Risk factors for sudden unexpected death in epilepsy: a case-control study

Background Sudden unexpected death is substantially more common in people with epilepsy than in the general population. Our objective was to investigate the association between some clinical variables and sudden unexpected death in epilepsy (SUDEP) to identify risk factors. Methods This nested case-control study was based on a Cohort of people aged between 15 and 70 years, who, during 1980-89, had been admitted to and discharged with a diagnosis of epilepsy from any hospital in the county of Stockholm. The study population was followed up through the National Cause of Death Register until Dec 31, 1991. Cases were individuals who had died, with a diagnosis of epilepsy registered on the death certificate, and who after review of medical and necropsy records were found to meet our SUDEP criteria. Three control participants, who were living epilepsy patients matched for age and sex, were selected from the same cohort for each case. All medical records were examined. Clinical data were collected and analysed on a predesigned protocol. Findings 57 SUDEP cases were included, of whom 91% had undergone necropsy. The relative risk of SUDEP increased with number of seizures per year. The estimated relative risk was 10.16 (95% CI 2.94-35.18) in patients with more than 50 seizures per year, compared with those with up to two seizures per year, The risk of SUDEP increased with increasing number of antiepileptic drugs takenconcomitantly-9.89 (3.20-30.60) for three antiepileptic drugs compared with monotherapy. Other major risk factors were early-onset versus late-onset epilepsy (7.72 [2.13-27.96]), and frequent changes of antiepileptic drug dosage compared with unchanged dosage (6.08 [1.99-18.56]). The association between SUDEP risk and early onset, and SUDEP risk and seizure frequency, was weaker for female than for male patients, whereas frequent dose changes showed a stronger association in female patients. Interpretation Our data suggest that SUDEP is a seizure-related event, although the pathophysiological substrate that predisposes individuals to SUDEP may be established at an early age, and there may be some sex differences. Improvement of seizure control and possibly the avoidance of polytherapy may be ways to reduce the risk of SUDEP.