Seizure semiology in antibody-associated autoimmune encephalitis

Kaaden T, Madlener M, Angstwurm K, Bien CG, Bogarin Y, Doppler K, Finke A, Gerner ST, Reimann G, Häusler M, Handreka R, Hellwig K, Kaufmann M, Kellinghaus C, Koertvelyessy P, Kraft A, Lewerenz J, Menge T, Paliantonis A, von Podewils F, Prüss H, Rauer S, Ringelstein M, Rostásy K, Schirotzek I, Schwabe J, Sokolowski P, Suesse M, Sühs KW, Surges R, Tauber SC, Thaler F, Bergh FT, Urbanek C, Wandinger KP, Wildemann B, Mues S, Zettl U, Leypoldt F, Melzer N, Geis C, Malter M, Kunze A; and the Generate study group. Seizure Semiology in Antibody-Associated Autoimmune Encephalitis. Neurol Neuroimmunol Neuroinflamm. 2022 Oct 20;9(6):e200034. doi: 10.1212/NXI.0000000000200034. PMID: 36266054; PMCID: PMC9621609.

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.