Epilepsy Among Major Risk Factors for Sudden Unexplained Death

Marius Klovgaard, MD, PhD

Findings from a nationwide retrospective population-based cohort study of Danish citizens aged less than 50 years old revealed that epilepsy is a major risk factor for sudden unexplained death (SUD), only second to cancer in adults and pneumonia in children. In addition, a lower sudden unexplained death in epilepsy (SUDEP) risk was observed in children compared to adults.

Lead author Marius Klovgaard, MD, PhD, Epilepsy Clinic, University of Copenhagen, and colleagues aimed to establish the risk of SUDEP in relation to other causes or modes of death and to evaluate the risk of SUD in persons with and without epilepsy younger than 50 years. Investigators defined persons aged 1-17 years as children and persons aged 18-49 as adults. Primary causes of death in persons with epilepsy were assessed independently by 3 neurologists and 1 neuropediatrician, using the unified SUDEP criteria.

The final dataset included 3,838,293 individuals, 30,437 (0.8%) of which had prevalent epilepsy, who were followed for 10,456,143 person-years (PY). Despite only representing 0.8% of the population, 700 of the 7825 recorded deaths were by persons with epilepsy, corresponding to 8.9% of all deaths. In comparison, 0.2% of persons without epilepsy died during the study period. Of the notable findings, persons with epilepsy had an almost 11-fold increased all-cause mortality rate and a 34-fold increased risk of SUD compared with the general population.

The 3 most frequent primary causes of death in persons with epilepsy younger than 50 years accounted for 59.7% of all deaths. These were cancer (2.38 per 1000 PY [95% CI, 2.06-2.74]), SUDEP (1.65 per 1000 PY [95% CI, 1.40-1.96]), and pneumonia (1.09 per 1000 PY [95% CI, 0.89-1.34]). In comparison, the 3 most frequent causes of death in persons without epilepsy, which accounted for 58% of all deaths in that population, were cancer (0.17 per 1000 PY [95% CI, 0.16-0.18]), accident-related deaths (0.14 per 1000 PY [95% CI, 0.13-0.15]), and cardiovascular diseases (0.09 per 1000 PY [95% CI, 0.08-0.09]).

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"Our results underscore the importance of identifying and addressing risk factors for SUDEP to prevent premature death in persons with epilepsy younger than 50 years," Klovgaard et al.

Considering definite, definite plus, and probable cases, children reported less cases of SUDEP than adults (0.27 per 1000 PY [95% CI, 0.11-0.64] vs 1.21 per 1000 PY [95% CI, 0.96-1.51]). Additionally, men had a higher risk of SUDEP (adjusted male/female HR, 2.08 [95% CI, 1.28-3.71]; P = .003), whereas the sex difference was not statistically significant in children (adjusted male/female HR, 3.15 [95% CI, 0.35-28.17]; P = .31).

Suicide accounted for 2.6% of all deaths in persons with epilepsy compared to 7.9% of all deaths in persons without epilepsy. Comparing SUDEP with means of suicide or causes of accidents, the risk of SUDEP was 7.5-fold higher than all means of suicide (95% CI, 4.59-12.26; P <.0001) and 2.55-fold higher than accident-related deaths (95% CI, 1.85-3.50; P <.0001).

In a sensitivity analysis, investigators categorized unwitnessed cases of SUDEP, where the decedent was not seen in habitual conditions within the past 24 hours prior to death, as unclassified. The subset included 65 cases of definite, definite plus, and probable SUDEP and 107 cases when adding possible SUDEP and fatal near-SUDEP. Klovgaard et al found the incidence of autopsy-verified SUD cases in persons without epilepsy to be 0.01 per 1000 PY (95% CI, 0.01-0.01). Thus, the age- and sex-adjusted HR for SUD between persons with and without epilepsy was 34.42 (95% CI, 23.57-50.28; P <.0001).

REFERENCES

Klovgaard M, Lynge TH, Tsiropoulos I, et al. Sudden unexpected death in epilepsy in persons younger than 50 years: a retrospective nationwide cohort study in Denmark. Epilepsia. Published online August 21, 2021. doi:10.1111/epi.17037