Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial.

Abstract:

BACKGROUND:To collect preliminary data on the effects of mexiletine on cortical and axonal hyperexcitability in sporadic amyotrophic lateral sclerosis (ALS) in a phase 2 double-blind randomized controlled trial. METHODS:Twenty ALS subjects were randomized to placebo and mexiletine 300 or 600 mg daily for 4 wk and assessed by transcranial magnetic stimulation and axonal excitability studies. The primary endpoint was change in resting motor threshold (RMT). RESULTS:RMT was unchanged with 4 wk of mexiletine (combined active therapies) as compared to placebo, which showed a significant increase (P = .039). Reductions of motor evoked potential (MEP) amplitude (P = .013) and accommodation half-time (P = .002), secondary outcome measures of cortical and axonal excitability, respectively, were also evident at 4 wk on mexiletine. CONCLUSIONS:The relative stabilization of RMT in the treated subjects was unexpected and could be attributed to unaccounted sources of error or chance. However, a possible alternative cause is neuromodulation preventing an increase. The change in MEP amplitude and accommodation half-time supports the reduction of cortical and axonal hyperexcitability with mexiletine.

journal_name

Muscle Nerve

journal_title

Muscle & nerve

authors

Weiss MD,Macklin EA,McIlduff CE,Vucic S,Wainger BJ,Kiernan MC,Goutman SA,Goyal NA,Rutkove SB,Ladha SS,Chen IA,Harms MB,Brannagan TH,Lacomis D,Zivkovic S,Ma M,Wang LH,Simmons Z,Rivner MH,Shefner JM,Cudkowicz ME,A

doi

10.1002/mus.27146

subject

Has Abstract

pub_date

2020-12-19 00:00:00

eissn

0148-639X

issn

1097-4598

pub_type

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