GABA_BR-IgG is an intermediate-risk paraneoplastic autoantibody commonly associated with encephalitis and/or seizures.

To review the clinical/oncological presentations of gamma aminobutyric acid-B receptor (GABA_BR)-IgG and evaluate the clinical specificity of antibody testing methodologies.

GABA_BR-IgG positive patients tested at Mayo Clinic Neuroimmunology Laboratory were identified. Available archived sera were retested by cell-based assay (CBA) at 1:10 and 1:100 dilutions.

105 GABA_BR-IgG seropositive patients with clinical details were identified (females, n=56; median age 63 [range 8-82]). Most patients had one of three anti-GABA_BR encephalitis/seizure presentations: focal-onset seizures with altered mental status (n=39), new-onset refractory status epilepticus (NORSE [n=23]) or rapidly progressive dementia (n=14). Fifty-three of 72 patients (74%) with available data had associated malignancy, primarily small cell lung cancer (SCLC). Two P/Q type VGCC-IgG positive patients had isolated Lambert-Eaton Myasthenic Syndrome. Additionally, 27 patients presented with non-specific symptoms or alternate diagnoses (atypical presentation); none had underlying SCLC (13 with malignancy data). Most patients with anti-GABA_BR encephalitis/seizure presentations had GABA_BR-IgG detected in CSF (95%, 52/55; of 3 who were negative, 1 had NMDA-IgG and another AMPA-IgG and CRMP5-IgG) and/or GABA_BR-IgG detected by CBA in serum at a dilution of 1:100 (76%, 31/41). Five encephalitis/seizure patients with GABA_BR-IgG detected in CSF were CBA positive only at 1:10 dilution in serum. Forty-eight of 76 patients had samples positive on tissue IFA (serum = 17/42, CSF = 40/49). Among 27 patients with atypical presentations, most did not have GABA_BR-IgG CSF CBA positivity (91%, 21/23) and/or GABA_BR-IgG 1:100 serum titer by CBA (0/17). None of 27 cases were tissue IFA positive (serum = 0/27, CSF = 0/21).

GABA_BR-IgG is associated with autoimmune encephalitis/seizure presentations. Our study highlights the importance of evaluating CSF and testing serum at both 1:10 and 1:100 dilutions, as seropositivity at only the 1:10 dilution by CBA without CSF GABA_BR-IgG positivity has poor clinical specificity.