Mapping the path to degeneration: How lesion location predicts post-stroke cerebellar atrophy

Stroke can lead to neurological changes beyond the initial lesion site, including post-stroke crossed-cerebellar degeneration. While traditional methods typically rely on total lesion volume to assess remote effects, the spatial distribution of lesions may more accurately predict cerebellar atrophy and associated functional deficits. This study investigated whether anatomically specific cortical lesions contribute to cerebellar gray matter volume loss, expanding on the hypothesis that cerebellar atrophy may reflect more than global brain injury severity, and instead result from targeted disruption of cortico-cerebellar pathways.

Data from 142 chronic left hemisphere stroke participants (57 females, 85 males; M = 61 years) were analyzed using voxel-based lesion-symptom mapping (VLSM) and region of interest (ROI) analyses. High-resolution structural MRI scans were processed to quantify cerebellar gray matter volume (GMV) across 28 spatially distinct regions, with lesions manually delineated and mapped.

Significant associations were found between lesion load in specific white matter tracts and cerebellar GMV atrophy. Lesions in the posterior limb of the internal capsule, retrolenticular part of the internal capsule, fornix/stria terminalis and superior corona radiata were strongly linked to GMV reductions in right cerebellar lobules and vermis. Notably, cortical lesions primarily impacted the right cerebellar regions, supporting the concept of post-stroke crossed cerebellar diaschisis. In a complementary analysis, voxel-based lesion-symptom mapping using Apraxia of Speech (AOS) severity scores revealed overlapping lesion predictors with those driving cerebellar degeneration, particularly within the superior corona radiata and retrolenticular part of the internal capsule. This overlap suggests that damage to these tracts may contribute jointly to speech-motor impairment and remote cerebellar atrophy.

The spatial distribution of cortical lesions, rather than total lesion volume, plays a crucial role in predicting cerebellar degeneration. These findings suggest the importance of considering lesion location in stroke rehabilitation, and provide further insights into the functional connections between the cerebrum and cerebellum.