GABABR IgG Associated Encephalitis: Clinical Presentations and Measures to Improve Diagnostic Assay Specificity. (5th December 2022)

• Record Type: Journal Article
• Authors: McCombe, Jennifer; Mills, John; Datta, Abhigyan; Rezk, Mohamed; Chia, Nicholas; Knight, Andrew; Zekeridou, Anastasia; Flanagan, Eoin; McKeon, Andrew; Pittock, Sean; Dubey, Divyanshu
• Is Part Of: Neurology. Volume 99:Number 23(2022)Supplement 2
• Page Start: S64
• Page End: S65
• Publication Date: 2022-12-05
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/01.wnl.0000903520.84465.3b
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To review the clinical/oncological presentations of gamma aminobutyric acid-B receptor (GABABR)-IgG and evaluate the clinical specificity of antibody testing methodologies. Background: GABABR-IgG is an intermediate-risk paraneoplastic autoantibody commonly associated with encephalitis and/or seizures. Design/Methods: GABABR-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. Results: 105 GABABR-IgG seropositive patients with clinical details were identified (females, n = 56; median age 63 [range 8-82]). Most patients had one of three anti-GABABR 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-GABABR encephalitis/seizure presentations had GABABR-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 GABABR-IgG detected by CBA in serum at a dilution of 1:100 (76%, 31/41). Five encephalitis/seizure patients with GABABR-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 GABABR-IgG CSF CBA positivity (91%, 21/23) and/or GABABR-IgG 1:100 serum titer by CBA (0/17). None of 27 cases were tissue IFA positive (serum = 0/27, CSF = 0/21). Conclusions: GABABR-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 GABABR-IgG positivity has poor clinical specificity.