Friday, April 28, 2017

Sudden unexpected death in epilepsy incidence rates and risk factors

Harden C, Tomson T, Gloss D, Buchhalter J, Cross JH, Donner E, French JA, Gil-Nagel A, Hesdorffer DC, Smithson WH, Spitz MC, Walczak TS, Sander JW, Ryvlin P. Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2017 Apr 25;88(17):1674-1680.

Abstract
OBJECTIVE:
To determine the incidence rates of sudden unexpected death in epilepsy (SUDEP) in different epilepsy populations and address the question of whether risk factors for SUDEP have been identified.
METHODS:
Systematic review of evidence; modified Grading Recommendations Assessment, Development, and Evaluation process for developing conclusions; recommendations developed by consensus.
RESULTS:
Findings for incidence rates based on 12 Class I studies include the following: SUDEP risk in children with epilepsy (aged 0-17 years) is 0.22/1,000 patient-years (95% confidence interval [CI] 0.16-0.31) (moderate confidence in evidence). SUDEP risk increases in adults to 1.2/1,000 patient-years (95% CI 0.64-2.32) (low confidence in evidence). The major risk factor for SUDEP is the occurrence of generalized tonic-clonic seizures (GTCS); the SUDEP risk increases in association with increasing frequency of GTCS occurrence (high confidence in evidence).
RECOMMENDATIONS:
Level B: Clinicians caring for young children with epilepsy should inform parents/guardians that in 1 year, SUDEP typically affects 1 in 4,500 children; therefore, 4,499 of 4,500 children will not be affected. Clinicians should inform adult patients with epilepsy that SUDEP typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually 999 of 1,000 adults will not be affected. For persons with epilepsy who continue to experience GTCS, clinicians should continue to actively manage epilepsy therapies to reduce seizures and SUDEP risk while incorporating patient preferences and weighing the risks and benefits of any new approach. Clinicians should inform persons with epilepsy that seizure freedom, particularly freedom from GTCS, is strongly associated with decreased SUDEP risk.
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A new practice guideline on sudden unexpected death in epilepsy (SUDEP) has been released by the American Academy of Neurology (AAN) and the American Epilepsy Society (AES).

For the document, the writing committee sought to establish incidence rates of SUDEP and identify any risk factors.

"We found that SUDEP is relatively rare in children, affecting 1 in 4500 children with epilepsy per year; that's according to moderate evidence," said coauthor Elizabeth Donner, MD, Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Ontario, Canada, and chair of the AES SUDEP Task Force.

SUDEP was more common in adults than in children, typically affecting 1 in 1000 adults living with epilepsy per year, Dr Donner said.

The major risk factor was generalized tonic-clonic seizures. "People with three or more of this type of seizure…were 15 times more likely to die suddenly than people who did not have this seizure type, so that's a very significant finding," Dr Donner said. "In total, this translates to up to 18 in 1000 deaths per year for people with epilepsy with frequent generalized tonic-clonic seizures."

"Our guideline brings clarity to the discussion, giving healthcare providers information they can use to help people with epilepsy reduce their risk," said lead author, Cynthia Harden, MD, Department of Neurology, Mount Sinai Health System, New York, New York, during a press conference here.
The guideline was co-developed by AAN and AES, and is endorsed by the International Child Neurology Association. It is published online April 24 in Neurology and was presented during a press conference here at the American Academy of Neurology 2017 Annual Meeting (AAN)…

A previous study showed that patients and their families prefer to be informed of individual risk for an event like SUDEP, they note, but after being informed of an adverse event, they tend to overestimate the risk for that adverse event affecting them.

"Overestimation can be lessened by presenting the risk as a probability of both having and not having the event, and by using numbers in addition to words and frequencies rather than percentages to convey the risk," the authors write.

Accordingly, they suggest some language physicians may use to inform patients in a balanced way.
"Clinicians caring for young children with epilepsy should inform parents/guardians that in 1 year, SUDEP typically affects 1 in 4,500 children with epilepsy; therefore, annually 4,499 of 4,500 children will not be affected," they write (Level B).

Similarly, "Clinicians should inform adult patients with epilepsy that SUDEP typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually 999 of 1,000 adults will not be affected (Level B)."…

The major risk factors they found were the presence and frequency of generalized tonic-clonic seizure (GTCS). People with three or more of these seizures per year had a 15-fold increased SUDEP risk.

"The large SUDEP risk increase from GTCS, coupled with epilepsy monitoring unit evidence demonstrating that a GTCS was always the precipitating event of SUDEP, strongly suggests that GTCS are not just associated with SUDEP but, rather, are in the causal path to SUDEP," the authors note. "From this, it seems reasonable to infer that improved control of an individual's GTCS will result in a reduced risk of SUDEP. Thus, a reduction in SUDEP risk is an additional benefit to the many benefits resulting from improved seizure control."…

In terms of recommendations, then, they suggest that for patients who continue to have GTCS, "clinicians should continue to actively manage epilepsy therapies to reduce seizures and SUDEP risk while incorporating patient preferences and weighing the risks and benefits of the new approach."
They also suggest that clinicians inform their patients that seizure freedom, "particularly freedom from GTCS (which is more likely to occur with medication adherence), is strongly associated with a decreased SUDEP risk."…


Children with Dravet syndrome have an unusually high risk for SUDEP, they add. "Mutations in sodium channel gene SCN1A are the most common cause of Dravet syndrome and this gene is expressed in brain and heart. It is possible that these mutations render patients more susceptible to cardiac arrhythmias in the setting of a seizure.

http://www.medscape.com/viewarticle/879029?

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