Tobias Baumgartner, Moritz Freyberg, Lucia Campetella, Yvette Crijnen, Justina Dargvainiene, Charlotte Behning, Christian G Bien, Anna Rada, Harald Prüss, Rosa Rössling, Stjepana Kovac, Christine Strippel, Franziska S Thaler, Katharina Eisenhut, Jan Lewerenz, Felicitas Becker, Raphael Reinecke, Michael Peter Malter, Kurt-Wolfram Sühs, Simone C Tauber, Felix Von Podewils, Nico Melzer, Klaus-Peter Wandinger, Romina-Anna-Maria Fernandez Ceballos, Jens Kuhle, Klaus Berger, Tobias Bauer, Theodor Rüber, Attila Racz, Albert J Becker, Julika Pitsch, Gregor Kuhlenbäumer, Sergio Muñiz-Castrillo, Jerome Honnorat, Maarten J Titulaer, Frank Leypoldt, Rainer Surges
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Immunotherapy (IT) leads to the cessation of seizures in most patients, yet some develop AIE-associated epilepsy (AEAE) and persistent cognitive deficits. The aim of this large multicentric retrospective observational cohort study was to assess long-term outcomes of patients with anti-LGI1 encephalitis regarding seizures and AEAE and to identify associated factors.</p><p><strong>Methods: </strong>We included patients with anti-LGI1 encephalitis from 3 national referral centers/consortia meeting the following inclusion criteria: (I) definite LGI1 limbic encephalitis (Graus criteria); (II) occurrence of seizures; and (III) follow-up period ≥24 months. We aimed to (1) determine the risk of seizure recurrence (ROSR) on remission, (2) investigate clinical and paraclinical biomarkers for an effect on time to seizure remission using Cox proportional hazard modeling (n = 188), and (3) assess the risk of AEAE and determine associated factors (n = 236).</p><p><strong>Results: </strong>AEAE was observed in 5.9% (16/271) of the full cohort. Both AEAE (16/16 vs 129/215, <i>p</i> = 0.001) and longer time to seizure remission (OR 1.36 per year, <i>p</i> = 0.025) were associated with persistent cognitive impairment. Patients with pilomotor seizures had a lower rate of seizure remission (hazard ratio [HR] 0.58, 95% CI 0.55-0.60, <i>p</i> < 0.001) while patients under IT administration had a higher rate of seizure remission over time (HR 12.4, 95% CI 9.67-16.0, <i>p</i> < 0.001). In addition, patients receiving second-line IT tended to achieve earlier seizure remission (log-rank test, <i>p</i> = 0.019). The ROSR at 12, 60, and 120 months on seizure remission was 9% (95% CI 4.5%-13%), 20% (95% CI 11%-28%), and 53% (95% CI 14%-74%), respectively.</p><p><strong>Discussion: </strong>In conclusion, our results demonstrate that AEAE in anti-LGI1 encephalitis is rare and suggest that the diagnosis of epilepsy is inappropriate in patients reaching seizure remission because of a relatively low ROSR. Accordingly, on seizure remission, the diagnosis of acute symptomatic seizures would be appropriate. Moreover, we validate and quantify the importance of IT for seizure remission and identify biomarkers associated with lower rates of seizure remission. 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引用次数: 0
摘要
背景和目的：自身免疫性脑炎（AIE）伴抗富含亮氨酸的胶质瘤失活1 （LGI1）抗体，典型表现为亚急性认知障碍、癫痫发作和精神症状，主要发生在老年人中。免疫治疗（IT）导致大多数患者癫痫发作停止，但一些患者发展为ae相关癫痫（AEAE）和持续认知缺陷。这项大型多中心回顾性观察队列研究的目的是评估抗lgi1脑炎患者癫痫发作和AEAE的长期结局，并确定相关因素。方法：我们纳入了来自3个国家转诊中心/联盟的符合以下纳入标准的抗LGI1脑炎患者：(1)明确的LGI1边缘脑炎（Graus标准）；（二）癫痫发作情况；（三）随访≥24个月。我们的目的是(1)确定发作复发（ROSR）缓解的风险，(2)使用Cox比例风险模型研究临床和临床旁生物标志物对发作缓解时间的影响（n = 188），以及(3)评估AEAE的风险并确定相关因素（n = 236）。结果：全队列患者中有5.9%（16/271）出现AEAE。AEAE （16/16 vs 129/215, p = 0.001）和更长的癫痫发作缓解时间（OR 1.36 /年，p = 0.025）与持续性认知障碍相关。前驱运动发作患者的发作缓解率较低（风险比[HR] 0.58, 95% CI 0.55-0.60, p < 0.001），而接受IT治疗的患者随着时间的推移发作缓解率较高（风险比[HR] 12.4, 95% CI 9.67-16.0, p < 0.001）。此外，接受二线IT治疗的患者往往更早实现癫痫发作缓解（log-rank检验，p = 0.019）。癫痫发作缓解12、60和120个月时的ROSR分别为9% （95% CI 4.5%-13%）、20% （95% CI 11%-28%）和53% （95% CI 14%-74%）。讨论：总之，我们的研究结果表明，抗lgi1脑炎的AEAE是罕见的，并且由于相对较低的ROSR，在癫痫发作缓解的患者中诊断癫痫是不合适的。因此，在发作缓解时，诊断为急性症状性发作是合适的。此外，我们验证并量化了IT对癫痫发作缓解的重要性，并确定了与癫痫发作缓解率较低相关的生物标志物。癫痫发作晚期缓解和AEAE与持续性认知障碍相关。
Risk of Epilepsy and Factors Associated With Time to Seizure Remission in Anti-LGI1 Encephalitis: Long-Term Outcome in 236 Patients.
Background and objectives: Autoimmune encephalitis (AIE) with anti-leucine-rich glioma-inactivated 1 (LGI1) antibodies typically manifests with subacute cognitive deficits, seizures, and psychiatric symptoms, mostly in older adults. Immunotherapy (IT) leads to the cessation of seizures in most patients, yet some develop AIE-associated epilepsy (AEAE) and persistent cognitive deficits. The aim of this large multicentric retrospective observational cohort study was to assess long-term outcomes of patients with anti-LGI1 encephalitis regarding seizures and AEAE and to identify associated factors.
Methods: We included patients with anti-LGI1 encephalitis from 3 national referral centers/consortia meeting the following inclusion criteria: (I) definite LGI1 limbic encephalitis (Graus criteria); (II) occurrence of seizures; and (III) follow-up period ≥24 months. We aimed to (1) determine the risk of seizure recurrence (ROSR) on remission, (2) investigate clinical and paraclinical biomarkers for an effect on time to seizure remission using Cox proportional hazard modeling (n = 188), and (3) assess the risk of AEAE and determine associated factors (n = 236).
Results: AEAE was observed in 5.9% (16/271) of the full cohort. Both AEAE (16/16 vs 129/215, p = 0.001) and longer time to seizure remission (OR 1.36 per year, p = 0.025) were associated with persistent cognitive impairment. Patients with pilomotor seizures had a lower rate of seizure remission (hazard ratio [HR] 0.58, 95% CI 0.55-0.60, p < 0.001) while patients under IT administration had a higher rate of seizure remission over time (HR 12.4, 95% CI 9.67-16.0, p < 0.001). In addition, patients receiving second-line IT tended to achieve earlier seizure remission (log-rank test, p = 0.019). The ROSR at 12, 60, and 120 months on seizure remission was 9% (95% CI 4.5%-13%), 20% (95% CI 11%-28%), and 53% (95% CI 14%-74%), respectively.
Discussion: In conclusion, our results demonstrate that AEAE in anti-LGI1 encephalitis is rare and suggest that the diagnosis of epilepsy is inappropriate in patients reaching seizure remission because of a relatively low ROSR. Accordingly, on seizure remission, the diagnosis of acute symptomatic seizures would be appropriate. Moreover, we validate and quantify the importance of IT for seizure remission and identify biomarkers associated with lower rates of seizure remission. Late remission of seizures and AEAE were associated with persistent cognitive impairment.
期刊介绍：
Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.
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