Motor and extra-motor gray matter atrophy in amyotrophic lateral sclerosis: quantitative meta-analyses of voxel-based morphometry studies

Considerable evidence from previous voxel-based morphometry studies indicates widespread but heterogeneous gray matter (GM) deficits in amyotrophic lateral sclerosis (ALS). Here, we aimed to investigate the concurrence across voxel-based morphometry studies to help clarify the spatial pattern of GM abnormalities that underlie this condition. Comprehensive meta-analyses to assess regional GM anomalies in ALS were conducted with the Anisotropic Effect Size version of Signed Differential Mapping software package. Twenty studies, which reported 22 comparisons and were composed of 454 ALS patients and 426 healthy controls, were included in the meta-analyses. Regional GM atrophy in ALS was consistently found in the frontal, temporal, and somatosensory areas. Meta-regression demonstrated that the disease duration, disease severity, and age were significantly related to GM deficits in ALS patients. The present meta-analysis provides convergent evidence that ALS is a multisystem degenerative disorder that is accompanied by a unique and widespread pattern of robust cortical GM atrophy. Future studies should investigate whether this atrophy pattern is a diagnostic and prognostic marker.