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The landscape of neurophysiological outcome measures in ALS interventional trials: A systematic review

Lookup NU author(s): Professor Mark BakerORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022 International Federation of Clinical Neurophysiology. Objective: We collated all interventional clinical trials in amyotrophic lateral sclerosis (ALS), which utilised at least one neurophysiological technique as a primary or secondary outcome measure. By identifying the strengths and limitations of these studies, we aim to guide study design in future trials. Methods: We conducted and reported this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight databases were searched from inception. In total, 703 studies were retrieved for screening and eligibility assessment. Results: Dating back to 1986, 32 eligible interventional clinical trials were identified, recruiting a median of 30 patients per completed trial. The most widely employed neurophysiological techniques were electromyography, motor unit number estimation (including motor unit number index), neurophysiological index and transcranial magnetic stimulation (including resting motor threshold and short-interval intracortical inhibition). Almost 40% of trials reported a positive outcome with respect to at least one neurophysiological measure. The interventions targeted either ion channels, immune mechanisms or neuronal metabolic pathways. Conclusions: Neurophysiology offers many promising biomarkers that can be utilised as outcome measures in interventional clinical trials in ALS. When selecting the most appropriate technique, key considerations include methodological standardisation, target engagement and logistical burden. Significance: Future trial design in ALS would benefit from a standardised, updated and easily accessible repository of neurophysiological outcome measures.

Publication metadata

Author(s): Ahmed N, Baker MR, Bashford J

Publication type: Article

Publication status: Published

Journal: Clinical Neurophysiology

Year: 2022

Volume: 137

Pages: 132-141

Print publication date: 01/05/2022

Online publication date: 08/03/2022

Acceptance date: 18/02/2022

Date deposited: 29/06/2023

ISSN (print): 1388-2457

ISSN (electronic): 1872-8952

Publisher: Elsevier Ireland Ltd


DOI: 10.1016/j.clinph.2022.02.020


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