Friday, June 21, 2019

SUDEP in the full spectrum of epilepsies


Verducci C, Hussain F, Donner E, Moseley BD, Buchhalter J, Hesdorffer D, Friedman D, Devinsky O. SUDEP in the North American SUDEP Registry: The full spectrum of epilepsies. Neurology. 2019 Jun 19. pii:10.1212/WNL.0000000000007778. doi: 10.1212/WNL.0000000000007778. [Epub ahead of print]

Abstract

OBJECTIVE:
To obtain medical records, family interviews, and death-related reports of sudden unexpected death in epilepsy (SUDEP) cases to better understand SUDEP.

METHODS:
All cases referred to the North American SUDEP Registry (NASR) between October 2011 and June 2018 were reviewed; cause of death was determined by consensus review. Available medical records, death scene investigation reports, autopsy reports, and next-of-kin interviews were reviewed for all cases of SUDEP. Seizure type, EEG, MRI, and SUDEP classification were adjudicated by 2 epileptologists.

RESULTS:
There were 237 definite and probable cases of SUDEP among 530 NASR participants. SUDEP decedents had a median age of 26 (range 1-70) years at death, and 38% were female. In 143 with sufficient information, 40% had generalized and 60% had focal epilepsy. SUDEP affected the full spectrum of epilepsies, from benign epilepsy with centrotemporal spikes (n = 3, 1%) to intractable epileptic encephalopathies (n = 27, 11%). Most (93%) SUDEPs were unwitnessed; 70% occurred during apparent sleep; and 69% of patients were prone. Only 37% of cases of SUDEP took their last dose of antiseizure medications (ASMs). Reported lifetime generalized tonic-clonic seizures (GTCS) were <10 in 33% and 0 in 4%.

CONCLUSIONS:
NASR participants commonly have clinical features that have been previously been associated with SUDEP risk such as young adult age, ASM nonadherence, and frequent GTCS. However, a sizeable minority of SUDEP occurred in patients thought to be treatment responsive or to have benign epilepsies. These results emphasize the importance of SUDEP education across the spectrum of epilepsy severities. We aim to make NASR data and biospecimens available for researchers to advance SUDEP understanding and prevention.
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SUDEP can affect men, women, and children. It can affect "children diagnosed with benign epilepsies who are told they don't need to be on medication, that they will outgrow the epilepsy. Unfortunately, [some] die before they have a chance to outgrow it," Devinsky said. The severity of epilepsy cases in which SUDEP occurs varies widely, from cases characterized by centrotemporal spikes to epileptic encephalopathies and failed resective surgeries...


SUDEP is not the only epilepsy-related cause of death — drowning, car accidents, falling down a flight of stairs, and severe burns also occur. Several risk factors are modifiable, so it is possible to lower the risk for SUDEP.

"Medication adherence is probably the most important one. Getting adequate sleep is probably a close second or tied, more or less, and in adult populations, it's also excess alcohol," Devinsky said.

Combining one or more of these risk factors, such as drinking more alcohol than usual while sleep deprived, has a synergistic impact on risk.

Many previous population-based studies, medical examiner case-control series, and clinical case-control studies have focused on subgroups of epilepsy patients or patients whose condition was refractory to medication or surgery. 

In contrast, Devinsky and colleagues evaluated a more general epilepsy population enrolled in a large international registry...

"The other finding from our paper, which has been identified before...is 84% of the family members we spoke to had never heard of SUDEP, and they believed their loved one had never been told about SUDEP," Devinsky said.

Clinicians should discuss SUDEP with all patients with epilepsy for two reasons.

"First, some reassurance can be given to relieve anxiety for those at low risk (eg, focal aware or absence seizures only). Second and most important, patients and families must understand the critical — and potentially lifesaving — importance of seizure control," he said.

"Someone might think: 'If I have an occasional seizure because I missed a med, no big deal, I will be a little tired for an hour, and then I will be on my way.' But if they understand there is a chance they could die from that seizure, one would hope they would be better about being fully adherent with their medication," Devinsky added...

A conversation with a patient whose seizures are well controlled could start, for example, as follows: "Listen, I just want you to know you're doing fantastic. There is a problem called SUDEP, or sudden death in epilepsy. Your chances of suffering it are extremely low; however, they do exist. If you can take your medications religiously and you can get good sleep and avoid excess alcohol, you will dramatically reduce your chances of getting this from very low to close to zero. But if you miss a single dose of medication, unfortunately, you could have a big seizure, and that big seizure could be deadly,' " said Devinsky.

Going forward, the investigators will evaluate individuals who experienced seizures that were recorded in an epilepsy unit. They plan to assess those who subsequently died in order to identify distinguishing factors in their clinical histories or diagnostic test findings in comparison with age- and sex-matched control persons who had a similar seizure but did not die from SUDEP.

"We hope studies like this will allow us to identify markers that more accurately identify patients at high risk for SUDEP and inform us about the mechanisms for SUDEP so we can more effectively prevent it," he said.

"There are many unknowns about SUDEP, and we do not talk about it with our patients, likely because of the lack of knowledge about the mechanism causing this condition, or the risk factors associated with it," Jorge G. Burneo, MD, MSPH, FAAN, writes in an accompanying editorial.

The current study "represents a great effort, as it collected a substantial amount of data from different referral sources in the United States and Canada, and is the largest cohort of SUDEP cases so far," writes Burneo, the Jack Cowin Chair in Epilepsy Research at Western University and coleader of EpLink, the epilepsy research program of the Ontario Brain Institute.

"The important take-home message from this study is that from now on, clinicians should start conversations about SUDEP with their patients with epilepsy earlier rather than later," he notes.

https://www.medscape.com/viewarticle/914617

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