{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:58:07Z","timestamp":1789102687694,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Despite its clinical heterogeneity, amyotrophic lateral sclerosis is unified by early and prominent alterations in cortical excitability, increasingly recognized as contributors to disease progression. This study assessed whether the ratio between motor evoked potential (MEP) amplitude, reflecting upper motor neuron integrity, and compound muscle action potential (CMAP) amplitude, indexing lower motor neuron function, could provide an accessible marker of corticospinal excitability to stratify patients by phenotype, stage, and survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multicenter retrospective study, 743 amyotrophic lateral sclerosis patients from 16 tertiary centers in Italy were analyzed. The MEP:CMAP ratio, recorded from upper limb muscles, was categorized as hyperexcitable, normal, or hypoexcitable. Phenotypes included progressive muscular atrophy (or lower motor neuron), flail arm\/leg, classic, bulbar, patient with predominant upper motor neuron signs (or pyramidal), and primary lateral sclerosis. Disease stage was assessed using King's staging. Survival was analyzed using Kaplan\u2013Meier curves and Cox regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The MEP:CMAP ratio differed significantly across phenotypes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), with hyperexcitability predominating in lower motor neuron, flail, classic, and bulbar forms, and hypoexcitability in pyramidal and primary lateral sclerosis. Hypoexcitability increased in advanced King's stages (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Hyperexcitable patients had shorter survival (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004), including when tested within 1\u2009year of onset (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006). Cox regression identified the MEP:CMAP ratio as an independent survival predictor (HR 1.84, 95% CI 1.12\u20133.03,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This real\u2010world study supports the clinical value of the MEP:CMAP ratio as a scalable biomarker of cortical excitability in amyotrophic lateral sclerosis, with prognostic relevance across phenotypes and disease stages. ANN NEUROL 2025;98:801\u2013813<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.27305","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T07:48:41Z","timestamp":1750837721000},"page":"801-813","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cortical Excitability as a Prognostic and Phenotypic Stratification Biomarker in Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6530-1857","authenticated-orcid":false,"given":"Federico","family":"Ranieri","sequence":"first","affiliation":[{"name":"Neurology Unit, Department of Neuroscience, Biomedicine, and Movement Sciences University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1386-1411","authenticated-orcid":false,"given":"Gianmaria","family":"Senerchia","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive Sciences, and Odontostomatology University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Bonan","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Casali","sequence":"additional","affiliation":[{"name":"Unit of Neurology and Clinical Neurophysiology, Department of Medicine, Surgery, and Neuroscience University of Siena  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrado","family":"Cabona","sequence":"additional","affiliation":[{"name":"Division of Clinical Neurophysiology, IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9072-4971","authenticated-orcid":false,"given":"Mariagiovanna","family":"Cantone","sequence":"additional","affiliation":[{"name":"Neurology Unit Policlinico University Hospital \u201cG. 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