title: Basal ganglia involvement in amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  To characterize the nature and extent of basal ganglia involvement in amyotrophic lateral sclerosis (ALS) genotypes in vivo.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the Biomedical Sciences Institute (P.B., M.E., S.B., A.V., O.H.), and Smurfit Institute of Genetics (R.L.M., K.K., D.G.B.), Trinity College Dublin; and Department of Neuropsychology (N.P.), Beaumont Hospital, Dublin, Ireland.
authors.forename: Peter
authors.initials: P
authors.lastname: Bede
authors.forename: Marwa
authors.initials: M
authors.lastname: Elamin
authors.forename: Susan
authors.initials: S
authors.lastname: Byrne
authors.forename: Russell L
authors.initials: RL
authors.lastname: McLaughlin
authors.forename: Kevin
authors.initials: K
authors.lastname: Kenna
authors.forename: Alice
authors.initials: A
authors.lastname: Vajda
authors.forename: Niall
authors.initials: N
authors.lastname: Pender
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bradley
authors.forename: Orla
authors.initials: O
authors.lastname: Hardiman
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D001479:Basal Ganglia / Q000473:pathology*; D000073885:C9orf72 Protein; D015331:Cohort Studies; D042622:DNA Repeat Expansion / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D011506:Proteins / Q000235:genetics*; D012042:Registries
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins