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

Abstract

BACKGROUND AND PURPOSE: In multiple sclerosis, the choroid plexus is thought to promote and sustain the disease immunopathologic inflammatory process. However, its association with cortical pathology and disease progression is still uncertain. We aimed to characterize choroid plexus enlargement and evolution in MS and its relationship with imaging markers of compartmentalized inflammation and clinical outcome. MATERIALS AND METHODS: One hundred patients with MS (74 relapsing-remitting [RRMS]; 26 secondary-progressive MS [SPMS] and 41 matched healthy controls (HC) underwent 3T MRI to measure brain volumes and 7T MRI for cortical and WM lesions, including paramagnetic rim lesion (PRL) segmentation. Choroid plexus volumes of the lateral ventricles were manually edited from FreeSurfer segmentation by 1 neurologist and normalized by total intracranial volume to estimate the choroid plexus ratio (CPR). The 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 versus SPMS) and progression independent of relapse activity. RESULTS: Relative to HC, CPR was higher in patients (11.66 [3.21] versus 14.98 [4.37] × 10-4, P ¼ .001), both in RRMS and SPMS (P ¼ .007, P ¼ .003), and there was a mean ~4% increase per year in CPR at follow-up, though it was not significant[ (P ¼ .14). Choroid plexus enlargement correlated with greater PRL and cortical lesion volumes (r ¼ 0.35, P, .001). CPR did not discriminate MS phenotype but predicted progression independent of relapse activity alongside CSF 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], and specificity of 0.52 [0.22]). CONCLUSIONS: In MS, a CPR increase relates to imaging markers of compartmentalized disease activity including cortical lesions and PRLs and is a critical predictor of disease progression. Our findings could provide the rationale for implementing CPR estimation for prognosis prediction in MS.