Association Between Disability and Longitudinal Brain Volumetric Measures Across the Peri-Pregnancy Period in Women with Multiple Sclerosis: A Pilot Study

Background: Pregnancy is a distinct neuroendocrine and immunological state in women with multiple sclerosis (MS). Relapse activity typically decreases during gestation and increases after delivery, but the relationship between peri-pregnancy brain volumetric measures and disability remains unclear. Methods: This retrospective longitudinal pilot study included 14 women with relapsing-remitting MS who underwent MRI examinations before pregnancy and after delivery. Thirty-eight MRI scans were analyzed, with a mean of 2.71 timepoints per patient (SD 0.99). Global and regional brain volumes were measured using the longitudinal FreeSurfer pipeline. Choroid plexus (CP) volume was evaluated as an exploratory neuroimmune imaging marker. Associations between volumetric measures and Expanded Disability Status Scale (EDSS) scores were assessed using linear mixed-effects modeling with forward stepwise selection. Results: The final EDSS model retained bilateral ventral diencephalon (ventral DC) volumes, left amygdala volume, right pallidum volume, left nucleus accumbens volume, and cerebral cortex volume. The most prominent association involved the left ventral DC, where lower volume was associated with higher EDSS scores (p = 0.0008). CP volume showed no significant longitudinal change across peri-pregnancy MRI timepoints (p = 0.21) and was not retained in the final EDSS model. Conclusion: Regional brain volumetric measures, particularly ventral DC volumes, were associated with disability across the peri-pregnancy period despite low EDSS levels. To our knowledge, this is the first longitudinal evaluation of CP volume across the peri-pregnancy period in women with MS; no significant change was observed over time. These exploratory findings require confirmation in larger prospective studies using standardized serial MRI protocols.