TY - JOUR
T1 - Relapses, Comorbidities, and Predictors of Outcome in Anti-GABAA Receptor Encephalitis
AU - Papi, Claudia
AU - Milano, Chiara
AU - Anti-GABAAR encephalitis study group
AU - Marmolejo, Laura
AU - Serafim, Ana Beatriz
AU - Aguilar, Esther
AU - Guasp, Mar
AU - Fonseca, Elianet
AU - Simabukuro, Mateus Mistieri
AU - Iorio, Raffaele
AU - Fukami, Yuki
AU - Santos, Maria Lucia Schmitz Ferreira
AU - Miwa, Takashi
AU - Araga, Takashi
AU - Uchida, Yuto
AU - Kurihara, Masanori
AU - Okada, Satoshi
AU - Garcia, Luz Victoria
AU - Kaida, Kenichi
AU - Cunha, Natalia Spinola Costa da
AU - Vogrig, Alberto
AU - Lamblin, Florian
AU - de Vries, Juna M.
AU - Dutra, Livia Almeida
AU - Höftberger, Romana
AU - Titulaer, Maarten J.
AU - Planagumà, Jesús
AU - Sabater, Lidia
AU - Martinez-Hernandez, Eugenia
AU - Armangué, Thais
AU - Graus, Francesc
AU - Iizuka, Takahiro
AU - Dalmau, Josep
AU - Spatola, Marianna
N1 - Publisher Copyright:
© 2026 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2026/7
Y1 - 2026/7
N2 - Objectives: To characterize the magnetic resonance imaging (MRI) lesion dynamics, comorbidities, predictors of relapse, and outcomes in anti-γ-aminobutyric acid type A receptor (GABAAR) encephalitis, and assess the utility of LIM-domain-only-protein 5 (LMO5) antibodies as tumor markers. Methods:GABAAR antibodies were confirmed by 2 techniques in serum or cerebrospinal fluid. Long-term outcomes were defined as good (modified Rankin scale, mRS = 0–1) or poor (mRS 2–5) at ≥12 months. LMO5 antibodies were assessed by cell-based assays and Western blot. Results: Thirty-three patients were identified (4 children, 29 adults; median age, 5.5 and 60 years; 61% male). Ten patients (10/32, 31%) had concurrent systemic autoimmunity. Adults presented with seizures and cognitive/behavioral symptoms, often with thymoma, gastrointestinal, or other tumors (18/33, 55%), whereas children frequently had seizures and ataxia with cerebellar MRI lesions. Multifocal T2/fluid-attenuated inversion recovery hyperintensities were present at onset in 23 of 31 (74%) or developed later in those with absent or single lesions. Lesions showed dynamic changes, suggesting ongoing inflammation even without clinical correlate. Relapses occurred in 17 of 31 (55%, all adults) and were associated with older age (p = 0.02) and lack of second-line immunotherapy (p = 0.02). Four patients (4/33, 12%) died. After a 32.5-month median follow-up, 9 of 20 (45%) had persistent cognitive deficits, and 6 of 20 (30%) had a poor outcome, which was associated with relapses (p = 0.04). LMO5 antibodies were absent in patients and controls. Interpretation: Anti-GABAAR encephalitis shows age-dependent presentations, most commonly seizures. MRI reveals dynamic changes consistent with an ongoing “clinically silent” inflammation. Relapses and cognitive sequelae are common and associate with not receiving second-line immunotherapy. LMO5 antibodies lack tumor-predictive value. ANN NEUROL 2026;100:139–150.
AB - Objectives: To characterize the magnetic resonance imaging (MRI) lesion dynamics, comorbidities, predictors of relapse, and outcomes in anti-γ-aminobutyric acid type A receptor (GABAAR) encephalitis, and assess the utility of LIM-domain-only-protein 5 (LMO5) antibodies as tumor markers. Methods:GABAAR antibodies were confirmed by 2 techniques in serum or cerebrospinal fluid. Long-term outcomes were defined as good (modified Rankin scale, mRS = 0–1) or poor (mRS 2–5) at ≥12 months. LMO5 antibodies were assessed by cell-based assays and Western blot. Results: Thirty-three patients were identified (4 children, 29 adults; median age, 5.5 and 60 years; 61% male). Ten patients (10/32, 31%) had concurrent systemic autoimmunity. Adults presented with seizures and cognitive/behavioral symptoms, often with thymoma, gastrointestinal, or other tumors (18/33, 55%), whereas children frequently had seizures and ataxia with cerebellar MRI lesions. Multifocal T2/fluid-attenuated inversion recovery hyperintensities were present at onset in 23 of 31 (74%) or developed later in those with absent or single lesions. Lesions showed dynamic changes, suggesting ongoing inflammation even without clinical correlate. Relapses occurred in 17 of 31 (55%, all adults) and were associated with older age (p = 0.02) and lack of second-line immunotherapy (p = 0.02). Four patients (4/33, 12%) died. After a 32.5-month median follow-up, 9 of 20 (45%) had persistent cognitive deficits, and 6 of 20 (30%) had a poor outcome, which was associated with relapses (p = 0.04). LMO5 antibodies were absent in patients and controls. Interpretation: Anti-GABAAR encephalitis shows age-dependent presentations, most commonly seizures. MRI reveals dynamic changes consistent with an ongoing “clinically silent” inflammation. Relapses and cognitive sequelae are common and associate with not receiving second-line immunotherapy. LMO5 antibodies lack tumor-predictive value. ANN NEUROL 2026;100:139–150.
UR - https://www.scopus.com/pages/publications/105036651116
U2 - 10.1002/ana.78208
DO - 10.1002/ana.78208
M3 - Article
C2 - 41968416
AN - SCOPUS:105036651116
SN - 0364-5134
VL - 100
SP - 139
EP - 150
JO - Annals of Neurology
JF - Annals of Neurology
IS - 1
ER -