Progressive neurochemical abnormalities in cognitive and motor subgroups of ALS: a prospective multicentre study

Objective: To evaluate progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) by assessing alterations in N-acetylaspartate (NAA) ratios in the motor and prefrontal cortex within clinical subgroups of ALS.

Methods: Seventy-six ALS patients and 59 healthy controls were enrolled a prospective, longitudinal, multicenter study in the Canadian ALS Neuroimaging Consortium (CALSNIC). Participants underwent serial clinical evaluations and MRS at baseline, 4 and 8 months using a harmonized protocol across 5 centers. NAA ratios were quantified in the motor cortex and prefrontal cortex. Patients were stratified into subgroups based on disease progression rate, upper motor neuron (UMN) signs, and cognitive status. Linear mixed models were used for baseline and longitudinal comparisons of NAA metabolite ratios.

Results: Patients with ALS had reduced NAA ratios in the motor cortex at baseline (P < 0.001). Ratios were lower in those with more rapid disease progression and gr...