Imaging the hidden player: Choroid plexus enlargement in multiple sclerosis

The choroid plexus (CP), one key regulator of cerebrospinal fluid (CSF) production and immune surveillance at the blood-CSF barrier, has recently emerged as a relevant structure in multiple sclerosis (MS) pathophysiology. This review synthesizes current evidence highlighting CP enlargement as measured with magnetic resonance imaging (MRI) as a potential biomarker of neuroinflammation and neurodegeneration in MS. We first outline the basic immunological roles of the CP, emphasizing its function as a dynamic interface facilitating immune cell trafficking and cytokine production within the CNS. Advances in MRI and PET (positron emission tomography) imaging have enabled the quantification of CP volume, revealing enlargement across different MS stages, including radiologically isolated syndrome and pediatric MS. CP volume correlates with lesion load, chronic lesion expansion, microglial activation, and inflammatory CSF profiles, suggesting its responsiveness to neuroinflammatory activity. Notably, CP enlargement is also associated with neurodegenerative processes, including gray matter atrophy, cognitive decline, and disability progression, indicating its potential role also as a surrogate marker of MS-related neurodegeneration. However, methodological variability, confounding factors and a lack of longitudinal standardization challenge the interpretation of CP metrics. We highlight the need for multimodal approaches to unravel the temporal and mechanistic significance of CP enlargement. Future research should also explore CP-targeted interventions and their relevance for MS progression. Overall, CP imaging, in particular its enlargement, offers a novel, biologically meaningful perspective into MS pathogenesis, bridging inflammatory and degenerative pathways, and holds promise for improved disease monitoring.