Choroid Plexus Enlargement in Pediatric Multiple Sclerosis: Clinical Relevance and Effect of Sex
Monica Margoni1, Mor Gueye1, Alessandro Meani2, Elisabetta Pagani2, Lucia Moiola3, Paolo Preziosa4, Massimo Filippi5, Maria Rocca4
1Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, 2Neuroimaging Research Unit, Division of Neuroscience, 3Neurology Unit, IRCCS San Raffaele Scientific Institute, 4Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, 5Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; Vita-salute San Raffaele University
Objective:
We investigated choroid plexus (CP) volume in pediatric multiple sclerosis (MS) patients compared to matched healthy controls (HC), possible sex-related effect, and the associations with clinical and structural MRI variables.
Background:
CP enlargement has been suggested as a reliable marker of neuroinflammation in adult MS patients, correlating with measures of brain structural damage and clinical disability. The presence and clinical relevance of CP enlargement in pediatric MS patients has not been evaluated yet.
Design/Methods:
Brain 3.0 T dual-echo and 3D T1-weighted sequences were identified retrospectively from 69 pediatric MS patients and 23 age- and sex-matched HC. CP volume was manually obtained from 3D T1-weighted scans by two expert raters.
Results:
CP segmentation was highly reproducible (intra-observer agreement: rater I=0.963, rater II=0.958; inter-observer agreement=0.968). Compared to HC, pediatric MS patients showed higher normalized CP volume (p<0.001). When looking at sex-specific effect, both female and male pediatric MS patients showed higher normalized CP volume compared to sex-matched HC (females: p<0.001; males: p=0.021), with a significant disease (MS vs HC) ´ sex (females vs males) interaction (p=0.040). In MS patients, a higher normalized CP volume was significantly associated with higher brain T2-hyperintense white matter (WM) lesion volume (β=0.252, p=0.017), larger lateral ventricle volume (β=0.470, FDR p<0.001), lower normalized brain volume (β=-0.413, FDR p=0.002) and lower normalized thalamic volume (β=0.291, FDR p=0.046). No associations with disease duration, EDSS score, normalized cortical and WM volumes were found (FDR p≥0.172). A significant effect of the disease in the negative association between normalized volumes of CP and thalami was found (FDR p=0.046).
Conclusions:
CP enlargement occurs in pediatric MS patients, suggesting its early involvement in the pathophysiology of the disease. The higher CP volume, that is found especially in female patients, supports the hypothesis of sex-related differences in the neuroinflammatory processes occurring already in pediatric MS patients.