Reliable Count of Seizures using Diaries versus Video Electroencephalography for Seizures of KCNQ2-DEE

Objective: We sought evidence as to whether seizures in infants and young children with KCNQ2 Development Epileptic Encephalopathy (KCNQ2-DEE) could be reliably counted using diaries, with seizure behaviors previously confirmed using video electroencephalography (VEEG). Background: The Food and Drug Administration has recommended VEEG to measure the outcome of anti-seizure mediation clinical trials for infants and young children. Reasons include difficulty with seizure recognition due to clinically subtle seizure behaviors, and occurrence of subclinical electro-encephalographic seizures in this age groups. However, use of VEEG presents technical and feasibility challenges, and limits enrollment to subjects with very high seizure frequencies. Design/Methods: PubMED was searched for papers in which patients with KCNQ2-DEE included seizure and EEG correlate descriptions. Additionally, a survey of caregivers from the Cure Alliance (Patient Advocacy Group) was reviewed for information regarding recognition of seizure occurrence. Results: Sixteen papers were included, encompassing 124 KCNQ2-DEE patients. Each described stereotyped focal tonic seizures beginning on days 1–5 after birth. Focal tonic seizure was the predominant and often only seizure type present in the loss-of-function variants. The seizures were readily observed and were associated with a clear EEG correlate of contralateral amplitude suppression. There were no reports of electro-encephalographic subclinical seizures. To understand the ability of caregivers to record seizures, a survey of KCNQ2-DEE families was undertaken, with 55 evaluable responses obtained. On a scale of 1 to10 (low to high) confidence in recognizing seizures after training using VEEG, 75% of caregivers reported high confidence (8 or above). Conclusions: We conclude that the seizures of KCNQ2-DEE are stereotyped, clinically evident and do not occur without an observable clinical correlation. Parents/caregivers are recognizing seizures confidently. This strategy of training families to count seizures accurately using VEEG mitigates the need to use VEEG directly as the method to assess primary outcome in a KCNQ2-DEE anti-seizure medication treatment trial. Disclosure: Dr. Harden has nothing to disclose. Dr. Grayson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xenon Pharmaceuticals Inc. Dr. Luzon has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xenon Pharmaceuticals, Inc.. Dr. Butterfield has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xenon Pharmaceuticals, Inc. Dr. Aycardi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xenon Pharmaceuticals Inc. Dr. Aycardi holds stock and/or stock options in Xenon Pharmaceuticals Inc.Dr. Pimstone has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xenon Pharmaceuticals, Inc.. Dr. Pimstone has received compensation for serving on the Board of Directors of Xenon Pharmaceuticals, Inc.. Dr. Millichap has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xenon Pharmaceuticals, Inc..