Choroid plexus in MS-Patients, Healthy Controls and other neurological diseases

The choroid plexus has been proposed as a modulator of multiple sclerosis (MS)-related inflammation. Our study group recently found that the choroid plexus is larger in MS than healthy controls and patients with migraine.

The aim is to investigate the associations between the choroid plexus volume and MS disease characteristics including clinical and MRI outcomes and serum biomarkers such as neurofilament-light chain (sNfL) and glial fibrillary acidic protein (sGFAP) longitudinally in a large cohort of MS patients. We aim to make use of the data from one of the largest MS cohorts in the world - the Swiss MS cohort (SMSC) study. By time of this application, this database includes high quality clinical data of 1899 MS patients with a median follow-up time of 7 years. There are more than 13'000 documented visits with standardized clinical examinations by Neurostatus-certified treating physicians, more than 8'000 brain MRI scans and more than 300'000 bio-samples of which >3'000 exist as CSF/serum/plasma pairs. This setting provides a unique opportunity to find biomarkers associated with choroid plexus enlargement in MS. Moreover, co-morbidities and treatments of these patients are well-documented. We will use Freesurfer - a standard MRI analysis software - to segment automatically the choroid plexus of the brain lateral ventricles. We will check the outcomes of this analysis manually using 3D Slicer. The associations between choroid plexus volume and clinical parameters (Expanded disability status scale (EDSS) score, disease duration, time since last relapse and disease-modifying therapy), radiological outcomes (T2-weighted lesion number and volume, lateral ventricle volume, gray and white matter volume fraction, brain parenchymal fraction) and body fluid parameters (serum neurofilament light chain, glial fibrillary acidic protein) will be investigated using multivariable linear regression models adjusted for age, sex and total intracranial volume.There are many studies suggesting the specific role of the choroid plexus in MS pathology and clinical studies have found that t he choroid plexus is enlarged in MS compared to healthy individuals. Our study group also found that this might be specific for MS as the choroid plexus was significantly larger in MS than e.g. neuromyelitis optica spectrum disorders. However, it is unknown whether the choroid plexus volume is suitable as an MRI biomarker in MS. If this study shows that the choroid plexus volume is longitudinally associated clinical, MRI and body fluid biomarkers in MS, it might serve as an outcome parameter for future Phase II studies and potentially as a biomarker for treatment monitoring in MS.