Anna Rada1, Robert Birnbacher2, Claudio Gobbi3,4, Martin Kurthen5, Albert Ludolph6, Markus Naumann7, Ulrike Neirich8, Tim J von Oertzen9, Gerhard Ransmayr10, Matthias Riepe11, Mareike Schimmel12, Oliver Schwartz13, Rainer Surges14, Christian G Bien15,16. 1. Epilepsy Center Bethel, Krankenhaus Mara, Epilepsy Centre Bethel, Krankenhaus Mara, Maraweg 17-21, 33617, Bielefeld, Germany. 2. Department of Pediatrics and Adolescent Medicine, Villach General Hospital, Villach, Austria. 3. Department of Neurology, Neurocenter of Southern Switzerland (NSI), 6900, Lugano, Switzerland. 4. Faculty of Biomedical Sciences, Università Della Svizzera Italiana (USI), 6900, Lugano, Switzerland. 5. Swiss Epilepsy Center, Zürich, Switzerland. 6. Department of Neurology, University of Ulm, Ulm, Germany. 7. Department of Neurology and Clinical Neurophysiology, University of Augsburg, Augsburg, Germany. 8. Department of Pediatrics, Neurology, Stiftungskrankenhäuser Frankfurt Am Main, Clementine Kinderhospital, Frankfurt am Main, Germany. 9. Department of Neurology 1, Kepler University Hospital GmbH, Johannes Kepler University Linz, Linz, Austria. 10. Department of Neurology 2, Kepler University Hospital GmbH, Johannes Kepler University Linz, Linz, Austria. 11. Division of Gerontopsychiatry, Ulm University, Günzburg, Germany. 12. Department of Pediatrics, Section of Neuropediatrics, University of Augsburg, Augsburg, Germany. 13. Department of Pediatric Neurology, Münster University Hospital, Münster, Germany. 14. Department of Epileptology, University Hospital of Bonn, Bonn, Germany. 15. Epilepsy Center Bethel, Krankenhaus Mara, Epilepsy Centre Bethel, Krankenhaus Mara, Maraweg 17-21, 33617, Bielefeld, Germany. christian.bien@gmx.de. 16. Laboratory Krone, Bad Salzuflen, Germany. christian.bien@gmx.de.
Abstract
BACKGROUND: Clinicians have questioned whether any disorder involving seizures and neural antibodies should be called "(auto)immune epilepsy." The concept of "acute symptomatic seizures" may be more applicable in cases with antibodies against neural cell surface antigens. We aimed at determining the probability of achieving seizure-freedom, the use of anti-seizure medication (ASM), and immunotherapy in patients with either constellation. As a potential pathophysiological correlate, we analyzed antibody titer courses. METHODS: Retrospective cohort study of 39 patients with seizures and neural antibodies, follow-up ≥ 3 years. RESULTS: Patients had surface antibodies against the N-methyl-D-aspartate receptor (NMDAR, n = 6), leucine-rich glioma inactivated protein 1 (LGI1, n = 11), contactin-associated protein-2 (CASPR2, n = 8), or antibodies against the intracellular antigens glutamic acid decarboxylase 65 kDa (GAD65, n = 13) or Ma2 (n = 1). Patients with surface antibodies reached first seizure-freedom (88% vs. 7%, P < 0.001) and terminal seizure-freedom (80% vs. 7%, P < 0.001) more frequently. The time to first and terminal seizure-freedom and the time to freedom from ASM were shorter in the surface antibody group (Kaplan-Meier curves: P < 0.0001 for first seizure-freedom; P < 0.0001 for terminal seizure-freedom; P = 0.0042 for terminal ASM-freedom). Maximum ASM defined daily doses were higher in the groups with intracellular antibodies. Seizure-freedom was achieved after additional immunotherapy, not always accompanied by increased ASM doses. Titers of surface antibodies but not intracellular antibodies decreased over time. CONCLUSION: Seizures with surface antibodies should mostly be considered acute symptomatic and transient and not indicative of epilepsy. This has consequences for ASM prescription and social restrictions. Antibody titers correlate with clinical courses.
BACKGROUND: Clinicians have questioned whether any disorder involving seizures and neural antibodies should be called "(auto)immune epilepsy." The concept of "acute symptomatic seizures" may be more applicable in cases with antibodies against neural cell surface antigens. We aimed at determining the probability of achieving seizure-freedom, the use of anti-seizure medication (ASM), and immunotherapy in patients with either constellation. As a potential pathophysiological correlate, we analyzed antibody titer courses. METHODS: Retrospective cohort study of 39 patients with seizures and neural antibodies, follow-up ≥ 3 years. RESULTS:Patients had surface antibodies against the N-methyl-D-aspartate receptor (NMDAR, n = 6), leucine-rich glioma inactivated protein 1 (LGI1, n = 11), contactin-associated protein-2 (CASPR2, n = 8), or antibodies against the intracellular antigens glutamic acid decarboxylase 65 kDa (GAD65, n = 13) or Ma2 (n = 1). Patients with surface antibodies reached first seizure-freedom (88% vs. 7%, P < 0.001) and terminal seizure-freedom (80% vs. 7%, P < 0.001) more frequently. The time to first and terminal seizure-freedom and the time to freedom from ASM were shorter in the surface antibody group (Kaplan-Meier curves: P < 0.0001 for first seizure-freedom; P < 0.0001 for terminal seizure-freedom; P = 0.0042 for terminal ASM-freedom). Maximum ASM defined daily doses were higher in the groups with intracellular antibodies. Seizure-freedom was achieved after additional immunotherapy, not always accompanied by increased ASM doses. Titers of surface antibodies but not intracellular antibodies decreased over time. CONCLUSION:Seizures with surface antibodies should mostly be considered acute symptomatic and transient and not indicative of epilepsy. This has consequences for ASM prescription and social restrictions. Antibody titers correlate with clinical courses.
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