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

Authors

  • Anders Gaarsdal Holst,

    Corresponding author
    1. The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC), Copenhagen, Denmark
    2. Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
    • Address correspondence to Anders G. Holst, Department of Cardiology, Copenhagen University Hospital, section 2142, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. E-mail: anders@kanten.dk

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  • Bo Gregers Winkel,

    1. The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC), Copenhagen, Denmark
    2. Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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  • Bjarke Risgaard,

    1. The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC), Copenhagen, Denmark
    2. Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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  • Jonas Bille Nielsen,

    1. The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC), Copenhagen, Denmark
    2. Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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  • Peter Vibe Rasmussen,

    1. The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC), Copenhagen, Denmark
    2. Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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  • Stig Haunsø,

    1. The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC), Copenhagen, Denmark
    2. Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
    3. Department of Medicine and Surgery, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
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  • Anne Sabers,

    1. Department of Neurology, The Epilepsy Clinic, The Neuroscience Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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  • Peter Uldall,

    1. Department of Pediatrics, Neuropediatric Clinic, Juliane Marie Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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  • Jacob Tfelt-Hansen

    1. The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC), Copenhagen, Denmark
    2. Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
    3. Department of Medicine and Surgery, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
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Summary

Purpose

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.

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