Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis

TLDR

ALS is characterized by corticospinal tract and lower motor neuron degeneration, yet clinical involvement of these compartments varies and the onset site is debated. The study aimed to determine whether a consistent cerebral white‑matter abnormality signature exists in heterogeneous ALS cases. Using diffusion tensor imaging and tract‑based spatial statistics on 24 ALS patients and matched controls, the authors performed whole‑brain analysis and voxel‑based morphometry to assess white‑ and gray‑matter changes. The analysis revealed a consistent reduction in fractional anisotropy and increased radial diffusivity in the corpus callosum, along with gray‑matter loss in motor, supplementary motor, anterior cingulate, and temporal regions; a post‑hoc model achieved 92 % sensitivity, 88 % specificity, and 90 % accuracy, indicating callosal involvement is a consistent ALS feature independent of clinical upper‑motor‑neuron signs and suggesting interhemispheric spread of pathology.

Abstract

While the hallmark of amyotrophic lateral sclerosis (ALS) is corticospinal tract in combination with lower motor neuron degeneration, the clinical involvement of both compartments is characteristically variable and the site of onset debated. We sought to establish whether there is a consistent signature of cerebral white matter abnormalities in heterogeneous ALS cases.In this observational study, diffusion tensor imaging was applied in a whole-brain analysis of 24 heterogeneous patients with ALS and well-matched healthy controls. Tract-based spatial statistics were used, with optimized voxel-based morphometry of T1 images to determine any associated gray matter involvement.A consistent reduction in fractional anisotropy was demonstrated in the corpus callosum of the ALS group, extending rostrally and bilaterally to the region of the primary motor cortices, independent of the degree of clinical upper motor neuron involvement. Matched regional radial diffusivity increase supported the concept of anterograde degeneration of callosal fibers observed pathologically. Gray matter reductions were observed bilaterally in primary motor and supplementary motor regions, and also in the anterior cingulate and temporal lobe regions. A post hoc group comparison model incorporating significant values for fractional anisotropy, radial diffusivity, and gray matter was 92% sensitive, 88% specific, with an accuracy of 90%.Callosal involvement is a consistent feature of ALS, independent of clinical upper motor neuron involvement, and may reflect independent bilateral cortical involvement or interhemispheric spread of pathology. The predominantly rostral corticospinal tract involvement further supports the concept of independent cortical degeneration even in those patients with ALS with predominantly lower motor neuron involvement clinically.