On April 24, 2017, the American Academy of Neurology (AAN) and American Epilepsy Society (AES) jointly released their first guideline on sudden unexpected death in epilepsy, known as SUDEP. This statement by Harden et al., developed in collaboration with the AAN’s guideline development, dissemination, and implementation subcommittee, is the culmination of a multi-year effort to synthesize the evidence on SUDEP risk and provide recommendations on how neurologists can best communicate risks to patients and families.
The Purpose of Guidelines
In evidence-based medicine, guidelines play a critical role in turning scientific evidence into clinical practice. Guideline development is a rigorous process that begins with asking a focused question (or set of questions), performing a systematic review of the literature, assessing the quality of the studies, and synthesizing the evidence. Based on this assessment, the guidelines make specific recommendations to guide practice as well as highlight areas for further study.
Developing the SUDEP Guideline
In this guideline, the authors sought to address two clinical questions:
- What are the rates of SUDEP in children and adults with epilepsy?
- What are the risk factors for SUDEP?
In their synthesis of the literature, the authors identified 12 high quality studies of SUDEP incidence and determined that:
- The overall rate of SUDEP in children (ages 0-17 years) is 0.22 per 1000 patient-years. There was a moderate degree of confidence in this estimate.
- The SUDEP rate in adults is 1.2 per 1000 patient-years, but confidence in this estimate was low because of the variability of the original studies.
The authors also identified 22 high quality studies on SUDEP risk factors and determined that:
- Ongoing generalized tonic-clonic seizures (GTCS) were the major risk factor for SUDEP.
- Nocturnal supervision or use of a nocturnal listening device can reduce risk.
- There is insufficient evidence on the independent influence of other proposed risk factors, such as nocturnal seizures, duration of epilepsy, number of AEDs, male sex, or specific drugs.
Summary of the SUDEP Guideline
Based on these findings, the guideline authors make the following recommendations:
- Neurologists should inform patients and caregivers of the risks of SUDEP.
- The risk of SUDEP in children is rare (1 in 4500 per year or, conversely 4499 in 4500 will not die).
- The risk of SUDEP in adults is small (1 in 1000 per year or, 999 in 1000 will not die).
- Clinicians should strive to reduce or eliminate GTCS and inform patients that seizure-freedom, especially from GTCS, is the best way to reduce SUDEP risk.
- Nocturnal supervision or monitoring device may be an appropriate measure to reduce risk in patients with frequent GTCS or nocturnal seizures if compatible with the patient’s circumstances and not overly burdensome.
The key recommendation of the guideline echo prior assertions by the AES SUDEP Task Force, the UK National Institute for Health and Care Excellence, and other bodies:
- SUDEP should be discussed with patients with epilepsy and their caregivers and they should be informed of their risks.
- Furthermore, and perhaps more importantly, the SUDEP guideline emphasizes that ongoing GTCS, the single greatest risk factor for SUDEP, should not be accepted and clinicians should make all possible efforts to control these seizures through medication changes, surgical referral, or other therapies.
While this is not new to epilepsy specialists, the majority of patients with epilepsy are cared for by general neurologists who treat a broad range of neurological diseases. It critical to emphasize that all practioners caring for epilepsy patients should not be complacent with ongoing seizures and should escalate care, including referral to a comprehensive epilepsy center when appropriate.
Questions Needing Further Study
There are limitations to the guideline process that is in part related to high standards for the quality of evidence; some nuance may be lost in the process.
- The guideline does not provide satisfactory answers to many important questions, such as what is the SUDEP incidence in specific epilepsy syndromes or what is the role of specific therapies because there are no studies of sufficient quality.
- The lack of evidence meeting the rigorous standards for clinical guidelines highlights key areas of SUDEP epidemiology and prevention that should be the focus of further study.