Abstract
INTRODUCTION: Concern of falling (CoF) affects approximately 50-60% of people with MS (pwMS) and is associated with physical and cognitive deficits. Despite its functional impact, CoF's neuroanatomical correlates in pwMS are poorly understood. OBJECTIVES: Using structural MRI, we investigated associations between subcortical brain volumes and CoF in a large pwMS cohort. METHODS: This study involved 407 pwMS that were divided into three groups based on their CoF, as assessed by the Falls Efficacy Scale-International (FES-I). Volumetric MRI analysis was performed using FreeSurfer to assess subcortical brain structures, including the basal ganglia, hippocampus, and corpus callosum. Analyses were adjusted for age, sex, intracranial volume, scanner type, and magnetic field strength. RESULTS: Significant differences in brain volume were found between groups with low, moderate, and high CoF. PwMS with high CoF exhibited reduced volumes in the pallidum, putamen, and corpus callosum compared to those with low CoF (p < 0.05). Regression analysis revealed that subcortical volume reductions, particularly in the basal ganglia, were significantly associated with higher CoF scores, even after controlling for disability. CONCLUSIONS: CoF in pwMS is associated with structural brain changes in areas related to motor control and emotional regulation. This may indicate that CoF reflects both psychological and neuroanatomical factors.