Brainstem and cerebellar volume changes in multiple sclerosis: associations with clinical disability and disease duration using 3T MRI

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease characterized by progressive neurodegeneration and brain atrophy. To evaluate brainstem and cerebellar volumetric changes in patients with relapsing-remitting multiple sclerosis (RRMS) using 3T MRI and to investigate their relationship with disease duration, lesion burden, and neurological disability. This cross-sectional case-control study included 26 RRMS patients and 26 age- and sex-matched healthy controls. Automated volumetric analysis was performed using the volBrain platform. Brainstem and cerebellar volumes were assessed. Disability was evaluated using the Expanded Disability Status Scale (EDSS). RRMS patients demonstrated significantly reduced total brainstem volume and normalized brainstem volume percentage compared with controls (p = 0.016 and p = 0.01, respectively). Normalized total cerebellar volume and normalized left cerebellar volume were significantly lower in patients (p = 0.043 and p = 0.02, respectively), whereas absolute cerebellar volumes showed no significant differences. Cerebellar gray matter volumes demonstrated strong negative correlations with disease duration (r ranging from −  0.53 to − 0.63, p ≤ 0.005). Cerebellar white matter volumes were negatively associated with lesion load (r = − 0.42 to − 0.59, p ≤ 0.035) and EDSS scores (r = − 0.44 to − 0.54, p ≤ 0.026). Receiver Operating Characteristic (ROC) analysis revealed moderate discriminatory performance for brainstem volume (Area Under the Curve (AUC) = 0.694), brainstem volume percentage (AUC = 0.706), normalized cerebellar volume (AUC = 0.691), and cerebellar gray matter percentage measures (AUC = 0.660–0.689). Infratentorial volumetric abnormalities are evident in RRMS, with cerebellar measurements demonstrating stronger associations with disease duration, lesion burden, and disability than brainstem measurements. Cerebellar volumetry, particularly normalized gray matter metrics, may represent a sensitive imaging biomarker of disease burden and progression in MS.