Skip to main content
Top
Published in: Fluids and Barriers of the CNS 1/2015

Open Access 01-12-2015 | Research

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

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

Published in: Fluids and Barriers of the CNS | Issue 1/2015

Login to get access

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 < 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.

Conclusion

These results indicate that MRZR seems to be the most specific available CSF marker of MS.
Literature
1.
go back to reference Felgenhauer K, Reiber H. The diagnostic significance of antibody specificity indices in multiple sclerosis and herpes virus induced diseases of the nervous system. Clin Investig. 1992;70:28–37.CrossRefPubMed Felgenhauer K, Reiber H. The diagnostic significance of antibody specificity indices in multiple sclerosis and herpes virus induced diseases of the nervous system. Clin Investig. 1992;70:28–37.CrossRefPubMed
2.
go back to reference Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler. 1998;4:111–7.CrossRefPubMed Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler. 1998;4:111–7.CrossRefPubMed
3.
go back to reference Godec MS, Asher DM, Murray RS, Shin ML, Greenham LW, Gibbs CJ Jr, et al. Absence of measles, mumps, and rubella viral genomic sequences from multiple sclerosis brain tissue by polymerase chain reaction. Ann Neurol. 1992;32:401–4.CrossRefPubMed Godec MS, Asher DM, Murray RS, Shin ML, Greenham LW, Gibbs CJ Jr, et al. Absence of measles, mumps, and rubella viral genomic sequences from multiple sclerosis brain tissue by polymerase chain reaction. Ann Neurol. 1992;32:401–4.CrossRefPubMed
4.
go back to reference Andersson M, Alvarez-Cermeño J, Bernardi G, Cogato I, Fredman P, Frederiksen J, et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry. 1994;57:897–902.PubMedCentralCrossRefPubMed Andersson M, Alvarez-Cermeño J, Bernardi G, Cogato I, Fredman P, Frederiksen J, et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry. 1994;57:897–902.PubMedCentralCrossRefPubMed
5.
go back to reference Djukic M, Schmidt-Samoa C, Lange P, Spreer A, Neubieser K, Eiffert H, et al. Cerebrospinal fluid findings in adults with acute Lyme neuroborreliosis. J Neurol. 2012;259:630–6.PubMedCentralCrossRefPubMed Djukic M, Schmidt-Samoa C, Lange P, Spreer A, Neubieser K, Eiffert H, et al. Cerebrospinal fluid findings in adults with acute Lyme neuroborreliosis. J Neurol. 2012;259:630–6.PubMedCentralCrossRefPubMed
6.
go back to reference Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14.PubMedCentralCrossRefPubMed Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14.PubMedCentralCrossRefPubMed
7.
go back to reference Jarius S, Eichhorn P, Jacobi C, Wildemann B, Wick M, Voltz R. The intrathecal, polyspecific antiviral immune response: specific for MS or a general marker of CNS autoimmunity? J Neurol Sci. 2009;280:98–100.CrossRefPubMed Jarius S, Eichhorn P, Jacobi C, Wildemann B, Wick M, Voltz R. The intrathecal, polyspecific antiviral immune response: specific for MS or a general marker of CNS autoimmunity? J Neurol Sci. 2009;280:98–100.CrossRefPubMed
8.
go back to reference Jarius S, Franciotta D, Bergamaschi R, Rauer S, Wandinger KP, Petereit HF, et al. Polyspecific, antiviral immune response distinguishes multiple sclerosis and neuromyelitis optica. J Neurol Neurosurg Psychiatry. 2008;79:1134–6.CrossRefPubMed Jarius S, Franciotta D, Bergamaschi R, Rauer S, Wandinger KP, Petereit HF, et al. Polyspecific, antiviral immune response distinguishes multiple sclerosis and neuromyelitis optica. J Neurol Neurosurg Psychiatry. 2008;79:1134–6.CrossRefPubMed
9.
go back to reference Graef IT, Henze T, Reiber H. Polyspecific immune reaction in the central nervous system in autoimmune diseaseswith CNS involvement. Z Arztl Fortbild. 1994;88:587–91. Graef IT, Henze T, Reiber H. Polyspecific immune reaction in the central nervous system in autoimmune diseaseswith CNS involvement. Z Arztl Fortbild. 1994;88:587–91.
10.
go back to reference Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292–302.PubMedCentralCrossRefPubMed Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292–302.PubMedCentralCrossRefPubMed
11.
go back to reference Stich O, Kluge J, Speck J, Rauer S. Oligoclonal restriction of antiviral immunoreaction in oligoclonal band-negative MS patients. Acta Neurol Scand. 2015;131:381–8.CrossRefPubMed Stich O, Kluge J, Speck J, Rauer S. Oligoclonal restriction of antiviral immunoreaction in oligoclonal band-negative MS patients. Acta Neurol Scand. 2015;131:381–8.CrossRefPubMed
12.
go back to reference Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, Moseley IF, et al. Central nervous system sarcoidosis–diagnosis and management. QJM. 1999;92:103–17.CrossRefPubMed Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, Moseley IF, et al. Central nervous system sarcoidosis–diagnosis and management. QJM. 1999;92:103–17.CrossRefPubMed
13.
go back to reference Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, et al. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler. 2013;19:1261–7.CrossRefPubMed Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, et al. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler. 2013;19:1261–7.CrossRefPubMed
14.
go back to reference Teunissen CE, Petzold A, Bennett JL, Berven FS, Brundin L, Comabella M, et al. A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology. 2009;73:1914–22.PubMedCentralCrossRefPubMed Teunissen CE, Petzold A, Bennett JL, Berven FS, Brundin L, Comabella M, et al. A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology. 2009;73:1914–22.PubMedCentralCrossRefPubMed
15.
go back to reference Reiber H, Lange P. Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clin Chem. 1991;37:1153–60.PubMed Reiber H, Lange P. Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clin Chem. 1991;37:1153–60.PubMed
16.
go back to reference Brettschneider J, Tumani H, Kiechle U, Muche R, Richards G, Lehmensiek V, et al. IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome. PLoS One. 2009;4:e7638.PubMedCentralCrossRefPubMed Brettschneider J, Tumani H, Kiechle U, Muche R, Richards G, Lehmensiek V, et al. IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome. PLoS One. 2009;4:e7638.PubMedCentralCrossRefPubMed
17.
go back to reference Rosche B, Laurent S, Conradi S, Hofmann J, Ruprecht K, Harms L. Measles IgG antibody index correlates with T2 lesion load on MRI in patients with early multiple sclerosis. PLoS One. 2012;7:e28094.PubMedCentralCrossRefPubMed Rosche B, Laurent S, Conradi S, Hofmann J, Ruprecht K, Harms L. Measles IgG antibody index correlates with T2 lesion load on MRI in patients with early multiple sclerosis. PLoS One. 2012;7:e28094.PubMedCentralCrossRefPubMed
18.
go back to reference Bednarova J, Stourac P, Adam P. Relevance of immunological variables in neuroborreliosis and multiple sclerosis. Acta Neurol Scand. 2005;112:97–102.CrossRefPubMed Bednarova J, Stourac P, Adam P. Relevance of immunological variables in neuroborreliosis and multiple sclerosis. Acta Neurol Scand. 2005;112:97–102.CrossRefPubMed
19.
go back to reference Puccioni-Sohler M, Kitze B, Felgenhauer K, Graef IT, Lange P, Novis S, et al. The value of CSF analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis. Arq Neuropsiquiatr. 1995;53:760–5.CrossRefPubMed Puccioni-Sohler M, Kitze B, Felgenhauer K, Graef IT, Lange P, Novis S, et al. The value of CSF analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis. Arq Neuropsiquiatr. 1995;53:760–5.CrossRefPubMed
20.
go back to reference Tumani H, Deisenhammer F, Giovannoni G, Gold R, Hartung HP, Hemmer B, et al. Revised McDonald criteria: the persisting importance of cerebrospinal fluid analysis. Ann Neurol. 2011;70:520 (Author reply 521).CrossRefPubMed Tumani H, Deisenhammer F, Giovannoni G, Gold R, Hartung HP, Hemmer B, et al. Revised McDonald criteria: the persisting importance of cerebrospinal fluid analysis. Ann Neurol. 2011;70:520 (Author reply 521).CrossRefPubMed
21.
go back to reference Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, et al. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol. 2014;261:1–16.PubMedCentralCrossRefPubMed Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, et al. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol. 2014;261:1–16.PubMedCentralCrossRefPubMed
22.
go back to reference Steiner I, Kennedy PG. Acute disseminated encephalomyelitis: current knowledge and open questions. J Neurovirol. 2015;21(5):473–9.CrossRefPubMed Steiner I, Kennedy PG. Acute disseminated encephalomyelitis: current knowledge and open questions. J Neurovirol. 2015;21(5):473–9.CrossRefPubMed
23.
go back to reference Segal BM. Neurosarcoidosis: diagnostic approaches and therapeutic strategies. Curr Opin Neurol. 2013;26:307–13.CrossRefPubMed Segal BM. Neurosarcoidosis: diagnostic approaches and therapeutic strategies. Curr Opin Neurol. 2013;26:307–13.CrossRefPubMed
24.
go back to reference Reiber H, Teut M, Pohl D, Rostasy KM, Hanefeld F. Paediatric and adult multiple sclerosis: age related differences and time course of the neuroimmunological response in cerebrospinal fluid. Mult Scler. 2009;15:1466–80.CrossRefPubMed Reiber H, Teut M, Pohl D, Rostasy KM, Hanefeld F. Paediatric and adult multiple sclerosis: age related differences and time course of the neuroimmunological response in cerebrospinal fluid. Mult Scler. 2009;15:1466–80.CrossRefPubMed
25.
go back to reference Robinson-Agramonte M, Reiber H, Cabrera-Gomez JA, Galvizu R. Intrathecal polyspecific immune response to neurotropic viruses in multiple sclerosis: a comparative report from Cuban patients. Acta Neurol Scand. 2007;115:312–8.CrossRefPubMed Robinson-Agramonte M, Reiber H, Cabrera-Gomez JA, Galvizu R. Intrathecal polyspecific immune response to neurotropic viruses in multiple sclerosis: a comparative report from Cuban patients. Acta Neurol Scand. 2007;115:312–8.CrossRefPubMed
Metadata
Title
The intrathecal, polyspecific antiviral immune response in neurosarcoidosis, acute disseminated encephalomyelitis and autoimmune encephalitis compared to multiple sclerosis in a tertiary hospital cohort
Authors
Tilman Hottenrott
Rick Dersch
Benjamin Berger
Sebastian Rauer
Matthias Eckenweiler
Daniela Huzly
Oliver Stich
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2015
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-015-0024-8

Other articles of this Issue 1/2015

Fluids and Barriers of the CNS 1/2015 Go to the issue