Abstracts

Rationale: The incidence of sudden unexpected death in epilepsy (SUDEP) is approximately 1/1000 people with epilepsy per year. Ongoing tonic clonic seizures are the major risk factor, particularly when they occur from sleep. The EpiNet study group is undertaking an international prospective case-control study of SUDEP to identify other risk factors, and factors which may reduce the risk. We intend to follow more than 100,000 people with epilepsy (PWE) for up to four years, and expect to identify 200 SUDEP cases. Each case will be matched with four controls. Methods: We have commenced a prospective, international, multicentre case-control study of SUDEP.  We are conducting the study in over 40 centres from 12 countries. Each center defines a cohort from which cases and controls will be identified. We are including incident cases and new PWE. Cases are PWE who die from definite or probable SUDEP, identified to study researchers within six months of their death.Cases will be recruited over four years. For each case, three controls are randomly selected from all patients in the same cohort individually matched by age (+/- 2 year) and sex, as cases enter the study (incidence-density sampling.) The fourth control is a proxy control. This is a spouse, relative, close friend, or caregiver of one control, randomly sampled from the control triplet. This will allow comparison of results from the actual control with the proxy control to estimate the measurement error from using proxies; odds ratios will be corrected.Research staff write to relatives of SUDEP cases and controls; a participant information sheet is included. A trained nurse or research assistant then administers a structured questionnaire; controls are asked questions relating to a specific nominated night's sleep.Data for this study is recorded in a special registry within the EpiNet database re:Epilepsy: syndrome; aetiology; duration; seizure type(s) and frequency; frequency of nocturnal seizures; time since the most recent seizure;Treatment and co-morbidities; AEDs used; compliance; AED levels; treatment with other drugs - in particular, SSRI drugs; treatment with surgery or VNS;Monitoring: whether the patient used a personal seizure-detection device; if so, what type;Sleeping arrangements: did the patient sleep alone; use of anti-suffocation pillow; was any nocturnal supervision / monitoring device used; did someone check on the patient in response to a seizure-notification, and how quickly;Other co-morbidities;Ethnicity, family history of sudden death; socio-economic factors.For SUDEP cases: whether death occurred while the patient was sleeping; was a seizure witnessed; was there supportive evidence to suggest a seizure;.Sample size calculations: 200 cases and 800 controls will detect an odds ratio of 1.7 over a control exposure range of 20% to 70%, with 80% power and 95% confidence level (2-sided). The cohorts are enriched, with a high incidence of patients with drug resistant epilepsy; the risk of SUDEP in this patient group may be as high as 1 in 200.Data analyses: odds ratios will be calculated using the Mantel-Haenszel method and conditional logistic regression to control for covariates. Results: Cohorts have been defined in multiple centres and surveillance is now underway to identify all people who die from SUDEP. Conclusions: This study will be the largest case control study of SUDEP. Because of its prospective design, it will allow us to identify risk factors with much more certainty than previous studies have done. New investigators are welcome to contact the EpiNet team to participate in this study. Funding: Health Research Council of New Zealand (Grant 19/420)