TY - JOUR
T1 - Risk of Epilepsy and Factors Associated With Time to Seizure Remission in Anti-LGI1 Encephalitis
T2 - Long-Term Outcome in 236 Patients
AU - Baumgartner, Tobias
AU - Freyberg, Moritz
AU - and the GENERATE study group
AU - Campetella, Lucia
AU - Crijnen, Yvette
AU - Dargvainiene, Justina
AU - Behning, Charlotte
AU - Bien, Christian G.
AU - Rada, Anna
AU - Prüss, Harald
AU - Rössling, Rosa
AU - Kovac, Stjepana
AU - Strippel, Christine
AU - Thaler, Franziska S.
AU - Eisenhut, Katharina
AU - Lewerenz, Jan
AU - Becker, Felicitas
AU - Reinecke, Raphael
AU - Malter, Michael Peter
AU - Sühs, Kurt Wolfram
AU - Tauber, Simone C.
AU - Von Podewils, Felix
AU - Melzer, Nico
AU - Wandinger, Klaus Peter
AU - Fernandez Ceballos, Romina Anna Maria
AU - Kuhle, Jens
AU - Berger, Klaus
AU - Bauer, Tobias
AU - Rüber, Theodor
AU - Racz, Attila
AU - Becker, Albert J.
AU - Pitsch, Julika
AU - Kuhlenbäumer, Gregor
AU - Muñiz-Castrillo, Sergio
AU - Honnorat, Jerome
AU - Titulaer, Maarten J.
AU - Leypoldt, Frank
AU - Surges, Rainer
N1 - Publisher Copyright:
Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2025/9/15
Y1 - 2025/9/15
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105016473273
U2 - 10.1212/NXI.0000000000200469
DO - 10.1212/NXI.0000000000200469
M3 - Article
C2 - 40953325
AN - SCOPUS:105016473273
SN - 2332-7812
VL - 12
JO - Neurology(R) neuroimmunology & neuroinflammation
JF - Neurology(R) neuroimmunology & neuroinflammation
IS - 6
M1 - e200469
ER -