A multimodal longitudinal study of structural brain involvement in amyotrophic lateral sclerosis

Objective: To understand the progressive nature of amyotrophic lateral sclerosis (ALS) by investigating differential brain patterns of gray and white matter involvement in clinically or genetically defined subgroups of patients using cross-sectional, longitudinal and multimodal MRI. Methods: We assessed cortical thickness, subcortical volumes and white matter connectivity from T1-weighted and diffusion-weighted MRI in 292 ALS patients (follow-up: n=150) and 156 controls (follow-up: n=72). Linear mixed-effects models were used to assess changes in structural brain measurements over time in patients compared to controls. Results: Patients with a C9orf72 mutation (n=24) showed widespread gray and white matter involvement at baseline, and extensive loss of white matter integrity in the connectome over time. In C9orf72-negative patients, we detected cortical thinning of motor and frontotemporal regions, and loss of white matter integrity of connections linked to the motor cortex. Spina...