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Open Access 01-12-2018 | Research article

The MRZ reaction helps to distinguish rheumatologic disorders with central nervous involvement from multiple sclerosis

Authors: Tilman Hottenrott, Rick Dersch, Benjamin Berger, Dominique Endres, Daniela Huzly, Jens Thiel, Sebastian Rauer, Oliver Stich, Ulrich Salzer, Nils Venhoff

Published in: BMC Neurology | Issue 1/2018

Abstract

Background

Some rheumatologic disorders may initially manifest with central nervous system (CNS) affection, mimicking the clinical, magnetic resonance imaging, and cerebrospinal fluid findings of multiple sclerosis (MS). The MRZ reaction (MRZR), composed of the three respective antibody indices (AIs) against measles, rubella, and varicella zoster virus, has been found positive frequently in MS patients. However, it is unclear whether the MRZR is helpful to distinguish rheumatologic disorders with CNS involvement (RDwCNS) from MS.

Methods

The MRZR was evaluated in patients with RDwCNS (n = 23), MS (n = 46; age and sex matched to patients with RDwCNS), and other inflammatory autoimmune neurological diseases affecting the CNS (OIND; n = 48). Both the stringency levels that have been used in previous MRZR studies, MRZR-1 (≥ 1 of 3 AIs positive) and MRZR-2 (≥ 2 of 3 AIs positive), were applied.

Results

There was no statistically significant difference in the prevalence of positive MRZR between patients with RDwCNS (MRZR-1: 13.0% and MRZR-2: 8.7%, respectively) and OIND (MRZR-1: 22.9% and MRZR-2: 8.3%, respectively). Compared to these two study cohorts, the MS group exhibited significantly higher prevalences of positive MRZR (MRZR-1: 82.6%, MRZR-2: 63.0%; p < 0.005 each).

Conclusions

Considering the high specificity of MRZR-2 for MS found in this study, MRZR-2 can be a useful diagnostic tool for distinguishing MS from RDwCNS or OIND.

Rhiannon JJ. Systemic lupus erythematosus involving the nervous system: presentation, pathogenesis, and management. Clin Rev Allergy Immunol. 2008;34:356–60. https://doi.org/10.1007/s12016-007-8052-z.CrossRefPubMed

Govoni M, Bortoluzzi A, Padovan M, Silvagni E, Borrelli M, Donelli F, et al. The diagnosis and clinical management of the neuropsychiatric manifestations of lupus. J Autoimmun. 2016;74:41–72. https://doi.org/10.1016/j.jaut.2016.06.013.CrossRefPubMed

Harirchian MH, Saberi H, Najafizadeh SR, Hashemi SA. Evaluation of brain and cervical MRI abnormality rates in patients with systemic lupus erythematosus with or without neurological manifestations. Iran J Radiol. 2011;8:157–60. https://doi.org/10.5812/kmp.iranjradiol.17351065.3138.CrossRefPubMedPubMedCentral

Asakura K, Muto T. Neurological involvement in Wegener's granulomatosis. Brain Nerve. 2013;65:1311–7.PubMed

Brinar VV, Cikes N, Petelin Z, Hlavati M, Poser CM. Cerebral demyelination in Wegener's granulomatosis. Clin Neurol Neurosurg. 2004;106:233–6. https://doi.org/10.1016/j.clineuro.2004.02.021.CrossRefPubMed

Abdel Razek AAK, Alvarez H, Bagg S, Refaat S, Castillo M. Imaging spectrum of CNS vasculitis. Radiographics. 2014;34:873–94. https://doi.org/10.1148/rg.344135028.CrossRefPubMed

Akman-Demir G, Mutlu M, Kiyat-Atamer A, Shugaiv E, Kurtuncu M, Tugal-Tutkun I, et al. Behçet’s disease patients with multiple sclerosis-like features: discriminative value of Barkhof criteria. Clin Exp Rheumatol. 2015;33:S80–4.PubMed

Yong H, Chartier G, Quandt J. Modulating inflammation and neuroprotection in multiple sclerosis. J Neurosci Res. 2017; https://doi.org/10.1002/jnr.24090.

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

10.

Jarius S, Eichhorn P, Franciotta D, Petereit HF, Akman-Demir G, Wick M, Wildemann B. The MRZ reaction as a highly specific marker of multiple sclerosis: re-evaluation and structured review of the literature. J Neurol. 2017;264:453–66. https://doi.org/10.1007/s00415-016-8360-4.CrossRefPubMed

11.

Hottenrott T, Dersch R, Berger B, Rauer S, Huzly D, Stich O. The MRZ reaction in primary progressive multiple sclerosis. Fluids Barriers CNS. 2017;14:2. https://doi.org/10.1186/s12987-016-0049-7.CrossRefPubMedPubMedCentral

12.

Wurster U, Stachan R, Windhagen A, Petereit HF, Leweke FM. Reference values for standard cerebrospinal fluid examinations in multiple sclerosis.: results from 99 healthy volunteers. Mult Scler. 2006;P248

13.

Bednárová J, Stourac P, Adam P. Relevance of immunological variables in neuroborreliosis and multiple sclerosis. Acta Neurol Scand. 2005;112:97–102. https://doi.org/10.1111/j.1600-0404.2005.00418.x.CrossRefPubMed

14.

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

15.

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. https://doi.org/10.1136/jnnp.2007.133330.CrossRefPubMed

16.

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. https://doi.org/10.1016/j.jns.2008.08.002.CrossRefPubMed

17.

Hottenrott T, Dersch R, Berger B, Rauer S, Eckenweiler M, Huzly D, Stich O. The intrathecal, polyspecific antiviral immune response in neurosarcoidosis, acute disseminated encephalomyelitis and autoimmune encephalitis compared to multiple sclerosis in a tertiary hospital cohort. Fluids Barriers CNS. 2015;12:27. https://doi.org/10.1186/s12987-015-0024-8.CrossRefPubMedPubMedCentral

18.

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(22):1914. https://doi.org/10.1212/WNL.0b013e3181c47cc2.CrossRefPubMedPubMedCentral

19.

Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(1725) https://doi.org/10.1002/1529-0131(199709)40:9<1725::AID-ART29>3.0.CO;2-Y.

20.

Jennette JC, Falk RJ, bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised international Chapel Hill consensus conference nomenclature of Vasculitides. Arthritis Rheum. 2013;65:1–11. https://doi.org/10.1002/art.37715. CrossRefPubMed

21.

Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum. 1990;33:1101–7.CrossRefPubMed

22.

Evaluation of diagnostic (‘classification’) criteria in Behçet’s disease--towards internationally agreed criteria. The International Study Group for Behçet's disease. Br J Rheumatol. 1992;31:299–308.

23.

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. https://doi.org/10.1002/ana.22366.CrossRefPubMedPubMedCentral

24.

Kaller CP, Loosli SV, Rahm B, Gössel A, Schieting S, Hornig T, et al. Working memory in schizophrenia: behavioral and neural evidence for reduced susceptibility to item-specific proactive interference. Biol Psychiatry. 2014;76:486–94. https://doi.org/10.1016/j.biopsych.2014.03.012.CrossRefPubMed

25.

Reiber H. Cerebrospinal fluid--physiology, analysis and interpretation of protein patterns for diagnosis of neurological diseases. Mult Scler. 1998;4:99–107. https://doi.org/10.1177/135245859800400302.PubMed

26.

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.CrossRefPubMedPubMedCentral

27.

Brinks R, Fischer-Betz R, Sander O, Richter JG, Chehab G, Schneider M. Age-specific prevalence of diagnosed systemic lupus erythematosus in Germany 2002 and projection to 2030. Lupus. 2014;23:1407–11. https://doi.org/10.1177/0961203314540352.CrossRefPubMed

28.

Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) advisory committee on clinical trials of new agents in multiple sclerosis. Neurology. 1996;46:907–11.CrossRefPubMed

29.

Petereit H-F, Reske D. Expansion Of antibody reactivity in the cerebrospinal fluid of multiple sclerosis patients - follow-up and clinical implications. Cerebrospinal Fluid Res. 2005;2:3. https://doi.org/10.1186/1743-8454-2-3. CrossRefPubMedPubMedCentral

30.

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. https://doi.org/10.1177/1352458509348418.CrossRefPubMed

31.

Graef IT, Henze T, Reiber H. Polyspezifische Immunreaktion im ZNS bei Autoimmunerkrankungen mit ZNS-Beteiligung. Z Arztl Fortbild (Jena). 1994;88:587–91.

32.

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. https://doi.org/10.1371/journal.pone.0028094.CrossRefPubMedPubMedCentral

33.

Kułakowska A, Mroczko B, Mantur M, Lelental N, Tarasiuk J, Kapica-Topczewska K, et al. Multiplexing analysis of the polyspecific intrathecal immune response in multiple sclerosis. Methods. 2012;56:528–31. https://doi.org/10.1016/j.ymeth.2012.03.002.CrossRefPubMed

34.

Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler. 1998;4:111–7. https://doi.org/10.1177/135245859800400304. CrossRefPubMed

35.

Siritho S, Freedman MS. The prognostic significance of cerebrospinal fluid in multiple sclerosis. J Neurol Sci. 2009;279:21–5. https://doi.org/10.1016/j.jns.2008.12.029.CrossRefPubMed

36.

McLean BN, Luxton RW, Thompson EJ. A study of immunoglobulin G in the cerebrospinal fluid of 1007 patients with suspected neurological disease using isoelectric focusing and the log IgG-index. A comparison and diagnostic applications. Brain. 1990;113(Pt 5):1269–89.CrossRefPubMed

37.

Tumani H, Deisenhammer F, Giovannoni G, Gold R, Hartung H-P, Hemmer B, et al. Revised McDonald criteria: the persisting importance of cerebrospinal fluid analysis. Ann Neurol. 2011;70:520; author reply 521. https://doi.org/10.1002/ana.22508.CrossRefPubMed

38.

Liebsch R, Kornhuber ME, Dietl D, Gräfin von Einsiedel H, Conrad B. Blood-CSF barrier integrity in multiple sclerosis. Acta Neurol Scand. 1996;94:404–10.CrossRefPubMed

39.

Theodoridou A, Settas L. Demyelination in rheumatic diseases. Postgrad Med J. 2008;84:127–32. https://doi.org/10.1136/jnnp.2005.075861.CrossRefPubMed

40.

Filippi M, Rocca MA, Ciccarelli O, de SN, Evangelou N, Kappos L, et al. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 2016;15:292–303. https://doi.org/10.1016/S1474-4422(15)00393-2.CrossRefPubMedPubMedCentral

41.

Barned S, Goodman AD, Mattson DH. Frequency of anti-nuclear antibodies in multiple sclerosis. Neurology. 1995;45:384–5.CrossRefPubMed

42.

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. https://doi.org/10.1111/j.1600-0404.2006.00755.x.CrossRefPubMed

43.

Samanta A, Feehally J, Roy S, Nichol FE, Sheldon PJ, Walls J. High prevalence of systemic disease and mortality in Asian subjects with systemic lupus erythematosus. Ann Rheum Dis. 1991;50:490–2.CrossRefPubMedPubMedCentral

44.

Thumboo J, Uramoto K, O'Fallon WM, Fong KY, Boey ML, Feng PH, et al. A comparative study of the clinical manifestations of systemic lupus erythematosus in Caucasians in Rochester, Minnesota, and Chinese in Singapore, from 1980 to 1992. Arthritis Rheum. 2001;45:494–500.CrossRefPubMed

45.

Peschken CA, Katz SJ, Silverman E, Pope JE, Fortin PR, Pineau C, et al. The 1000 Canadian faces of lupus: determinants of disease outcome in a large multiethnic cohort. J Rheumatol. 2009;36:1200–8. https://doi.org/10.3899/jrheum.080912.CrossRefPubMed

Title: The MRZ reaction helps to distinguish rheumatologic disorders with central nervous involvement from multiple sclerosis
Authors: Tilman Hottenrott
Rick Dersch
Benjamin Berger
Dominique Endres
Daniela Huzly
Jens Thiel
Sebastian Rauer
Oliver Stich
Ulrich Salzer
Nils Venhoff
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Neurology / Issue 1/2018
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-018-1018-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The MRZ reaction helps to distinguish rheumatologic disorders with central nervous involvement from multiple sclerosis

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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