Amelia Evoli

3,4-Diaminopyridine may improve myasthenia gravis with MuSK antibodies

We evaluated the co-occurrence of autoimmune diseases (ADs) in a large population of myasthenia gravis (MG) patients from a single center. Our survey included 984 patients, 904 with anti-acetylcholine receptor antibodies and 80 with anti-muscle specific kinase antibodies. The anti-acetylcholine receptor positive population included patients with early-onset (age at onset ≤ 50 years), late-onset and thymoma-associated disease. Follow-up ranged 2-40 years. Two-hundred and fourteen ADs were diagnosed in 185 patients; 26 of them had two or more ADs in association with MG. Thyroid disorders were the most common and, together with vitiligo and thrombocytopenia, occurred in all disease subsets. Otherwise, there was a broad variability with partial overlap among patient groups. The highest rate of ADs was observed in early-onset patients, while clusters, i.e. 2 or more ADs other than MG in the same individual, were more common among thymoma cases. Thirty-four diseases were diagnosed at the same time, 88 occurred before and 92 after the onset of MG. On multivariate analysis, immunosuppressive treatment was the only independent variable which negatively influenced the risk of developing other ADs in our cohort.

Myasthenia gravis (MG) is characterized by fatigable weakness of voluntary muscles caused by immunoglobulin G autoantibodies binding to post‐synaptic proteins at the neuromuscular junction. Antibodies specific for the acetylcholine receptor are detected in the great majority (85%) of MG patients. Serum immunoglobulin G binding to the muscle‐specific kinase (MuSK) are found in approximately 40% of anti‐acetylcholine receptor‐negative patients. Recently, the low‐density lipoprotein receptor‐related protein 4 (Lrp4), which is the MuSK co‐receptor for agrin, has been recognized as a new antigen in MG. Specific antibodies bind to the extracellular domains of MuSK and Lrp4 and, as experimental models have shown, interfere with the protein function. The present review describes the MuSK‐Lrp4 complex, and summarizes the effects of MuSK and Lrp4 antibodies at the neuromuscular junction. Furthermore, the epidemiological and clinical characteristics, the response to therapy and the controversies in management of the specific diseases are discussed.

Lambert–Eaton myasthenic syndrome (LEMS) is a pre-synaptic disorder of the neuromuscular and autonomic transmission mediated by antibodies to voltage-gated calcium channels at the motor nerve terminal. LEMS is a quite rare and probably under-diagnosed disease: the onset may be slow and clinical signs are typically fluctuating, thus adding to the delay in diagnosis. LEMS weakness typically involves lower and upper limbs and the proximal muscles are predominantly affected. A significant proportion of patients also have dysfunction of the autonomic nervous system that may include dry mouth, constipation, blurred vision, impaired sweating, and orthostatic hypotension. LEMS recognition is based on clinical, electrophysiological and immunological criteria. Nearly 50–60 % of patients with LEMS have an underlying tumour that, in almost all cases, is a small-cell lung cancer; the onset of neurological symptoms generally precedes tumour detection. A careful screening for the early detection of the possible associated cancer is a crucial step for optimal disease management. The Italian Working Group on Myasthenic Syndromes developed diagnostic and therapeutic algorithms that could serve in routine clinical practice as tools for a patient-tailored approach.