CSF-Progranulin and Neurofilament Light Chain Levels in Patients With Radiologically Isolated Syndrome-Sign of Inflammation.

Marc Pawlitzki,Catherine M Sweeney-Reed,Jens Neumann,Friedemann Paul,Stefan Vielhaber,Stefanie Schreiber,Anke Lux,Daniel Bittner

doi:10.3389/fneur.2018.01075

Abstract

Background: Cerebrospinal fluid (CSF) markers of disease in patients with radiologically isolated syndrome (RIS) are the subject of intense investigation, because they have the potential to enhance our understanding of the natural disease course and provide insights into similarities and differences between RIS and other multiple sclerosis (MS) disease identities.Methods: Here we compared neurofilament light chain (NFL) and progranulin (PGRN) levels in the CSF in RIS patients with levels in patients with different subtypes of MS and healthy controls (HC) using Kruskal–Wallis one-way analysis of variance.Results: Median CSF NFL concentrations in RIS patients did not differ to those in HC and clinically isolated syndrome (CIS) patients, but were significantly lower than in relapsing remitting (RRMS) and primary progressive (PPMS) MS patients. In contrast, RIS patients exhibited higher median CSF PGRN levels than HC and showed no significant differences compared with CIS, RRMS, and PPMS cases.Conclusion: We postulate that elevated PGRN values in the CSF of RIS patients might indicate inflammatory and repair activity prior to axonal disintegration.

Highlights

Widespread routine clinical implementation of magnetic resonance imaging (MRI) leads to incidental detection of MRI abnormalities suggestive of multiple sclerosis (MS) in patients undergoing cerebral MRI due to non-specific neurological symptoms [1]
Median age and sex [χ2(4) = 0.07] did not differ between SC, radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), and RRMS patients, whereas PPMS patients were significantly older than SC, RIS (p < 0.001, respectively) and RRMS patients (p = 0.002)
Median disease duration was longer in PPMS compared to RIS and CIS (p < 0.001, respectively)

Summary

Introduction

Widespread routine clinical implementation of magnetic resonance imaging (MRI) leads to incidental detection of MRI abnormalities suggestive of multiple sclerosis (MS) in patients undergoing cerebral MRI due to non-specific neurological symptoms (e.g., headache, dizziness) [1]. Among these patients, a considerable number, mainly young men, develop radiological and clinical progression to relapsing (RRMS) or primary progressive (PPMS) forms of MS within 5 years [2, 3]. Cerebrospinal fluid (CSF) markers of disease in patients with radiologically isolated syndrome (RIS) are the subject of intense investigation, because they have the potential to enhance our understanding of the natural disease course and provide insights into similarities and differences between RIS and other multiple sclerosis (MS) disease identities

Methods

Results

Conclusion