Anti-γ-aminobutyric acid B receptor autoimmune encephalitis: Clinical presentation and diagnostic insights.

OBJECTIVES: γ-Aminobutyric acid B receptor (GABABR)-IgG (immunoglobulin G) is an intermediate-risk paraneoplastic autoantibody often associated with seizures. We aimed to assess the clinical and oncological features of GABABR-IgG autoimmune encephalitis (AE) and evaluate the performance of antibody testing. METHODS: Patients testing positive for GABABR-IgG in serum/cerebrospinal fluid (CSF) at Mayo Clinic Neuroimmunology Laboratory were identified. Archived sera were retested by cell-based assay (CBA) at 1:100 and 1:200 dilutions. A live-cell flow cytometry-based assay (LCFBA) was developed and validated using archived sera and CSF. True positivity included patients with classic presentations of GABABR-IgG AE or oncological explanations for antibody presence. RESULTS: Eighty-six patients (median age 63 years; 43 female) presented with classic presentations of GABABR-IgG AE: encephalopathy with prominent seizures (n = 55), status epilepticus (n = 23), and rapidly progressive dementia (n = 8). In addition, 44 patients (33%) had a false-positive result for GABABR-IgG characterized by non-specific symptoms/alternate diagnoses. Malignancy was identified in 78% of true-positive patients, predominantly small cell lung carcinoma (SCLC). Testing serum at 1:100 dilution on CBA and using tissue immunofluorescence assay (IFA) in serum and CSF improved the identification of true-positive patients (p < 0.001). CBA at 1:100 dilution performed better than conventional CBA (at 1:10 dilution, p < 0.001) and tissue IFA (p = 0.031). An in-house LCFBA showed 100% sensitivity and specificity in CSF, performing similarly to conventional CBA (p = 0.125) in CSF, but better than tissue IFA (p = 0.031). Furthermore, serum LCFBA performed better than conventional CBA (p = 0.022) and tissue IFA (p = 0.006). LCFBA had the highest diagnostic accuracy and was closely followed by CBA at 1:100 dilution. SIGNIFICANCE: GABABR-IgG AE often presents as encephalopathy with seizures or status epilepticus in the context of an underlying SCLC. Multimodal evaluation using tissue IFA and fixed CBA at higher dilutions improves detection of true cases. LCFBA performs very well as a diagnostic test with very high sensitivity and specificity.