Treatment Updates for Neuromuscular Channelopathies
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Neuromuscular Disorders (C Fournier, Section Editor)
Treatment Updates for Neuromuscular Channelopathies Nantaporn Jitpimolmard, MD1,2 Emma Matthews, MRCP, PhD1,3 Doreen Fialho, FRCP, PhD1,* Address *,1 Queen Square Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, UCL, London, UK Email: [email protected] 2 Rehabilitation Medicine Department, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand 3 Atkinson-Morley Neuromuscular Centre, St George’s University Hospitals Foundation Trust, London, UK
* The Author(s) 2020
This article is part of the Topical Collection on Neuromuscular Disorders Keywords Myotonia congenita I Sodium channel myotonia I Paramyotonia congenita I Periodic paralysis I Andersen-Tawil syndrome I Channelopathy
Abstract Purpose of review This article aims to review the current and upcoming treatment options of primary muscle channelopathies including the non-dystrophic myotonias and periodic paralyses. Recent findings The efficacy of mexiletine in the treatment of myotonia is now supported by two randomised placebo-controlled trials, one of which utilised a novel aggregated n-of-1 design. This has resulted in licencing of the drug via orphan drug status. There is also good evidence that mexiletine is well tolerated and safe in this patient group without the need for intensive monitoring. A range of alternative antimyotonic treatment options include lamotrigine, carbamazepine and ranolazine exist with variable evidence base. In vitro studies have shown insight into reasons for treatment failure of some medications with certain genotypes opening the era of mutation-specific therapy such as use of flecainide. In the periodic paralyses, the ability of MRI to distinguish between reversible oedema and irreversible fatty replacement makes it an increasingly useful tool to guide and assess pharmacological treatment. Unfortunately, the striking efficacy of bumetanide in hypokalaemic periodic paralysis animal models was not replicated in a recent pilot study in humans.
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Curr Treat Options Neurol
(2020) 22:34
Summary The treatment of skeletal muscle channelopathies combines dietary and lifestyle advice together with pharmacological interventions. The rarity of these conditions remains a barrier for clinical studies but the example of the aggregated n-of-1 trial of mexiletine shows that innovative trial design can overcome these hurdles. Further research is required to test efficacy of drugs shown to have promising characteristics in preclinical experiments such as safinamide, riluzule and magnesium for myotonia or bumetanide for hypokalaemic periodic paralysis.
Introduction Skeletal muscle channelopathies are rare and heterogeneous genetic disorders caused by dysfunction of voltage-gated ion channels. These conditions are broadly classified as non-dystrophic myotonias (NDMs) and the periodic paralyses. Estimated prevalences range from 1 to 2.4/100000 in European cohorts [1, 2]. The NDMs are comprised of myotonia congenita (MC) due to mutations in t
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