Association of cerebrospinal inflammatory profile with radiological features in newly diagnosed treatment-naïve patients with multiple sclerosis

Abstract

ObjectiveMultiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Without reliable diagnostic biomarkers, the clinical and radiological heterogeneity of MS makes diagnosis difficult. Although magnetic resonance imaging (MRI) is a major diagnostic tool for MS, the association of MRI findings with the inflammatory profile in cerebrospinal fluid (CSF) has been insufficiently investigated. Therefore, we focused on CSF profile of MS patients and examined its association with MRI findings.MethodsConcentrations of 26 cytokines and chemokines were determined in CSF of 28 treatment-naïve MS patients and 12 disease-control patients with aquaporin-4 antibody-seropositive neuromyelitis optica spectrum disorder (NMOSD).ResultsHigh levels of interleukin (IL)-6, IL-17A, B-cell activating factor (BAFF), a proliferation inducing ligand (APRIL), and CD40 ligand were correlated with the absence of at least one of the following three MRI findings in MS: an ovoid lesion, three or more periventricular lesions, and a nodular and/or ring-shaped contrast-enhancing lesion. The multivariate analysis revealed that elevated IL-17A was an independent predictor of absence of ovoid lesion and periventricular lesions less than three. MS patients were classified into a group with all three MRI findings (MS-full) and a group with less than three (MS-partial). The discriminant analysis model distinguished three groups: MS-full, MS-partial, and NMOSD, with 98% accuracy.ConclusionThe CSF inflammatory profile was associated with radiological findings of treatment-naïve MS. This result indicates the possible utility of combined CSF and MRI profiling in identifying different MS phenotypes related to the heterogeneity of underlying immune processes.