To characterize the nature and extent of basal ganglia involvement in amyotrophic lateral sclerosis (ALS) genotypes in vivo. Forty-four healthy controls and 39 patients with ALS were included in the study. Thirty patients with ALS had a negative C9orf72 status and 9 patients with ALS carried the C9orf72 hexanucleotide repeat expansion. High-resolution T1-weighted MRI data were used for model-based subcortical registration and segmentation. Fifteen subcortical structures were studied with both volumetric and vertex-wise approaches. Changes in basal ganglia diffusivity parameters were also assessed. Using age as a covariate, patients with ALS who were C9orf72 repeat negative showed significant volume reductions in the left caudate nucleus (p = 0.01), left hippocampus (p = 0.007), and right accumbens nucleus (p = 0.001) compared with healthy controls. Vertex-wise shape analyses revealed changes affecting the superior and inferior aspects of the bilateral thalami, the lateral and inferior portion of the left hippocampus, and the medial and superior aspect of the left caudate. Basal ganglia pathology was more extensive in patients with ALS carrying the C9orf72 hexanucleotide repeat expansion. ALS is associated with widespread basal ganglia involvement. Caudate nucleus, hippocampus, and nucleus accumbens atrophy are key features of ALS. Dysfunction of frontostriatal networks is likely to contribute to the unique neuropsychological profile of ALS, dominated by executive dysfunction, apathy, and deficits in social cognition. Our quantitative imaging findings are consistent with postmortem studies and indicate that subcortical gray matter structures should be included in future biomarker studies of ALS.
Trinity College Dublin ->