To evaluate changes in choroid plexus (ChP) volume over time in a large cohort of patients with radiologically isolated syndrome (RIS) and the relationship to other brain volumes as well as disease activity measured by imaging or clinical events, and serum biomarkers. We also explore the potential effects of disease-modifying treatment (DMT) on the ChP volume (ChPv) annually over three years.

ChP enlargement is an emerging radiological marker in multiple sclerosis (MS) and has been associated with greater disease activity.

Data from RIS individuals were collected from two randomized trials (the TERIS and ARISE studies). The imaging protocol was standardized using 3DT2-FLAIR and pre- and post-contrast 3DT1 isotropic images. The ChP was automatically segmented and volumes determined using an in-house automated algorithm. The number of new gadolinium-enhancing or T2 lesions was quantified annually. Serum biological markers were assessed using standardized procedures according to the manufacturer instructions.

A total of 176 individuals meeting 2009 RIS criteria were included with 44 treated with dimethyl-fumarate, 44 with teriflunomide, and 44 not exposed to DMT. An longitudinal increase in ChPv was observed in untreated subjects. ChPv correlated with T2 lesion load at baseline (ρ=0.26;r²=0.036;p<0.001) and at two years (ρ=0.43;r²=0.128;p=0.001), serum neurofilament light chain (ρ=0.41;r²=0.077;p=0.031) and glial fibrillary acidic protein (ρ=0.44;r²=0.178;p=0.02) biomarkers, although no association was observed with gadolinium-enhancing lesions or dissemination in time. A delayed DMT effect was noted in treated patients, with a significant reduction in ChPv at 3 years. The mean ChPv (×10^-3mm³) was 0.3(SD=0.08) in untreated patients and 0.25(SD=0.1) in treated patients, respectively (p=0.006). No difference was found between patients who did or did not experience a clinical event over time.

These results suggest that ChP might reflect chronic, silent inflammation in the presymptomatic stage of MS without possessing standalone predictive clinical significance, and DMT exposure appears to modulate this inflammation.