Myasthenia gravis (MG) with antibodies against the muscle-specific tyrosine kinase (MuSK abs) is often a severe disease requiring aggressive treatment. Various immunosuppressive (IS) regimens have been employed; the efficacy of plasma exchange is unanimously recognized, while the indication for thymectomy is controversial. We evaluated the response to therapy in 57 MuSK-positive patients (12 M/45 F) comparing our experience with other authors' results. Disease severity and response to treatment were graded according to MG Foundation of America; follow-up ranged from 0.5-29 years. Owing to both MG severity and the unsatisfactory response to cholinesterase inhibitors, most patients (54/57) needed IS treatment, and 35 received one or more courses of plasma exchange and intravenous immunoglobulin. At the end of follow-up, the rate of complete remission was 8.8%, and IS treatment had been withdrawn in only 10/54 patients. The extent of therapeutic response varied considerably. With conventional IS therapy (prednisone alone or in combination with azathioprine or cyclosporine), most patients achieved good control of their disease, but 30% of them were left with permanent facial and bulbar weakness. In patients with refractory disease, the use of mycophenolate mofetil and rituximab proved very effective, as also reported by other authors. In our and others' experience, MuSK-positive MG markedly improves with IS therapy, although, in comparison with the AChR-positive disease, it is characterized by a lower remission rate, as a higher proportion of patients remain dependent on treatment. Thymectomy is mostly considered scarcely effective; however, at present, no firm conclusions can be drawn on its role in the treatment of this form of MG.

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Morphologic findings of thymuses from 32 anti-acetylcholine receptor (AChR)-negative myasthenia gravis patients, 12 with and 20 without antibodies against the muscle-specific kinase (MuSK), were compared with those from 30 AChR-positive subjects. In contrast with the high frequency of thymic hyperplastic changes in AChR-positive patients, in MuSK-positive subjects histologic alterations were minimal, arguing against an intrathymic disease pathogenesis. Since hyperplastic changes were seen in 35% of MuSK-negative patients, the thymus could be involved in some of these cases.

Myasthenia gravis with antibodies to the muscle-specific tyrosine kinase (MuSK MG) is a rare disease with distinctive pathogenic mechanisms and clinical features. An acute onset and predominant bulbar muscle weakness are very common and highly suggestive of the disease. On the other hand, a more indolent course, atypical ocular presentation, and signs of cholinergic hyperactivity may complicate the diagnosis. Though MuSK MG is still a severe disease, over the years we have observed a steady reduction in the rate of respiratory crisis and a significant improvement in the clinical outcome, both likely related to earlier diagnosis and timely treatment. Despite the improved management, MuSK MG patients tend to remain dependent on long-term immunosuppressive treatment and may develop permanent disabling weakness. In uncontrolled studies, B cell depletion with rituximab proved effective in most patients with refractory disease, inducing prolonged clinical responses associated with a sustained reduction of serum antibody levels. Promising results from experimental studies and case reports suggest that both 3,4-diaminopyridine and albuterol may be effective as symptomatic agents.