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CSF Findings in Acute NMDAR and LGI1 Antibody–Associated Autoimmune Encephalitis

2021; Wolters Kluwer; Volume: 8; Issue: 6 Linguagem: Inglês

10.1212/nxi.0000000000001086

2332-7812

Marc Dürr, Gunnar Nissen, Kurt‐Wolfram Sühs, Philipp Schwenkenbecher, Christian Geis, Marius Ringelstein, Hans‐Peter Hartung, Manuel A. Friese, Max Kaufmann, Michael P. Malter, Marie Madlener, Franziska S. Thaler, Tania Kümpfel, Makbule Şenel, Martin Häusler, Hauke Schneider, Florian Then Bergh, Christoph Kellinghaus, Uwe K. Zettl, Klaus‐Peter Wandinger, Nico Melzer, Catharina C. Groß, Peter Lange, Jens Dreyhaupt, Hayrettin Tumani, Frank Leypoldt, Jan Lewerenz, Alexander Finke, Alexandra Philipsen, Andeas Linsa, Andre Dik, Andrea Kraft, Andreas Binder, Andreas van Baalen, Anna Gorsler, Anne‐Katrin Pröbstel, Annette Baumgärtner, Armin Grau, Astrid Blaschek, Benjamin Wunderlich, Bettina Balint, Brigitte Wildemann, Carsten Finke, Catharina C. Groß, Christian G. Bien, Christian Geis, Christian Urbanek, Christine Strippel, Christoph Kellinghaus, Christoph Lehrich, Christos Krogias, Chung Ha-Yeun, Claudia Sommer, Constanze Mönig, Corinna I. Bien, Corinna Trebst, Daniel Bittner, Dirk Fitzner, Dominique Endres, Fatme Seval Ismail, Felix Rosenow, Felix von Poderwils, Florian Then Bergh, Frank Hoffmann, Frank Leypoldt, Franz Blaes, Franziska S. Thaler, Friedrich Ebinger, George Trendelenburg, Gernot Reimann, Gunnar Nissen, G Seidel, Hans‐Peter Hartung, Harald Prüß, Hauke Schneider, Hayretti Tumani, Heinz Wiendl, Hendrik Rohner, Henning Stolze, Ilya Ayzenberg, Ina Schröder, Ina-Isabelle Schmütz, Jan Lewerenz, Jens Dreyhaupt, Jens Schaumberg, Jens Schmidt, Joachim Havla, Johanna Maria Helena Rau, Johannes Piepgras, Jonathan Wickel, Josef Priller, Jost Obrocki, Judith Wagner, Jürgen Faiss, Justina Dargvainiene, Kai Siebenbrodt, Karsten Witt, Katharina Eisenhut, Kathrin Doppler, Kerstin Hellwig, Kevin Rostásy, Klaus‐Peter Wandinger, Kristin Stefanie Melzer, Kurt‐Wolfram Sühs, Lara Zieger, Lena Edelhoff, Loana Penner, Luise Appeltshauser, Makbule Şenel, Manuel A. Friese, Marc Dürr, M. M. Gebhard, Marco Gallus, Marie Madlener, Marie‐Luise Mono, Marina Entscheva, Marina Flotats‐Bastardas, Marius Ringelstein, Markus Krämer, Martin Häusler, Martin Stangel, Martina Jansen, Matthias von Mering, Max Kaufmann, Mehtap Türedi, Michael Adelmann, Michael P. Malter, Michael Nagel, Muriel Stoppe, Nico Melzer, Niels Hansen, Oliver Stammel, Friedemann Paul, Peter Körtvélyessy, Peter Lange, Philip Hillebrand, Philipp Schwenkenbecher, Raphael Reinecke, Regina Trollmann, Robert L. Berger, Robert Handreka, Robert Weissert, Sarah Bernsen, Sascha Berning, Saskia Räuber, Sebastian Baatz, Sebastian Bauer, Sigrid Wöpking, Simone C. Tauber, Sonka Benesch, Stefan Bittner, Steffen Syrbe, Stephan Rüegg, Stephan J. Schreiber, Susanne Knake, Sven Ehrlich, Sven G. Meuth, Tanja Kümpfel, Thomas Pfefferkorn, Til Menge, Tobias Neumann‐Haefelin, Ulrich Hofstadt‐van Oy, Uwe K. Zettl, Valentin Held, Wolfgang Heide,

Genetics and Neurodevelopmental Disorders

Background and Objectives CSF in antibody-defined autoimmune encephalitis (AE) subtypes shows subtype-dependent degrees of inflammation ranging from rare and often mild to frequent and often robust. AEs with NMDA receptor antibodies (NMDAR-E) and leucine-rich glioma-inactivated protein 1 antibodies (LGI1-E) represent opposite ends of this spectrum: NMDAR-E with typically frequent/robust and LGI1-E with rare/mild CSF inflammation. For a more in-depth analysis, we characterized CSF findings in acute, therapy-naive NMDAR-E and LGI1-E in a multicentric, retrospective, cross-sectional setting. Methods Eighty-two patients with NMDAR-E and 36 patients with LGI1-E from the GErman NEtwork for Research of AuToimmune Encephalitis (GENERATE) with lumbar puncture within 90 days of onset and before immunotherapy were included. CSF parameters comprised leukocytes, oligoclonal bands (OCBs), and CSF/serum ratios for albumin, immunoglobulin G (IgG), A (IgA), and M (IgM), the latter 3 converted to Z scores according to Reiber formulas. The MRZ reaction was tested in 14 patients with NMDAR-E and 6 patients with LGI1-E, respectively. Results CSF was abnormal in 94% of NMDAR-E but only in 36% of LGI1-E patients. Robust quantitative intrathecal immunoglobulin synthesis (IIS, IgG > IgM >> IgA) was characteristic for NMDAR-E, but absent in LGI-E. In NMDAR-E, CSF leukocytes were higher when IIS was present or more pronounced. In addition, in NMDAR-E, CSF leukocytes were lower and IIS occurred less often and if so to a lesser degree at older age. Patients with NMDAR-E with severe functional impairment more often had positive OCBs. In CSF obtained later than 3 weeks of onset, leukocytes were lower. In parallel, the correlation of leukocytes with IIS disappeared as IIS was partially independent of disease duration. The MRZ reaction was positive in 5 (36%) patients with NMDAR-E. All these associations were completely absent in LGI1-E. Here, younger patients showed more blood-CSF barrier dysfunction. In LGI1-E, but not in NMDAR-E, the blood-CSF barrier was more dysfunctional when CSF leukocytes were higher. Discussion NMDAR-E and LGI-E differ in their typical extent of CSF inflammation. In addition, the patterns formed by the different inflammatory CSF parameters and their relationship with disease severity, age, and disease duration are subtype-characteristic. Moreover, signs for multiple sclerosis-like chronic inflammation are present in a subgroup of patients with NMDAR-E. These CSF patterns might be markers for the different immunopathogeneses of LGI1-E and NMDAR-E.