The MRZ reaction and a quantitative intrathecal IgG synthesis may be helpful to differentiate between primary central nervous system lymphoma and multiple sclerosis

Abstract

Some patients with primary central nervous system lymphoma (PCNSL) may initially present with similar clinical, magnetic resonance imaging, and routine cerebrospinal fluid (CSF) findings as those observed in multiple sclerosis (MS). The MRZ reaction (MRZR), composed of the three respective antibody indices (AIs) against measles, rubella, and varicella zoster virus, appears to be the most specific CSF marker for MS. This study aimed to determine whether a positive MRZR and other routine CSF markers help differentiate between MS and PCNSL. Data regarding brain biopsy, CSF routine tests, cytopathological examination and immunophenotyping of CSF cells were assessed in 68 PCNSL patients. MRZR was determined, as possible, in PCNSL patients (n = 37) and in those with MS (n = 74; age and sex matched to PSCNL patients) and psychiatric disorders (PD; n = 78). Two stringency levels for a positive antibody index (AI) evaluation (AI ≥ 1.5 and 2.0) were applied, and MRZR was considered positive in cases with ≥ 2 positive AIs (MRZR-2). Using the common AI threshold of ≥ 1.5, MS patients exhibited positive MRZR-2 (58.1%) more frequently than PCNSL (8.1%) and PD patients (2.6%; p < 0.0001 for each comparison with the MS group) corresponding to a positive predictive value (PPV) of 89.6% and a negative predictive value (NPV) of 78.0%. On applying the stricter AI threshold of ≥ 2.0, 37.8% of MS patients were MRZR-2 positive; however, all patients with PCNSL and PD were MRZR-2 negative (p < 0.0001 for each comparison with the MS cohort) resulting in a PPV of 100% and an NPV of 71.4%. Consequently, a positive MRZR-2 result may contribute toward the distinction between MS and PCNSL owing to its high specificity and PPV for MS in the context of the present study. Among the other CSF parameters only a quantitative intrathecal IgG synthesis (present in 49.3% of MS patients but in none of the PCNSL or PD patients; p < 0.0001 for each comparison with the MS group) reliably indicated MS rather than PCNSL.

Keywords: Intrathecal polyspecific antiviral immune response; MRZ reaction; Multiple sclerosis; Primary central nervous system lymphoma.