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

BACKGROUND/OBJECTIVES: We investigated whether the interthalamic adhesion (IA), a midline structure connecting the thalami, is altered in multiple sclerosis (MS) and associated with thalamic damages and cognition. METHODS: We prospectively included 32 clinically isolated syndrome/early MS, 31 relapsing-remitting MS, 31 primary-progressive MS patients, and 103 matched controls. All underwent anatomical 3 T 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. A deep-learning-based IA segmentation tool was also developed and externally validated on 30 new patients. 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). The automated IA segmentation tool showed good agreement with manual delineation (median Dice coefficient 0.64; volume correlation r = 0.89). 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. The automated IA segmentation tool will enable future larger scale and longitudinal investigations. TRIAL REGISTRATION: MICROSEP: NCT03692975; AUBACOG: NCT03768648; PROCOG: NCT03455582.