Longitudinal Progression of Subcortical Structural Damage in Amyotrophic Lateral Sclerosis
Edoardo Spinelli1, Alma Ghirelli1, Silvia Basaia3, Elisa Canu3, Veronica Castelnovo3, Tommaso Russo4, Paride Schito4, Yuri Falzone4, Massimo Filippi2, Federica Agosta1
1Neuroimaging Research Unit, Division of Neuroscience; and Neurology Unit, 2Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit; Neurorehabilitation Unit; and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; and Vita-Salute San Raffaele University, 3Neuroimaging Research Unit, Division of Neuroscience, 4Neurology Unit, IRCCS San Raffaele Scientific Institute
Objective:
Our specific aim was to explore the longitudinal evolution of structural damage to subcortical and hippocampal structures in a cohort of incident amyotrophic lateral sclerosis (ALS) patients.
Background:
Converging evidence suggests an early involvement of subcortical structures in the course of neuropathological progression underlying the development of ALS. However, the longitudinal evolution of such damage along the clinical progression of the disease still needs to be clarified.
Design/Methods:

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.

Results:

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).

Conclusions:

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.

10.1212/WNL.0000000000205441