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 taken concomitantly--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.

[1]  J E Leestma,et al.  A prospective study on sudden unexpected death in epilepsy , 1989, Annals of neurology.

[2]  R. Dasheiff,et al.  Sudden unexpected death in epilepsy: a series from an epilepsy surgery program and speculation on the relationship to sudden cardiac death. , 1991, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[3]  T. B. Cole,et al.  Sudden unexplained death in young persons with primary epilepsy , 1992 .

[4]  P. Schraeder,et al.  Paroxysmal autonomie dysfunction, epileptogenic activity and sudden death , 1989, Epilepsy Research.

[5]  Josemir W Sander,et al.  Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[6]  J A Perper,et al.  Unexpected, unexplained death in epileptic patients , 1975, Neurology.

[7]  T. Tomson,et al.  Arrhythmia, Heart Rate Variability, and Antiepileptic Drugs , 1997, Epilepsia.

[8]  W. Hauser.  Sudden Unexpected Death in Patients with Epilepsy: Issues for Further Study , 1997, Epilepsia.

[9]  H Jick,et al.  Sudden Unexplained Death Among Subjects with Refractory Epilepsy , 1996, Epilepsia.

[10]  C. Dodrill,et al.  Predictors of early mortality and sudden death in epilepsy: A multidisciplinary approach , 1991 .

[11]  J. Duncan.  Positron Emission Tomography Receptor Studies , 1997, Advances in neurology.

[12]  Josemir W Sander,et al.  Circumstances of death in sudden death in epilepsy: interviews of bereaved relatives , 1998, Journal of neurology, neurosurgery, and psychiatry.

[13]  D. Chadwick,et al.  Randomised study of antiepileptic drug withdrawal in patients in remission , 1991, The Lancet.

[14]  K. Hossack,et al.  The Sudden Unexplained Death Syndrome in Epilepsy: Demographic, Clinical, and Postmortem Features , 1992, Epilepsia.

[15]  L. Nashef,et al.  Epilepsy and sudden death , 1996, The Lancet.

[16]  Josemir W Sander,et al.  Sudden Death in Epilepsy: A Study of Incidence in a Young Cohort with Epilepsy and Learning Difficulty , 1995, Epilepsia.

[17]  W. Hauser,et al.  Heart Disease Mortality and Morbidity in Patients with Epilepsy , 1984, Epilepsia.

[18]  G. Lip,et al.  Sudden Death in Epilepsy: An Avoidable Outcome? , 1992, Journal of the Royal Society of Medicine.

[19]  L. Nashef.  Sudden Unexpected Death in Epilepsy: Terminology and Definitions , 1997, Epilepsia.

[20]  Josemir W Sander,et al.  The Mortality Associated with Epilepsy, with Particular Reference to Sudden Unexpected Death: A Review , 1997, Epilepsia.

[21]  G. Jay,et al.  Sudden Unexpected Death Associated with Seizures: Analysis of 66 Cases , 1984, Epilepsia.

[22]  Josemir W Sander,et al.  Incidence of sudden unexpected death in an adult outpatient cohort with epilepsy at a tertiary referral centre. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[23]  Paul Schraeder,et al.  Sudden Unexplained Death in Epilepsy: Observations from a Large Clinical Development Program , 1997, Epilepsia.

[24]  J. Annegers,et al.  Cohort Study of Incidence of Sudden Unexplained Death in Persons with Seizure Disorder Treated with Antiepileptic Drugs in Saskatchewan, Canada , 1995, Epilepsia.

[25]  Prognosis.  Guidelines for Epidemiologic Studies on Epilepsy , 1993, Epilepsia.

[26]  L. Nilsson,et al.  Cause‐Specific Mortality in Epilepsy: A Cohort Study of More Than 9,000 Patients Once Hospitalized for Epilepsy , 1997, Epilepsia.

[27]  S. Johnston,et al.  The role of hypoventilation in a sheep model of epileptic sudden death , 1995, Annals of neurology.

[28]  Josemir W Sander,et al.  Mortality in patients with epilepsy: a study of patients in long term residential care. , 1993, Journal of neurology, neurosurgery, and psychiatry.