The intrathecal, polyspecific antiviral immune response in neurosarcoidosis, acute disseminated encephalomyelitis and autoimmune encephalitis compared to multiple sclerosis in a tertiary hospital cohort.

Rick Dersch,Oliver Stich,Daniela Huzly,Sebastian Rauer,Tilman Hottenrott,Matthias Eckenweiler,Benjamin Berger

doi:10.1186/s12987-015-0024-8

Rick Dersch, Oliver Stich

Open Access

https://doi.org/10.1186/s12987-015-0024-8

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Abstract

BackgroundA polyspecific, intrathecal humoral immune response against the neurotropic viruses, measles, rubella and varicella zoster virus, called “MRZ reaction” (MRZR), is present in the majority of patients with multiple sclerosis (MS). Neurosarcoidosis (NS) and acute disseminated encephalomyelitis (ADEM) are important clinical differential diagnoses of MS. Autoimmune encephalitis (AIE) represents a well characterized autoimmune CNS disorder with intrathecal antibody synthesis. The aim of this study was to investigate the specificity of MRZR for MS in patients with NS, ADEM and AIE for the first time, and to compare it with the diagnostic value of oligoclonal bands (OCB).Patients and methodsTwenty-two patients with NS, 17 with AIE, 8 with ADEM and 33 with MS serving as controls were analyzed for OCB and MRZR by calculation of the antibody index (AI) for each virus. MRZR was considered as positive if at least two AIs were ≥1.5.ResultsA positive MRZR was statistically significantly less frequent in NS (9 %), AIE (11 %) and ADEM (0 %) compared to MS patients (70 %; p < 0.001 each). The specificity of MRZR for MS was 92 % in the study cohort. In comparison to MRZR, the OCB showed a higher sensitivity (100 %), but a lower specificity (69 %) for MS.ConclusionThese results indicate that MRZR seems to be the most specific available CSF marker of MS.

Highlights

A polyspecific, intrathecal humoral immune response against the neurotropic viruses, measles, rubella and varicella zoster virus, called “MRZ reaction” (MRZR), is present in the majority of patients with multiple sclerosis (MS)
In comparison to MRZR, the oligoclonal bands (OCB) showed a higher sensitivity (100 %), but a lower specificity (69 %) for MS. These results indicate that MRZR seems to be the most specific available CSF marker of MS
OCB are positive in infectious CNS disorders, such as neuroborreliosis (OCB in 70 % [5]), and in autoimmune CNS disorders such as neuromyelitis optica (NMO; OCB in >30 % [6]), and are much less specific than MRZR

Summary

Introduction

A polyspecific, intrathecal humoral immune response against the neurotropic viruses, measles, rubella and varicella zoster virus, called “MRZ reaction” (MRZR), is present in the majority of patients with multiple sclerosis (MS). Especially using the revised McDonald criteria [10], the correct diagnosis of MS at initial clinical presentation can be difficult, if there are hints towards differential diagnoses such as NS or acute disseminated encephalomyelitis (ADEM). From a more pathophysiological point of view, Jarius et al questioned in 2009 if the MRZR is specific to MS at all or should rather be considered as a general marker for CNS autoimmune diseases [11]. In this regard, autoimmune encephalitis (AIE) is a well characterized example of CNS autoimmunity suitable for further investigation of the specificity of MRZR.

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