The intrathecal, polyspecific antiviral immune response in neurosarcoidosis, acute disseminated encephalomyelitis and au
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Fluids and Barriers of the CNS Open Access
RESEARCH
The intrathecal, polyspecific antiviral immune response in neurosarcoidosis, acute disseminated encephalomyelitis and autoimmune encephalitis compared to multiple sclerosis in a tertiary hospital cohort Tilman Hottenrott1*, Rick Dersch1, Benjamin Berger1, Sebastian Rauer1,2, Matthias Eckenweiler3, Daniela Huzly4 and Oliver Stich1
Abstract Background: 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). 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 methods: Twenty-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. Results: A positive MRZR was statistically significantly less frequent in NS (9 %), AIE (11 %) and ADEM (0 %) compared to MS patients (70 %; p 30 % [6]), and thus are much less specific than MRZR. Apart from MS, prevalence of MRZR has been studied in two other autoimmune CNS diseases: paraneoplastic neurological disorders (PND) [7] and NMO [8]. Additionally, there is only one case series reporting positive MRZR in a very few patients with systemic autoimmune disorders with CNS involvement including one patient with neurosarcoidosis (NS), three patients with systemic lupus erythematosus and one patient each with Wegener`s granulomatosis and Sjögren syndrome [9]. Occasionally, especially using the revised McDonald criteria [10], the correct diagnosis of MS at initial clinical presentation can be difficult, particularly if there are hints towards differential diagnoses such as NS or acute disseminated encephalomyelitis (ADEM). In such clinical situations, it would be helpful to know how well the MRZR distinguishes between MS and these differential diagnoses. 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. The present study is believed to be the first to systematically address the frequency of a positive MRZR in NS, ADEM and AIE.
Methods Patients
For the purpose of this retrospective study, NS, AIE and ADEM patients treated either at the Department of Neurology or at the Department of N
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