Multicenter Study

. 2022 Oct 20;9(6):e200034.

doi: 10.1212/NXI.0000000000200034. Print 2022 Nov.

Seizure Semiology in Antibody-Associated Autoimmune Encephalitis

Tillman Kaaden¹, Marie Madlener², Klemens Angstwurm², Christian G Bien², Yuri Bogarin², Kathrin Doppler², Alexander Finke², Stefan T Gerner², Gernot Reimann², Martin Häusler², Robert Handreka², Kerstin Hellwig², Max Kaufmann², Christoph Kellinghaus², Peter Koertvelyessy², Andrea Kraft², Jan Lewerenz², Til Menge², Asterios Paliantonis², Felix von Podewils², Harald Prüss², Sebastian Rauer², Marius Ringelstein², Kevin Rostásy², Ingo Schirotzek², Julia Schwabe², Piotr Sokolowski², Marie Suesse², Kurt-Wolfram Sühs², Rainer Surges², Simone C Tauber², Franziska Thaler², Florian Then Bergh², Christian Urbanek², Klaus-P Wandinger², Brigitte Wildemann², Sigrid Mues², Uwe Zettl², Frank Leypoldt², Nico Melzer², Christian Geis², Michael Malter², Albrecht Kunze²; and the Generate study group

Affiliations

¹ From the Hans-Berger Department of Neurology (T.K., C.G., Albrecht Kunze), University Hospital Jena; Department of Neurology (Marie Madlener, Michael Malter), Faculty of Medicine and University Hospital Cologne, University of Cologne; Department of Neurology (K.A.), University of Regensburg; Department of Epileptology (Krankenhaus Mara) (C.G.B.), Bielefeld University, Medical School, Campus Bielefeld-Bethel; Department of Psychiatry and Psychotherapy (Y.B.), Asklepios Hospital Teupitz; Department of Neurology (K.D.), University of Würzburg; Department of Neurology (A.F.), Hospital Lüneburg; Department of Neurology (S.T.G.), University Hospital Erlangen; Department of Neurology (G.R.), Klinikum Dortmund; Department of Neuro-pediatrics (M.H.), RWTH University Hospital Aachen; Department of Neurology (R.H.), Carl-Thiem Klinikum Cottbus; Department of Neurology (K.H.), University of Bochum; Institut für Neuroimmunologie und Multiple Sklerose (M.K.), Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; Department of Neurology (C.K.), Klinikum Osnabrück; Department of Neurology (P.K.), University of Magdeburg; Department of Neurology (Andrea Kraft), Martha-Maria Hospital Halle; Department of Neurology (J.L.), University of Ulm; Department of Neurology (T.M., M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University Düsseldorf, Germany; Department of Neurology (A.P.), Klinikum Hirslanden, Zürich; Department of Neurology (F.v.P., M.S.), University of Greifswald; Department of Neurology and Experimental Neurology (H.P.), Charité Berlin, and German Center for Neurodegenerative Diseases (DZNE); Department of Neurology (S.R., N.M.), University of Freiburg; Department of Neurology (M.R.), Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany; Department of Neuropediatrics (K.R.), Vestische Kinder-und Jugendklinik Datteln; Department of Neurology (I.S.), University Hospital Giessen and Marburg, Giessen; Department of Neurology (J.S.), Asklepios Hospital Nord, Hamburg; Department of Neurology (P.S.), Hospital Hubertusburg, Wermsdorf; Department of Neurology (K.-W.S.), University Hospital Hannover; Department of Epileptology (R.S.), University Hospital Bonn; Department of Neurology (S.C.T.), RWTH University Hospital Aachen; Institute of Clinical Neuroimmunology (F.T.), University Hospital, Ludwig-Maximilians-Universität Munich, Germany and Biomedical Center (BMC), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried, Germany; Department of Neurology (F.T.B.), University of Leipzig; Department of Neurology (C.U.), Hospital Ludwigshafen; Institute of Clinical Chemistry (K.-P.W.), University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany; Department of Neurology (B.W.), University of Heidelberg; Department of Neurology (S.M.), University Hospital, Technische Universität Dresden; Universitätsklinikum Knappschaftskrankenhaus Bochum Langendreer (S.M.), Klinik für Neurologie; Department of Neurology (U.Z.), University of Rostock; Department of Neurology (F.L.), Christian-Albrechts-University Kiel; Department of Neurology with Institute of Translational Neurology (N.M.), University Hospital Muenster; and Department of Neurology (Albrecht Kunze), Zentralklinik Bad Berka, Germany. tillman.kaaden@med.uni-jena.de.
² From the Hans-Berger Department of Neurology (T.K., C.G., Albrecht Kunze), University Hospital Jena; Department of Neurology (Marie Madlener, Michael Malter), Faculty of Medicine and University Hospital Cologne, University of Cologne; Department of Neurology (K.A.), University of Regensburg; Department of Epileptology (Krankenhaus Mara) (C.G.B.), Bielefeld University, Medical School, Campus Bielefeld-Bethel; Department of Psychiatry and Psychotherapy (Y.B.), Asklepios Hospital Teupitz; Department of Neurology (K.D.), University of Würzburg; Department of Neurology (A.F.), Hospital Lüneburg; Department of Neurology (S.T.G.), University Hospital Erlangen; Department of Neurology (G.R.), Klinikum Dortmund; Department of Neuro-pediatrics (M.H.), RWTH University Hospital Aachen; Department of Neurology (R.H.), Carl-Thiem Klinikum Cottbus; Department of Neurology (K.H.), University of Bochum; Institut für Neuroimmunologie und Multiple Sklerose (M.K.), Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; Department of Neurology (C.K.), Klinikum Osnabrück; Department of Neurology (P.K.), University of Magdeburg; Department of Neurology (Andrea Kraft), Martha-Maria Hospital Halle; Department of Neurology (J.L.), University of Ulm; Department of Neurology (T.M., M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University Düsseldorf, Germany; Department of Neurology (A.P.), Klinikum Hirslanden, Zürich; Department of Neurology (F.v.P., M.S.), University of Greifswald; Department of Neurology and Experimental Neurology (H.P.), Charité Berlin, and German Center for Neurodegenerative Diseases (DZNE); Department of Neurology (S.R., N.M.), University of Freiburg; Department of Neurology (M.R.), Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany; Department of Neuropediatrics (K.R.), Vestische Kinder-und Jugendklinik Datteln; Department of Neurology (I.S.), University Hospital Giessen and Marburg, Giessen; Department of Neurology (J.S.), Asklepios Hospital Nord, Hamburg; Department of Neurology (P.S.), Hospital Hubertusburg, Wermsdorf; Department of Neurology (K.-W.S.), University Hospital Hannover; Department of Epileptology (R.S.), University Hospital Bonn; Department of Neurology (S.C.T.), RWTH University Hospital Aachen; Institute of Clinical Neuroimmunology (F.T.), University Hospital, Ludwig-Maximilians-Universität Munich, Germany and Biomedical Center (BMC), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried, Germany; Department of Neurology (F.T.B.), University of Leipzig; Department of Neurology (C.U.), Hospital Ludwigshafen; Institute of Clinical Chemistry (K.-P.W.), University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany; Department of Neurology (B.W.), University of Heidelberg; Department of Neurology (S.M.), University Hospital, Technische Universität Dresden; Universitätsklinikum Knappschaftskrankenhaus Bochum Langendreer (S.M.), Klinik für Neurologie; Department of Neurology (U.Z.), University of Rostock; Department of Neurology (F.L.), Christian-Albrechts-University Kiel; Department of Neurology with Institute of Translational Neurology (N.M.), University Hospital Muenster; and Department of Neurology (Albrecht Kunze), Zentralklinik Bad Berka, Germany.

PMID: 36266054
PMCID: PMC9621609
DOI: 10.1212/NXI.0000000000200034

Multicenter Study

Seizure Semiology in Antibody-Associated Autoimmune Encephalitis

Tillman Kaaden et al. Neurol Neuroimmunol Neuroinflamm. 2022.

. 2022 Oct 20;9(6):e200034.

doi: 10.1212/NXI.0000000000200034. Print 2022 Nov.

Authors

Affiliations

¹ From the Hans-Berger Department of Neurology (T.K., C.G., Albrecht Kunze), University Hospital Jena; Department of Neurology (Marie Madlener, Michael Malter), Faculty of Medicine and University Hospital Cologne, University of Cologne; Department of Neurology (K.A.), University of Regensburg; Department of Epileptology (Krankenhaus Mara) (C.G.B.), Bielefeld University, Medical School, Campus Bielefeld-Bethel; Department of Psychiatry and Psychotherapy (Y.B.), Asklepios Hospital Teupitz; Department of Neurology (K.D.), University of Würzburg; Department of Neurology (A.F.), Hospital Lüneburg; Department of Neurology (S.T.G.), University Hospital Erlangen; Department of Neurology (G.R.), Klinikum Dortmund; Department of Neuro-pediatrics (M.H.), RWTH University Hospital Aachen; Department of Neurology (R.H.), Carl-Thiem Klinikum Cottbus; Department of Neurology (K.H.), University of Bochum; Institut für Neuroimmunologie und Multiple Sklerose (M.K.), Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; Department of Neurology (C.K.), Klinikum Osnabrück; Department of Neurology (P.K.), University of Magdeburg; Department of Neurology (Andrea Kraft), Martha-Maria Hospital Halle; Department of Neurology (J.L.), University of Ulm; Department of Neurology (T.M., M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University Düsseldorf, Germany; Department of Neurology (A.P.), Klinikum Hirslanden, Zürich; Department of Neurology (F.v.P., M.S.), University of Greifswald; Department of Neurology and Experimental Neurology (H.P.), Charité Berlin, and German Center for Neurodegenerative Diseases (DZNE); Department of Neurology (S.R., N.M.), University of Freiburg; Department of Neurology (M.R.), Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany; Department of Neuropediatrics (K.R.), Vestische Kinder-und Jugendklinik Datteln; Department of Neurology (I.S.), University Hospital Giessen and Marburg, Giessen; Department of Neurology (J.S.), Asklepios Hospital Nord, Hamburg; Department of Neurology (P.S.), Hospital Hubertusburg, Wermsdorf; Department of Neurology (K.-W.S.), University Hospital Hannover; Department of Epileptology (R.S.), University Hospital Bonn; Department of Neurology (S.C.T.), RWTH University Hospital Aachen; Institute of Clinical Neuroimmunology (F.T.), University Hospital, Ludwig-Maximilians-Universität Munich, Germany and Biomedical Center (BMC), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried, Germany; Department of Neurology (F.T.B.), University of Leipzig; Department of Neurology (C.U.), Hospital Ludwigshafen; Institute of Clinical Chemistry (K.-P.W.), University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany; Department of Neurology (B.W.), University of Heidelberg; Department of Neurology (S.M.), University Hospital, Technische Universität Dresden; Universitätsklinikum Knappschaftskrankenhaus Bochum Langendreer (S.M.), Klinik für Neurologie; Department of Neurology (U.Z.), University of Rostock; Department of Neurology (F.L.), Christian-Albrechts-University Kiel; Department of Neurology with Institute of Translational Neurology (N.M.), University Hospital Muenster; and Department of Neurology (Albrecht Kunze), Zentralklinik Bad Berka, Germany. tillman.kaaden@med.uni-jena.de.
² From the Hans-Berger Department of Neurology (T.K., C.G., Albrecht Kunze), University Hospital Jena; Department of Neurology (Marie Madlener, Michael Malter), Faculty of Medicine and University Hospital Cologne, University of Cologne; Department of Neurology (K.A.), University of Regensburg; Department of Epileptology (Krankenhaus Mara) (C.G.B.), Bielefeld University, Medical School, Campus Bielefeld-Bethel; Department of Psychiatry and Psychotherapy (Y.B.), Asklepios Hospital Teupitz; Department of Neurology (K.D.), University of Würzburg; Department of Neurology (A.F.), Hospital Lüneburg; Department of Neurology (S.T.G.), University Hospital Erlangen; Department of Neurology (G.R.), Klinikum Dortmund; Department of Neuro-pediatrics (M.H.), RWTH University Hospital Aachen; Department of Neurology (R.H.), Carl-Thiem Klinikum Cottbus; Department of Neurology (K.H.), University of Bochum; Institut für Neuroimmunologie und Multiple Sklerose (M.K.), Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; Department of Neurology (C.K.), Klinikum Osnabrück; Department of Neurology (P.K.), University of Magdeburg; Department of Neurology (Andrea Kraft), Martha-Maria Hospital Halle; Department of Neurology (J.L.), University of Ulm; Department of Neurology (T.M., M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University Düsseldorf, Germany; Department of Neurology (A.P.), Klinikum Hirslanden, Zürich; Department of Neurology (F.v.P., M.S.), University of Greifswald; Department of Neurology and Experimental Neurology (H.P.), Charité Berlin, and German Center for Neurodegenerative Diseases (DZNE); Department of Neurology (S.R., N.M.), University of Freiburg; Department of Neurology (M.R.), Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany; Department of Neuropediatrics (K.R.), Vestische Kinder-und Jugendklinik Datteln; Department of Neurology (I.S.), University Hospital Giessen and Marburg, Giessen; Department of Neurology (J.S.), Asklepios Hospital Nord, Hamburg; Department of Neurology (P.S.), Hospital Hubertusburg, Wermsdorf; Department of Neurology (K.-W.S.), University Hospital Hannover; Department of Epileptology (R.S.), University Hospital Bonn; Department of Neurology (S.C.T.), RWTH University Hospital Aachen; Institute of Clinical Neuroimmunology (F.T.), University Hospital, Ludwig-Maximilians-Universität Munich, Germany and Biomedical Center (BMC), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried, Germany; Department of Neurology (F.T.B.), University of Leipzig; Department of Neurology (C.U.), Hospital Ludwigshafen; Institute of Clinical Chemistry (K.-P.W.), University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany; Department of Neurology (B.W.), University of Heidelberg; Department of Neurology (S.M.), University Hospital, Technische Universität Dresden; Universitätsklinikum Knappschaftskrankenhaus Bochum Langendreer (S.M.), Klinik für Neurologie; Department of Neurology (U.Z.), University of Rostock; Department of Neurology (F.L.), Christian-Albrechts-University Kiel; Department of Neurology with Institute of Translational Neurology (N.M.), University Hospital Muenster; and Department of Neurology (Albrecht Kunze), Zentralklinik Bad Berka, Germany.

PMID: 36266054
PMCID: PMC9621609
DOI: 10.1212/NXI.0000000000200034

Abstract

Background and objectives: To assess seizure characteristics in antibody (ab)-associated autoimmune encephalitis (ab + AE) with the 3 most prevalent abs against N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), and glutamic acid decarboxylase (GAD).

Methods: Multicenter nationwide prospective cohort study of the German Network for Research in Autoimmune Encephalitis.

Results: Three hundred twenty patients with ab + AE were eligible for analysis: 190 NMDAR+, 89 LGI1+, and 41 GAD+. Seizures were present in 113 (60%) NMDAR+, 69 (78%) LGI1+, and 26 (65%) GAD+ patients and as leading symptoms for diagnosis in 53 (28%) NMDAR+, 47 (53%) LGI+, and 20 (49%) GAD+ patients. Bilateral tonic-clonic seizures occurred with almost equal frequency in NMDAR+ (38/51, 75%) and GAD+ (14/20, 70%) patients, while being less common in LGI1+ patients (27/59, 46%). Focal seizures occurred less frequently in NMDAR+ (67/113; 59%) than in LGI1+ (54/69, 78%) or in GAD+ patients (23/26; 88%). An aura with déjà-vu phenomenon was nearly specific in GAD+ patients (16/20, 80%). Faciobrachial dystonic seizures (FBDS) were uniquely observed in LGI1+ patients (17/59, 29%). Status epilepticus was reported in one-third of NMDAR+ patients, but only rarely in the 2 other groups. The occurrence of seizures was associated with higher disease severity only in NMDAR+ patients.

Discussion: Seizures are a frequent and diagnostically relevant symptom of ab + AE. Whereas NMDAR+ patients had few localizing semiological features, semiology in LGI1+ and GAD+ patients pointed toward a predominant temporal seizure onset. FBDS are pathognomonic for LGI1 + AE. Status epilepticus seems to be more frequent in NMDAR + AE.

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Figures

**Figure 1. Scores of the Modified Rankin Scale (mRS) at Disease Maximum in the Acute Stage**
(A) Shows the distribution of scores of all patients in the 3 subgroups of ab + AE. mRS was significantly higher in NMDAR+ patients in comparison with that in LGI1+ (mRS >4, OR = 11.2, p < 0.001) and GAD+ patients (mRS >4, OR = 6.2, p < 0.001). (B) Shows the scores in patients with and without seizures within the individual ab + subgroups. In the NMDAR+ subgroup, the occurrence of seizures was associated with a 2.8-fold increased risk to show a higher level of disease severity (mRS >4, OR = 2.800; p < 0.001), whereas it had no significant effect in LGI1+ and GAD+ patients. GAD = glutamic acid decarboxylase; LGI1 = leucine-rich glioma-inactivated protein 1; NMDAR = N-methyl-d-aspartate receptor.

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Comment in

Registry-Based Phenotyping to Improve the Diagnosis of Autoimmune Encephalitis.
Steriade C. Steriade C. Epilepsy Curr. 2023 Apr 12;23(3):166-168. doi: 10.1177/15357597231162488. eCollection 2023 May-Jun. Epilepsy Curr. 2023. PMID: 37334419 Free PMC article. No abstract available.

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1. Graus F, Titulaer MJ, Balu R, et al. . A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404. - PMC - PubMed
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Seizure Semiology in Antibody-Associated Autoimmune Encephalitis

Affiliations

Seizure Semiology in Antibody-Associated Autoimmune Encephalitis

Authors

Affiliations

Abstract

Figures

Comment in

References

Publication types

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous