White matter tracts involved in complex regional pain syndrome after subcortical stroke

Post-stroke complex regional pain syndrome (CRPS) is a challenging complication that impairs recovery during stroke rehabilitation, particularly during the subacute phase. Despite its clinical significance, the neural substrates underlying post-stroke CRPS, specifically following subcortical stroke, remain unclear. This retrospective observational study included 40 patients with first-ever subcortical stroke diagnosed with CRPS via a three-phase bone scan, and 40 propensity score-matched controls without CRPS. White matter tract involvement was analyzed using atlas-based lesion mapping and voxel-based lesion overlap analysis in patients with available clinical scores and imaging findings (magnetic resonance imaging or computed tomography). Between-group comparisons of white matter tract involvement were conducted with false discovery rate (FDR) correction. Clinical characteristics were similar between groups, except for fewer CRPS patients with a shoulder flexor manual muscle test score ≥3. Lesion overlap with the cingulum in the cingulate gyrus was significantly greater in the CRPS group (<i>F</i> = 5.197, FDR-adjusted <i>p</i> = 0.040). Although the forceps minor showed marginal significance before correction, it was non-significant after adjustment. These findings raise the possibility that the cingulate cortex, particularly the cingulum, may contribute to post-stroke CRPS pathophysiology. However, further confirmation in larger prospective studies is needed.