Quantitative MRI Volumetry as a Potential Neuroimaging Biomarker in Levetiracetam-Treated Epilepsy

Background/Objectives: Quantitative magnetic resonance imaging (MRI) volumetry may provide an objective approach for detecting subtle longitudinal structural brain changes in patients with epilepsy. This retrospective longitudinal study investigated regional and global brain volume changes observed during levetiracetam (LEV) monotherapy. Methods: Thirty-seven adults with epilepsy who underwent brain MRI before initiation of LEV monotherapy (MRI-1) and approximately 12 months later (MRI-2) were included. Automated volumetric segmentation was performed using volBrain, and within-subject changes in macrostructural, subcortical, and cortical volumes were evaluated. Results: No significant longitudinal changes were detected in global macrostructural measures, including white matter, gray matter, cerebrospinal fluid, total intracranial cavity, cerebral, cerebellar, brainstem, or ventricular volumes (all p > 0.05). In contrast, significant volume reductions were observed in the bilateral putamen, caudate nuclei, and thalami, as well as the left nucleus accumbens, bilateral insular cortex, and left occipital cortex (p < 0.05), whereas the right globus pallidus volume increased significantly. Conclusions: These findings demonstrate region-specific longitudinal volumetric changes during LEV monotherapy despite preserved global brain volumes. However, because this study lacked a longitudinal healthy control group, the observed changes cannot be definitively attributed to LEV and may also reflect epilepsy-related processes, normal aging, or other clinical factors. Automated MRI volumetry may represent a promising quantitative approach for longitudinal assessment, but its potential biomarker utility requires validation in larger prospective studies incorporating protocol-harmonized healthy controls and detailed clinical and treatment-exposure measures.