Temporal Change: Evaluation of Brain Atrophy in Patients with Radiologically Isolated Syndrome Using volBrain

Background and Objective: Radiologically isolated syndrome (RIS) is characterized by magnetic resonance imaging (MRI) findings suggestive of multiple sclerosis (MS) in individuals without a history of clinical demyelinating events. Increasing evidence indicates that structural brain abnormalities may be present in RIS before the development of overt neurological symptoms. However, most previous studies have employed cross-sectional designs, limiting the ability to characterize the temporal evolution of neurodegenerative changes. This study aimed to investigate longitudinal changes in global, regional, and lobar brain volumes in individuals with RIS using serial MRI examinations obtained at least six months apart. Methods: Patients with RIS who had undergone two 3 Tesla (3T) brain MRI examinations separated by an interval of at least six months were retrospectively identified. Three-dimensional (3D) T1-weighted MRI scans obtained at both time points were analyzed using the volBrain pipeline of the volBrain platform to quantify global, regional, and lobar brain volumes. Longitudinal volumetric changes were expressed as annualized percentage volume changes. The number of T2 lesions and total T2 lesion volume were additionally assessed, and their associations with longitudinal brain volume changes were investigated. Results: A total of 28 patients with RIS were included. After correction for multiple comparisons using the Benjamini-Hochberg false discovery rate (FDR) procedure, significant annual volume loss was observed in total brain volume (p = 0.043), total cerebrum volume (p = 0.033), right cerebrum volume (p = 0.033), left cerebrum volume (p = 0.044), total thalamic volume (p = 0.033), right thalamic volume (p = 0.047), and left thalamic volume (p = 0.043). No significant associations were observed between annualized brain volume changes and follow-up duration, total or regional T2 lesion counts, or total T2 lesion volume. Similarly, annualized brain volume changes did not differ significantly between subgroups defined according to MRI progression, the presence of gadolinium-enhancing lesions, or the presence of spinal cord lesions. Conclusions: Longitudinal volumetric analysis demonstrated progressive brain volume loss involving both global and regional structures in patients with RIS. These findings provide further evidence of measurable longitudinal structural brain changes in RIS before the development of clinically overt demyelinating disease. Larger longitudinal studies incorporating appropriate control groups are warranted to further characterize the temporal trajectory of volumetric changes in RIS.