title: Potential structural and functional biomarkers of upper motor neuron dysfunction in ALS.
abstract: Assessment of upper motor neuron (UMN) function in amyotrophic lateral sclerosis (ALS) remains clinically based. Given the potential difficulties in identifying UMN signs, objective biomarkers of UMN dysfunction are important. Consequently, the present study assessed utility of cortical thickness analysis combined with threshold tracking transcranial magnetic stimulation (TMS) as biomakers of UMN dysfunction in ALS. Cortical thickness analysis and threshold tracking TMS studies were undertaken on 25 ALS patients and results were compared to healthy control subjects, with different control groups used for each technique. Structural and functional abnormalities were evident in both motor cortices in the ALS cohort and were heralded by marked reduction of short-interval intracortical inhibition (SICI RAPB 1.4 ± 2.4%; SICI LAPB 3.6 ± 1.9%; SICI CONTROLS10.5 ± 1.1%, p <0.01), resting motor threshold (p <0.05) and cortical silent period duration (p <0.001) combined with increase in MEP amplitude (p <0.05) and intracortical facilitation (p <0.05). Significant cortical thinning was evident in the bitemporal regions (p <0.05), while precentral gyrus cortical thinning was evident in 56% of cases and when combined with TMS abnormalities disclosed UMN dysfunction in 88% of cases. In conclusion, findings from the present study establish that a combination of structural and functional assessment of corticomotoneurons may increase the yield of objectively identifying UMN dysfunction in ALS.
authors.affiliation: a The Brain Dynamics Centre, Westmead Millennium Institute, Westmead, NSW, and Sydney Medical School, University of Sydney , Sydney.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Grieve
authors.affiliation: b Department of Neurology , Westmead Hospital , Westmead , NSW.|c Westmead Clinical School, University of Sydney , NSW.
authors.forename: Parvathi
authors.initials: P
authors.lastname: Menon
authors.affiliation: a The Brain Dynamics Centre, Westmead Millennium Institute, Westmead, NSW, and Sydney Medical School, University of Sydney , Sydney.|d Department of Radiology , Westmead Hospital , Westmead , NSW.
authors.forename: Mayuresh S
authors.initials: MS
authors.lastname: Korgaonkar
authors.affiliation: d Department of Radiology , Westmead Hospital , Westmead , NSW.
authors.forename: Lavier
authors.initials: L
authors.lastname: Gomes
authors.affiliation: d Department of Radiology , Westmead Hospital , Westmead , NSW.
authors.forename: Sheryl
authors.initials: S
authors.lastname: Foster
authors.affiliation: e The Brain and Mind Research Institute and Sydney Medical School, University of Sydney , Sydney , Australia.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
authors.affiliation: a The Brain Dynamics Centre, Westmead Millennium Institute, Westmead, NSW, and Sydney Medical School, University of Sydney , Sydney.|c Westmead Clinical School, University of Sydney , NSW.
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D001132:Arm; D015415:Biomarkers; D001931:Brain Mapping / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000473:pathology* / Q000503:physiopathology*; D009135:Muscular Diseases / Q000175:diagnosis / Q000503:physiopathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
chemical_list: D015415:Biomarkers
keywords: ALS; Cortical thickness; SICI