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Utility of cortical inhibitory and facilitatory neuronal circuits in amyotrophic lateral sclerosis diagnosis

dc.contributor.authorSantos Silva, Cláudia
dc.contributor.authorPavey, Nathan
dc.contributor.authorCalma, Aicee Dawn
dc.contributor.authorKiernan, Matthew C.
dc.contributor.authorMenon, Parvathi
dc.contributor.authorvan den Bos, Mehdi
dc.contributor.authorVucic, Steve
dc.date.accessioned2025-06-20T13:47:30Z
dc.date.available2025-06-20T13:47:30Z
dc.date.issued2025
dc.description© 2025 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.pt_PT
dc.description.abstractBackground: Cortical hyperexcitability is an early feature of amyotrophic lateral sclerosis (ALS), linked to dysfunction in inhibitory and facilitatory cortical circuits, measurable using paired-pulse transcranial magnetic stimulation (TMS). Short-interval intracortical inhibition (SICI) is a robust biomarker of inhibitory function and an ALS diagnostic marker. Short interval intracortical facilitation (SICF) serves as a biomarker of facilitatory function, while the index of excitation assesses the contribution of these circuits to hyperexcitability. This study aimed to evaluate the diagnostic effectiveness of SICF and the index of excitation in distinguishing ALS from non-ALS mimic disorders. Methods: This cross-sectional study assessed cortical excitability in participants with suspected ALS from two Sydney centres, classified using the Gold Coast criteria. Threshold tracking TMS measured SICI, SICF, and the index of excitation. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis, with sensitivity, specificity, and optimal cut-off values determined. Results: Of 154 participants, 95 were diagnosed with ALS and 48 with non-ALS mimics. SICI demonstrated a marginally higher diagnostic accuracy (AUC 0.84, 95% CI:0.77-0.89) compared to SICF (AUC 0.77, 95% CI:0.68-0.84, p = 0.028). The index of excitation showed comparable accuracy to SICI (AUC 0.82, 95% CI: 0.75-0.88, p = 0.328). The optimal SICF cut-off (≤ -13.6%) provided 70.5% sensitivity and 70.8% specificity, while the index of excitation cut-off (≥ 64.5%) yielded 71.6% sensitivity and 70.8% specificity. Conclusions: The present study established modest diagnostic potential of increased SICF and index of excitation in differential ALS from mimic disorders, thereby enhancing understanding of the role of inhibitory and facilitatory cortical circuits in ALS diagnosis.pt_PT
dc.description.sponsorshipThis study was supported by research grants from the National Health and Medical Research Council of Australia (project grants 510233, GIA 1726, 1024915, and 1055778) and the Motor Neuron Disease Research Institute of Australia (Betty-Laidlaw grant).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEuropean Journal of Neurology, 2025; 32:e70203pt_PT
dc.identifier.doi10.1111/ene.70203pt_PT
dc.identifier.eissn1468-1331
dc.identifier.issn1351-5101
dc.identifier.urihttp://hdl.handle.net/10400.5/101652
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/journal/14681331pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectAmyotrophic lateral sclerosispt_PT
dc.subjectIndex of excitationpt_PT
dc.subjectShort interval intracortical facilitationpt_PT
dc.subjectShort interval intracortical inhibitionpt_PT
dc.subjectTranscranialmagnetic stimulationpt_PT
dc.titleUtility of cortical inhibitory and facilitatory neuronal circuits in amyotrophic lateral sclerosis diagnosispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue6pt_PT
oaire.citation.titleEuropean Journal of Neurologypt_PT
oaire.citation.volume32pt_PT
person.familyNameSantos Silva
person.givenNameCláudia
person.identifier.ciencia-id211D-4BEE-28DD
person.identifier.orcid0000-0003-4495-6314
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationfc8ee92f-0134-4cb4-a2fe-bcf07fc2353d
relation.isAuthorOfPublication.latestForDiscoveryfc8ee92f-0134-4cb4-a2fe-bcf07fc2353d

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