Reduction in short interval intracortical inhibition from the early stage reflects the pathophysiology in amyotrophic lateral sclerosis: A meta-analysis study

Mana Higashihara; Nathan Pavey; Parvathi Menon; Mehdi van den Bos; Kazumoto Shibuya; Satoshi Kuwabara; Matthew C Kiernan; Masayoshi Koinuma; Steve Vucic

doi:10.1111/ene.16281

Reduction in short interval intracortical inhibition from the early stage reflects the pathophysiology in amyotrophic lateral sclerosis: A meta-analysis study

Eur J Neurol. 2024 Jul;31(7):e16281. doi: 10.1111/ene.16281. Epub 2024 Mar 20.

Authors

Affiliations

¹ Department of Neurology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.
² Brain and Nerve Research Center, University of Sydney, Sydney, New South Wales, Australia.
³ Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
⁴ Neuroscience Resarch Australia, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
⁶ Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo, Japan.
⁷ Healthy Aging Innovation Center, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.

PMID: 38504632
DOI: 10.1111/ene.16281

Abstract

Background and purpose: Cortical hyperexcitability has been identified as a diagnostic and pathogenic biomarker of amyotrophic lateral sclerosis (ALS). Cortical excitability is assessed by transcranial magnetic stimulation (TMS), a non-invasive neurophysiological technique. The TMS biomarkers exhibiting highest sensitivity for cortical hyperexcitability in ALS remain to be elucidated. A meta-analysis was performed to determine the TMS biomarkers exhibiting the highest sensitivity for cortical hyperexcitability in ALS.

Methods: A systematic literature review was conducted of all relevant studies published in the English language by searching PubMed, MEDLINE, Embase and Scopus electronic databases from 1 January 2006 to 28 February 2023. Inclusion criteria included studies reporting the utility of threshold tracking TMS (serial ascending method) in ALS and controls.

Results: In total, more than 2500 participants, incorporating 1530 ALS patients and 1102 controls (healthy, 907; neuromuscular, 195) were assessed with threshold tracking TMS across 25 studies. Significant reduction of mean short interval intracortical inhibition (interstimulus interval 1-7 ms) exhibited the highest standardized mean difference with moderate heterogeneity (-0.994, 95% confidence interval -1.12 to -0.873, p < 0.001; Q = 38.61, p < 0.05; I² = 40%). The reduction of cortical silent period duration along with an increase in motor evoked potential amplitude and intracortical facilitation also exhibited significant, albeit smaller, standardized mean differences.

Conclusion: This large meta-analysis study disclosed that mean short interval intracortical inhibition reduction exhibited the highest sensitivity for cortical hyperexcitability in ALS. Combined findings from this meta-analysis suggest that research strategies aimed at understanding the cause of inhibitory interneuronal circuit dysfunction could enhance understanding of ALS pathogenesis.

Keywords: SICI; amyotrophic lateral sclerosis; cortical hyperexcitability; motor neuron disease; threshold tracking TMS.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Amyotrophic Lateral Sclerosis* / physiopathology
Evoked Potentials, Motor / physiology
Humans
Motor Cortex* / physiopathology
Neural Inhibition* / physiology
Transcranial Magnetic Stimulation*