Choroid Plexus Enlargement in Multiple Sclerosis Correlates with Cortical and Phase Rim lesions on 7-T MRI and Predicts Progression Independent of Relapse Activity.

Abstract

Background and purpose: In multiple sclerosis (MS), the choroid plexus is thought to promote and sustain the disease immunopathological inflammatory process. However, its association with cortical pathology and disease progression is still uncertain. We aim to characterize choroid plexus enlargement and evolution in MS, its relationship with imaging markers of compartmentalized inflammation and clinical outcome.

Materials and methods: One-hundred MS patients (74 relapsing-remitting, 26 secondary progressive, RRMS, SPMS) and 41 matched healthy controls (HC) underwent 3-T MRI to measure brain volumes and 7-T MRI for cortical and WM lesions, including paramagnetic rim lesions (PRL), segmentation. Choroid plexus volumes of the lateral ventricles were manually edited from FreeSurfer segmentation by one neurologist and normalized by total intracranial volume to estimate choroid plexus ratio (CPR). Expanded Disability Status Scale was assessed at baseline and longitudinally in 71 patients, 43 of whom had a follow-up MRI at 1.5 years. An extreme gradient boosting algorithm estimated the importance of CPR, alongside other imaging markers, in predicting disease phenotype (RRMS vs SPMS) and Progression Independent of Relapse Activity (PIRA).

Results: Relative to HC, CPR was higher in patients (11.66 (3.21) vs 14.98 (4.37) x 10^-4, p=0.001), both in RRMS and SPMS (p=0.007, p=0.003), and there was mean ∼4% increase per year in CPR at follow-up, though not significant (p=0.14). Choroid plexus enlargement correlated with greater PRL and cortical lesion volumes (r=0.35, p<0.001). CPR did not discriminate MS phenotype but predicted PIRA alongside cerebrospinal fluid subarachnoid space volume, PRL and cortical lesion volumes (median (median absolute deviation) area under the curve 0.71 (0.12), accuracy 0.74 (0.10), sensitivity 0.81 (0.12), specificity of 0.52 (0.22)).

Conclusions: In MS, CPR increase relates to imaging markers of compartmentalized disease activity including cortical lesions and PRL and is a critical predictor of disease progression. Our findings could provide the rationale for implementing CPR estimation for prognosis prediction in MS.

Abbreviations: MS, multiple sclerosis, HC, healthy controls, PRL, paramagnetic rim lesions, CPR, choroid plexus ratio, PIRA, progression independent of relapse activity, RRMS, relapsing-remitting MS, SPMS, secondary progressive MS, XGBoost, extreme gradient boosting, EDSS, Expanded Disability Status Scale, CDP, confirmed disability progression.