Longitudinal assessment of cortical motor function in amyotrophic lateral sclerosis

Abstract Background Short interval intracortical inhibition (SICI) remains the most sensitive parameter to assess motor cortical function in amyotrophic lateral sclerosis (ALS). While an initial value of SICI has been utilised to support a diagnosis of ALS, less is known about progression of change....

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Main Authors: Dhayalen Krishnan, Dayna-Lee Talbot, Jasmine F. Ashhurst, Susanna B. Park, Steve Vucic, Hannah C. Timmins, Matthew C. Kiernan
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-01570-6
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author Dhayalen Krishnan
Dayna-Lee Talbot
Jasmine F. Ashhurst
Susanna B. Park
Steve Vucic
Hannah C. Timmins
Matthew C. Kiernan
author_facet Dhayalen Krishnan
Dayna-Lee Talbot
Jasmine F. Ashhurst
Susanna B. Park
Steve Vucic
Hannah C. Timmins
Matthew C. Kiernan
author_sort Dhayalen Krishnan
collection DOAJ
description Abstract Background Short interval intracortical inhibition (SICI) remains the most sensitive parameter to assess motor cortical function in amyotrophic lateral sclerosis (ALS). While an initial value of SICI has been utilised to support a diagnosis of ALS, less is known about progression of change. Methods Motor cortex function was prospectively assessed in ALS patients, through serial threshold tracking transcranial magnetic stimulation (TMS) assessment over more than 12 months. Motor cortical potentials were recorded from the abductor pollicis brevis (APB). Demographic information and clinical variables were analysed. Results A cohort of 52 ALS patients (69.2% limb-onset disease; 47.2% right-side) were assigned to undergo longitudinal assessment of cortical motor function. Mean ALSFRS-R score at baseline was 39.5 ± 1.0 denoting relatively milder clinical deficits at study commencement. Cortical motor dysfunction was evident at baseline, with reduction in averaged SICI (p = 0.004) when compared to healthy controls. In terms of disease trajectory, ALS patients experienced a significant decline in averaged SICI overtime. When compared to initial assessment, averaged SICI was significantly reduced after 12 months (p = 0.004). There was no significant main effect of site of onset on averaged SICI (p = 0.78). The progressive change in averaged SICI was more robust in the dominant hemisphere, with the proportion of ALS patients who demonstrated a clinically abnormal averaged SICI value (< 5.5%) increasing by 50%, compared to 15.4% for the non-dominant hemisphere. Conclusion ALS patients demonstrate progressive cortical motor abnormalities, evident through longitudinal assessment. While SICI represents a diagnostic biomarker, the rate of decline in the present series is consistent with disease progression, suggesting a potential role to monitor the efficacy of therapeutic intervention.
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spelling doaj-art-d200bfe7846e49ffb854dd48e9c565142025-08-20T01:51:27ZengNature PortfolioScientific Reports2045-23222025-05-011511910.1038/s41598-025-01570-6Longitudinal assessment of cortical motor function in amyotrophic lateral sclerosisDhayalen Krishnan0Dayna-Lee Talbot1Jasmine F. Ashhurst2Susanna B. Park3Steve Vucic4Hannah C. Timmins5Matthew C. Kiernan6Neuroscience Research AustraliaNeuroscience Research AustraliaNeuroscience Research AustraliaSchool of Medical Sciences, University of SydneyBrain and Nerve Centre, Concord HospitalNeuroscience Research AustraliaNeuroscience Research AustraliaAbstract Background Short interval intracortical inhibition (SICI) remains the most sensitive parameter to assess motor cortical function in amyotrophic lateral sclerosis (ALS). While an initial value of SICI has been utilised to support a diagnosis of ALS, less is known about progression of change. Methods Motor cortex function was prospectively assessed in ALS patients, through serial threshold tracking transcranial magnetic stimulation (TMS) assessment over more than 12 months. Motor cortical potentials were recorded from the abductor pollicis brevis (APB). Demographic information and clinical variables were analysed. Results A cohort of 52 ALS patients (69.2% limb-onset disease; 47.2% right-side) were assigned to undergo longitudinal assessment of cortical motor function. Mean ALSFRS-R score at baseline was 39.5 ± 1.0 denoting relatively milder clinical deficits at study commencement. Cortical motor dysfunction was evident at baseline, with reduction in averaged SICI (p = 0.004) when compared to healthy controls. In terms of disease trajectory, ALS patients experienced a significant decline in averaged SICI overtime. When compared to initial assessment, averaged SICI was significantly reduced after 12 months (p = 0.004). There was no significant main effect of site of onset on averaged SICI (p = 0.78). The progressive change in averaged SICI was more robust in the dominant hemisphere, with the proportion of ALS patients who demonstrated a clinically abnormal averaged SICI value (< 5.5%) increasing by 50%, compared to 15.4% for the non-dominant hemisphere. Conclusion ALS patients demonstrate progressive cortical motor abnormalities, evident through longitudinal assessment. While SICI represents a diagnostic biomarker, the rate of decline in the present series is consistent with disease progression, suggesting a potential role to monitor the efficacy of therapeutic intervention.https://doi.org/10.1038/s41598-025-01570-6
spellingShingle Dhayalen Krishnan
Dayna-Lee Talbot
Jasmine F. Ashhurst
Susanna B. Park
Steve Vucic
Hannah C. Timmins
Matthew C. Kiernan
Longitudinal assessment of cortical motor function in amyotrophic lateral sclerosis
Scientific Reports
title Longitudinal assessment of cortical motor function in amyotrophic lateral sclerosis
title_full Longitudinal assessment of cortical motor function in amyotrophic lateral sclerosis
title_fullStr Longitudinal assessment of cortical motor function in amyotrophic lateral sclerosis
title_full_unstemmed Longitudinal assessment of cortical motor function in amyotrophic lateral sclerosis
title_short Longitudinal assessment of cortical motor function in amyotrophic lateral sclerosis
title_sort longitudinal assessment of cortical motor function in amyotrophic lateral sclerosis
url https://doi.org/10.1038/s41598-025-01570-6
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