Whole-brain and regional brain atrophy in amyotrophic lateral sclerosis

BACKGROUND AND PURPOSE: Recent evidence from neuropsychologic and neuroimaging studies suggests that central nervous system involvement in amyotrophic lateral sclerosis (ALS) extends beyond motor neurons. Our purpose was to obtain measures of global and regional atrophy in nondemented patients with ALS to assess subtle structural brain changes. METHODS: MR images, acquired from 16 patients and 9 healthy subjects (HS), were processed by using the Structural Imaging Evaluation of Normalized Atrophy (SIENA) software to estimate wholebrain atrophy measures and the voxel-based morphometry (VBM) method to highlight the selective volumetric decrease of single cerebral areas. In addition, each subject underwent a neuropsychologic examination. RESULTS: In patients with ALS, brain parenchymal fraction was slightly lower compared with HS (P = .012), and seemed to be related to the presence of cognitive impairment. Patients showed a gray matter volume decrease in several frontal and temporal areas bilaterally (P < .001 uncorrected) compared with HS, with a slight prevalence in the right hemisphere. No volume reduction in primary motor cortices of patients was detected. Performances on Symbol Digit Modalities Test were significantly worse in patients compared with HS (P = .025). CONCLUSIONS: The presence of mild whole-brain volume loss and regional frontotemporal atrophy in patients with ALS could explain the presence of cognitive impairment and confirms the idea of ALS as a degenerative brain disease not confined to motor system.