Guptill_2010_Curr.Opin.Neurol_23_530

PURPOSE OF REVIEW: Important concepts regarding the pathogenesis, clinical features, diagnosis and treatment of muscle-specific tyrosine kinase (MuSK) antibody positive myasthenia gravis will be reviewed. Special attention will be paid to clinical phenotypes and treatment, particularly encouraging responses that have been reported to rituximab. RECENT FINDINGS: Worldwide studies confirm three major phenotypes in MuSK antibody positive myasthenia gravis (MMG) patients: indistinguishable from acetylcholine receptor antibody positive patients, prominent faciopharyngeal weakness, usually with marked muscle atrophy, and relatively isolated neck extensor and respiratory weakness. MMG predominates in women and weakness is typically more severe, with more frequent respiratory crises than non-MuSK myasthenia gravis. Patients with sub-acute bulbar, shoulder, and neck weakness pose unique challenges in terms of differential diagnosis and electrodiagnosis. Electrodiagnostic studies evaluating for disorders of neuromuscular transmission should focus on proximal limb and facial muscles, as well as clinically weak muscles. The response to acetylcholinesterase inhibitors is often disappointing. Long-term outcomes appear favorable though patients typically require more aggressive immunosuppression. Uncontrolled observations report encouraging results with rituximab in the treatment of refractory MMG. The role of thymectomy in the management of these patients remains uncertain. SUMMARY: MuSK antibody positive patients represent a unique subset of myasthenia gravis. Identification of these patients has important diagnostic and disease management implications.