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. , p. 73
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 211
Keywords [en]
Neurosciences, myasthenia gravis, MuSK antibody, AChR antibody, myopathy, single-fiber EMG, mitochondria, Swedish MG questionnaire, quality of life
Keywords [sv]
Neurovetenskap
Identifiers
URN: urn:nbn:se:uu:diva-7408ISBN: 91-554-6752-0 (print)OAI: oai:DiVA.org:uu-7408DiVA, id: diva2:169410
Public defence
2007-02-02, Grönwallssalen, Akademiska sjukhuset, ingång 70, 75185 Uppsala, 13:15
Opponent
Supervisors
2006-12-152006-12-152022-01-28Bibliographically approved
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