Regional callosal integrity and bilaterality of limb weakness in amyotrophic lateral sclerosis

Background and Objectives: The corpus callosum is a site of pathological involvement in the neurodegenerative disorder amyotrophic lateral sclerosis (ALS). The corpus callosum shows widespread cortical connectivity topographically distributed along its length. Initial limb weakness in ALS is typically unilateral, becoming bilateral with disease progression. The precise anatomical substrate for this spread is uncertain. The present study investigated sub-regional variations in corpus callosum integrity in ALS, and whether these reflect a relationship with the development of unilateral or bilateral limb weakness. Methods: Sporadic ALS patients were categorized into unilateral (n = 14) or bilateral (n = 25) limb weakness at the time of assessment and underwent diffusion tensor imaging. Probabilistic bundle-specific tracking was carried out using MRtrix and TractSeg to parcellate the corpus callosum into seven anatomical segments (rostrum; genu; rostral body; anterior midbody; posterior midbody; isthmus; splenium). White matter tract integrity was assessed in all segments and compared with MRI data acquired from 25 healthy controls. Results: In the combined patient group, the most prominent differences in diffusivity metrics were in the rostral body, posterior midbody and isthmus of the corpus callosum (p < 0.04). Loss of corpus callosum integrity was most prominent in the sub-group with unilateral limb weakness at the time of scanning (p < 0.05). Conclusions: Corpus callosum involvement in ALS is detectable across multiple segments, in keeping with a widespread cortical distribution of pathology. The association of unilateral limb weakness with greater loss of corpus callosum integrity informs connectivity-based hypotheses of symptom propagation in ALS.