Motor and extra-motor involvement in amyotrophic lateral sclerosis

Abstract

Amyotrophic Lateral Sclerosis (ALS) is primarily associated with pathology in the motor cortex and corticospinal tract. Based on clinical observations, it is increasingly recognised that extra-motor symptoms add to the clinical heterogeneity of the disease and a varying degree of neuropsychological, extra-pyramidal, and cerebellar involvement are also often observed. The objective of this work is the characterisation of motor and extra-motor involvement in ALS using multimodal quantitative neuroimaging. Eighty-five patients and 76 healthy controls were enrolled in this translational research study which has been specifically approved by the appropriate Ethics Committee. All patients underwent standardised clinical assessments and participated in a purpose-designed 3 Tesla magnetic resonance imaging protocol. Whole-brain and region of interest grey and white matter analyses were performed assessing regional brain volumes and indices of white matter integrity. Our results suggest that the unifying disease-specific imaging signature of ALS includes precentral gyrus atrophy, corpus callosum degeneration and corticospinal tract involvement. Additionally, considerable extra-motor changes including frontotemporal degeneration have also been identified. The characterisation of extra-motor motor involvement in ALS has implications for clinical trials designs, individualised patient care, multidisciplinary interventions and the support of family members and caregivers.