Registry-Based Phenotyping to Improve the Diagnosis of Autoimmune Encephalitis

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, Hausler M, Handreka R, Hellwig K, Kaufmann M, Kellinghaus C, Koertvelyessy P, Kraft A, Lewerenz J, Menge T, Paliantonis A, von Podewils F, Pruss H, Rauer S, Ringelstein M, Rostasy K, Schirotzek I, Schwabe J, Sokolowski P, Suesse M, Suhs K-W, Surges R, Tauber SC, Thaler F, Bergh FT, Urbanek C, Wandinger K-P, Wildemann B, Mues S, Zettl U, Leypoldt F, Melzer N, Geis C, Malter M, Kunze A; The Generate Study Group. Neurol Neuroimmunol Neuroinflamm. 2022;9(6):e200034. doi:10.1212/NXI.0000000000200034 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 deja-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. Epileptic Phenotypes in Autoimmune Encephalitis: From Acute Symptomatic Seizures to Autoimmune-Associated Epilepsy Matricardi S, Casciato S, Bozzetti S, Mariotto S, Stabile A, Freri E, Deleo F, Sartori S, Nosadini M, Pappalardo I, Meletti S, Giovannini G, Zucchi E, Di Bonaventura C, Di Gennaro G, Ferrari S, Zuliani L, Zoccarato M, Vogrig A, Lattanzi S, Michelucci R, Gambardella A, Ferlazzo E, Fusco L, Granata T, Villani F; On behalf of the Immune Epilepsies Study Group of the Italian League Against Epilepsy. J Neurol Neurosurg Psychiatry. 2022;93(11). doi:10.1136/jnnp-2022-329195 Objective: To describe the clinical and paraclinical findings, treatment options and long-term outcomes in autoimmune encephalitis (AE), with a close look to epilepsy. Methods: In this retrospective observational cohort study, we enrolled patients with new-onset seizures in the context of AE. We compared clinical and paraclinical findings in patients with and without evidence of antibodies. Results: Overall, 263 patients (138 females; median age 55 years, range 4-86) were followed up for a median time of 30 months (range 12-120). Antineuronal antibodies were detected in 63.50%. Antibody-positive patients had multiple seizure types (p = 0.01) and prevalent involvement of temporal regions (p = 0.02). A higher prevalence of episodes of SE was found in the antibody-negative group (p < 0.001). Immunotherapy was prescribed in 88.60%, and effective in 61.80%. Independent predictors of favourable outcome of the AE were early immunotherapy (p < 0.001) and the detection of antineuronal surface antibodies (p = 0.01). Autoimmune-associated epilepsy was the long-term sequela in 43.73%, associated with cognitive and psychiatric disturbances in 81.73%. Independent predictors of developing epilepsy were difficult to treat seizures at onset (p = 0.04), a high number of antiseizure medications (p < 0.001), persisting interictal epileptiform discharges at follow-up (p < 0.001) and poor response to immunotherapy during the acute phase (p < 0.001). Conclusions: The recognition of seizures secondary to AE represents a rare chance for aetiology-driven seizures management. Early recognition and treatment at the pathogenic level may reduce the risk of long-term irreversible sequelae. However, the severity of seizures at onset is the major risk factor for the development of chronic epilepsy. This study provides class IV evidence for management recommendations.