GABA _A receptor autoimmunity

Abstract

ObjectiveWe sought to validate methods for detection and confirmation of GABAA receptor (R)-IgG and clinically characterize seropositive cases.MethodsArchived serum and CSF specimens (185 total) suspected to harbor GABAAR-IgG were evaluated by indirect immunofluorescence assay (IFA). Twenty-six specimens from 19 patients appeared suspicious for GABAAR–IgG positivity by IFA, based on prior reports and comparison with commercial GABAAR antibody staining. Aliquots of those specimens were tested at the University of Oxford, United Kingdom, and Euroimmun, Lubeck, Germany, for GABAAR-IgG by cell-based assays (CBAs) using HEK293-indicator cells transfected with plasmids encoding different GABAAR subunits.ResultsEight specimens (of 26 tested; 4 serums, 4 CSFs) from 5 patients were confirmed by CBA to be GABAAR-IgG positive. Patient IgGs were always reactive with α1β3 GABAAR subunits. One more patient was identified clinically after this validation study. Median age for the 6 patients at serologic diagnosis was 44 years (range, 1–71 years), and 4 of them were male. Among the 4 for whom clinical information was available (2 treated by the authors), all had encephalitis and antiepileptic drug refractory seizures. Three out of 4 patients treated with a combination of immunotherapies had good outcomes. The fourth, recognized to have an autoimmune cause late in the clinical course, had severe permanent neurologic sequelae and brain atrophy.ConclusionsThough not as common as NMDA-R encephalitis, GABAAR encephalitis generally has a characteristic clinical-radiologic presentation and is treatable, making accurate laboratory diagnosis critical.

Clinical spectrum of high-titre GAD65 antibodies

“…Among all patients treated with immunotherapy, a complete response was reported in only 2/142 (1%); one patient had mild ataxic dysarthria that resolved after corticosteroids, and one patient had new-onset seizures with cortical-subcortical lesions on MRI that resolved after corticosteroids, intravenous IG and PLEX. In retrospect this patient’s clinicoradiographic presentation was concerning for co-existing for gamma-aminobutyric acid type A receptor encephalitis, 26 but confirmatory testing for this antibody was not performed.…”

Encephalitis, severe seizures, and multifocal brain lesions

“…The current paper 1 shows excellent examples of the striking and dynamic brain lesions of the disorder, which are readily apparent on T2-weighted MRI studies, and affect both gray and white matter. Some patients may show large areas of cortical edema.…”

“…In this issue of N2 , the paper by O'Connor et al 1 reports the clinical, immunologic, and radiographic features of a series of patients with anti-γ-aminobutyric acid type A (GABA A ) receptor encephalitis. Anti-GABA A receptor encephalitis is characterized by cognitive disruption, severe seizures, and characteristic brain lesions.…”

GABAA receptor encephalitis associated with human parvovirus B19 virus infection

“…[ 3 ] Typically, GABA A receptor antibody-associated encephalitis presents with refractory epilepsy or continuous partial epilepsy. [ 4 , 5 ] Other symptoms of the disease that have been described in the literature include cognitive impairment, psychiatric symptoms, and disordered movement. [ 4 , 6 ] In a study of 26 patients with anti-GABA A receptor autoimmunity, identified from a population of 2,914 patients with suspected autoimmune neurologic disorders, Spatola et al [ 7 ] found that all 26 patients had seizures accompanied by at least one of the following core symptoms: cognitive impairment, decreased level of consciousness, altered behavior, or movement disorder.…”

“…With respect to imaging, brain MRI results for patients with GABA A receptor autoimmunity encephalitis may sometimes be normal; otherwise, patients often exhibit multifocal, non-diffusion-restricting, non-enhancing medium-to-large sized cortical, juxtacortical, and subcortical lesions, usually in the temporal lobe. [ 4 , 5 ] These MRI changes may be consequent to immune activity or prolonged seizures. [ 7 ] There is no clear correlation of the presence of neuroimaging alterations with clinical severity or prognosis, with some asymptomatic patients presenting with neuroimaging alterations and some patients with brain lesions exhibiting improvement with treatment.…”