Datta, Abhigyan

Abstract Objectives γ‐Aminobutyric acid B receptor (GABA B R)‐IgG (immunoglobulin G) is an intermediate‐risk paraneoplastic autoantibody often associated with seizures. We aimed to assess the clinical and oncological features of GABA B R‐IgG autoimmune encephalitis (AE) and evaluate the performance of antibody testing. Methods Patients testing positive for GABA B R‐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 GABA B R‐IgG AE or oncological explanations for antibody presence. Results Eighty‐six patients (median age 63 years; 43 female) presented with classic presentations of GABA B R‐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 GABA B R‐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 GABA B R‐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.

Abstract Objective To report the clinical presentations and outcomes of patients with seizure and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). Methods We retrospectively reviewed the electronic medical records for clinical and paraclinical features among patients with seizures and MOG‐IgG (immunoglobulin G) seropositivity. Results We identified 213 patients with MOG‐IgG seropositivity who fulfilled criteria for MOGAD. Seizures attributed to central nervous system (CNS) autoimmunity were observed in 10% of patients ( n = 23: 19 children, 4 adults). The majority ( n = 19, 83%) had pediatric disease onset. Focal motor seizures were the most common seizure semiology (16/23; 70%). Focal to bilateral tonic‐clonic seizures were present in 12 patients (53%), and 3 patients (13%) developed status epilepticus. All patients had features of encephalitis at onset of seizures. Cerebral cortical encephalitis (CCE) was the most common radiological finding (10 unilateral and 5 bilateral cases). Eight of 23 patients (35%) had only CCE, six of 23 patients (26%) had only acute disseminated encephalomyelitis (ADEM), and seven of 23 patients (30%) had features of both. Fifteen patients (65%) had leptomeningeal enhancement. Three patients (13%) had coexistence of N ‐methyl‐ d ‐aspartate receptor (NMDAR) IgG. Only 3 of 23 patients (13%) developed drug‐ resistant epilepsy. Although the majority had MOGAD relapses (14/23, 60%) had only 5 of 23 patients had recurrence of episodes of encephalitis with associated seizures. Twenty‐one of 23 patients (91%) had seizure freedom at last follow‐up. Significance MOG‐IgG evaluation should be considered in patients who present with encephalitis and focal motor and/or focal to bilateral tonic‐clonic seizures, especially pediatric patients with magnetic resonance imaging (MRI) brain findings consistent with CCE, ADEM, or other MOGAD presentations. The majority of these seizures are self‐limited and do not require maintenance/chronic antiseizure medications. Although seizure recurrence is uncommon, many patients have MOGAD relapses in the form of encephalitis and optic neuritis.