Association between corpus callosum microstructure and upper limb motor outcome in moderate-to-severe ischemic stroke patients at 3–6 months post-stroke

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Abstract
Background: Corticospinal tract (CST) integrity is a well-established imaging correlate of post-stroke motor outcome but does not fully explain interindividual variability, particularly in moderate-to-severe impairment. The corpus callosum (CC) may provide complementary structural information. This study examined whether early subacute callosal microstructure is associated with upper limb motor outcome and recovery. Methods: We retrospectively analyzed 38 patients with moderate-to-severe middle cerebral artery stroke who underwent diffusion tensor imaging during the early subacute phase. Fractional anisotropy (FA) values of the CST and CC were obtained. Upper limb motor function was assessed using the Shoulder Abduction and Finger Extension (SAFE) score. Simple linear regression and hierarchical multiple linear regression analyses examined associations of corrected CC FA (CC-FA ~ corrected~) with SAFE scores and ΔSAFE (change in SAFE score from baseline to 6 months). Results: CST FA laterality index (CST FALI), lesion volume, and CC-FA ~ corrected~ were significantly associated with SAFE scores at 3 and 6 months post-stroke. In hierarchical multiple regression models, CC-FA ~ corrected~ of the genu showed a consistent nominal incremental contribution beyond CST FALI, age, and lesion volume at both timepoints (3 months: ΔR 2 = 0.061, adjusted R 2 = 0.600; 6 months: ΔR 2 = 0.065, adjusted R 2 = 0.646), though these findings require confirmation in larger prospective cohorts. The body and splenium did not reach statistical significance after accounting for these covariates. In exploratory analysis, CC-FA ~ corrected~ of the genu was the only variable significantly associated with ΔSAFE (R = 0.396, p = 0.041); CST FALI was not ( p = 0.097). Conclusion: CC-FA ~ corrected~ of the genu showed a consistent nominal association with upper limb motor outcome beyond CST integrity in moderate-to-severe stroke, suggesting a complementary role of callosal microstructure alongside CST integrity, with an exploratory association also observed for the magnitude of motor improvement over time. Early combined assessment of CC and CST integrity during the subacute phase may provide preliminary information regarding post-stroke motor outcomes.

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