Choroid plexus enlargement correlates with demyelinating lesions and thalamic atrophy in radiologically isolated syndrome

Background: Choroid plexus (ChP) enlargement correlates with neuroinflammation, brain atrophy, and disability in multiple sclerosis (MS); its relevance in people with radiologically isolated syndrome (pwRIS) is unclear. Objective: To investigate ChP volume (ChPvol) differences across age-/sex-matched pwRIS, people with MS (pwMS), and healthy controls (HCs), and to examine associations between ChPvol, brain volumetric measures, and development of clinically definite MS (CDMS). Methods: 3 Tesla magnetic resonance imagings (3T-MRIs) from 59 pwRIS, 59 pwMS, and 59 HCs were analyzed. ChPvol, white matter lesion volume (WMLvol), central vein sign (CVS), paramagnetic rim lesions (PRLs), and brain volumes were assessed. pwRIS were prospectively monitored for CDMS. Results: ChPvol was larger in pwRIS ( p < 0.0001) and pwMS ( p = 0.042) compared to HCs. Multivariable regression showed that higher ChPvol (odds ratio (OR) = 7.21, 95% confidence interval (CI) = 1.44–36.03, p = 0.016) and lower thalamic volume (OR = 0.23, 95% CI = 0.10–0.52, p < 0.001) independently distinguished RIS from HCs. In pwRIS, ChP enlargement correlated with higher WMLvol ( r s = 0.495, p < 0.0001), higher proportion of CVS-positive lesions ( r s = 0.28, p = 0.042), and lower thalamic volume ( r s = −0.451, p < 0.0001). Of 35 pwRIS with longitudinal follow-up, 10 (28.6%) developed CDMS; however, baseline ChPvol did not differ between those who developed CDMS and those who did not ( p = 0.77). Conclusions: ChP enlargement is evident at the earliest stage of MS, is associated with demyelination and neurodegeneration, highlighting ChP volume as a potential diagnostic biomarker. Although baseline ChPvol alone did not predict progression to CDMS, its similarity in RIS and MS cohorts supports the forthcoming 2024 revised McDonald criteria suggesting that RIS can be considered MS in specific situations.