In the present study, we included 24 patients with a clinical diagnosis of ALS and 34 age- and sex-matched healthy controls who underwent at least two longitudinal clinical evaluations and brain MRI scans on a 3 Tesla scanner (median follow-up time = 0.96 years). Age- and sex-adjusted ANOVA models were performed between groups at baseline. Linear mixed effect models were used to test differences of longitudinal trajectories between patients and controls. Results were Bonferroni-corrected for multiple comparisons.

At baseline, ALS patients showed significant bilateral reduction of hippocampal volumes compared with healthy controls (left: p=0.05; right: p=0.038), and a trend toward significance for atrophy in the right thalami (p=0.08). Baseline volumes of the basal ganglia were comparable between patients and controls. Longitudinally, ALS patients showed a significant reduction of grey matter volumes of the left pallidum (p=0.01) and right putamen (p=0.02).

The results of this longitudinal analysis suggest a different temporal involvement of hippocampal and subcortical structures in the course of ALS, with an early involvement of hippocampi and thalami followed by a subsequent progression of damage to the basal ganglia. Our study highlights the importance of evaluating subcortical structural alterations for a more comprehensive pathophysiological understanding of ALS and supports the use of MRI volumetric measures for tracking disease progression.