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Neurophysiological and mitochondrial abnormalities in MuSK antibody seropositive myasthenia gravis compared to other immunological subtypes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
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2006 (English)In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 117, no 7, 1434-1443 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To compare the electrophysiological and histopathological features of immunological myasthenia gravis (MG) subtypes.Methods: Fifty MG patients underwent clinical examination, MuSK-Ab and AChR-Ab analysis. The majority underwent quantitative andsingle-fiber electromyography (QEMG, SFEMG), repetitive nerve stimulation and deltoid muscle biopsy. From muscle specimens withhistological mitochondrial dysfunction, we amplified mitochondrial DNA (mtDNA). In specimens with mtDNA deletions, the nuclear genePOLG1 was sequenced.Results: Five AChR-Ab seropositive [AChR(C)] and 5 seronegative [AChR(K)] patients were MuSK-Ab seropositive [MuSK(C)]. Five of7 neurophysiologically examined MuSK(C) patients (71%) had proximal myopathic pattern, compared to 7 of 31 MuSK(K)/AChR(C)patients (23%) (PZ0.012). SFEMG was abnormal in all examined MuSK(C) patients. All 7 biopsied MuSK(C) and 32 MuSK(K) patients(89%) had cytochrome c oxidase (COX) negative fibers. Three of five MuSK(C) and 13 of 20 MuSK(K) patients analyzed had multiplemtDNA deletions but no POLG1 mutations.Conclusions: Similar degree of SFEMG abnormalities was present in proximal muscles among MuSK(C) and AChR(C) patients. Proximalmyopathy was over-represented in MuSK(C) patients; however, both MuSK(C) and MuSK(K) patients had mild myopathy with frequentmitochondrial abnormalities.Significance: The weakness in MuSK(C) patients is most likely due to disturbed neuromuscular transmission. The frequently encounteredmitochondrial dysfunction in MG warrants further study.

Place, publisher, year, edition, pages
2006. Vol. 117, no 7, 1434-1443 p.
Keyword [en]
Myasthenia gravis, Quantitative EMG, Single-fiber EMG, MuSK, Myopathy, mtDNA deletions
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-95260DOI: 10.1016/j.clinph.2006.03.028ISI: 000239227100004OAI: oai:DiVA.org:uu-95260DiVA: diva2:169408
Available from: 2006-12-15 Created: 2006-12-15 Last updated: 2014-09-01Bibliographically approved
In thesis
1. MuSK Antibody(+) Versus AChR Antibody(+) Myasthenia Gravis: Clinical, Neurophysiological and Morphological Aspects
Open this publication in new window or tab >>MuSK Antibody(+) Versus AChR Antibody(+) Myasthenia Gravis: Clinical, Neurophysiological and Morphological Aspects
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that causes fluctuating muscle weakness. MG may be divided into an ocular form and a generalized form based on the involved muscles. Treatment differs between these different MG forms. The majority (80%) of patients with generalized MG are seropositive for antibodies against the acetylcholine receptor (AChR-Ab). Recently a new antibody was detected against muscle specific tyrosine kinase (MuSK) in about 40% of patients who are AChR-Ab seronegative. A few patients with MuSK-Abs have muscular atrophies, as well as electrophysiological myopathy.

In this thesis we have characterized MuSK-Ab seropositive [MuSK(+)] patients using clinical parameters, including health-related quality of life (hrQoL), neurophysiology and muscle morphology, and compared them to patients with and without AChR-Abs. The question concerned which factors contribute to their muscle weakness. Additionally, we wanted to determine if single-fiber electromyography (SFEMG) in a limb muscle has any predictive value for generalization of ocular MG.

Our results suggest that MuSK(+) patients more often have a myopathic electromyography pattern, although this pattern is found also in other immunological subtypes of MG. The myopathic pattern may be associated with the frequently found mitochondrial abnormalities. However, disturbed neuromuscular transmission is the primary cause of muscle weakness in the majority of MuSK(+) patients, as well as in AChR-Ab seropositive patients. The disease-specific hrQoL MG questionnaire was successfully validated into Swedish and these scores correlated with disturbed neuromuscular transmission in a proximal arm muscle. Abnormal SFEMG findings occur also in muscles outside of the facial area in ocular MG, although this is not predictive of subsequent generalization.

MuSK (+) patients have little or no beneficial effect of acetylcholine esterase inhibitors (AChEI). On the contrary AChEI may produce profound adverse effects. We present the hypothesis that this effect of AChEI is due to abnormal receptor morphology in MuSK(+) patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 73 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 211
Neurosciences, myasthenia gravis, MuSK antibody, AChR antibody, myopathy, single-fiber EMG, mitochondria, Swedish MG questionnaire, quality of life, Neurovetenskap
urn:nbn:se:uu:diva-7408 (URN)91-554-6752-0 (ISBN)
Public defence
2007-02-02, Grönwallssalen, Akademiska sjukhuset, ingång 70, 75185 Uppsala, 13:15
Available from: 2006-12-15 Created: 2006-12-15Bibliographically approved

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Rostedt Punga, Anna
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