Interthalamic adhesion alterations in multiple sclerosis: associations with thalamic damage and cognition

Abstract Background / Objectives We investigated whether the interthalamic adhesion (IA), a midline structure connecting the thalami, is altered in MS and associated with thalamic damages and cognition. Methods We prospectively included 32 clinically isolated syndrome/early MS, 31 RRMS, 31 PPMS patients, and 103 matched controls. All underwent anatomical 3T MRI and completed a comprehensive cognitive battery. IA presence, subtype, and volume were assessed by two blinded readers. Thalamic nuclei and other brain structures were segmented automatically. We compared IA subtypes/volumes across groups, analyzed their predictors and explored cognitive associations with multivariate regressions. Results IA prevalence did not differ between MS and controls (81.9% vs 74.7%). MS patients showed a shift toward a short IA subtype and reduced IA volume (mean [SD], 146.8 [117.9] vs 230.2 [138.2] mm³; p<0.0001), worsening across phenotypes. Reduced IA volume was independently associated with medial and posterior thalamic nuclei volumes, but not with white matter lesion load or global atrophy. Among cognitive domains, smaller IA volume was independently associated only with executive dysfunction (OR = 0.89 [0.77–0.99], p = 0.021). Conclusion IA volume reduction in MS reflects vulnerability of adjacent thalamic nuclei and is associated with executive dysfunction, supporting IA as a marker of thalamic neurodegeneration. Trial Registration MICROSEP: NCT03692975 ; AUBACOG: NCT03768648 ; PROCOG: NCT03455582 .