CSF Findings in Acute NMDAR and LGI1 Antibody-Associated Autoimmune Encephalitis
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CSF Findings in Acute NMDAR and LGI1 Antibody-Associated Autoimmune Encephalitis. / Dürr, Marc; Nissen, Gunnar; Sühs, Kurt-Wolfram; Schwenkenbecher, Philipp; Geis, Christian; Ringelstein, Marius; Hartung, Hans-Peter; Friese, Manuel A; Kaufmann, Max; Malter, Michael P; Madlener, Marie; Thaler, Franziska S; Kümpfel, Tania; Senel, Makbule; Häusler, Martin G; Schneider, Hauke; Bergh, Florian Then; Kellinghaus, Christoph; Zettl, Uwe K; Wandinger, Klaus-Peter; Melzer, Nico; Gross, Catharina C; Lange, Peter; Dreyhaupt, Jens; Tumani, Hayrettin; Leypoldt, Frank; Lewerenz, Jan; German Network for Research on Autoimmune Encephalitis (GENERATE).
in: NEUROL-NEUROIMMUNOL, Jahrgang 8, Nr. 6, 11.2021, S. e1086.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - CSF Findings in Acute NMDAR and LGI1 Antibody-Associated Autoimmune Encephalitis
AU - Dürr, Marc
AU - Nissen, Gunnar
AU - Sühs, Kurt-Wolfram
AU - Schwenkenbecher, Philipp
AU - Geis, Christian
AU - Ringelstein, Marius
AU - Hartung, Hans-Peter
AU - Friese, Manuel A
AU - Kaufmann, Max
AU - Malter, Michael P
AU - Madlener, Marie
AU - Thaler, Franziska S
AU - Kümpfel, Tania
AU - Senel, Makbule
AU - Häusler, Martin G
AU - Schneider, Hauke
AU - Bergh, Florian Then
AU - Kellinghaus, Christoph
AU - Zettl, Uwe K
AU - Wandinger, Klaus-Peter
AU - Melzer, Nico
AU - Gross, Catharina C
AU - Lange, Peter
AU - Dreyhaupt, Jens
AU - Tumani, Hayrettin
AU - Leypoldt, Frank
AU - Lewerenz, Jan
AU - German Network for Research on Autoimmune Encephalitis (GENERATE)
N1 - Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
U2 - 10.1212/NXI.0000000000001086
DO - 10.1212/NXI.0000000000001086
M3 - SCORING: Journal article
C2 - 34697224
VL - 8
SP - e1086
JO - NEUROL-NEUROIMMUNOL
JF - NEUROL-NEUROIMMUNOL
SN - 2332-7812
IS - 6
ER -