Epilepsy and risk of death and sudden unexpected death in the young: A nationwide study

Abstract

SUMMARYPurpose: Patients with epilepsy are at increased risk of premature death from all causes and likely also from sudden unexplained death (SUD). Many patients with epilepsy have significant comorbidity, and it is unclear how much of the increased risk can be explained by epilepsy itself. We aimed to chart the incidence of sudden unexpected death in epilepsy (SUDEP) and estimate the risk of death from all causes and SUD conferred by epilepsy independently. Methods: We conducted a historical cohort study using data from Danish registries and a complete manual review of all death certificates. The population studied consisted of all Danish residents in the age group 1-35 years, in the period 2000-2006 (inclusive), and the main outcome measures were risk of death and SUD. Key Findings: We identified 33,022 subjects with epilepsy (median follow-up 3.7 years) and 3,001,952 subjects without (median follow-up 7.0 years). Among 685 deaths in the population with epilepsy, we identified 50 cases of definite and probable SUDEP corresponding to an incidence rate of 41.1 (95% confidence interval [CI] 31.6-54.9) per 100,000 person-years. Incidence rates increased with age from 17.6 (95% CI 9.5-32.8) in the age group 1-18 years to 73.8 (95% CI 52.5-103.8) for the age group 24-35 years. Having epilepsy increased the crude risk of death with a hazard ratio (HR) of 11.9 (95% CI 11.0-12.9). When adjusting for sex and comorbidities often encountered in patients with epilepsy (neurologic disease including cerebral palsy, psychiatric disease including mental retardation, and congenital disorders), as well as the Charlson comorbidity score, the HR fell to 5.4 (95% CI 4.9-6.0). The crude HR for SUD was 27.5 (95% CI 18.1-41.8) and fell to 16.3 (95% CI 9.8-26.9) when adjusted for the same covariates as above. Significance: Epilepsy in and of itself carries a significant risk of premature death and SUD. These findings highlight the potential gains of risk factor modification for the prevention of premature death and SUDEP in patients with epilepsy.

Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors

“…Twelve Class I studies provided incidence rate data. [6][7][8][9][10][11][12][13][14][15][16][17] Imprecision in study findings resulted in moderate confidence in the evidence for SUDEP rates in childhood and low confidence in the evidence for SUDEP rates in adulthood and overall (table 1). Because of imprecision in the incidence study results with a lack of overlap of 95% confidence interval (CIs) between several comparable study populations, the guideline panel performed a randomeffects meta-analysis to provide summary measures of the absolute or relative risk of SUDEP.…”

Automated seizure detection systems and their effectiveness for each type of seizure

“…Despite optimal medication management, about 20-30% of patients with epilepsy will continue to have more than one seizure per month, 12% will have weekly seizures, and 8% daily seizures [3,7,8]. Patients with active epilepsy have 4-5 times higher standardized mortality ratios than epilepsy patients who are seizure free, especially in the initial years after a diagnosis of epilepsy [9][10][11][12][13]. The mortality associated with epilepsy has remained stable in the last 50 years despite the introduction of multiple new anti-seizure medications [14,15].…”

Ictal ontogeny in Dravet syndrome

“…Postictal generalized EEG suppression has been considered as a possible biomarker for SUDEP (Lhatoo et al, 2010), and has been reported in all monitored SUDEP cases (Ryvlin et al, 2013). Also, postictal generalized EEG suppression occur less frequently and is significantly shorter in children compared to adults (Freitas et al, 2013) and the incidence of SUDEP is significantly lower in children (Holst et al, 2013). Nearly 40% of our patients with DS had generalized convulsive seizures followed by postictal EEG suppression.…”