OP13 – 2799: Landau-Kleffner syndrome (LKS), continuous spike and waves during slow-wave sleep syndrome (CSWSS), and Rolandic epilepsy (RE) – A genetic and immunological study

Abstract

Objective LKS and CSWSS present with seizures, language and cognitive regression. Genetic studies have identified mutations in the GRIN2A gene, and copy-number-variants in genes encoding cell adhesion proteins (including CASPR2, contactin-2). Given that some affected patients respond to steroids we looked for autoantibodies to similar neuronal targets. Methods A previously genetically characterised cohort of patients with LKS (4 patients), CSWSS (23), RE (14), epilepsy with autism or neurodevelopmental disorder (2) and unaffected controls (10) was tested for neuronal surface antibodies (Abs) to GRIN1, GRIN2A and 2B, CASPR2 and contactin-2 proteins using cell-based-assays, and VGKC-complex-Abs by radioimmunoprecipitation. Results 8 samples were positive (8/53; 15%), 4 for CASPR2-Abs (low positive) and 4 for VGKC-complex-Abs (113–1102 pM). All samples were negative for contactin-2, GRIN1, 2A and 2B-Abs. Positive results were found in CSWSS patients (n=3; 2 VGKC-complex, 1 CASPR2), Rolandic epilepsy (n=3; 1 VGKC-complex, 2 CASPR2-Ab positive), and a neurodevelopmental disorder (dyspraxia, CASPR2-Ab); one control was VGKC-complex-Ab positive (unaffected father of an antibody positive patient). 3 positives were found in a single three-generation French family affected by LKS, CSWSS and RE, 2 also had GRIN2A mutations. Conclusion Overall, none of the 4 LKS patients in the cohort were antibody positive, 13% CSWSS (3/23) and 21% Rolandic epilepsies (3/14) had low positive CASPR2 or VGKC-complex-Abs. The three positive results in 3 different generations of the same GRIN2A family, which included an unaffected sibling with the disease associated GRIN2A mutation and an unaffected father with a positive antibody, suggests a possible dual aetiology in a small subset of epilepsy patients where autoantibodies might influence the presentation and severity of genetic cases. However, low level neuronal antibodies, and even genetic mutations, may not always be causal, but their coexistence in some patients suggests that these complex genetic diseases may also have a neuroinflammatory component.