Thanuja Dharmadasa1, José M Matamala2, James Howells2, Steve Vucic3, Matthew C Kiernan4. 1. Brain and Mind Centre, University of Sydney, Sydney, NSW 2050, Australia. Electronic address: thanuja.dharmadasa@sydney.edu.au. 2. Brain and Mind Centre, University of Sydney, Sydney, NSW 2050, Australia. 3. Westmead Clinical School, University of Sydney, Sydney, NSW 2145, Australia. 4. Brain and Mind Centre, University of Sydney, Sydney, NSW 2050, Australia; Department of Neurology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
Abstract
OBJECTIVE: To characterise the regional cortical patterns underlying clinical symptomatology in amyotrophic lateral sclerosis (ALS). METHODS: 138 patients prospectively underwent transcranial magnetic stimulation studies from hand and leg cortical regions of each hemisphere, obtaining motor evoked potentials from all four limbs. Patients were categorised by clinical phenotype and underwent clinical and peripheral evaluation of disease. RESULTS: Cortical dysfunction was evident across the motor cortices, with reduction in short-interval intracortical inhibition (SICI) suggesting the presence of widespread cortical hyperexcitability, most prominently from clinically affected regions (hand p < 0.0001; leg p < 0.01). In early disease, cortical abnormalities were asymmetric between hemispheres, focally corresponding to clinical site-of-onset (p < 0.05). Degrees of cortical dysfunction varied between phenotypes, with the bulbar-onset cohort demonstrating greatest reduction in SICI (p = 0.03). CONCLUSIONS: The pattern of cortical dysfunction appears linked to clinical evolution in ALS, with early focal asymmetry preceding widespread changes in later disease. Cortical differences across phenotypes may influence clinical variability. SIGNIFICANCE: This is the first study to extensively map cortical abnormalities from multiple motor regions across hemispheres. The early cortical signature mirrors symptom laterality, supporting a discrete region of disease onset. Phenotypes appear to exist within a pathophysiological continuum, but cortical heterogeneity may mediate observed differences in clinical outcome. Crown
OBJECTIVE: To characterise the regional cortical patterns underlying clinical symptomatology in amyotrophic lateral sclerosis (ALS). METHODS: 138 patients prospectively underwent transcranial magnetic stimulation studies from hand and leg cortical regions of each hemisphere, obtaining motor evoked potentials from all four limbs. Patients were categorised by clinical phenotype and underwent clinical and peripheral evaluation of disease. RESULTS:Cortical dysfunction was evident across the motor cortices, with reduction in short-interval intracortical inhibition (SICI) suggesting the presence of widespread cortical hyperexcitability, most prominently from clinically affected regions (hand p < 0.0001; leg p < 0.01). In early disease, cortical abnormalities were asymmetric between hemispheres, focally corresponding to clinical site-of-onset (p < 0.05). Degrees of cortical dysfunction varied between phenotypes, with the bulbar-onset cohort demonstrating greatest reduction in SICI (p = 0.03). CONCLUSIONS: The pattern of cortical dysfunction appears linked to clinical evolution in ALS, with early focal asymmetry preceding widespread changes in later disease. Cortical differences across phenotypes may influence clinical variability. SIGNIFICANCE: This is the first study to extensively map cortical abnormalities from multiple motor regions across hemispheres. The early cortical signature mirrors symptom laterality, supporting a discrete region of disease onset. Phenotypes appear to exist within a pathophysiological continuum, but cortical heterogeneity may mediate observed differences in clinical outcome. Crown
Authors: Stephen A Goutman; Orla Hardiman; Ammar Al-Chalabi; Adriano Chió; Masha G Savelieff; Matthew C Kiernan; Eva L Feldman Journal: Lancet Neurol Date: 2022-03-22 Impact factor: 59.935
Authors: Matthew C Kiernan; Steve Vucic; Kevin Talbot; Christopher J McDermott; Orla Hardiman; Jeremy M Shefner; Ammar Al-Chalabi; William Huynh; Merit Cudkowicz; Paul Talman; Leonard H Van den Berg; Thanuja Dharmadasa; Paul Wicks; Claire Reilly; Martin R Turner Journal: Nat Rev Neurol Date: 2020-12-18 Impact factor: 42.937