Marianna Spatola1, Mar Petit-Pedrol1, Mateus Mistieri Simabukuro1, Thaís Armangue1, Fernanda J Castro1, Maria I Barcelo Artigues1, Maria R Julià Benique1, Leslie Benson1, Mark Gorman1, Ana Felipe1, Ruben L Caparó Oblitas1, Myrna R Rosenfeld1, Francesc Graus1, Josep Dalmau2. 1. From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (M.S., M.P.-P., T.A., M.R.R., F.G., J.D.), University of Barcelona, Spain; University of Lausanne (UNIL) (M.S.), Switzerland; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) (M.P.-P., T.A., M.R.R., J.D., F.G.), Madrid, Spain; Neurology Service (T.A., J.D.), Hospital Sant Joan de Déu, Barcelona, Spain; Neurology Division, Hospital das Clínicas (M.M.S.), São Paulo University, Brazil; Hospital de Base (F.J.C.), Brasília, Brazil; Service of Neurology (M.I.B.A.) and Service of Immunology (M.R.J.B.), University Hospital of Son Espases, Mallorca, Spain; Department of Neurology (L.B., M.G.), Children's Hospital, Boston, MA; Pediatric Neurology Section (A.F.), Vall d'Hebron University Hospital, Barcelona, Spain; Hospital Nacional Edgardo Rebagliati Martins (R.L.C.O.), Lima, Peru; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; Service of Neurology (F.G., J.D.), Hospital Clínic; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain. 2. From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (M.S., M.P.-P., T.A., M.R.R., F.G., J.D.), University of Barcelona, Spain; University of Lausanne (UNIL) (M.S.), Switzerland; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) (M.P.-P., T.A., M.R.R., J.D., F.G.), Madrid, Spain; Neurology Service (T.A., J.D.), Hospital Sant Joan de Déu, Barcelona, Spain; Neurology Division, Hospital das Clínicas (M.M.S.), São Paulo University, Brazil; Hospital de Base (F.J.C.), Brasília, Brazil; Service of Neurology (M.I.B.A.) and Service of Immunology (M.R.J.B.), University Hospital of Son Espases, Mallorca, Spain; Department of Neurology (L.B., M.G.), Children's Hospital, Boston, MA; Pediatric Neurology Section (A.F.), Vall d'Hebron University Hospital, Barcelona, Spain; Hospital Nacional Edgardo Rebagliati Martins (R.L.C.O.), Lima, Peru; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; Service of Neurology (F.G., J.D.), Hospital Clínic; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain. Jdalmau@clinic.ub.es.
Abstract
OBJECTIVE: To report the clinical features, comorbidities, receptor subunit targets, and outcome in patients with anti-GABAA receptor (GABAAR) encephalitis. METHODS: Clinical study of 26 patients, including 17 new (April 2013-January 2016) and 9 previously reported patients. Antibodies to α1, β3, and γ2 subunits of the GABAAR were determined using reported techniques. RESULTS: Patients' median age was 40.5 years (interquartile range 48.5 [13.75-62.35] years; the youngest 2.5 months old; 13 female). Symptoms included seizures (88%), alteration of cognition (67%), behavior (46%), consciousness (42%), or abnormal movements (35%). Comorbidities were identified in 11 (42%) patients, including 7 tumors (mostly thymomas), 2 herpesvirus encephalitis (herpes simplex virus 1, human herpesvirus 6; coexisting with NMDAR antibodies), and 2 myasthenia without thymoma. Brain MRI was abnormal in 23 (88%) patients, showing in 20 (77%) multifocal, asynchronous, cortical-subcortical T2/fluid-attenuated inversion recovery abnormalities predominantly involving temporal (95%) and frontal (65%) lobes, but also basal ganglia and other regions. Immunologic or tumor therapy resulted in substantial improvement in 18/21 (86%) assessable patients; the other 3 (14%) died (2 status epilepticus, 1 sepsis). Compared with adults, children were more likely to have generalized seizures (p = 0.007) and movement disorders (p = 0.01) and less likely to have a tumor (p = 0.01). The main epitope targets were in the α1/β3 subunits of the GABAAR. CONCLUSIONS: Anti-GABAAR encephalitis is characterized by frequent seizures and distinctive multifocal cortical-subcortical MRI abnormalities that provide an important clue to the diagnosis. The frequency of symptoms and comorbidities differ between children (more viral-related) and adults (more tumor-related). The disorder is severe but most patients respond to treatment.
OBJECTIVE: To report the clinical features, comorbidities, receptor subunit targets, and outcome in patients with anti-GABAA receptor (GABAAR) encephalitis. METHODS: Clinical study of 26 patients, including 17 new (April 2013-January 2016) and 9 previously reported patients. Antibodies to α1, β3, and γ2 subunits of the GABAAR were determined using reported techniques. RESULTS:Patients' median age was 40.5 years (interquartile range 48.5 [13.75-62.35] years; the youngest 2.5 months old; 13 female). Symptoms included seizures (88%), alteration of cognition (67%), behavior (46%), consciousness (42%), or abnormal movements (35%). Comorbidities were identified in 11 (42%) patients, including 7 tumors (mostly thymomas), 2 herpesvirus encephalitis (herpes simplex virus 1, human herpesvirus 6; coexisting with NMDAR antibodies), and 2 myasthenia without thymoma. Brain MRI was abnormal in 23 (88%) patients, showing in 20 (77%) multifocal, asynchronous, cortical-subcortical T2/fluid-attenuated inversion recovery abnormalities predominantly involving temporal (95%) and frontal (65%) lobes, but also basal ganglia and other regions. Immunologic or tumor therapy resulted in substantial improvement in 18/21 (86%) assessable patients; the other 3 (14%) died (2 status epilepticus, 1 sepsis). Compared with adults, children were more likely to have generalized seizures (p = 0.007) and movement disorders (p = 0.01) and less likely to have a tumor (p = 0.01). The main epitope targets were in the α1/β3 subunits of the GABAAR. CONCLUSIONS: Anti-GABAAR encephalitis is characterized by frequent seizures and distinctive multifocal cortical-subcortical MRI abnormalities that provide an important clue to the diagnosis. The frequency of symptoms and comorbidities differ between children (more viral-related) and adults (more tumor-related). The disorder is severe but most patients respond to treatment.
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