Kelch-like Protein 11 (KLHL11) Antibodies in Children With Seizures of Undetermined Cause

Abstract

Background/Aim: Kelch-like protein 11 (KLHL11)antibody may be found in paraneoplastic neurological disorders presenting with epileptic seizures. The aim of this study was to investigate the prevalence and clinical significance of KLHL11-antibody in epilepsy. Patients and Methods: Sera of 42 pediatric and 59 adult patients with seizures of undetermined cause were screened using a cellbased assay. Results: KLHL11-antibody was found in three of 168 control patients with paraneoplastic neurological disorders and four pediatric patients (4-8-year-old, 2 boys/2 girls) with seizures of unknown cause presenting with myoclonic-atonic epilepsy, generalized epilepsy or childhood epilepsy with centrotemporal spikes. In these four cases, seizures continued for 2-7 months, responded promptly and favorably to conventional anti-seizure drugs and did not recur in follow-up durations ranging between 2-5 years. Patients had normal brain MRI findings and motor-mental development before and after seizures. KLHL11-antibody was not detected in adult epilepsy patients with undetermined cause, MOG antibody-positive patients and healthy controls. Conclusion: KLHL11-antibody may be detected in pediatric epilepsy patients with a relatively benign disease course.Antibodies targeting Kelch-like protein 11 (KLHL11) were initially identified in young men presenting with rhombencephalitis and testicular seminoma (1). However, recent studies have shown that KLHL11 antibody can be detected in patients without cancer (2-4). Moreover, the associated clinical spectrum is more heterogeneous than previously recognized and includes limbic encephalitis, psychosis, memory deficits and opsoclonus-myoclonus syndrome (2-4). Seizures are occasionally encountered in KLHL11 encephalitis at frequencies ranging from 18% to 23% (3, 4).Antibodies directed against neuronal intracellular or cellsurface antigens are detected in a sizeable proportion of epilepsy patients of undetermined cause (5). Thus, to identify whether KLHL11 antibody belongs to the anti-neuronal antibodies associated with epilepsy, we screened adult and pediatric patients with epilepsy of undetermined cause together with disease controls using a cell-based assay. Patients and MethodsPatient cohorts. We consecutively recruited 42 pediatric patients (female/male 22/20; mean age±standard deviation 7.2±2.5; range for age 1-9 years; mean duration of epilepsy 3.6±1.9 years) admitted to our outpatient clinic with seizures of undetermined cause. Informed consent was obtained from all participants included in the study.All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Istanbul University 351