Department of Neurology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.
Brain and Nerve Research Center, University of Sydney, Sydney, New South Wales, Australia.
Eur J Neurol. 2024 Jul;31(7):e16281. doi: 10.1111/ene.16281. Epub 2024 Mar 20.
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.
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.
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; I = 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.
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.
皮质兴奋性过高已被确定为肌萎缩侧索硬化症（ALS）的诊断和致病生物标志物。皮质兴奋性通过经颅磁刺激（TMS）评估，这是一种非侵入性神经生理学技术。用于评估 ALS 皮质兴奋性过高的 TMS 生物标志物的敏感性最高的指标仍有待阐明。本文进行了一项荟萃分析，以确定用于评估 ALS 皮质兴奋性过高的 TMS 生物标志物中敏感性最高的指标。
通过检索 PubMed、MEDLINE、Embase 和 Scopus 电子数据库，对 2006 年 1 月 1 日至 2023 年 2 月 28 日发表的所有相关英文文献进行了系统的文献回顾。纳入标准包括报告应用阈刺激追踪 TMS（连续递增法）评估 ALS 和对照组的研究。
共有 25 项研究纳入了超过 2500 名参与者，其中包括 1530 名 ALS 患者和 1102 名对照者（健康对照者 907 名，神经肌肉疾病对照者 195 名）。采用阈刺激追踪 TMS 评估。结果显示，短间隔皮质内抑制（刺激间隔 1-7 ms）的均值显著降低，且具有中度异质性（-0.994，95%置信区间 -1.12 至 -0.873，p < 0.001；Q = 38.61，p < 0.05；I = 40%）。皮质静息期缩短以及运动诱发电位幅度和皮质内易化增加也显示出显著但较小的标准化均数差。
这项大型荟萃分析研究揭示，短间隔皮质内抑制减少显示出对 ALS 皮质兴奋性过高的最高敏感性。本荟萃分析的综合结果表明，旨在理解抑制性中间神经元回路功能障碍原因的研究策略，可能有助于深入了解 ALS 的发病机制。
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