Diagnostic and prognostic significance of serum interleukins in epileptic encephalopathy with spike wave activation in sleep (EE-SWAS) syndrome

Abstract

Objective: To study serum interleukin-6(IL-6), interleukin-8(IL-8) and interleukin-10(IL-10) levels in Epilpetic encephalopathy with spike-wave activation in sleep(EE-SWAS), drug refractory epilepsy(DRE) and well controlled epilepsy(WCE).

Methods: Children(2-12 years) with immunotherapy naïve EE-SWAS, DRE and WCE were enrolled. Valid psychometric tools were used to assess cognition and behavior. Children with EE-SWAS were longitudinally followed. They received a three-month steroid course alongwith the ongoing antiseizure drugs. Electroclinical responders were defined as change in social quotient by 5-points with improvement in atleast one behavioral domain by 5-points and 50 % reduction in mean seizure frequency if active seizures were present alongwith a 25 % reduction in Spike-wave-index(SWI) at three months. Change in serum Interleukin levels at one month follow up was compared between participants who eventually became responders or non-responders at three months.

Results: Twenty children with EE-SWAS, 18 with DRE and WCE each were enrolled. Serum IL-6(pg/ml){(EE-SWAS: 3.775(IQR 2.205, 11.28); DRE: 3.01(IQR 2.04, 4.56); WCE: 1.655(IQR 1.27, 2.29), p = 0.0065} and IL-8(pg/ml){(EE-SWAS: 103.2(IQR 34.01, 200.82); DRE: 19.595(IQR 16.54, 39.7); WCE: 18.97(IQR 16.54, 21.91) p = 0.0002} was significantly different between the three groups. In EE-SWAS group 12/20(60 %) showed electroclinical response to steroids. Responders had significant reduction in IL6 levels (pg/ml){4.045(IQR 2.605, 18.96) to 1.13(IQR 054, 1.74)} at one month follow up compared to non responders {3.12(IQR 1.655, 5.27) to 4.37(IQR 2.83, 9.855)} (p = 0.0069).

Conclusions: Proinflammatory cytokines (IL-6 and IL-8) are significantly elevated in EE-SWAS compared to DRE and WCE. Reduction in IL-6 levels at one month post-therapy predicted electroclinical responders at 3months follow up.

Keywords: Biomarker in epilepsy; Drug refractory epilepsy; ESES; Interleukin-6; Proinflammatory cytokines; Steroid therapy.