). Immune-mediated
mechanisms characteristic for each group appear to play a primary role in the
pathogenesis of these diseases. In DM there is an intramuscular microangiopathy
mediated by the C5b-9 membranolytic attack complex, leading sequentially to
loss
of capillaries, muscle ischemia, muscle fiber necrosis and perifascicular
atrophy. In contrast, in PM and IBM the muscle fiber injury is initiated by
sensitized CD8+ cytotoxic T cells that recognize MHC-I restricted muscle
antigens, leading to phagocytosis and fiber necrosis. Among the viruses
implicated in the cause of inflammatory myopathies, only the retroviruses, HIV,
HTLV-1 and simian retroviruses, have been convincingly associated with PM.
Retroviruses, therefore, appear to be the leading group of viruses capable of
triggering these diseases. The treatment of inflammatory myopathies has been
largely empirical. A detailed therapeutic plan based on our experience with
a
large number of patients is presented. Patients with bona fide PM or DM respond
to steroids to some degree and for some period of time. In contrast, patients
with IBM do not respond to any therapy and the disease should be suspected when
a patient with presumed PM has failed treatment. Methotrexate and
cyclophosphamide are disappointing. Cyclosporine and Azathioprine are commonly
used but they are of uncertain benefit. Plasmapheresis is ineffective. High-dose
intravenous immunoglobulin is a promising new therapeutic modality.
Publication Types:
Review
Review, Tutorial
PMID: 1423335 [PubMed - indexed for MEDLINE]
473: J Neurol Sci. 1992 Oct;112(1-2):192-8.
Quantitative morphometric study of muscle in inclusion body myositis.
Verma A, Bradley WG, Soule NW, Pendlebury WW, Kelly J, Adelman LS, Chou SM,
Karpati G, Brenner JF.
Department of Neurology, University of Vermont College of Medicine, Burlington.
Clinical and electromyographic findings do not clearly distinguish inclusion
body myositis (IBM) from chronic polymyositis (PM). The rimmed vacuoles and
filamentous nuclear and cytoplasmic inclusions that characterize IBM are often
sparse and may be overlooked; conversely, these features may occasionally be
seen in other diseases. Preliminary studies suggested that muscle fiber
hypertrophy occurred more frequently in IBM than in PM. To investigate whether
fiber hypertrophy can be used to improve the ability to separate IBM from PM,
we
report a morphometric analysis of 28 IBM cases, 22 PM and 22 dermatomyositis
(DM) cases. The analysis, using a computer automated system, included proportion
of hypertrophied fibers and also fiber type proportions, average fiber diameter,
proportion of atrophic and angulated fibers, and the co-dispersion index (CDI).
The proportion of hypertrophied fibers was greater in IBM than the other two
conditions (IBM (mean +/- SEM) 31.0 +/- 4.7% and 12.2 +/- 2.4% for type 1 and
type 2 fibers, respectively, compared to 9.8 +/- 3.0% and 3.3 +/- 1.7% in PM,
and 7.7 +/- 2.7% and 3.9 +/- 1.9% in DM). These differences were statistically
significant (P < 0.05) in both sexes for type 1 fibers and in women for type
2
fibers. Also, the average fiber size and hypertrophy factors for type 1 and
type
2 fibers were increased in IBM compared to PM and DM. This study confirms that
the presence of muscle fiber hypertrophy in biopsies from IBM patients may help
differentiate them from other clinically similar inflammatory myopathies.
PMID: 1335036 [PubMed - indexed for MEDLINE]
474: Curr Opin Neurol Neurosurg. 1992 Oct;5(5):645-54.
Inflammatory and toxic myopathies.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, Maryland.
The major advances in the immunopathogenesis and treatment of inflammatory
myopathies, and the main criteria that distinguish polymyositis (PM) from
dermatomyositis (DM) or inclusion-body myositis (IBM) are presented. The origin
and implications of the amyloid and ubiquitin deposits found within the
vacuolated fibers of patients with IBM are considered. The pathogenesis of human
immunodeficiency virus (HIV) and human T-cell lymphotrophic virus
(HTLV)-I-associated PM is presented, and the role of retroviruses in triggering
PM, even in the absence of detectable viral genome within the muscle fibers,
is
discussed. In addition, three toxic myopathies with distinct morphologic,
biochemical, or molecular characteristics, caused by zidovudine [azidothymidine
(AZT) myopathy], the cholesterol-lowering-agent myopathy (CLAM), and the
combination of blocking agents with corticosteroids are presented.
Publication Types:
Review
Review, Tutorial
PMID: 1327303 [PubMed - indexed for MEDLINE]
475: J Rheumatol. 1992 Sep;19(9):1385-9.
Comment in:
J Rheumatol. 1992 Sep;19(9):1327-9.
Inclusion body myositis: analysis of 32 cases.
Sayers ME, Chou SM, Calabrese LH.
Cleveland Clinic Foundation Department of Rheumatic and Immunologic Disease, OH.
Inclusion body myositis is characterized by an insidious onset, progressive
indolent course, and is generally felt to be refractory to standard therapy
for
myositis. We reviewed the charts of 32 patients with muscle biopsy findings
suggestive of inclusion body myositis. The average time from symptom onset to
diagnosis was 37 months, but initially 40% were incorrectly diagnosed.
Twenty-eight patients (88%) were classified as definite or probable inclusion
body myositis and were treated with various combinations of prednisone and
immunosuppressive agents. Sixty-eight percent of those treated experienced a
decrement in function and muscle strength. Three patients exhibited longterm
improvement while 12 patients experienced delayed progression, defined by short
term improvement in strength or a stable functional class, All of these patients
received therapy, 5 in the form of methotrexate and prednisone. All untreated
patients deteriorated clinically. In summary, (1) inclusion body myositis is
a
clinically distinct entity which is frequently misdiagnosed initially. (2) While
clinical improvement with therapy is rare, our observations support recent
reports that therapy may be associated with a slower rate of clinical
progression. (3) Optimal therapy remains uncertain, but the use of low dose
methotrexate and prednisone may warrant further study.
PMID: 1331441 [PubMed - indexed for MEDLINE]
476: J Rheumatol. 1992 Sep;19(9):1327-9.
Comment on:
J Rheumatol. 1992 Sep;19(9):1385-9.
The dilemma of treating patients with inclusion body myositis.
Wortmann RL.
Publication Types:
Comment
Editorial
PMID: 1331440 [PubMed - indexed for MEDLINE]
477: Ann Neurol. 1992 Aug;32(2):219-22.
Absence of persistent infection with enteroviruses in muscles of patients with
inflammatory myopathies.
Leon-Monzon M, Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, MD 20892.
We searched for enteroviral nucleic acid sequences using the polymerase chain
reaction and slot-blot hybridization in coded muscle biopsy specimens from 39
patients with active inflammatory myopathies (polymyositis, dermatomyositis,
and
inclusion-body myositis) and from 16 patients with other neuromuscular diseases,
including patients with postpolio syndrome. For primers, we used sequences of
the noncoding region at the 5' end of the viral RNA. We failed to detect
specific enteroviral nucleic acid sequences in the muscle biopsy specimens.
Because this sensitive technique can amplify even low copy numbers of the viral
genome, it appears unlikely that a persistent enteroviral infection is the cause
of inflammatory myopathies.
PMID: 1324633 [PubMed - indexed for MEDLINE]
478: Am J Pathol. 1992 Jul;141(1):31-6.
Light and electron microscopic localization of beta-amyloid protein in muscle
biopsies of patients with inclusion-body myositis.
Askanas V, Engel WK, Alvarez RB.
University of Southern California Neuromuscular Center, Los Angeles 90017.
In 11 of 11 inclusion-body myositis (IBM) patients, including one hereditary
case, vacuolated muscle fibers contained large and multiple small inclusions
immunoreactive for beta-amyloid protein (beta AP). All IBM muscle biopsies had
characteristic cytoplasmic tubulo-filaments (CTFs) by electron microscopy. None
of 14 control muscle biopsies contained the beta AP immunoreactive (IR)
inclusions characteristic of IBM. On the light microscopy level, beta AP-IR
inclusions colocalized with ubiquitin immunoreactivity. By immunogold
electronmicroscopy, beta AP immunoreactivity was localized to a) amorphous,
poorly defined structures, b) dense floccular material, c) clusters of loosely
packed amyloidlike fibrils 6-8 nm in diameter, and d) poorly defined loose
fibrillar structures 6-8 nm in diameter. beta AP immunoreactive structures were
often in proximity to CTFs, but CTFs themselves never contained beta AP-IR.
Our
study provides the first demonstration of beta AP accumulations in abnormal
human muscle. This finding suggests that in addition to Alzheimer's disease,
Down syndrome, and Dutch-type hereditary cerebrovascular amyloidosis, beta AP
may play an important role in the pathogenesis of other diseases, including
ones
outside the central nervous system, for example, IBM.
PMID: 1321564 [PubMed - indexed for MEDLINE]
479: Neurology. 1992 Apr;42(4):897-902.
Comment in:
Neurology. 1992 Nov;42(11):2231-2.
Familial inclusion body myositis: evidence for autosomal dominant inheritance.
Neville HE, Baumbach LL, Ringel SP, Russo LS Jr, Sujansky E, Garcia CA.
Department of Neurology, University of Colorado School of Medicine, Denver.
We report a kindred manifesting clinical features and muscle biopsy findings
of
inclusion body myositis (IBM). In this family, multiple members were affected
in
two generations with direct male-to-male and female-to-male transmission. This
is the first reported instance of autosomal dominant inheritance in IBM, which
usually occurs sporadically or, rarely, may be transmitted as an autosomal
recessive disorder.
Publication Types:
Case Reports
PMID: 1314344 [PubMed - indexed for MEDLINE]
480: Arch Otolaryngol Head Neck Surg. 1992 Mar;118(3):313-7.
Management of dysphagia in inclusion body myositis.
Darrow DH, Hoffman HT, Barnes GJ, Wiley CA.
Division of Otolaryngology-Head and Neck Surgery, University of California,
San
Diego School of Medicine.
Inclusion body myositis is an inflammatory myopathy in which dysphagia has
been
considered a rare finding. However, recent literature finds dysphagia an
increasingly common symptom as more cases of inclusion body myositis are
identified. Unlike some inflammatory myopathic disorders, inclusion body
myositis is resistant to treatment with corticosteroids, and therefore, the
otolaryngologist may be consulted regarding surgical options for relief of
dysphagia. A patient is described in whom severe progressive dysphagia
associated with inclusion body myositis developed. Impaired pharyngeal wall
motion and cricopharyngeal achalasia were demonstrated by videofluoroscopic
evaluation, and the patient was successfully treated by cricopharyngeal myotomy.
The pathophysiologic nature of inclusion body myositis and the mechanisms of
cervical dysphagia in the inflammatory myopathies are reviewed.
Publication Types:
Case Reports
Review
Review of Reported Cases
PMID: 1313247 [PubMed - indexed for MEDLINE]
481: Lancet. 1992 Feb 29;339(8792):560-1.
beta-Amyloid protein immunoreactivity in muscle of patients with inclusion-body
myositis.
Askanas V, Engel WK, Alvarez RB, Glenner GG.
Publication Types:
Letter
PMID: 1346915 [PubMed - indexed for MEDLINE]
482: J Rheumatol. 1992 Feb;19(2):306-9.
Inclusion body myositis in association with vitamin B12 deficiency and Sjogren's
syndrome.
Khraishi MM, Jay V, Keystone EC.
Rheumatic Disease Unit, Wellesley Hospital, Toronto, ON, Canada.
Autoimmune disorders are very rarely associated with inclusion body myositis
(IBM). We describe a patient with IBM in association with Sjogren's syndrome
(SS) and Vitamin B12 deficiency. B12 deficiency has not been reported in SS,
and
this deficiency may explain the neuropathic features of some patients with IBM.
Publication Types:
Case Reports
PMID: 1629834 [PubMed - indexed for MEDLINE]
483: Neurology. 1992 Feb;42(2):460-1.
Immunocytochemical localization of ubiquitin in inclusion body myositis allows
its light-microscopic distinction from polymyositis.
Askanas V, Serdaroglu P, Engel WK, Alvarez RB.
Department of Neurology, University of Southern California School of Medicine,
Los Angeles.
PMID: 1310532 [PubMed - indexed for MEDLINE]
484: Chem Immunol. 1992;53:75-85.
The role of gamma-delta T lymphocytes in inflammatory muscle disease.
Hohlfeld R, Engel AG.
Department of Neurology, University of Munich, FRG.
During the course of a systematic study of T cell lines derived from muscle
of
patients with various inflammatory myopathies, we identified a new form of
polymyositis that is mediated by gamma-delta T cells. In the affected patient's
muscle CD3+CD4-CD8- gamma-delta T cells surrounded and invaded nonnecrotic
muscle fibers in the same way as CD3+CD8+ alpha-beta T cells surround and invade
nonnecrotic muscle fibers in inclusion body myositis and other forms of
polymyositis. Gamma-delta T cells were extremely rare or absent in muscles and
muscle-derived T cell lines in other patients with polymyositis, inclusion-body
myositis, dermatomyositis or granulomatous myopathy. This new form of
polymyositis has provided us with a unique opportunity to study cytotoxic
gamma-delta T cells and their muscle-fiber targets in situ. All muscle fibers
expressed HLA-class I antigen and the 65-kD heat-shock protein. The
autoaggressive behavior of the gamma-delta T cells is consistent with the
hypothesis that in some inflammatory myopathies autoinvasive T cells recognize
muscle fiber associated antigen(s). Further studies are needed to define the
type of gamma-delta T cell receptor used and the antigen(s) recognized by
gamma-delta T cells in this rare type of autoimmune muscle disease.
Publication Types:
Review
PMID: 1534237 [PubMed - indexed for MEDLINE]
485: Brain Pathol. 1992 Jan;2(1):13-9.
The pathological diagnosis of specific inflammatory myopathies.
Carpenter S, Karpati G.
Department of Neurology, Neurosurgery, McGill University, Montreal, Quebec,
Canada.
Pathological diagnosis of dermatomyositis (DM), polymyositis (PM), and inclusion
body myositis (IBM) should be possible in almost all cases when an appropriately
involved muscle is biopsied. DM shows characteristic patterns of muscle fiber
damage and capillary damage. Lymphocytes and macrophages are seen in PM and
IBM
partially invading non-necrotic fibers. IBM is also characterized by rimmed
vacuoles with membranous whorls, characteristic masses of filaments in cytoplasm
and sometimes in nuclei, and grouped atrophic fibers. Muscle fiber damage in
PM
is more variable. Inflammatory myopathy can be associated with HTLV-1 and HIV
infection. In the latter a strong resemblance to PM is reported. Separate, still
less well characterized forms of inflammatory myopathy occur in young children.
Publication Types:
Review
Review, Tutorial
PMID: 1341942 [PubMed - indexed for MEDLINE]
486: Neuropatol Pol. 1992;30(3-4):199-207.
Inclusion body myositis (IBM). Morphological study.
Fidzianska A, Drac H, Glinka Z.
Department of Neurology, School of Medicine, Polish Academy of Sciences, Warsaw.
Among the chronic idiopathic inflammatory myopathies inclusion body myositis
(IBM) has emerged as a clinicopathologic variant. Slowly progressive weakness
of
the distal and the proximal muscle groups, the presence of rimmed vacuoles with
basophilic granules as well as 15-18-nm filamentous inclusions in affected
muscle confirm the clinical and histopathological distinction between inclusion
body myositis and chronic polymyositis.
Publication Types:
Case Reports
PMID: 1340913 [PubMed - indexed for MEDLINE]
487: Acta Neuropathol (Berl). 1992;85(1):105-10.
Inclusion body myositis with abundant ring fibers.
Del Bigio MR, Jay V.
Department of Pathology, Hospital for Sick Children, University of Toronto,
Ontario, Canada.
A 37-year-old male presenting with a 7-year history of leg weakness was found
to
have moderate weakness confined to the quadriceps and myopathic changes on
electromyography. Serum creatine phosphokinase was 2130 units/liter. Biopsy
of
the quadriceps muscle revealed an inflammatory myopathy with cytoplasmic and
nuclear filamentous inclusions characteristic of inclusion body myositis. An
unusual finding was the large proportion of ring fibers along with severe
atrophy and fibrosis. The pathogenesis of the ring fibers in this setting is
discussed.
Publication Types:
Case Reports
PMID: 1337419 [PubMed - indexed for MEDLINE]
488: Acta Neuropathol (Berl). 1992;84(3):335-6.
Fast and reliable new method for electron-microscopic identification of
cytoplasmic tubulo-filaments in muscle biopsies of patients with inclusion-body
myositis.
Askanas V, Alvarez RB.
USC Neuromuscular Center, University of Southern California School of Medicine
90017-1969.
PMID: 1329431 [PubMed - indexed for MEDLINE]
489: Clin Neurol Neurosurg. 1992;94 Suppl:S118-20.
Inclusion body myositis: its relative frequency in elderly people.
Maat-Schieman ML, Macfarlane JD, Bots GT, Wintzen AR.
Department of Neurology, University Hospital, Leiden, The Netherlands.
Inclusion body myositis (IBM) is a distinct, steroid resistant, form of
inflammatory myopathy. Its recognition is the more important because of the
preponderant occurrence in the elderly, in whom steroid treatment is hazardous.
Since the relative frequency of IBM among inflammatory myopathies in the elderly
is undetermined, we retrospectively studied its frequency among all our patients
over 50 years, diagnosed between 1980 and 1991 with inflammatory myopathy. Nine
of 15 patients with inflammatory myopathy appeared to suffer from IBM. In a
further 2 patients this diagnosis was strongly suspected. We conclude that IBM
is the most frequent inflammatory myopathy in the elderly. This observation
warrants restraint with steroids in the management of inflammatory myopathy
in
the elderly.
PMID: 1320483 [PubMed - indexed for MEDLINE]
490: Muscle Nerve. 1992 Jan;15(1):115.
Comment on:
Muscle Nerve. 1991 May;14(5):470-3.
Inclusion body myositis with cricopharyngeus muscle involvement and severe
dysphagia.
Litchy WJ, Engel AG.
Publication Types:
Comment
Letter
PMID: 1310156 [PubMed - indexed for MEDLINE]
491: Muscle Nerve. 1992 Jan;15(1):115.
Comment on:
Muscle Nerve. 1991 May;14(5):470-3.
Inclusion body myositis with cricopharyngeus muscle involvement and severe
dysphagia.
Danon MJ, Friedman M.
Publication Types:
Comment
Letter
PMID: 1310155 [PubMed - indexed for MEDLINE]
492: Arch Neurol. 1991 Dec;48(12):1229-34.
Amyloid filaments in inclusion body myositis. Novel findings provide insight
into nature of filaments.
Mendell JR, Sahenk Z, Gales T, Paul L.
Department of Neurology, College of Medicine, Ohio State University, Columbus
43210.
Inclusion body myositis (IBM) represents a serious debilitating disease of
muscle without identifiable cause or treatment. Muscle biopsy specimens have
characteristic rimmed vacuoles, varying degrees of inflammation, and, most
importantly, cytoplasmic and intranuclear filamentous inclusions of unknown
composition. Fresh-frozen sections of muscle biopsy specimens from 24 IBM cases
were stained with Congo red dye (pH, 10.5 to 11.0). Control biopsy specimens
included polymyositis, dermatomyositis, hereditary vacuolar myopathies of
unknown cause, acid maltase deficiency, distal myopathy, oculopharyngeal
dystrophy, and chloroquine myopathy. Sections were also immunostained with
antibody to transthyretin, human P component, and immunoglobulin light chains.
In the vacuolated fibers in IBM, amyloidogenic green-birefringent deposits were
seen. Some deposits were delicate and wispy appearing, and others were
plaque-like. The size of deposits varied, measuring 1 x 2 to 8 microns, and
rarely up to 20 microns in length. The number of amyloid-positive fibers
correlated with the number of vacuolated fibers. Similar deposits were seen
in
one case of distal myopathy and one hereditary vacuolar myopathy. Other control
cases were negative for amyloid deposits. Antibody staining for known
amyloidogenic proteins was negative. This study demonstrates that the filaments
in IBM share properties with amyloid proteins. The location implies that this
amyloid material is formed intracellularly, rather than having a systemic
derivation. The association of amyloid deposits with autophagic vacuoles in
IBM
raises the likely possibility that the filaments represent a modification of
a
normal protein within an acidic degradative vacuolar compartment. An alternative
possibility, considering the shared properties of IBM filaments and prions
(which include size and amyloidogenic properties), is that IBM represents a
human prion disease.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 1668977 [PubMed - indexed for MEDLINE]
493: N Engl J Med. 1991 Nov 21;325(21):1487-98.
Comment in:
N Engl J Med. 1992 May 7;326(19):1293.
Polymyositis, dermatomyositis and inclusion-body myositis.
Dalakas MC.
Neuromuscular Diseases Section, National Institute of Neurological Disorders
and
Stroke, National Institutes of Health, Bethesda, MD 20892.
Publication Types:
Review
PMID: 1658649 [PubMed - indexed for MEDLINE]
494: Medicine (Baltimore). 1991 Nov;70(6):360-74.
A new approach to the classification of idiopathic inflammatory myopathy:
myositis-specific autoantibodies define useful homogeneous patient groups.
Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas M, Plotz PH, Miller FW.
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health, Bethesda, Maryland 20892.
The IIM are a heterogeneous group of systemic rheumatic diseases which share
the
common features of chronic muscle weakness and mononuclear cell infiltrates
in
muscle. A number of classification schemes have been proposed for them, but
none
takes into consideration the marked immunologic, clinical, and genetic
heterogeneity of the various clinical groups. We compared the usefulness of
myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP,
anti-Mi-2 and anti-MAS) to the standard clinical categories (polymyositis,
dermatomyositis, overlap myositis, cancer-associated myositis, and inclusion
body myositis) in predicting clinical signs and symptoms, HLA types, and
prognosis in 212 adult IIM patients. Although patients with inclusion body
myositis (n = 26) differed in having significantly more asymmetric and distal
weakness, falling, and atrophy than other patients, there were few other
significant differences among the other clinical groups. In contrast,
autoantibody status defined distinct sets of patients and each patient had only
1 myositis-specific autoantibody. Patients with anti-amino-acyl-tRNA synthetase
autoantibodies (n = 47), compared to those without these antibodies, had
significantly more frequent arthritis, fever, interstitial lung disease, and
"mechanic's hands"; HLA-DRw52; higher mean prednisone dose at survey,
higher
proportion of patients receiving cytotoxic drugs, and higher death rates. Those
with anti-signal recognition particle antibodies (n = 7) had increased
palpitations; myalgias; DR5, DRw52; severe, refractory disease; and higher death
rates. Patients with anti-Mi-2 antibodies (n = 10) had increased "V-sign"
and
"shawl-sign" rashes, and cuticular overgrowth; DR7 and DRw53; and
a good
response to therapy. The 2 patients with anti-MAS antibodies were the only ones
with alcoholic rhabdomyolysis preceding myositis; both had insulin-dependent
diabetes mellitus, and both had HLA-B60, -C3, -DR4, and -DRw53. These findings
suggest that myositis-specific autoantibody status is a more useful guide than
clinical group in assessing patients with myositis, and that specific
associations of immunogenetics, immune responses, and clinical manifestations
occur in IIM. Thus the myositis-specific autoantibodies aid in interpreting
the
diverse symptoms and signs of myositis patients and in predicting their clinical
course and prognosis. We propose, therefore, that an adjunct classification
of
the IIM, based on the myositis-specific autoantibody status, be incorporated
into future studies of their epidemiology, etiology, and therapy.
PMID: 1659647 [PubMed - indexed for MEDLINE]
495: Neurosci Lett. 1991 Sep 2;130(1):73-6.
Immunolocalization of ubiquitin in muscle biopsies of patients with inclusion
body myositis and oculopharyngeal muscular dystrophy.
Askanas V, Serdaroglu P, Engel WK, Alvarez RB.
USC Neuromuscular Center, University of Southern California School of Medicine,
Los Angeles 90017.
In 10/10 inclusion body myositis (IBM) patients and 2/2 oculopharyngeal muscular
dystrophy (OPMD) patients, vacuolated muscle fibers contained darkly stained
ubiquitin (Ub)-immunoreactive cytoplasmic inclusions. By electronmicroscopy,
Ub-immunoreactive material was strictly localized to the 15-21 nm pathologic
cytoplasmic tubulofilaments (CTFs). None of 18 control muscle biopsies contained
the Ub-immunoreactive inclusions that are typical for IBM and OPMD. Thus, (a)
finding that CTFs are ubiquitinated places their protein in the Ub-mediated
turnover pathway and provides their first molecular marker; (b) easy
accessibility, as compared to the central nervous system, of muscle tissue
containing ubiquitinated inclusions should be advantageous for biochemical and
molecular studies and may provide information important to both systems.
PMID: 1660975 [PubMed - indexed for MEDLINE]
496: Arch Neurol. 1991 May;48(5):519-22.
Familial inclusion body myositis among Kurdish-Iranian Jews.
Massa R, Weller B, Karpati G, Shoubridge E, Carpenter S.
Neuromuscular Research Group, Montreal (Quebec), Neurological Institute, Canada.
We report two cases of adult-onset, slowly progressive limb-girdle muscle
weakness with a remarkable sparing of quadriceps muscles that developed in
patients from different families of Iranian-Kurdish-Jewish origin. Each patient
had a similarly affected sibling. The findings by means of muscle biopsies
showed abnormalities typical of inclusion body myositis, including abundant
lined vacuoles and characteristic cytoplasmic inclusions of 15- to 18-nm
filaments. Remarkably, many vacuolated muscle fibers showed immunoreactivity
to
neural cell adhesion molecule, a fetal muscle antigen. The common origin of
these patients from an isolated ethnic group with frequent consanguinity and
the
familial incidence is indicative of a genetic causation or predisposition,
probably with an autosomal recessive inheritance. This familial myopathy is
one
of several clinical syndromes that share the typical pathological findings of
inclusion body myositis. The pathogenic relationship between these different
familial forms and the more common sporadic form of inclusion body myositis
is
not known.
Publication Types:
Case Reports
PMID: 1850594 [PubMed - indexed for MEDLINE]
497: Ann Neurol. 1991 May;29(5):498-507.
Coculture with autologous myotubes of cytotoxic T cells isolated from muscle
in
inflammatory myopathies.
Hohlfeld R, Engel AG.
Department of Neurology, Mayo Clinic Rochester, MN 55905.
T-cell lines were expanded from muscle of 10 patients with polymyositis, 5
with
inclusion body myositis, 5 with dermatomyositis, and 5 with other muscle
diseases. All cell lines uniformly expressed T-cell antigens, but not natural
killer cell or B-cell antigens. The proportion of helper (CD4+) and cytotoxic
(CD8+) T cells in the expanded lines was variable and showed no correlation
with
the diagnosis. Sixteen cell lines (6 polymyositis, 4 inclusion body myositis,
5
dermatomyositis, 1 other muscle disease) consisted predominantly of CD8+ T
cells. None of these lines displayed natural killer-like cytotoxicity but all
were capable of lectin-dependent cytotoxicity. Three of 6 polymyositis, 1 of
4
inclusion body myositis, and 1 of 5 dermatomyositis lines showed low but
statistically significant cytotoxicity against autologous myotubes (6 to 27%
specific 51Cr release; effector-target ratio, 20:1). The results demonstrate
that functionally competent cytotoxic T cells can be expanded from muscle
affected by inflammatory myopathies and are consistent with the hypothesis that
some cytotoxic T cells recognize an autoantigen on myotubes. Further studies
of
this experimental system may define the molecular mechanism of T cell-mediated
muscle fiber injury and may help to identify the relevant antigens.
PMID: 1830466 [PubMed - indexed for MEDLINE]
498: Muscle Nerve. 1991 May;14(5):470-3.
Comment in:
Muscle Nerve. 1992 Jan;15(1):115.
Muscle Nerve. 1992 Jan;15(1):115.
Inclusion body myositis with cricopharyngeus muscle involvement and severe
dysphagia.
Verma A, Bradley WG, Adesina AM, Sofferman R, Pendlebury WW.
Department of Neurology, University of Vermont College of Medicine, Burlington.
A patient with inclusion body myositis (IBM) is presented. Unusual aspects
of
this case include a myopathy of 36 years duration, severe dysphagia due to
cricopharyngeus muscle dysfunction, improvement with cricopharyngeus myotomy,
and a diagnostic cricopharyngeus muscle biopsy.
Publication Types:
Case Reports
PMID: 1651449 [PubMed - indexed for MEDLINE]
499: J Neurol Sci. 1991 May;103(1):76-81.
Inclusion body myositis and Welander distal myopathy: a clinical,
neurophysiological and morphological comparison.
Lindberg C, Borg K, Edstrom L, Hedstrom A, Oldfors A.
Department of Neurology, Sahlgrenska Hospital, Gothenburg, Sweden.
Five patients with inclusion body myositis (IBM), an acquired inflammatory
myopathy, and five patients with Welander hereditary distal myopathy (WDM) were
compared clinically and with neurophysiological and morphological techniques.
Both diseases have a late insidious onset, but the course of IBM is more severe.
IBM mainly affects proximal muscles in the lower extremities, while distal
muscle groups are involved in both upper and lower extremities. In WDM there
is
always a strict distal muscle involvement. The neurophysiological
characteristics of the two conditions include both myopathic and neurogenic
components. In both diseases there were rimmed vacuoles in muscle fibres and
at
the ultrastructural level cytoplasmic 15-18 nm filamentous inclusions. Although
the histopathology of muscle in IBM and WDM has some common features,
inflammatory infiltrates were never found in WDM. Such infiltrates seem to be
an
important clue to the correct diagnosis of IBM.
PMID: 1650819 [PubMed - indexed for MEDLINE]
500: N Engl J Med. 1991 Mar 28;324(13):877-81.
Comment in:
N Engl J Med. 1991 Aug 22;325(8):587-8.
Polymyositis mediated by T lymphocytes that express the gamma/delta receptor.
Hohlfeld R, Engel AG, Ii K, Harper MC.
Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905.
BACKGROUND. The invasion and destruction of nonnecrotic muscle fibers by CD8+
cytotoxic T cells is considered a hallmark of polymyositis. In the cases of
polymyositis reported so far, the autoinvasive CD8+ T cells expressed the common
form of T-cell receptor for the recognition of antigen, the so-called alpha/beta
T-cell receptor. We describe a 69-year-old man with polymyositis mediated by
CD4-, CD8- T cells expressing the recently discovered, uncommon gamma/delta
T-cell receptor. METHODS. We used immunofluorescence or immunoperoxidase
techniques to study frozen sections of muscle from our patient, who had mild
weakness of cervical and proximal limb muscles, and from control patients with
polymyositis, inclusion-body myositis, dermatomyositis, or granulomatous
myopathy with monoclonal antibodies against T-cell-related antigens (CD2, CD3,
CD4, CD8, and gamma/delta T-cell receptor), B cells (CD22), major
histocompatibility complex (MHC) and MHC-related antigens (MHC Class I, CD1a,
CD1b, and CD1c), and the 65-kd heat-shock protein. The membrane contacts between
the autoinvasive cells and the sarcolemma were investigated by electron
microscopy. RESULTS. In the patient described here, but not in 28 others with
inflammatory myopathies, myriad gamma/delta T cells surrounded and invaded
nonnecrotic muscle fibers. All muscle fibers were highly reactive for MHC Class
I antigen and the 65-kd heat-shock protein. Treatment with prednisone improved
the clinical and histologic findings. CONCLUSIONS. Polymyositis can be mediated
by gamma/delta T cells. This new form of polymyositis appears to be highly
responsive to steroids.
Publication Types:
Case Reports
PMID: 1705662 [PubMed - indexed for MEDLINE]
501: Clin Neuropathol. 1991 Mar-Apr;10(2):61-4.
Auriculo-ventricular block and distal myopathy with rimmed vacuoles and desmin
storage.
Telerman-Toppet N, Bauherz G, Noel S.
Department of Neurology, Brugmann University Hospital, Brussels, Belgium.
A young patient had an auriculo-ventricular block and a distal myopathy with
muscle biopsy findings suggestive of inclusion body myositis. What was most
unusual was the presence of numerous sarcoplasmic bodies identified as desmin
by
electron microscopy and immunocytochemistry. The nosological situation of this
condition is discussed.
Publication Types:
Case Reports
PMID: 1647283 [PubMed - indexed for MEDLINE]
502: J Rheumatol. 1991 Feb;18(2):289-92.
Clinically unsuspected inclusion body myositis.
Purvis J, Fam AG, Lewis A.
Department of Medicine, Sunnybrook Health Science Centre, University of Toronto,
ON, Canada.
We describe a patient with inclusion body myositis presenting as chronic,
therapy resistant polymyositis. Our report highlights the slow evolution of
inclusion body myositis in some patients, and emphasizes the diagnostic
importance of examining one or more muscle biopsy specimens by both frozen
section and electron microscopy.
Publication Types:
Case Reports
PMID: 1850803 [PubMed - indexed for MEDLINE]
503: Hum Pathol. 1991 Jan;22(1):29-32.
Inclusion body myositis and paramyxoviruses.
Kallajoki M, Hyypia T, Halonen P, Orvell C, Rima BK, Kalimo H.
Department of Pathology, University of Turku, Finland.
Inclusion body myositis (IBM) is a distinct type of muscle disease. The
characteristic electron microscopic findings, intranuclear or intracytoplasmic
inclusions composed of microtubular filaments, morphologically resemble
paramyxovirus nucleocapsids. These findings and the reported immunoreactivity
of
the inclusions with mumps virus antibodies have suggested that inclusion body
myositis is a chronic virus infection. We analyzed skeletal muscle specimens
from three patients with characteristic light microscopic features and electron
microscopically verified inclusions of IBM by immunocytochemistry using
antibodies raised against members of the paramyxovirus group, and by in situ
hybridization with a cRNA probe representing the mumps virus nucleocapsid gene.
The specificity of the reactions was demonstrated with infected and uninfected
cultured cells. No immunocytochemical staining or hybridization signal was
observed in biopsy specimens from IBM patients. These findings speak against
a
paramyxovirus etiology of IBM.
PMID: 1845865 [PubMed - indexed for MEDLINE]
504: Acta Neuropathol (Berl). 1991;82(2):102-6.
Intranuclear and cytoplasmic filamentous inclusions in distal myopathy
(Welander).
Borg K, Tome FM, Edstrom L.
Department of Neurology, Karolinska Hospital, Stockholm, Sweden.
Ultrastructural examination of anterior tibial muscle from four patients with
late-onset autosomal dominant distal myopathy of Welander-type revealed
intrasarcoplasmic filamentous inclusions in association with rimmed vacuoles.
In
one of the patients, identical intranuclear filamentous inclusions were also
found. These filamentous inclusions are similar to those described in inclusion
body myositis (IBM). They have also been observed in hereditary neuromuscular
disorders including autosomal recessive distal myopathy. Thus, the filamentous
inclusions occur in different neuromuscular conditions with different
etiologies. These findings further raise the question of the specificity of
the
filamentous inclusions in IBM.
Publication Types:
Case Reports
PMID: 1656692 [PubMed - indexed for MEDLINE]
505: J Neurol Sci. 1990 Nov;99(2-3):327-38.
Inclusion body myositis: peripheral nerve involvement. Combined morphological
and electrophysiological studies on peripheral nerves.
Lindberg C, Oldfors A, Hedstrom A.
Department of Neurology, Sahlgrenska Hospital, Goteborg, Sweden.
The occurrence of neuropathy in 5 cases of inclusion body myositis (IBM) was
studied. The intramuscular nerve branches showed variable ultrastructural
changes in all cases. The observed changes were loss of axons, wallerian
degeneration and axon terminal atrophy. EMG with concentric needles showed
myopathic motor unit potentials in all cases. A reduced interference pattern
due
to loss of motor units was found in all cases. All but one patient showed
fibrillation potentials in several muscle groups. Motor nerve conduction
velocities and F-wave latencies were pathological in two of the cases, in which
there were motor unit potentials with increased amplitude and duration as
evidence of reinnervation. Sural nerve biopsy in one of these cases revealed
slight neuropathy of the axonal type. These findings support the concept of
peripheral nerve involvement in many cases of IBM.
PMID: 1964960 [PubMed - indexed for MEDLINE]
506: Neuropathol Appl Neurobiol. 1990 Oct;16(5):393-400.
Presence of inclusion body myositis-like filaments in oculopharyngeal muscular
dystrophy. Ultrastructural study of 10 cases.
Coquet M, Vital C, Julien J.
Department of Neuropathology, Hopital Pellegrin, Bordeaux, France.
Ten cases of oculopharyngeal muscular dystrophy (OPMD) were examined
ultrastructurally. Two very different types of filamentous inclusions were
observed: (1) Nuclear inclusions composed of 8.5 nm external diameter tubular
filaments organized in palisades and similar to those described by Tome and
Fardeau (1980). They have not yet been reported in other muscle diseases. Their
presence in 100% of our cases confirms they are the morphological hallmark of
OPMD. (2) 16-18 nm external diameter tubular filaments. These were similar to
the inclusions observed in inclusion body myositis (IBM) and morphologically
very different from the first type. They were randomly dispersed or arranged
in
bundles near cytoplasmic debris and whorls of membranes. They were found in
cytoplasm. Only once were they observed in a nucleus. These inclusions have
been
described in IBM but also in other diseases. They were found in 80% of our OPMD
cases.
PMID: 2175847 [PubMed - indexed for MEDLINE]
507: Muscle Nerve. 1990 Oct;13(10):949-51.
Electrophysiological spectrum of inclusion body myositis.
Joy JL, Oh SJ, Baysal AI.
Department of Neurology, University of Alabama, Birmingham 35294.
We present electrodiagnostic data on 30 patients with inclusion body myositis
(IBM) in order to better delineate its electrophysiological features.
Comprehensive electromyography (EMG) and nerve conduction studies (NCS) were
performed in all cases. Twelve patients had single fiber electromyography
(SFEMG). EMG showed abundant short-small motor unit potentials (MUP) with
fibrillations and positive sharp waves in 56.6% of patients, and a mixed pattern
of large and small MUP in 36.7%. In 6.7%, only "neurogenic" features
were seen.
NCS were slow in 33.3%. SFEMG revealed a mildly abnormal jitter and a slightly
increased fiber density. IBM demonstrates a heterogeneous EMG profile. A pattern
of large and small MUP is highly suggestive of IBM but is seen in only about
one
third of cases.
PMID: 2172812 [PubMed - indexed for MEDLINE]
508: J Am Acad Dermatol. 1990 Oct;23(4 Pt 1):753-4.
In vivo complement C3 binding to the intercellular substance and cytoplasm
of
epidermal basal cells in a patient with scleroderma and inclusion body myositis.
Helm TN, Valenzuela R, Bergfeld WF, Guitart J, Poolos CJ.
Cleveland Clinic Foundation, OH.
Publication Types:
Case Reports
PMID: 2172335 [PubMed - indexed for MEDLINE]
509: Clin Exp Immunol. 1990 Sep;81(3):373-9.
Lymphocyte activation markers in idiopathic myositis: changes with disease
activity and differences among clinical and autoantibody subgroups.
Miller FW, Love LA, Barbieri SA, Balow JE, Plotz PH.
Arthritis and Rheumatism Branch, National Institute of Arthritis and
Musculoskeletal and Skin diseases, National Institutes of Health, Bethesda,
MD
20892.
We studied the immunologic correlates of disease activity and differences among
subgroups of patients with idiopathic inflammatory myopathy by analysing
phenotypic and activation marker expression on peripheral blood mononuclear
cells (PBMC). Compared with controls, myositis patients with clinically active
disease (n = 51) had significantly lower proportions of CD8+ cells and higher
proportions of PBMC that expressed DR, CD3- DR, CD14- DR, interleukin-2
receptors, and the late T cell activation markers CD26 and TLiSA1. TLiSA1
expression, a marker for cytotoxic differentiation, correlated significantly
with both clinical activity indices and serum levels of muscle-associated
enzymes. In serial studies of seven patients, the proportion of PBMC expressing
MHC class II antigen and late T cell activation markers decreased as myositis
disease activity decreased, independent of type of therapy. Among the clinical
subgroups, polymyositis (n = 21) and inclusion body myositis (n = 11) were
virtually indistinguishable; dermatomyositis patients (n = 19) showed decreased
proportions of CD3+DR+ and TLiSA1+ cells, and increased proportions of CD20+
and
CD20+DR+ cells compared with the other two groups. Patients with autoantibodies
to histidyl-tRNA synthetase (Jo-1 antigen, n = 11) had significantly lower
proportions of CD3+ and CD4+ cells, lower CD4/CD8 ratios, and higher proportions
of CD+ cells expressing CD20, compared with patients without anti-Jo-1
antibodies. These findings support the concept that activated lymphocytes,
especially cells undergoing anamnestic responses and cytotoxic differentiation,
are important in the pathogenesis of idiopathic myositis. Moreover, taken
together with other studies, these data suggest that groups of patients
segregated by clinical or autoantibody status have different mechanisms of
systemic immune activation and immunopathology.
PMID: 2168821 [PubMed - indexed for MEDLINE]
510: Neuropathol Appl Neurobiol. 1990 Aug;16(4):333-44.
Inclusion body myositis in French patients. A clinicopathological evaluation.
Mhiri C, Gherardi R.
Departement de Pathologie (Neuropathologie), Hopital Henri Mondor, Creteil,
France.
In order to establish the frequency of inclusion body myositis (IBM) in a
European neuropathological unit and to evaluate the specificity of IBM
pathology, we reviewed the 850 muscle biopsies performed in our laboratory over
the past 7 years. Clinical histopathological and ultrastructural evaluation
of
all cases showing rimmed vacuoles, a constant histopathological feature of IBM,
was done and the diagnosis of IBM was assessed using the clinico-pathological
criteria of Calabrese, Mitsumoto & Chou (1987). Among the nine cases showing
rimmed vacuoles, five were classified as IBM (group 1), either definite (3/5)
or
probable (2/5), and four suffered from a chronic denervating process of muscle
(group 2). The overall frequency of IBM (0.6% of all muscle biopsies) was
similar to that reported by North American authors. IBM represented 16% of adult
idiopathic inflammatory myopathies investigated in our laboratory. Clinical
and
histopathological findings in group 1 were homogeneous and distinctive. Muscle
biopsy was consistent with an inflammatory myopathy in all patients in group
1
and with a non-inflammatory denervating process in 3/4 patients in group 2.
Typical intrasarcoplasmic inclusions were detected by electron microscopy in
3/5
cases in group 1 and 1/4 in group 2, which raises questions about the
specificity of the 16-18 nm tubulofilaments. Failure to demonstrate inclusions
in two patients with otherwise typical IBM, was probably related to the paucity
of rimmed vacuoles observed in these cases.
PMID: 2172855 [PubMed - indexed for MEDLINE]
511: Pathol Res Pract. 1990 Jun;186(3):371-82.
Lacunar dilatations of intrafusal and extrafusal terminal cisternae, annulate
lamellae, confronting cisternae and tubulofilamentous inclusions within the
spectrum of muscle and nerve fiber changes in myotonic dystrophy.
Dieler R, Schroder JM.
Institut fur Neuropathologie, Klinikum der Rheinisch-Westfalischen Technischen
Hochschule, Aachen, FRG.
In 3 out of 5 muscle spindles available in skeletal muscle biopsy specimens
from
30 patients with myotonic dystrophy (MD) unusually large lacunar dilatations
of
terminal cisternae were observed that had thus far only been reported in
extrafusal muscle fibers. Cytoplasmic annulate lamellae, confronting cisternae
and regularly proliferated terminal cisternae, as well as intranuclear
tubulovesicular inclusions were found in extrafusal muscle fibers that in
combination with concentric membranous bodies seen in perineurial cells and
Schwann cells generally emphasize an involvement of the endoplasmic reticulum
in
the pathogenesis of MD. In addition, a nuclear inclusion body was observed
composed of tubulofilamentous structures with close similarity to those thought
to be rather specific for inclusion body myositis. Vesicles filled with
amorphous material originating from outer spindle capsule cells were suggested
to indicate matrical lipidic debris leading to "ghost bodies" and
calcifying
globules. Light microscopical evaluation of 8 sural nerve specimens revealed
a
neuropathy in only 2 patients that was predominantly axonal in type and of
slight to moderate severity with a secondary demyelinating component in 1
patient. These findings add to the large spectrum of muscle and nerve fiber
changes in MD underlining the phenotypic multiplicity of a well defined genetic
defect.
PMID: 2143018 [PubMed - indexed for MEDLINE]
512: Ann Neurol. 1990 Apr;27(4):343-56.
Microvascular changes in early and advanced dermatomyositis: a quantitative
study.
Emslie-Smith AM, Engel AG.
Muscle Research Laboratory, Mayo Clinic, Rochester, MN 55905.
In adult dermatomyositis 10 muscle specimens with no or minimal histological
alterations were compared with 7 that showed typical alterations. Five specimens
from patients with inclusion body myositis, 5 from patients with polymyositis,
and 8 from normal subjects served as controls. Vascular endothelium, visualized
with the lectin Ulex europaeus agglutinin I, and complement membrane attack
complex were demonstrated in the same cryostat sections by paired
immunofluorescence. Large randomly selected fields were analyzed to determine
the number of capillaries per square millimeter of fiber area (capillary
density), per 1,000-microns 2 area of each muscle fiber (capillary index), and
in 100 x 100-microns grid squares. In dermatomyositis specimens with minimal
structural alterations there was focal capillary depletion, the capillary
density was significantly reduced, and the frequency distributions of the
capillary index and grid count were shifted to the left. In advanced
dermatomyositis specimens, the findings were similar but more severe. In both
kinds of specimens, clusters of capillaries reacted for complement membrane
attack complex. The 2 patients with the highest proportion of vessels positive
for membrane attack complex had a fulminant and fatal course. In polymyositis
and inclusion body myositis specimens, the capillaries had a normal overall
density and none reacted for membrane attack complex. The findings imply that
the capillaries are an early and specific target of the disease process in
dermatomyositis.
PMID: 2353792 [PubMed - indexed for MEDLINE]
513: Am J Phys Med Rehabil. 1990 Feb;69(1):2-5.
Inclusion body myositis. An electrophysiologic study.
Dumitru D, Newell-Eggert M.
Department of Physical Medicine and Rehabilitation, University of Texas Health
Science Center, San Antonio 78284-7798.
Inclusion body myositis is a rare and slowly progressive myositis associated
with cytoplasmic inclusions and fibrillar nuclear material. These
histopathologic findings are of unknown significance. The clinical presentation
of IBM has marked similarities to that of chronic polymyositis with proximal
greater than distal weakness and muscle wasting more pronounced in the lower
than upper extremities. In contrast to polymyositis, however, relatively few
individuals report neck flexor weakness or dysphagia. Corticosteroid treatment
is usually ineffective. The clinical, histopathologic and electrophysiologic
findings in a patient with IBM are presented. Of particular interest in this
report is the detailed motor unit recruitment frequency data. A number of
previous IBM reports fail to mention specific electrophysiologic data or present
evidence suggestive of a possible combined neuropathic and myopathic disease.
Recruitment intervals of 150 ms or greater in combination with decreased motor
unit duration and amplitudes in the involved muscles imply a myopathic
pathophysiology. These findings are discussed in relation to electrophysiologic
data from previously reported cases.
Publication Types:
Case Reports
PMID: 2154241 [PubMed - indexed for MEDLINE]
514: Acta Neuropathol (Berl). 1990;79(5):528-36.
Inflammatory and non-inflammatory inclusion body myositis. Characterization
of
the mononuclear cells and expression of the immunoreactive class I major
histocompatibility complex product.
Figarella-Branger D, Pellissier JF, Bianco N, Devictor B, Toga M.
Laboratoire de Neuropathologie, Faculte de Medecine Timone, Marseille, France.
In ten patients with inclusion body myositis (IBM) five muscular biopsies showed
profuse inflammatory exudates and three showed a few scattered inflammatory
cells with partial invasion in some muscle fibers. No inflammatory cells were
seen in two cases. In all patients, histopathological, histomorphometric and
immunocytochemical studies were performed. Immunocytochemistry for the class
I
and class II major histocompatibility complex gene product (MHC) was performed
in all cases and in ten control muscles including: normal muscles [3],
dermatomyositis [3], polymyositis [3], scleroderma [1]. In the five cases of
IBM
with inflammatory exudates, subsets of lymphocytes were analyzed with a panel
of
monoclonal antibodies against B cells, T4 cells, T8 cells, K and natural killer
cells and macrophages. Some muscle fibers expressed class I MHC antigens in
the
inflammatory cases of IBM. These fibers were near the inflammatory exudates
and
occasionally showed a partial invasion. No expression of class I MHC was found
in normal muscles and in non-inflammatory cases of IBM. The antigen which
triggers the mononuclear cells in the inflammatory forms of IBM is probably
not
the filamentous inclusions in rimmed vacuoles. In other inflammatory myopathies,
expression of class I MHC was present on all fibers in polymyositis, only in
the
perifascicular area in dermatomyositis and in scleroderma. It could be suggested
that the term "inclusion body muscle disease" be applied to cases
with rimmed
vacuoles and "IBM-like" filaments without inflammatory cells.
PMID: 2158202 [PubMed - indexed for MEDLINE]
515: Curr Opin Rheumatol. 1989 Dec;1(4):460-7.
Inclusion body myositis.
Kula RW, Sawchak JA, Sher JH.
State University of New York Health Science Center, Brooklyn.
Publication Types:
Review
Review, Tutorial
PMID: 2562009 [PubMed - indexed for MEDLINE]
516: Can J Neurol Sci. 1989 Nov;16(4):436-8.
Inclusion body myositis associated with progressive dysphagia: treatment with
cricopharyngeal myotomy.
Danon MJ, Friedman M.
Department of Pathology, Illinois Masonic Center, Chicago 60657.
A 68-year-old man known to have inclusion body myositis underwent a
cricopharyngeal myotomy in an attempt to improve his progressive dysphagia.
Morphological studies from tissues obtained during this procedure showed the
diagnostic features typical of this chronic inflammatory myopathy. To our
knowledge this is the first pathological demonstration of inclusion body
myositis involving the pharyngeal skeletal musculature.
Publication Types:
Case Reports
PMID: 2553229 [PubMed - indexed for MEDLINE]
517: J Child Neurol. 1989 Oct;4(4):283-5.
Childhood onset inclusion body myositis mimicking limb-girdle muscular
dystrophy.
Riggs JE, Schochet SS Jr, Gutmann L, Lerfald SC.
Department of Neurology, West Virginia University School of Medicine, Morgantown
26506.
Inclusion body myositis was initially recognized in patients with
"steroid-resistant polymyositis" and subsequently in patients with
other
immune-mediated disorders. The finding of inclusion body myositis in a patient
diagnosed for 30 years as having limb-girdle muscular dystrophy suggests yet
another patient pool that may harbor this entity.
Publication Types:
Case Reports
PMID: 2551952 [PubMed - indexed for MEDLINE]
518: Ann Intern Med. 1989 Jul 15;111(2):143-57.
Current concepts in the idiopathic inflammatory myopathies: polymyositis,
dermatomyositis, and related disorders.
Plotz PH, Dalakas M, Leff RL, Love LA, Miller FW, Cronin ME.
National Institutes of Health, Bethesda, MD 20892.
Idiopathic inflammatory myopathy, a category encompassing polymyositis,
dermatomyositis, and a number of other disorders, is very uncommon, but has
been
the focus of intense study in the Arthritis and Rheumatism Branch of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases for the
past several years. We describe the clinical picture, stressing the need for
biopsy to ensure correct diagnosis. It is especially important to recognize
the
treatment-resistant variant, inclusion body myositis. The extraskeletal
manifestations, particularly the cardiopulmonary, oropharyngeal,
gastrointestinal, and endocrine involvement, are described. The cardiopulmonary
involvement, especially interstitial lung disease, arrhythmias, and cardiac
failure, may dominate the clinical picture. The known causes are varied, and
include drugs, toxins, and some infectious agents, however, in most cases a
cause cannot yet be identified. Circumstantial evidence suggests that
picornaviruses may initiate some cases in humans, and a very similar disease
in
mice caused by a picornavirus is actively under study. Studies of autoantibodies
and cellular immune function support a central role for disordered immunity
in
the pathogenesis. The myositis-specific autoantibodies, especially those
directed at certain enzymes important in protein synthesis (the
aminoacyl-transfer RNA synthetases), are found in a clinically distinct subset
of patients. Although most patients respond initially to corticosteroids,
cytotoxic drugs are sometimes added when steroid toxicity or refractoriness
develops. We describe several newer therapies under study for such cases and
outline future directions in research.
Publication Types:
Review
PMID: 2662848 [PubMed - indexed for MEDLINE]
519: Arthritis Rheum. 1989 Jun;32(6):734-40.
Clinical heterogeneity and treatment response in inclusion body myositis.
Cohen MR, Sulaiman AR, Garancis JC, Wortmann RL.
Department of Internal Medicine, Medical College of Wisconsin, Milwaukee.
Inclusion body myositis has been described as an inflammatory myopathy with
distinctive clinical and pathologic features that is refractory to treatment.
Ten cases of inclusion body myositis, as defined by histopathologic findings,
were reviewed to determine whether the clinical characteristics are different
in
patients whose disease has been defined by light and electron microscopic
studies compared with those whose disease has been defined by light microscopic
studies alone. The clinical characteristics of both groups of patients were
similar, and 2 patients have had excellent responses to treatment. Although
inclusion body myositis represents a histologic subset of polymyositis, from
a
clinical perspective, it must be considered a nonspecific designation. Despite
a
generally poor prognosis, therapeutic intervention is still warranted.
PMID: 2544185 [PubMed - indexed for MEDLINE]
520: Brain. 1989 Jun;112 ( Pt 3):727-47.
Inclusion body myositis. Observations in 40 patients.
Lotz BP, Engel AG, Nishino H, Stevens JC, Litchy WJ.
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Inclusion body myositis (IBM) was suspected on light microscopic grounds in
48
of 170 consecutive patients with inflammatory myopathies. One or more vacuoles
containing membranous material, groups of atrophic fibres, and an autoaggressive
endomysial inflammatory exudate occurred in 100, 96 and 92% of the muscle
specimens. All three of these features were present in 88% of the specimens.
Electron microscopy confirmed the presence of filamentous inclusions in 40 of
43
patients. The inclusions are typically near vacuoles and a minimum of three
vacuolated fibres must be scrutinized to detect them with confidence. There
is
no electromyographic pattern that can reliably distinguish IBM from other
inflammatory myopathies. The typical clinical features in the patients diagnosed
by histological criteria as IBM were: insidious onset after age 50 yrs with
painless, proximal lower extremity weakness; slow but relentless progression
with selectively severe involvement of quadriceps, iliopsoas, tibialis anterior,
biceps and triceps muscles; relatively early depression of the knee reflexes;
and a normal or mildly elevated serum creatine kinase level. The male: female
ratio was 3:1. Distal weakness occurred in about 50%, but only in 35% was it
as
great or greater than proximal weakness. Significant associated illnesses
include other autoimmune disorders (15%), diabetes mellitus (20%), and diffuse
peripheral neuropathy (18%). Prednisone treatment at dose levels frequently
effective in polymyositis failed to prevent disease progression in those
patients observed for 2 or more years. Our findings support the notion that
IBM
is a distinct entity in which a set of pathological features is associated with
a constellation of clinical findings.
PMID: 2543478 [PubMed - indexed for MEDLINE]
521: Ann Neurol. 1989 Mar;25(3):260-4.
Inclusion body myositis: the mumps virus hypothesis.
Nishino H, Engel AG, Rima BK.
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
The resemblance of the filamentous inclusions in inclusion body myositis (IBM)
to mumps virus nucleoproteins and the report of immunoreactivity of the
inclusions for mumps virus antigens have implicated the mumps virus in the
etiology of IBM. We tested the mumps virus hypothesis by in-situ hybridization
with a cDNA probe specific for the mumps virus nucleocapsid gene, and
immunocytochemically with antibodies against "soluble" and "viral"
mumps
antigens. The tests were performed on muscle specimens (IBM, 20; acid maltase
deficiency, 4; chloroquine myopathy, 2; nonweak control subjects, 5) and mumps
virus-infected and uninfected HEp-2 cells. The in-situ hybridization study
showed a strong specific signal in the infected HEp-2 cells but no specific
signal in IBM, other myopathies, or nonweak control subjects. The
immunocytochemical study showed specific binding of the antimumps antibodies
to
the infected HEp-2 cells but demonstrated only nonspecific binding of these
antibodies around rimmed vacuoles in IBM, acid maltase deficiency, and
chloroquine myopathy. These studies cast doubt on the mumps hypothesis of IBM.
PMID: 2729916 [PubMed - indexed for MEDLINE]
522: Hum Pathol. 1989 Mar;20(3):224-31.
Major histocompatibility complex class I antigen expression, immunolocalization
of interferon subtypes, and T cell-mediated cytotoxicity in myopathies.
Emslie-Smith AM, Arahata K, Engel AG.
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Major histocompatibility complex class I (MHC-I) expression on target cells
is a
prerequisite for antigen-specific T cell-mediated cytotoxicity (TCMC). Enhanced
MHC-I expression has been attributed to interferons (IFNs) released from
inflammatory cells. In previous studies, we found evidence of TCMC (invasion
of
non-necrotic muscle fibers by cytotoxic T cells) in polymyositis (PM) and in
inclusion body myositis (IBM). We occasionally found evidence of TCMC in
Duchenne dystrophy (DD) but not in dermatomyositis (DM). This study examines
the
relationships between TCMC, MHC-I expression, and IFN immunoreactivity in these
diseases and normal controls. In controls, reactivity for MHC-I was confined
to
blood vessels. In all diseases, regenerating fibers expressed MHC-I. In IBM,
PM
and DD, all nonnecrotic muscle fibers invaded by CD8+ cells and some adjacent
fibers expressed MHC-I. In DM, myriad muscle fibers expressed MHC-I but none
were invaded by CD8+ cells. In all diseases, only a few mononuclear cells and
no
muscle fiber surfaces were immunoreactive for IFNs. We conclude that MHC-I
expression on muscle fibers is necessary but not sufficient for TCMC in
myopathy; that the biological significance of increased MHC-I expression in
DM
remains undefined; and that currently available and appropriately controlled
immunocytochemical methods show no relationship between increased MHC-I
expression on muscle fibers and local IFN synthesis by mononuclear cells.
PMID: 2470663 [PubMed - indexed for MEDLINE]
523: Brain. 1989 Feb;112 ( Pt 1):65-83.
Distal myopathy with rimmed vacuole formation. A follow-up study.
Sunohara N, Nonaka I, Kamei N, Satoyoshi E.
Department of Neurology, National Center of Neurology and Psychiatry, Tokyo,
Japan.
A long-term follow-up study of patients with familial distal myopathy with
rimmed vacuole formation and a review of the literature indicates that the
prognosis of the disorder was extremely poor as to daily life. Although the
initial symptom appearing in early adulthood was muscular wasting and weakness
in the legs, especially the distal muscles, severe generalized skeletal muscle
involvement with sparing of the facial, extraocular, bulbar, intercostal and
diaphragm muscles was recognized in the advanced stage. The disease is probably
inherited as an autosomal recessive trait, while there is a considerable female
preponderance, the female-to-male ratio being 2:1. The disorder is
distinguishable from various types of distal myopathy on the basis of clinical
and pathological findings, and other myopathies with rimmed vacuole formation,
including inclusion body myositis, from a prognostic viewpoint.
Publication Types:
Review
Review of Reported Cases
PMID: 2645018 [PubMed - indexed for MEDLINE]
524: J Neurol Neurosurg Psychiatry. 1988 Dec;51(12):1542-5.
Dysphagia in inclusion body myositis.
Wintzen AR, Bots GT, de Bakker HM, Hulshof JH, Padberg GW.
Department of Neurology, University Hospital, Leiden, The Netherlands.
Four elderly patients with inclusion body myositis and dysphagia are described.
Dysphagia was the presenting symptom in three, preceding generalised weakness
by
1.5 to 7 years. Myotomy of the cricopharyngeal muscle improved the symptoms
and
signs in 3 of the 4 patients. It is suggested that inclusion body myositis is
not an infrequent cause of dysphagia in elderly people, and is amenable to
treatment.
PMID: 2851642 [PubMed - indexed for MEDLINE]
525: Brain. 1988 Oct;111 ( Pt 5):1025-37.
Familial myopathy with changes resembling inclusion body myositis and
periventricular leucoencephalopathy. A new syndrome.
Cole AJ, Kuzniecky R, Karpati G, Carpenter S, Andermann E, Andermann F.
Montreal Neurological Hospital and Institute, Quebec, Canada.
Five of 6 male siblings were affected by a progressive myopathy beginning in
early childhood. Muscle biopsies in all patients showed the characteristic
changes of inclusion body myositis. Computerized tomography and magnetic
resonance imaging revealed a markedly abnormal appearance of cerebral white
matter in the 4 affected patients tested, but clinical and other laboratory
examinations failed to demonstrate evidence of central white matter dysfunction.
Muscle biopsies and brain imaging were normal in all clinically unaffected
family members. On the basis of the genetics, muscle biopsy findings and
cerebral white matter changes, we conclude that this constellation represents
a
hitherto undescribed syndrome.
PMID: 2846114 [PubMed - indexed for MEDLINE]
526: Neurol Clin. 1988 Aug;6(3):545-61.
Inflammatory myopathies.
Kingston WJ, Moxley RT 3rd.
University of Rochester Medical Center, New York.
The inflammatory myopathies are a heterogeneous group of disorders with recent
evidence demonstrating differences in clinical features, pathologic changes,
pathogenesis, and response to therapy. The inflammatory myopathies generally
produce predominantly proximal, symmetric muscle weakness and wasting.
Additional criteria for diagnosis include elevated serum muscle enzymes,
myopathic features on EMG, and muscle biopsy abnormalities, including muscle
fiber necrosis, degeneration, and inflammatory infiltrates. Inclusion body
myositis is distinctive in that distal weakness is most commonly equal to or
greater than proximal weakness and muscle biopsy reveals rimmed, cytoplasmic
vacuoles, eosinophilic inclusions in the cytoplasm, and nucleus and abnormal
filamentous structures. Autoimmune mechanisms seem likely to be involved in
the
pathogenesis of these disorders and viral infection may be etiologically
involved in some of these diseases. The differences in the site of
immune-mediated damages suggest an angiography in dermatomyositis while direct
muscle fiber involvement is more likely in polymyositis and inclusion body
myositis. Therapy of these disorders is similar although some, particularly
inclusion body myositis, may be particularly resistant to therapy. Prednisone
is
currently recommended as the first treatment with azathioprine or methotrexate
added after 3 months if steroids are ineffective.
Publication Types:
Review
Review, Tutorial
PMID: 3065600 [PubMed - indexed for MEDLINE]
527: Acta Neurol Scand. 1988 Aug;78(2):81-4.
Inclusion body myositis in post-poliomyelitis muscular atrophy.
Abarbanel JM, Lichtenfeld Y, Zirkin H, Louzon Z, Osimani A, Farkash P, Herishanu
Y.
Department of Neurology, Soroka Medical Center, Beer Sheva, Israel.
A 38-year-old male developed a new muscle weakness in his left thigh 35 years
after having acute paralytic poliomyelitis with residual right distal leg
weakness and atrophy. EMG studies showed widespread denervation in proximal
and
distal muscles regardless the clinical involvement. Muscle biopsy from an
affected muscle showed the findings of inclusion-body myositis consisting of
perivascular and interstitial mononuclear infiltration, sarcoplasmic granular
inclusions with membranous whorls and typical filamentous inclusions in several
myonuclei. This raises the possibility of inclusion body myositis in other cases
of progressive post-poliomyelitis muscular atrophy, especially those with
perivascular infiltration of mononuclear cells in the muscle biopsy.
Publication Types:
Case Reports
PMID: 2845701 [PubMed - indexed for MEDLINE]
528: Arch Neurol. 1988 Jun;45(6):698-9.
Distal vacuolar myopathy with complete heart block.
Krendel DA, Gilchrist JM, Bossen EH.
Department of Internal Medicine, Division of Neurology, Duke University Medical
Center, Durham, NC.
We describe a 26-year-old man with a predominantly distal myopathy and complete
heart block. A muscle biopsy specimen demonstrated numerous vacuoles, which,
by
electron microscopy, contained membranous whorls. Filamentous inclusions
characteristic of inclusion body myositis were not seen. It is important to
be
aware that life-threatening cardiac disease may occur in this setting.
Publication Types:
Case Reports
PMID: 3369979 [PubMed - indexed for MEDLINE]
529: Ann Neurol. 1988 May;23(5):493-9.
Monoclonal antibody analysis of mononuclear cells in myopathies. V:
Identification and quantitation of T8+ cytotoxic and T8+ suppressor cells.
Arahata K, Engel AG.
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
In polymyositis (PM) and inclusion body myositis (IBM), but not in
dermatomyositis there is evidence of cell-mediated cytotoxicity: T8+ cells
accompanied by macrophages focally surround, invade, and destroy nonnecrotic
muscle fibers. However, the T8 marker appears on both cytotoxic (Tc) and
suppressor (Ts) cells. The Leu-15 marker appears on Ts but not on Tc cells,
but
it also appears on macrophages and on some killer/natural killer cells. To
obviate this problem, the T8, Leu-15, and Leu-7 markers were demonstrated by
sequential paired immunofluorescence in single cryostat sections. Using this
approach, we reliably differentiated for the first time between Tc and Ts cells
in tissue sections. Six cell phenotypes were identified: T8+ Leu-15-Leu7- Tc
cells, T8+ Leu-15+ Leu-7- Ts cells, three types of Leu-7+ killer/natural killer
cells, and T8-Leu-15+ Leu-7- macrophages. Muscle specimens from 5 patients with
PM and 5 with IBM were studied. In each case, 6 nonnecrotic muscle fibers
focally surrounded and invaded by mononuclear cells were selected randomly.
A
total of 2,022 mononuclear cells were analyzed, 870 from patients with PM and
1,152 from those with IBM. When counts of the identified cell phenotypes in
individual patients were pooled, there were four times as many T8+ Leu-15-
Leu-7- Tc cells as T8+ Leu-15+ Leu-7- Ts cells in either PM or IBM samples.
However, when the relative frequencies of the Tc and Ts cells were examined
in
individual patients, the Tc cells tended to become more abundant, and the Ts
cells correspondingly less abundant, with the duration of symptoms.(ABSTRACT
TRUNCATED AT 250 WORDS)
PMID: 2968776 [PubMed - indexed for MEDLINE]
530: Ann Neurol. 1988 Feb;23(2):168-73.
Monoclonal antibody analysis of mononuclear cells in myopathies. IV:
Cell-mediated cytotoxicity and muscle fiber necrosis.
Arahata K, Engel AG.
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Cell-mediated muscle fiber injury occurs in inclusion body myositis (IBM),
polymyositis (PM), and even in Duchenne dystrophy (DD). Most of the
autoaggressive cells are T cells and macrophages, but some are killer/natural
killer (K/NK) cells. We here compare the frequencies per 1,000 muscle fibers
of
endomysial K/NK cells of varying cytotoxicity with those of T cells and
macrophages in 8 cases each of IBM, PM, and DD. Two-micrometer serial cryostat
sections were analyzed. The Leu-4 marker, present on all T cells and some K/NK
cells, and the Leu-7 and Leu-11 markers, present on K/NK cells, were localized
by paired immunofluorescence. Macrophages were demonstrated by the acid
phosphatase reaction. In IBM, PM and DD, the respective average cell counts
per
1,000 muscle fibers were: Leu-4+7- cells (T cells not expressing a K/NK
marker)--710, 530, and 59; Leu-4+7+ cells (K/NK cells of low K/NK
cytotoxicity)--294, 163, and 13; Leu-4-7+ cells (K/NK cells of intermediate
cytotoxicity)--32, 10, and 2; and macrophages--292, 251, and 38. Leu-11+ K/NK
cells that have the highest killing activity were virtually absent in all cases.
The data suggest a limited role for antigen and major histocompatibility complex
unrestricted K/NK cells, as compared with antigen-specific and major
histocompatibility complex-restricted T cells, in IBM and PM. Further, the
findings cast doubt on the significance of either T cells or K/NK cells in
mature muscle in DD.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 3288082 [PubMed - indexed for MEDLINE]
531: Ann Neurol. 1988 Jan;23(1):64-72.
Expression of immunoreactive major histocompatibility complex products in human
skeletal muscles.
Karpati G, Pouliot Y, Carpenter S.
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec,
Canada.
Immunoreactive class 1 and class 2 major histocompatibility complex gene
products (MHCP) and beta 2 microglobulin (beta 2 MG) were demonstrated by
microscopic immunocytochemistry in cryostat sections of skeletal muscle biopsies
of 67 patients with various neuromuscular diseases. Diagnoses included normal
muscle, chronic partial denervation, Duchenne dystrophy, polymyositis,
dermatomyositis, inclusion body myositis, and miscellaneous neuromuscular
diseases. Normal mature muscle fibers did not express MHCP, but blood vessels
showed both class 1 and 2 MHCP and beta 2 MG. Regenerating muscle fibers showed
consistent sarcolemmal class 1 MHCP expression irrespective of the disease.
In
polymyositis, the majority of extrafusal muscle fibers of most patients showed
strong sarcolemmal class 1 MHCP expression. In dermatomyositis, muscle fibers
situated either in perifascicular or in randomly clustered distribution revealed
strong class 1 MHCP reactivity. In inclusion body myositis, scattered small
clusters of muscle fibers were positive for class 1 MHCP. In polymyositis and
inclusion body myositis, particularly strong class 1 MHCP expression was
invariably seen in nonnecrotic muscle fibers partially invaded by lymphocytes
whose cytotoxic effects are believed to be class 1 MHCP restricted. Factors
or
agents that trigger class 1 MHCP expression are presumed also to sensitize
lymphocytes to muscle fibers in these diseases, but their identity remains
obscure at this time. In dermatomyositis, the expression of MHCP in
perifascicular muscle fibers and in areas of capillary loss may represent the
triggering of MHCP expression by a nonspecific cellular stress reaction, in
this
case probably low-grade ischemia.
PMID: 3278673 [PubMed - indexed for MEDLINE]
532: Arch Neurol. 1987 Nov;44(11):1154-7.
Spectrum of inclusion body myositis.
Ringel SP, Kenny CE, Neville HE, Giorno R, Carry MR.
Department of Neurology, University of Colorado Health Sciences Center, Denver
80262.
The clinical, laboratory, and biopsy features are described for a large group
of
patients with inclusion body myositis (IBM) (15 men and four women; mean age,
63
years). A quantitative histopathologic analysis of muscle biopsy specimens
revealed less fiber necrosis and endomysial and perivascular inflammation in
IBM
than in polymyositis (PM) and dermatomyositis, but a more frequent occurrence
of
dark-angular and hypertrophied fibers. Rimmed vacuoles were present in 3.4%
of
all fibers and 15- to 18-nm filaments were identified in the biopsy specimens
of
nine of 11 patients. A panel of monoclonal antibodies immunoreactive with
lymphocytes and cells of monocyte/macrophage lineage suggested that the
inflammatory reaction in IBM was similar to that in PM (but not dermatomyositis)
and mediated by cellular immune responses. These studies confirm the clinical
and histopathologic distinctions between IBM and chronic PM, and that
differentiation between these disorders is often difficult.
PMID: 2823752 [PubMed - indexed for MEDLINE]
533: Arthritis Rheum. 1987 Apr;30(4):397-403.
Inclusion body myositis presenting as treatment-resistant polymyositis.
Calabrese LH, Mitsumoto H, Chou SM.
Inclusion body myositis (IBM) has been viewed as a distinct and rare form of
inflammatory myopathy. Previously reported findings from series of IBM patients
have suggested that clinical and pathologic features are present which readily
distinguish it from idiopathic polymyositis. We report 4 cases of IBM presenting
clinically and pathologically as polymyositis, each of which was refractory
to
therapy. Our data suggest that IBM may be a more common and heterogeneous form
of inflammatory myopathy than has been previously suggested. Furthermore, IBM
may be clinically and electrophysiologically indistinguishable from
polymyositis. Reasons for failing to recognize IBM by pathologic studies appear
to include: the skip lesion nature of the pathologic findings, failure to
examine tissues by electron microscopy, and a low level of suspicion or lack
of
recognition. Because of its insidious clinical course and its failure to respond
to immunosuppressive therapy, IBM may be an important variant of
treatment-resistant polymyositis.
PMID: 3034295 [PubMed - indexed for MEDLINE]
534: J Clin Apheresis. 1987;3(3):167-70.
Leukocytapheresis in inclusion body myositis.
Dau PC.
A patient with inclusion body myositis was treated with a course of 22
leukocytaphereses combined with prednisone and azathioprine therapy. He improved
clinically during an induction phase of frequent cytapheresis, which reduced
the
circulating levels of T lymphocytes and monocytes and decreased the ratio of
the
T4+ to T8+ lymphocyte subsets. During subsequent maintenance cytapheresis there
was partial recovery of the T4+ population without recovery of T8+ lymphocytes,
and the patient lost most of his clinical improvement. In contrast to T
lymphocytes and monocytes, there was no persistent reduction in circulating
B
lymphocyte levels during the course of therapy. T8+ lymphocyte populations may
regenerate more slowly than T4+ lymphocytes following depletion with
leukocyatpheresis combined with prednisone and azathioprine therapy. A loss
of
T8+ suppressor relative to T4+ helper-cell function could lead to an
intensification of autoimmune conditions.
Publication Types:
Case Reports
PMID: 3558342 [PubMed - indexed for MEDLINE]
535: Can J Neurol Sci. 1986 Nov;13(4):334-6.
Inclusion body myositis associated with systemic sarcoidosis.
Danon MJ, Perurena OH, Ronan S, Manaligod JR.
We report an autopsy study of a 64-year-old female with systemic sarcoidosis.
In
addition many muscles showed typical light and electron microscopic features
of
inclusion body myositis. To our knowledge this association has not been
previously reported.
Publication Types:
Case Reports
PMID: 3779534 [PubMed - indexed for MEDLINE]
536: J Neurol Neurosurg Psychiatry. 1986 Nov;49(11):1292-7.
The rigid spine syndrome.
van Munster ET, Joosten EM, van Munster-Uijtdehaage MA, Kruls HJ, ter Laak HJ.
Four patients are reported, 3 females and 1 male, with (as a prominent symptom
of muscle disease) limitation of flexion of cervical and dorsolumbar spine.
The
nosological classification of these cases is discussed. In two patients there
was evidence of an inclusion body myositis. At necropsy one of these patients
had a remarkable distribution of muscle changes.
Publication Types:
Case Reports
PMID: 3025374 [PubMed - indexed for MEDLINE]
537: Neurology. 1986 Sep;36(9):1264-6.
Total body irradiation not effective in inclusion body myositis.
Kelly JJ Jr, Madoc-Jones H, Adelman LS, Andres PL, Munsat TL.
Four patients with inclusion body myositis were treated with 150 rad of total
body irradiation given in 5 weeks. One patient responded subjectively and
transiently, but no patient showed clear benefit. This treatment is not
recommended for inclusion body myositis.
Publication Types:
Case Reports
PMID: 3748397 [PubMed - indexed for MEDLINE]
538: Hum Pathol. 1986 Aug;17(8):765-77.
Inclusion body myositis: a chronic persistent mumps myositis?
Chou SM.
Among the generalized chronic idiopathic inflammatory myopathies, inclusion
body
myositis (IBM) has emerged as a clinico-pathologic variant during the past two
decades. It occurs primarily in elderly persons (in approximately the sixth
decade of life), but young adults (in approximately the second decade of life)
may also be affected. Slowly progressive weakness of distal as well as proximal
muscle groups in IBM is usually not associated with skin rash, malignancy or
collagen-vascular disease, and is refractory to treatment with steroids or other
immunosuppressants. Exceptions to each of these general rules have been found.
Muscle biopsy and electromyography may suggest a neurogenic process mixed with
myopathic features. Rimmed vacuoles with basophilic granules in cryostat
sections stained with hematoxylin-eosin are strongly suggestive of IBM if
accompanied by the histopathologic triad of polymyositis. The presence of
eosinophilic intranuclear or cytoplasmic inclusions in affected myofibers is
further suggestive of IBM. The ultimate diagnosis, however, depends on
ultrastructural demonstration of characteristic microtubular filaments
resembling the nucleocapsids of the paramyxovirus group. Recent reports of
immunostaining of the inclusions for mumps virus antigen strongly suggest a
chronic persistent mumps virus infection as the cause of IBM. IBM is considered
to be pathologically related to both distal myopathy (DM) and oculopharyngeal
muscular dystrophy (OPMD).
PMID: 3015764 [PubMed - indexed for MEDLINE]
539: Hum Pathol. 1986 Jul;17(7):704-21.
Mononuclear cells in myopathies: quantitation of functionally distinct subsets,
recognition of antigen-specific cell-mediated cytotoxicity in some diseases,
and
implications for the pathogenesis of the different inflammatory myopathies.
Engel AG, Arahata K.
Monoclonal antibodies reactive for B cells, T cells, T-cell subsets, killer
(K)
and natural killer (NK) cells, and the Ia antigen were used to analyze
mononuclear cell subsets in scleroderma (SD), dermatomyositis (DM), polymyositis
(PM), inclusion body myositis (IBM), Duchenne dystrophy (DD), and normal muscle.
The analysis, which was quantitative, was performed according to diagnosis and
site of accumulation. Cells at perivascular, perimysial, and endomysial sites
of
accumulation, and cells focally surrounding and invading nonnecrotic muscle
fibers, were analyzed separately. Individual antigens were localized in 2-micron
serial sections, or multiple antigens were demonstrated in a given section by
sequential paired immunofluorescence. The latter approach allowed the
identification of the cell phenotypes in which functional properties are defined
by multiple markers, e.g., T8+ and T4+ cells that are either activated or not
activated, T8+ cells that are either cytotoxic or suppressor T cells, and K/NK
cells of varying maturity and killing capability. The interactions of
inflammatory cells of various types with each other and the muscle fiber were
further investigated by immunoelectron microscopy. In SD, the findings provide
evidence for a cell-mediated immune effector response against a connective
tissue and/or vascular element. In DM, the effector response appears to be
predominantly humoral. In PM and IBM (but not in DM or SD), there is invasion
and destruction of nonnecrotic muscle fibers by cytotoxic T cells, with or
without accompanying macrophages. Because T-cell-mediated injury is antigen-
and
major histocompatibility complex-restricted, clones of T cells must have been
sensitized previously to a muscle fiber-associated surface antigen. The identity
of the putative antigen(s) remains an important, unsolved question.
PMID: 3459704 [PubMed - indexed for MEDLINE]
540: Mt Sinai J Med. 1986 Feb;53(2):137-44.
Inclusion body myositis: case reports and a reappraisal of an underrecognized
type of inflammatory myopathy.
Lazaro RP, Barron KD, Dentinger MP, Lava NS.
Publication Types:
Case Reports
PMID: 3010093 [PubMed - indexed for MEDLINE]
541: Ann Neurol. 1986 Feb;19(2):112-25.
Monoclonal antibody analysis of mononuclear cells in myopathies. III:
Immunoelectron microscopy aspects of cell-mediated muscle fiber injury.
Arahata K, Engel AG.
We have previously obtained light microscopical immunocytochemical evidence
for
cell-mediated muscle fiber injury and destruction in polymyositis and inclusion
body myositis. To evaluate further interactions of the different cell phenotypes
with each other and with the muscle fibers, the T8, T4, and Leu 7 markers in
7
cases of polymyositis and in 9 cases of inclusion body myositis were localized
by immunoelectron microscopy. In the early stages of the cell-mediated process,
T8+ cells and macrophages are apposed against, and/or send spikelike processes
into, nonnecrotic muscle fibers. Leu-7+ cells penetrate fibers infrequently,
and
T4+ cells do not penetrate muscle fibers. Subsequently, an increasing number
of
T8+ cells and macrophages traverse the basal lamina; focally replace, displace,
or compress the fiber; and spikes from these cells honeycomb the adjacent muscle
fiber regions. The macrophages contain only few heterophagic vacuoles and
therefore act in a cytotoxic rather than a phagocytic capacity. The integrity
of
the muscle fiber surface membrane facing the invading cells is maintained, but
the possibility also exists that the membrane is damaged and rapidly repaired,
or that the damage cannot be detected by electron microscopy. Nearby fiber
regions often show either degenerative or regenerative changes. Ultimately,
segments of the entire muscle fiber are replaced by the invading cells.
PMID: 3008636 [PubMed - indexed for MEDLINE]
542: Arch Neurol. 1985 Oct;42(10):1021-2.
Inclusion body myositis and Sjogren's syndrome.
Gutmann L, Govindan S, Riggs JE, Schochet SS Jr.
Publication Types:
Case Reports
PMID: 2994608 [PubMed - indexed for MEDLINE]
543: Pathol Res Pract. 1985 Jul;180(1):1-9.
Recent advances in the morphology of myositis.
Goebel HH, Trautmann F, Dippold W.
Myositis in man may be divided into infectious and non-infectious forms. The
myopathologist more often deals with the latter forms which comprise
dermatomyositis/polymyositis, inclusion body myositis, mixed connective tissue
disease/collagenoses, and granulomatous myopathies. Modern morphological
techniques as enzyme-histochemistry, electron microscopy, immunohistology, and
morphometry are of different value in various forms of myositis, but are often
indispensable techniques in up-to-date diagnostic work up of a myositis.
Publication Types:
Review
PMID: 2994026 [PubMed - indexed for MEDLINE]
544: J Rheumatol. 1985 Jun;12(3):568-70.
Inclusion body myositis and systemic lupus erythematosus.
Yood RA, Smith TW.
Inclusion body myositis (IBM) has been recognized as a distinct type of
idiopathic inflammatory myopathy. Previous reports have emphasized the absence
of immunologic abnormalities and lack of response to corticosteroid therapy
in
patients with IBM. We report a case of IBM associated with systemic lupus
erythematosus and modest response of the myopathy to corticosteroid therapy.
The
clinical and immunologic features of IBM are more diverse than previously
appreciated.
Publication Types:
Case Reports
PMID: 2995660 [PubMed - indexed for MEDLINE]
545: Ann Neurol. 1985 Mar;17(3):215-27.
Inflammatory myopathies: Part 1.
Mastaglia FL, Ojeda VJ.
The inflammatory myopathies have diverse clinical and pathological features
and
multiple etiologies. Some are confined to a single muscle or group of muscles
(e.g., orbital myositis and localized nodular myositis) while others are
diffuse. Infective forms may be due to viral, bacterial, fungal, protozoal,
or
parasitic organisms. Viruses may cause acute self-limited forms of myositis
and
have been isolated from muscle in some cases of acute rhabdomyolysis and
inclusion body myositis. They have also been implicated in some cases of
congenital myopathy and in polymyositis and dermatomyositis, but there is no
evidence of viral invasion of muscle in these conditions. In polymyositis and
dermatomyositis there are derangements in humoral and cellular immune function,
and recent evidence suggests an underlying disturbance of immunoregulation.
The
roles of genetic factors, drugs, and Toxoplasma infection have been under
scrutiny. There is increasing recognition of immunological and pathological
differences in polymyositis and juvenile and adult dermatomyositis, and in cases
with associated connective tissue diseases, suggesting different underlying
pathogenetic mechanisms. Inclusion body myositis, eosinophilic myositis, and
granulomatous myositis can be separated from the other idiopathic inflammatory
myopathies because of distinctive clinical and pathological features and this
may also reflect different mechanisms of muscle injury. Recent developments
in
the treatment of the idiopathic inflammatory myopathies include the use of
plasmapheresis and total-body irradiation in cases that are resistant to
corticosteroids and immunosuppressive drugs.
PMID: 2986525 [PubMed - indexed for MEDLINE]
546: J Neurol Neurosurg Psychiatry. 1985 Mar;48(3):270-3.
Inclusion body myositis: a case with associated collagen vascular disease
responding to treatment.
Lane RJ, Fulthorpe JJ, Hudgson P.
Patients with inclusion body myositis demonstrate characteristic histological
and electronmicroscopical abnormalities in muscle and are generally considered
refractory to treatment. A patient with inclusion body myositis is described
with evidence of associated autoimmune disease, who responded to steroids.
Publication Types:
Case Reports
PMID: 2984335 [PubMed - indexed for MEDLINE]
547: Cleve Clin Q. 1985 Winter;52(4):583-9.
Inclusion body myositis. A possible chronic persistent muscle infection by
mumps
virus.
Chou SM.
Publication Types:
Case Reports
PMID: 3830473 [PubMed - indexed for MEDLINE]
548: Ann Neurol. 1984 Aug;16(2):193-208.
Monoclonal antibody analysis of mononuclear cells in myopathies. I: Quantitation
of subsets according to diagnosis and sites of accumulation and demonstration
and counts of muscle fibers invaded by T cells.
Arahata K, Engel AG.
In 76 muscle specimens (normal controls, 9; Duchenne dystrophy, 11; scleroderma,
11; dermatomyositis, 13; polymyositis, 15; inclusion body myositis, 17),
mononuclear cells were analyzed at perivascular, perimysial, and endomysial
sites of accumulation. Monoclonal antibodies reactive for B cells, T cells,
T
cell subsets, killer (K) or natural killer (NK) cells, and the Ia antigen were
used for cell typing. Macrophages were identified by the acid phosphatase
reaction. Few extravascular mononuclear cells occurred in normal muscle. In
all
inflammatory myopathies, a mixed exudate of T cells, B cells, and macrophages
was present. Mature K/NK cells were rare in all diseases. In dermatomyositis,
polymyositis, and inclusion body myositis, there was a positive gradient for
T
cells, T8+ cells, and activated T cells and a negative gradient for B cells
and
T4+ cells between perivascular and endomysial sites. In scleroderma the
predominant perimysial exudate consisted mostly of T cells and macrophages.
The
percentage of B cells at all sites, and the T4+/T cell ratio in the endomysium,
were significantly higher in dermatomyositis than in the other diseases. In
polymyositis and inclusion body myositis, the endomysial exudate contained a
large number of T cells, T8+ cells, and activated T cells but only sparse B
cells. T cells accompanied by macrophages focally surrounded and invaded
nonnecrotic fibers in polymyositis and inclusion body myositis. Rare fibers
in
Duchenne dystrophy and a very few fibers in dermatomyositis and scleroderma
were
similarly affected. We infer that (1) T-B, T-T, and T-macrophage cooperativities
are likely to exist in muscle in different myopathies; (2) T cell-mediated fiber
injury plays a role in polymyositis and inclusion body myositis; (3) T
cell-mediated fiber injury can also occur in inherited diseases, such as
Duchenne dystrophy; and (4) a local humoral response may occur in muscle in
dermatomyositis and possibly in polymyositis and inclusion body myositis.
PMID: 6383191 [PubMed - indexed for MEDLINE]
549: Ann Neurol. 1984 Aug;16(2):209-15.
Monoclonal antibody analysis of mononuclear cells in myopathies. II: Phenotypes
of autoinvasive cells in polymyositis and inclusion body myositis.
Engel AG, Arahata K.
In 6 cases of polymyositis and 6 of inclusion body myositis, phenotypes of
mononuclear cells focally surrounding and invading muscle fibers were analyzed.
By localizing the T8, T4, and Ia markers with direct immunofluorescence and
acid
phosphatase enzyme cytochemically in the same sections, five different
phenotypes were simultaneously identified in a given section: T8+ and T4+ cells
that were either activated (Ia+) or not activated (Ia-), and acid
phosphatase--reactive and Ia+ macrophages. This approach permitted the separate
and quantitative assessment of the distributions of the different phenotypes
among the invading versus the surrounding cells. In both polymyositis and
inclusion body myositis, the invading cells were selectively enriched in the
T8+
phenotype. One-third of all invading cells and one-half of the invading T8+
cells were activated. T4+ cells were more abundant among the surrounding than
the invading cells, and only a small proportion of the T4+ cells were activated.
These findings are especially significant in view of the cytotoxic capability
of
the T8+ cells and because histocompatibility factors permit T8+ but not T4+
cells to recognize an antigen on muscle fibers. Macrophages accounted for 21
to
31% of the cells invading or surrounding nonnecrotic fibers. For purposes of
comparison, we also analyzed mononuclear cells in necrotic fibers: 80% of these
cells were macrophages, and only 20% were T cells. The findings indicate that
in
polymyositis and inclusion body myositis, nonnecrotic muscle fibers are injured
by autoinvasive T8+ cells that act in concert with macrophages. Further, the
findings strongly imply previous sensitization of clones of T cells to muscle
fiber-associated surface antigen(s).
PMID: 6089646 [PubMed - indexed for MEDLINE]
550: Acta Neuropathol (Berl). 1984;63(1):24-32.
Intranuclear inclusions in muscle, nervous tissue, and adrenal gland.
Tateishi J, Nagara H, Ohta M, Matsumoto T, Fukunaga H, Shida K.
A 30-year-old man had had chronic progressive wasting and weakness of muscles
for 17 years. A muscle biopsy 5 years prior to death revealed myopathic changes
were rimmed vacuoles and intranuclear inclusions which corresponded to
"inclusion body myositis". At autopsy, intranuclear inclusions were
observed in
neurons, oligodendroglia, and in parenchymal cells of the adrenal medulla.
Ultrastructurally, the inclusions in muscles, nervous tissue, and adrenal
medulla were identical and consisted of abnormal tubulolinear structures
measuring 10-20 nm in diameter. Similar inclusions have been reported in muscles
with "inclusion body myositis" and in the nervous system with "neuronal
intranuclear hyaline inclusion disease", respectively. Absence of clinical
symptoms related to the CNS and adrenal gland, and well-preserved parenchymal
cells in these organs of our patient suggest a benign nature of the disease
except in the muscular system. Attempts to isolate a virus from the brain were
fruitless . This patient may serve to connect both diseases in muscles and the
nervous system, and to disclose the etiology of these inclusions.
Publication Types:
Case Reports
PMID: 6328832 [PubMed - indexed for MEDLINE]
551: Arch Neurol. 1984 Jan;41(1):93-5.
Inclusion body myositis and chronic immune thrombocytopenia.
Riggs JE, Schochet SS Jr, Gutmann L, McComas CF, Rogers JS 2nd.
We report a case of inclusion body myositis and chronic immune thrombocytopenia
with serum platelet antibodies and circulating immune complexes. Although immune
mechanisms probably play an important role in the pathogenesis of inclusion
body
myositis, a viral etiology cannot be excluded.
Publication Types:
Case Reports
PMID: 6316880 [PubMed - indexed for MEDLINE]
552: Neurology. 1983 Sep;33(9):1109-14.
Inclusion body myositis (IBM): myopathy or neuropathy?
Eisen A, Berry K, Gibson G.
Inclusion body myositis (IBM) is described in six elderly patients (three women)
and in a young familial patient. They all showed the morphologically
characteristic vacuoles containing osmiophilic membranous whorls and
intracytoplasmic or intranuclear inclusions. There is a well-delineated bimodal
age spectrum of IBM, with onset in the second and sixth decades, but otherwise
the disorder seems to be a specific entity. Clinical, electrophysiologic, and
morphologic features suggest a neurogenic origin in some cases.
PMID: 6310442 [PubMed - indexed for MEDLINE]
553: Arch Neurol. 1982 Dec;39(12):760-4.
Inclusion body myositis. A corticosteroid-resistant idiopathic inflammatory
myopathy.
Danon MJ, Reyes MG, Perurena OH, Masdeu JC, Manaligod JR.
In seven patients with slowly progressive muscle weakness, inclusion body
myositis (IBM) was diagnosed on biopsy. None had stigmata of collagen-vascular
disease or malignancy. Serum creatine kinase levels were mildly or moderately
increased. The six patients treated with prednisone did not improve. Needle
electromyography showed a "myopathic" pattern in all patients, but
four also had
diffuse neurogenic changes with normal nerve conductions. Histologic study of
muscle showed a mixture of small rounded fibers varying in size, atrophic
angulated fibers forming small groups, and hypertrophic fibers. Variable amounts
of inflammation, necrosis, and regeneration were seen in all specimens. All
showed numerous intracytoplasmic vacuoles lined with purple-blue granules.
Electron microscopy showed membranous whorls and masses of abnormal filaments
measuring 14 to 18 nm in diameter. Although IBM seems to be a distinct type
of
inflammatory myopathy, its etiology and pathogenesis are not clear.
PMID: 6291495 [PubMed - indexed for MEDLINE]
554: J Neurol Sci. 1982 Jul;55(1):15-24.
Inclusion body myositis. Clinical, biological and ultrastructural study.
Julien J, Vital C, Vallat JM, Lagueny A, Sapina D.
A 48-year-old patient presented for the past 4 years an amyotrophy of the
quadriceps and moderate involvement of the truncal and pelvic girdle muscles.
The CK level was elevated (10 times the normal rate) and the EMG revealed a
fibrillation pattern on relaxation, myotonic bursts on needle insertion and
reduced activity during contraction. The histological study of the muscle biopsy
showed nuclear cytoplasmic inclusion bodies and pseudo-myelinic membranes. The
case was classified in the inclusion body myositis group. Analysis of the other
published cases underlines the variety of the clinical, biological and
electromyographical aspects and abnormalities.
Publication Types:
Case Reports
PMID: 6286889 [PubMed - indexed for MEDLINE]
555: Ann Neurol. 1982 Jun;11(6):576-81.
Inclusion-body myositis: clinicopathological studies and isolation of an
adenovirus type 2 from muscle biopsy specimen.
Mikol J, Felten-Papaiconomou A, Ferchal F, Perol Y, Gautier B, Haguenau M,
Pepin
B.
Publication Types:
Case Reports
PMID: 6287912 [PubMed - indexed for MEDLINE]
556: Acta Neurol Scand. 1982 May;65(5):458-67.
Oculopharyngeal muscular dystrophy and distal myopathy. Intrafamilial difference
in the onset and distribution of muscular involvement.
Fukuhara N, Kumamoto T, Tsubaki T, Mayuzumi T, Nitta H.
A family is reported which included a patient with a variant form of
oculopharyngeal muscular dystrophy. The patient's son suffered from infantile
muscular dystrophy with a distal distribution in the lower extremities and no
oculopharyngeal symptoms. Case 1, the father, showed blepharoptosis, but no
limitation of ocular movements. Case 2, the son, showed early onset of weakness
and more rapid progression of muscle involvement than the father. In both
patients EMG, muscle biopsies and elevated serum CPK indicated the myopathic
nature of the disorder. A muscle biopsy specimen in Case 2 showed abundant
rimmed vacuoles and abnormal filaments 13-19 nm in diameter in the sarcoplasm,
usually reported to occur in inclusion body myositis. The findings indicate
that
oculopharyngeal muscular dystrophy and distal myopathy are related in their
etiology and distal myopathy and inclusion body myositis are regarded as variant
forms of the same disease.
Publication Types:
Case Reports
PMID: 7113658 [PubMed - indexed for MEDLINE]
557: Arch Neurol. 1982 Mar;39(3):186-8.
Inclusion body myositis associated with Sjogren's syndrome.
Chad D, Good P, Adelman L, Bradley WG, Mills J.
Publication Types:
Case Reports
PMID: 6978124 [PubMed - indexed for MEDLINE]
558: Acta Neuropathol Suppl (Berl). 1981;7:287-91.
Inclusion body myositis.
Tome FM, Fardeau M, Lebon P, Chevallay M.
The histochemical and ultrastructural study of muscle biopsies of two patients
with a chronic muscle weakness and wasting showed particular changes in muscle
fibers: (1) peripheral lined vacuoles, containing whorls of membranes and
cytoplasmic debris; (2) collections of intranuclear and intrasarcoplasmic
tubular filaments (16-18 nm in external diameter and 6.5 nm in inner diameter).
These changes are characteristic of a rare muscle disorder termed inclusion
body
myositis; its individuality is favoured by the present study. The resemblance
of
the tubular filaments to myxovirus nucleocapsid has been suggested by various
authors but attempts to isolate the virus were unsuccessful in several reported
cases as well as in those here presented. This does not exclude a viral origin
of the disease. The similarity of the tubular filaments to thick myofilaments
has been invoked by others, but has not been demonstrated. At the present the
nature of the abnormal filaments remains unknown.
PMID: 6261517 [PubMed - indexed for MEDLINE]
559: Acta Neuropathol (Berl). 1980;51(3):229-35.
Rimmed vacuoles.
Fukuhara N, Kumamoto T, Tsubaki T.
Rimmed vacuoles (Dubowitz and Brooke 1973) have been found in 12 cases with
various neuromuscular diseases and are considered to be autophagic in nature.
They consisted of multilaminated membranous structures accompanied by glycogen
granules, dense bodies, and amorphous, granular, and fibrillar material. The
contents of the vacuoles were regarded as having partially dissolved out of
the
vacuoles in cryostat sections but some were plastered along the walls of the
vacuoles and were depicted by the staining procedures for light microscopy.
The
"lined vacuoles" described by Carpenter et al. (1978) in inclusion
body myositis
closely agree with the rimmed vacuoles in respect of histochemical and
ultrastructural features.
Publication Types:
Case Reports
PMID: 7445977 [PubMed - indexed for MEDLINE]
560: Neurology. 1978 Jan;28(1):8-17.
Inclusion body myositis: a distinct variety of idiopathic inflammatory myopathy.
Carpenter S, Karpati G, Heller I, Eisen A.
We report six cases of inclusion body myositis (IBM), a distinct but
infrequently recognized inflammatory disease of skeletal muscle. Clinically,
IBM
differs from dermatomyositis and polymyositis. It lacks features of
collagen-vascular disease, has a relatively benign and protracted course,
frequently involves distal muscles, is found mainly in males, and does not
improve with corticosteroid treatment. Electronmicroscopic demonstration of
abnormal filaments in muscle cells is necessary for definite diagnosis, but
IBM
may be suspected by the finding on cryostat sections of numerous
hematoxylinophilic granules in "lined" vacuoles in muscle cells. These
correspond to whorls of cytomembranes. Although in dermatomyositis the capillary
network is partly destroyed, in IBM it is usually augmented. A viral etiology
of
IBM has been suggested but remains unproven.
PMID: 201886 [PubMed - indexed for MEDLINE]
561: Klin Wochenschr. 1977 Nov 1;55(21):1063-6.
Inclusion body myositis. A "slow-virus" infection of skeletal musculature?
Ketelsen UP, Beckmann R, Zimmermann H, Sauer M.
We report the case of a 56-years old patient with clinical symptoms of an
unresolved neuromuscular disease. The light microscopic studies of a muscle
biopsy from the m. triceps shows the picture of a diffuse muscular atrophy.
By
electron microscopy, myelin-like degeneration zones with tubular-filamentous
inclusions can be shown in the cytoplasma of the atrophic muscle cells. These
filamentous structures correspond morphologically to the nucleocapside of
paramyxoviruses. These results lead, even without the proof of inflammatory
cells, to the diagnosis of an "inclusion body" myositis also taking
into account
the clinical and electrophysiological findings.
Publication Types:
Case Reports
PMID: 926717 [PubMed - indexed for MEDLINE]
562: Lab Invest. 1971 Sep;25(3):240-8.
Inclusion body myositis.
Yunis EJ, Samaha FJ.
PMID: 5095321 [PubMed - indexed for MEDLINE]
.