Clinical Pearls in Differentiating Junctionopathies, Histologic Pearls in Defining IBM
Abstracts & Commentary
Sources: Wirtz PW, et al. Difference in distribution of muscle weakness between myasthenia gravis and the Lambert Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry. 2002;73:766-768; Dahlbom K, Lindberg C, Oldfors A. Inclusion body myositis: Morphological clues to correct diagnosis. Neuromuscul Disord. 2002;12:853-857.
Overlap of symptomatology can make differentiation of myasthenia gravis (MG) from Lambert Eaton myasthenic syndrome (LEMS) challenging. Among 101 patients with MG and 38 with LEMS, clinical features allowing more accurate differential diagnosis are noted below (see Table).
| Table | |||||||||
| Myasthenia gravis
(MG) vs Lambert Eaton myasthenic syndrome (LEMS) |
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|
LEMS never begins with extraocular muscle weakness, nor does it ever produce weakness limited to the arms. MG generally begins with cranial nerve weakness and progresses caudally, whereas LEMS begins in the legs and progresses cephalad.
Pathologic confirmation of suspected inclusion body myositis (IBM) may also be difficult, as rimmed vacuoles and inflammation can be absent. Additional diagnostic cues would be beneficial. Between 1984 and 2000, tissue diagnosis of sporadic IBM was made in 43 patients who underwent a total of 86 biopsies. Muscle specimens were obtained by open biopsy and included the deltoid (n = 51), vastus lateralis (n = 19), tibialis anterior (n = 5), or other muscles (n = 11). Morphological criteria for IBM were those of Griggs and associates1 and included invasion of non-necrotic fibers by mononuclear cells, vacuolated muscle fibers, and intracellular amyloid deposits or 15-18 nm tubofilaments. Review of these specimens yielded further morphological clues helpful for accurate diagnosis. All biopsies demonstrated upregulation of major histocompatibility complex class I, and 84 of 86 biopsies contained cytochrome c oxidase-negative (COX-deficient) muscle fibers. All vastus lateralis and tibialis anterior specimens were rimmed-vacuole positive, as were 43 of 51 deltoid biopsies. Even in the absence of inflammation or rimmed vacuoles, COX-negative fibers and major histocompatibility complex class I upregulation makes IBM the diagnosis of exclusion and should prompt rebiopsy to attempt confirmation.
Commentary
Gene expression profiles may also assist in the differential diagnosis and understanding of inflammatory myopathy including IBM, polymyositis, and dermatomyositis.2 Using spectrophotometry to measure cellular mRNA concentration, the relative levels of gene expression may be quantified, producing a molecular profile or "signature" for any tissue. Enhanced expression of various genes would underscore their importance in the etiopathogenesis of the disease process. Already successfully applied in the study of various tumors, including B-cell lymphoma, malignant melanoma, oligodendroglioma, colon and breast cancer, this technology correctly classified 10 of 11 patients with inflammatory myopathy, 10 of 12 with Duchenne dystrophy, 11 of 11 with nemaline myopathy, and all 11 controls.3 Molecular fingerprint technology demonstrates great potential for the advancement of myology and portends significant strides for medicine in general. — Michael Rubin
Dr. Rubin is Assistant Editor of Neurology Alert and Professor of Clinical Neurology at New York Presbyterian Hospital—Cornell Campus.
References
1. Griggs RC, et al. Ann Neurol. 1995;38:705-713.
2. Thornton CA, Welle SL. Neurology. 2002;59:1128-1129.
3. Greenberg SA, et al. Neurology. 2002;59:1170-1182.
Overlap of symptomatology can make differentiation of myasthenia gravis (MG) from Lambert Eaton myasthenic syndrome (LEMS) challenging. Among 101 patients with MG and 38 with LEMS, clinical features allowing more accurate differential diagnosis are noted.
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