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 At the end of follow-up, the rate of complete remission was 8.8%, and IS treatment had been withdrawn in only 10/54 patients.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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Facioscapulohumeral muscular dystrophy (FSHD) is an inherited disease, and although strongly suggested, a contribution of inflammation to its pathogenesis has never been demonstrated. In FSHD patients, we found by immunohistochemistry inflammatory infiltrates mainly composed by CD8(+) T cells in muscles showing hyperintensity features on T2-weighted short tau inversion recovery magnetic resonance imaging (T2-STIR-MRI) sequences. Therefore, we evaluated the presence of circulating activated immune cells and the production of cytokines in patients with or without muscles showing hyperintensity features on T2-STIR-MRI sequences and from controls. FSHD patients displaying hyperintensity features in one or more muscles showed higher CD8(+)pSTAT1(+), CD8(+)T-bet(+) T cells and CD14(+)pSTAT1(+), CD14(+)T-bet(+) cells percentages and IL12p40, IFNγ and TNFα levels than patients without muscles displaying hyperintense features and controls. Moreover, the percentages of CD8(+)pSTAT1(+), CD8(+)T-bet(+) and CD14(+)pSTAT1(+) cells correlated with the proportion of muscles displaying hyperintensity features at T2-STIR sequences. These data indicate that circulating activated immune cells, mainly CD8(+) T cells, may favour FSHD progression by promoting active phases of muscle inflammation.

A multicentre retrospective study was carried out on the characteristics and course of myasthenia gravis (MG) in Italy. Data from 1152 patients, fairly representative of the myasthenic population seeking medical advice, were analysed for diagnostic criteria, clinical aspects and therapeutic approaches. Mean follow-up was 4.9 years. The disease was correctly diagnosed within 2 years of the onset in 80% of cases. Onset of symptoms peaked in the second and third decade in females and fell between 20 and 59 years in males. At first observation 87% of the patients had generalized MG. Maximal worsening was observed within 3 years in 77% of patients. At the last follow-up, 35% of cases were symptom-free (pharmacological remission 24%, remission without treatment 11%). The more severe the disease at the first observation and at the maximal worsening of symptoms, the lower was the proportion of remissions. Steroids were given in 54% and immunosuppressants in 18%. Thymectomy was performed in 72%, mostly in women, younger than age 40, and with generalized MG. Thymectomy seemed to improve the course of the disease, mostly in patients operated on shortly after diagnosis and those with generalized mild-to-moderate disease and with a normally involuted thymus. MG was lethal in 4% of patients, principally men, older than 40, in grade 3 or worse at first observation, with a short history of disease, and with thymona.

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