Corpus callosum indices are correlated with disability and cognitive performance in patients with multiple sclerosis: A systematic review and meta-analysis.

Corpus callosum (CC) is a key biomarker in multiple sclerosis (MS), with indices such as CC volume (CCV) and CC area (CCA) being correlated with disability and cognitive performance. However, discrepancies remain in the comparative associations of these indices and among MS phenotypes. A systematic search identified studies on MS patients, where CC size or volume measures were correlated with clinical outcomes, including Expanded Disability Status Scale (EDSS), Symbol Digit Modalities Test (SDMT), or Paced Auditory Serial Addition Test. The relationship between a CC index and a clinical outcome, where the correlation coefficient was reported in three or more studies, was synthesized using random-effects models. Risk of bias, reporting bias and certainty of analyses were evaluated. Subgroup analyses and meta-regression explored the heterogeneity. According to 35 included studies, among overall MS population, normalized CCV (nCCV) and CCA (nCCA) were the strongest correlates of EDSS (r = -0.383) and SDMT (r = 0.600), respectively, when controlling for demographic characteristics using partial correlation. Correlation of nCCA with EDSS was modulated by age (R^2 = 0.42), while it was absent in the study that included only relapsing-remitting MS (RRMS). In RRMS patients, significant association was observed between nCCV and EDSS (r = -0.429). Association between nCCV and SDMT (r = 0.226) was strengthened with increased disease duration (R^2 = 0.57) and in primary progressive MS patients (R^2 = 0.23). CCV reflects progression of disability in RRMS, whereas in progressive MS CCV marks cognitive decline and CCA could reflect the disability. This emphasizes the potential of CC indices to monitor the disease impact.