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Voltage gated calcium channel (VGCC) antibodies are generally associated with Lambert-Eaton myasthenic syndrome. However the presence of this antibody has been associated with paraneoplastic as well as non-paraneoplastic cerebellar degeneration. Most patients with VGCC-antibody-positivity have small cell lung cancer (SCLC). Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the presynaptic part of the neuromuscular junction. Its classical clinical triad is proximal muscle weakness, areflexia and autonomic dysfunction. Fifty to sixty percent of LEMS patients have a neoplasia, usually SCLC. The co-occurrence of SCLC and LEMS causes more severe and progressive disease and shorter survival than non-paraneoplastic LEMS. Treatment includes 3,4 diaminopyridine for symptomatic purposes and immunotherapy with prednisolone, azathioprine or intravenous immunoglobulin in patients unresponsive to 3,4 diaminopyridine. Paraneoplastic cerebellar degeneration (PCD) is a syndrome characterized with severe, subacute pancerebellar dysfunction. Serum is positive for VGCC antibody in 41%-44% of patients, usually with the co-occurrence of SCLC. Clinical and electrophysiological features of LEMS are also present in 20%-40% of these patients. Unfortunately, PCD symptoms do not improve with immunotherapy. The role of VGCC antibody in the immunopathogenesis of LEMS is well known whereas its role in PCD is still unclear. All patients presenting with LEMS or PCD must be investigated for SCLC.

Amyotrophic lateral sclerosis (ALS) is a late-onset motor neuron disease with mostly dominant inheritance and a life expectancy of 2-5 years; however, a quite common occurrence of atypical forms of the disease, due to recessive inheritance, has become evident with the use of NGS technologies. In this paper, we describe a family with close consanguinity for at least four generations, suffering from a slowly progressive form of ALS. Spastic walking is observed since teenage years, while bulbar symptoms start much later, at the fifth or sixth decade of life. Patients usually die because of respiratory failure. Using whole-exome sequencing, we identified a novel homozygous p.(Val94Ala) (c.281T>C) (NG_052910.1) (NM_006459) variation in the endoplasmic reticulum lipid raft associated protein 1 (ERLIN1) gene, which segregates with the disease in the family. Here we suggest that ERLIN1 variants, previously shown in juvenile hereditary spastic paraplegia cases, may also be the cause of a slowly progressive early-onset ALS, starting with upper motor neuron features and developing into classical ALS with the addition of lower motor neuron dysfunction. We also demonstrate that ATP-binding cassette subfamily C member 2 (ABCC2) gene, responsible for hyperbilirubinemia, is linked to ERLIN1.

Dermal RAGE is increased in NSVN and DN, supporting the concept of a role of the RAGE pathway in the pathophysiology of dermal inflammation and skin denervation in NSVN and DN.

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with openlabel eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (−2.4 [1.34] and − 3.3 [0.65]); Quantitative Myasthenia Gravis (−2.9 [1.98] and − 4.3 [0.79]); Myasthenia Gravis Composite (−4.5 [2.63] and − 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (−8.6 [5.68] and − 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population.

The 6mWT and 2mWT have excellent test-retest reliability as well as moderate construct validity for the evaluation of functional exercise capacity patients with MG. Muscle Nerve, 2018.

Neuropathy per se may lead to skin inflammation. In cases of possible vasculitic neuropathy, skin biopsy may be an additional tool to support the diagnosis. Muscle Nerve 55: 884-893, 2017.