PMID- 37542085 OWN - NLM STAT- MEDLINE DCOM- 20230807 LR - 20231117 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 13 IP - 1 DP - 2023 Aug 4 TI - The relevance of NMDA receptor antibody-specific index for diagnosis and prognosis in patients with anti-NMDA receptor encephalitis. PG - 12696 LID - 10.1038/s41598-023-38462-6 [doi] LID - 12696 AB - The clinical implications of the presence of anti-N-methyl-D-aspartate receptor (NMDAR)-specific intrathecal immunoglobulin G synthesis and whether it determines the diagnosis of anti-NMDAR encephalitis have not been thoroughly investigated yet. Thus, the aim of this study was to investigate whether the detection of intrathecal anti-NMDAR-specific IgG synthesis contributes to the diagnostic confirmation of anti-NMDAR encephalitis, to disease severity, and to prognosis in patients with positive serum anti-NMDAR-IgG. In this study, patients with detectable anti-NMDAR IgG in serum and/or cerebrospinal fluid (CSF) were included and separated into two groups that either met the 2016 criteria by Graus et al. of definite anti-NMDAR encephalitis (n = 27) or did not (n = 15). In a total, of 80 paired CSF/serum samples, antibody titers were titrated manually and end-point titer levels were carefully determined in a blinded manner to the subgroup attribution. The disease course was assessed via the modified Rankin Scale (mRS) and prognosis was estimated by the anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score. With respect to whether the diagnostic Graus criteria for definite anti-NMDAR encephalitis were fulfilled, a significantly unequal distribution of intrathecal anti-NMDAR antibody-specific synthesis could be shown with a high negative predictive value in case of a negative anti-NMDAR antibody-specific index (NMDAR AI, p = .008. OR = 23.9, sensitivity = 1.0, specificity = 0.4, negative predictive value = 1). A weak correlation was found between the CSF antibody titer and mRS value at the time of sample collection (r(s) = .37, p = .008, 95% CI [.09, .59]). During the disease course a higher delta-mRS value formed of the mRS at initial presentation minus that at the last recorded presentation correlated with a higher NMDAR AI at first lumbar puncture (r(s) = - .56, p = .017, 95% CI [- .83, - .11]). No association with the prognostic NEOS score was found. In conclusion, a negative antibody-specific index for anti-NMDAR IgG antibodies has a highly negative predictive value for the diagnosis of anti-NMDAR encephalitis. Yet, a positive NMDAR AI alone does not allow the diagnosis of anti-NMDAR encephalitis. CI - (c) 2023. Springer Nature Limited. FAU - Hummert, Martin W AU - Hummert MW AD - Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. FAU - Jendretzky, Konstantin F AU - Jendretzky KF AD - Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. FAU - Fricke, Karin AU - Fricke K AD - Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. FAU - Gingele, Marina AU - Gingele M AD - Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. FAU - Ratuszny, Dominica AU - Ratuszny D AD - Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. FAU - Mohn, Nora AU - Mohn N AD - Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. FAU - Trebst, Corinna AU - Trebst C AD - Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. FAU - Skripuletz, Thomas AU - Skripuletz T AD - Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. FAU - Gingele, Stefan AU - Gingele S AD - Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. FAU - Suhs, Kurt-Wolfram AU - Suhs KW AD - Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. Suehs.Kurt-Wolfram@mh-hannover.de. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230804 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Antibodies) SB - IM MH - Humans MH - *Anti-N-Methyl-D-Aspartate Receptor Encephalitis MH - Receptors, N-Methyl-D-Aspartate MH - Prognosis MH - Antibodies MH - Disease Progression PMC - PMC10403579 COIS- MWH received research support from Myelitis e. V. KFJ received research support from Else Kroner Fresenius Foundation and travel compensation and congress fee from Merck. KF reports no disclosures. MG reports no disclosures. DR reports no disclosures. NM received honoraria for scientific lectures from Merck and Biogen. CT received honoraria for consultation and expert testimony from Alexion Pharma Germany GmbH, Chugai Pharma Germany GmbH, and Roche Pharma GmbH. TS received research support from Alnylam Pharmaceuticals, Bristol-Myers Squibb Foundation for Immuno-Oncology, Claudia von Schilling Foundation, CSL Behring, Else Kroner Fresenius Foundation, Hannover Biomedical Research School (HBRS), Sanofi Genzyme, VHV Foundation and honoraria for lectures and travel grants from Alexion, Alnylam Pharmaceuticals, Bayer Vital, Biogen, Celgene, Centogene, CSL Behring, Euroimmun, Janssen, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Siemens and Sobi. SG received research support from Alnylam Pharmaceuticals, CSL Behring, Else Kroner Fresenius Foundation, Deutsche Forschungsgemeinschaft and Hannover Biomedical Research School (HBRS), as well as consulting and/or lecture honoraria from Alnylam and Merck. KWS reports honoraria for lectures or travel reimbursements for attending meetings from Biogen, Merck and Bristol-Myers Squibb as well as research support from Bristol-Myers Squibb. EDAT- 2023/08/05 05:41 MHDA- 2023/08/07 06:42 PMCR- 2023/08/04 CRDT- 2023/08/04 23:19 PHST- 2023/02/10 00:00 [received] PHST- 2023/07/08 00:00 [accepted] PHST- 2023/08/07 06:42 [medline] PHST- 2023/08/05 05:41 [pubmed] PHST- 2023/08/04 23:19 [entrez] PHST- 2023/08/04 00:00 [pmc-release] AID - 10.1038/s41598-023-38462-6 [pii] AID - 38462 [pii] AID - 10.1038/s41598-023-38462-6 [doi] PST - epublish SO - Sci Rep. 2023 Aug 4;13(1):12696. doi: 10.1038/s41598-023-38462-6.