Rukovets, Olga

ARTICLE IN BRIEF

New practice guidelines on SUDEP identify risk factors and incidence rates in adults and children with epilepsy.

Although sudden unexpected death in epilepsy (SUDEP) is a terrifying risk for patients with epilepsy and their families, the lack of understanding and anxiety around this rare event make conversations on the topic difficult to broach. A new practice guideline from the American Academy of Neurology and the American Epilepsy Society set out to quantify the risk and incidence rate of this condition to improve physician-patient dialogue and identify potential avenues to reduce SUDEP risk. The guideline was published in the April 25 issue of Neurology.

Cynthia Harden, MD, system director of epilepsy services at Mount Sinai Health System in New York and lead author of the guideline, spoke with Neurology Today about the findings and how they should be put into practice.

WHAT WAS THE IMPETUS FOR DEVELOPING THESE PRACTICE GUIDELINES ON SUDEP?

The SUDEP guideline was initiated through a request by Dr. Jeffrey Buchhalter as part of his role in an advocacy group called Partners Against Mortality in Epilepsy (PAME), which partners with the American Epilepsy Society (AES), Citizens United for Research in Epilepsy (CURE), and the Epilepsy Foundation. One of the goals of this group is to increase awareness of SUDEP. The group includes persons with epilepsy, caregivers for persons with epilepsy, families who ha lost loved ones to SUDEP, and physicians and scientists working in epilepsy. The growing body of research and information about SUDEP combined with the growing realization that it was not being discussed with patients and families provided a powerful impetus to create a guideline.

Although there is quite a bit of published data, there was a perception on the part of the medical community that there was not enough reliable or accurate data to support a meaningful guideline regarding SUDEP. When we looked at the research systematically using the AAN process, we found that there was actually a lot of very good information to help guide the discussion and manage the risk of SUDEP.

WHAT WERE THE MOST IMPORTANT FINDINGS AND RECOMMENDATIONS? WERE ANY OF THE FINDINGS UNEXPECTED?

The most important findings were that SUDEP risk increases in adulthood; while thankfully rare in children (typically affecting one in 4,500 children with epilepsy in one year), it increases several-fold in adulthood (typically affecting one in 1,000 adults with epilepsy in one year). [For more data from the guideline, see “Conclusions for SUDEP Incidence.”]

The risk factor of generalized tonic-clonic seizures (GTCS) was not unexpected, but the magnitude of the risk with increasing frequency of GTCS has not really been appreciated. We found that people with three or more GTCS per year have a 15-fold increased risk of SUDEP, which translates to an absolute risk of up to 18 deaths per 1,000 patient-years for people with frequent GTCS. For those individuals who experience GTCS, we recommend that clinicians continue to actively manage epilepsy therapies to reduce seizure occurrences and the risk of SUDEP while considering patient preferences and weighing any risks of new therapies. [For more data from the guideline, see “Conclusions for SUDEP Risk Factors.”]

The intervention of nocturnal supervision as a strategy to mitigate and markedly decrease the risk of SUDEP came to the forefront during our analysis of the evidence; I think this was also unexpected. We found that having another individual (at least 10 years old) present in the bedroom overnight was associated with a decreased SUDEP risk in patients with epilepsy. However, the decision to undertake some strategy of nighttime supervision must be individualized, since this might not be a realistic option for some families.

We recommend that clinicians inform their patients with epilepsy that seizure freedom, particularly freedom from GTCS, which is more likely to occur with medication adherence, is strongly associated with a decreased risk of SUDEP.

HOW WILL THESE GUIDELINES IMPROVE OR CHANGE THE CONVERSATION ABOUT SUDEP BETWEEN CLINICIANS AND PATIENTS?

Until now, there has not been a synthesis of the evidence of the incidence and risk of SUDEP in a manner that is accurate and nuanced. Now, the discussion with patients and families, informed by the guidelines, can be facilitated with the quantification of the annual risk of SUDEP for children — which increases slightly with adulthood — and by some straightforward recommendations, derived from evidence, on how to truly reduce SUDEP risk.

It is an unspoken but very human truth that physicians and health care providers avoid conversations about things that they can't quantify, treat, manage or offer help, comfort or reassurance. The true end game of the guideline is to provide information to use in this difficult but necessary discussion. The epilepsy consumer community is stating that it is their right to know about this most dire risk of epilepsy, so the SUDEP guideline enables that right to be honored.

WHAT ARE THE NEXT STEPS FOR RESEARCH? WHAT BARRIERS EXIST?

One of the barriers to SUDEP research is not accurately capturing the frequency of SUDEP from the standpoint of the medical examiner. There are several research initiatives that have been trying to change this, as well as improve education and attention around SUDEP. For example, the Center for SUDEP Research was recently established to support research on the pathophysiology of SUDEP in human and animal models, and the SUDEP Institute was established by the Epilepsy Foundation to support research and provide education and patient resources on SUDEP. The SUDEP Center Without Walls, supported by the National Institutes of Health, was established in 2014 to accelerate research on complex problems in epilepsy by promoting collaborative research between nine groups of scientists with a total $5.9 million in funding.

The CURE Foundation has been the leader in funding SUDEP research for both clinical and basic science programs, such as genetic contributors to SUDEP risk. CURE has invested more than $3.1 million into SUDEP research, including 27 grants to 34 investigators in eight countries. And one of the most important initiatives is the North American SUDEP registry, which collects information about SUDEP from families and from health care providers, and importantly, collects DNA and other tissues for further study. The hope is that these multiple avenues for research support will be fruitful in understanding and preventing SUDEP.

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