ReviewJournal of neurology2017
The MRZ reaction as a highly specific marker of multiple sclerosis: re-evaluation and structured review of the literature.
Review in Journal of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 126 citations in OpenAlex.
- Herpes zoster preceding neuromyelitis optica spectrum disorder: casual or causal relationship? A systematic literature review.Journal of neurovirology · 2022Pooled it
- Myelinoclastic diffuse sclerosis (Schilder's disease) is immunologically distinct from multiple sclerosis: results from retrospective analysis of 92 lumbar punctures.Journal of neuroinflammation · 2019Pooled it
- EBNA1Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Effects of Biological Sex and Age on Cerebrospinal Fluid Markers-A Retrospective Observational Study.Annals of clinical and translational neurology · 2026Observational
- CSF κ-Free light chain index in suspected multiple sclerosis: diagnostic performance vs. Oligoclonal bands and alignment with 2017/2024 McDonald criteria.Acta neurologica Belgica · 2026Article
- Viral associations in multiple sclerosis: pathogenetic mechanisms and therapeutic implications.Virology journal · 2026Review
- Bilateral fuchs uveitis syndrome and its association with multiple sclerosis.International ophthalmology · 2026Article
- The Presence of MRZ Reactions Improves the Prediction of Multiple Sclerosis in Children with Optic Neuritis.Children (Basel, Switzerland) · 2025Article
- Broad Analysis of Serum and Intrathecal Antimicrobial Antibodies in Multiple Sclerosis Underscores Unique Role of Epstein-Barr Virus.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Intensity of Intrathecal Total IgG Synthesis in Multiple Sclerosis Correlates with the Degree of Pleocytosis, Diversity of Intrathecal Antiviral Antibody Specificities, and Female Sex.Antibodies (Basel, Switzerland) · 2024Article
- Intrathecal immune reactivity against Measles-, Rubella-, and Varicella Zoster viruses is associated with cerebrospinal fluid inflammation in multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024Article
- Rubella virus seropositivity after infection or vaccination as a risk factor for multiple sclerosis.European journal of neurology · 2024Article
- Detection of intrathecal IgG antibody for varicella and measles diagnosis by evaluation and comparison of a commercial IgG chemiluminescent immunoassay with two ELISAs.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- Review
- Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis.Frontiers in immunology · 2024Observational
- Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis.Journal of neurology · 2023Review
- Cerebrospinal Fluid Biomarkers in Differential Diagnosis of Multiple Sclerosis and Systemic Inflammatory Diseases with Central Nervous System Involvement.Biomedicines · 2023Article
- Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis.Frontiers in immunology · 2023Article
- Editorial: New cerebrospinal fluid research to uncover mechanisms driving neurological and psychiatric diseases, volume II.Frontiers in neurology · 2023Article
- Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases - a retrospective cross-sectional study.Frontiers in neurology · 2023Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIt has long been known that the majority of patients with multiple sclerosis (MS) display an intrathecal, polyspecific humoral immune response to a broad panel of neurotropic viruses. This response has measles virus, rubella virus and varicella zoster virus as its most frequent constituents and is thus referred to as the MRZ reaction (MRZR).
objectiveRe-evaluation of the specificity of MRZR as a marker of MS.
methodsStructured review of the existing English-, German- and Spanish-language literature on MRZR testing, with evaluation of MRZR in a cohort of 43 unselected patients with MS and other neurological diseases as a proof of principle.
resultsA positive MRZ reaction, defined as a positive intrathecal response to at least two of the three viral agents, was found in 78% of MS patients but only in 3% of the controls (p < 0.00001), corresponding to specificity of 97%. Median antibody index values were significantly lower in non-MS patients (measles, p < 0.0001; rubella, p < 0.006; varicella zoster, p < 0.02). The 30 identified original studies on MRZR reported results from 1478 individual MRZR tests. A positive MRZR was reported for 458/724 (63.3%) tests in patients with MS but only for 19/754 (2.5%) tests in control patients (p < 0.000001), corresponding to cumulative specificity of 97.5% (CI 95% 96-98.4), cumulative sensitivity of 63.3% (CI 95% 59.6-66.8) (or 67.4% [CI 95% 63.5-71.1] in the adult MS subgroup), a positive likelihood ratio of 25.1 (CI 95% 16-39.3) and a negative likelihood ratio of 0.38 (CI 95% 0.34-0.41). Of particular note, MRZR was absent in 52/53 (98.1%) patients with neuromyelitis optica or MOG-IgG-positive encephalomyelitis, two important differential diagnoses of MS.
conclusionMRZR is the most specific laboratory marker of MS reported to date. If present, MRZR substantially increases the likelihood of the diagnosis of MS. Prospective and systematic studies on the diagnostic and prognostic impact of MRZR testing are highly warranted.
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