Sudden Unexpected Deaths in Epilepsy Patients

Unexpected Death

nexpected death can happen to anyone; patients with epilepsy as well as patients with no illness can be affected.  In all cases, autopsy reports are inconclusive.

Before explaining about SUDEP, it is necessary to first understand a little background on epilepsy as an illness (www.epilepsy.ca). As with other illnesses, epileptic seizures should be controlled.  The consequences of poorly controlled seizures as well as taking unnecessary risks may lead to death. 

It is well documented that the mortality rate in persons with epilepsy is higher than in the general population.   There are many causes for death relating to epilepsy including, traumatic brain injury, accidents, neoplasia (tumours), idiosyncratic (unexpected) drug reactions, apnoea, and cardiac arrhythmias.  It is becoming increasingly evident that SUDEP also plays a role in many epilepsy deaths.

SUDEP, as the acronym suggests, is an unexpected death in an epileptic patient.  Cases of sudden death observed in epileptic patients have been documented since the 1800s (Bacon, G.M. On the modes of death in epilepsy.  Lancet 1868; 1:555-556). 

With the new anti-epileptic drugs being developed in the Twentieth Century, epilepsy was seen as a “non-fatal” illness.  Patients and even many physicians were misinformed on the risks of epilepsy.  Much of the research undertaken at the beginning of the century was put on hold.

As evidence regarding SUDEP deaths becomes more available and publicised, researchers can no longer be ignorant of the issue at hand.  Research in the past decade has started to increase.  Researchers are now continuously examining case studies to determine predisposing risk factors and similarities between SUDEP patients.

What is Sudden Unexpected Death in Epilepsy Patients(SUDEP)?

t has long been difficult for health professionals to come up with a common definition and method of classifying SUDEP deaths.

In 1993, the United States Food and Drug Administration (U.S. FDA), in conjunction with Burroughs-Wellcome (pharmaceutical company), came up with a definition to define and classify Sudden Unexpected Death in Epilepsy (SUDEP) in relation to clinical studies/trials carried out by pharmaceutical companies.

SUDEP was concluded as the cause of death if:

1. the victim suffered from epilepsy, defined as recurrent unprovoked seizures
2. the victim died unexpectedly while in a reasonable state of health
3. death occurred “suddenly” (in minutes) when known
4. death occurred during normal activities (e.g. in bed, at home, at work) and benign circumstances
5. an obvious medical cause of death was not found
6. death was not the direct result of a seizure or status epilepticus

SUDEP was concluded as the cause of death if:

1. Definite SUDEP: all the criteria for SUDEP was met and was confirmed by a post-mortem report
2. Probable SUDEP:  the criteria for SUDEP was met, however there was not post-mortem report
3. Possible SUDEP: the event of SUDEP was not ruled out, however there may be other causes of death; the criteria were not sufficiently met and no post-mortem report was available.
4. Not SUDEP: there were other causes of death

Researchers in the United Kingdom (Nashef et. al) proposed the following definition:

For statistical and prevention purposes, it is essential to have a common definition of how to classify an illness/form of death.  However, this can be extremely difficult with SUDEP.  This may introduce frustration and confusion for both medical examiners and those close to the patient. 

For the above reasons, the exact statistics indicating SUDEP cases are not easy to obtain.  This is nobody’s fault. 

SUDEP is now starting to become widely recognised as an important cause of death in epilepsy.  It has been estimated that it may be even as high as 2-3 times the mortality rate of the general population.  Some family doctors may not even know that SUDEP can occur.  In addition, autopsy reports may indicate suffocation for many SUDEP cases because the patients are found laying face down.  Status epilepticus may also be reported simply on the fact the patient was epileptic and there is no other apparent cause for death.

The result: SUDEP occurrences may be much higher than previously believed/recorded.

A rough estimate for the U.S. indicates SUDEP may play a role in 7-17% of all epilepsy-related deaths.  (Note the huge percentage margin.)   Estimates will vary from country to country and will also depend on how SUDEP is defined by the coroners.  Studies show that the incidence of SUDEP in young children appears to be very low.

Important facts:

n some ways, SUDEP is akin to SIDS (sudden infant death syndrome/crib death). The patient, in the majority of cases, dies unattended in their sleep and is found dead lying on his/her stomach.  This may often be misleading for medical examiners.  Often, diagnosis may be based on what telltale signs of other types of death are not there because of the mysterious nature of SUDEP.

In fact, there have not been many witnessed incidences of SUDEP.  A seizure may influence the occurrence of SUDEP, however SUDEP does not always appear to be preceded by a visible seizure event.  In many cases, the patient was very healthy and had no other health-related problems before going to bed.

Risk Factors:

ue to the difficulty in finding a mechanism of action for SUDEP that is common in most patients, it is difficult to assess what are the exact risk factors.  A few similarities have been noted across many of SUDEP patients.  These similarities include:

• Age: late 20s, early 30s
• Males
• Generalised tonic-clonic seizures
• High frequency of seizures
• Chronic epilepsy
• Symptomatic epilepsy (this may be the result of an underlying brain damage caused by accidents, tumours, infections, metabolic disorders)
• Structural brain lesion
• Post-traumatic epilepsy
• Recent unusually stressful life event
• Poor anti-epileptic drug compliance
• Psychotropic drug treatment (including for anxiolytic use)
• Alcohol

**Many websites have stated that some SUDEP cases have been observed to have sub-therapeutic levels of antiepileptic drugs.  This has not been proven. There are many reasons for why the levels could be sub-therapeutic.  People with well-controlled seizures could have sub-therapeutic levels of AEDs and still be at low risk for SUDEP.  For this reason, often measurements of post-mortem AED levels in the blood can prove misleading. **

Prevention

hile the exact risk factors are unknown, it does not hurt to prevent against the possible ones.  Prevention does not need to involve serious life-altering changes.  A few changes, including reducing alcohol consumption and recreational drug use are beneficial not only for epileptic patients but also for everyone in general.   Small changes such as this, along with support from family, friends, and physicians can help to reduce the chances of SUDEP. 

It must be noted that: these precautions may not avoid SUDEP in all cases, however they may help to prevent it in some others.  It is best to be cautious, even if your physician claims the likelihood of SUDEP to be rare.

1. Diagnosis of epilepsy should be confirmed.  (If you do not feel comfortable with the diagnosis, seek a second opinion.)  It is best to see a specialist who deals with epileptic patients.  Your family physician should be able to refer you to one. 

   Once confirmed, the specialist/physician will prescribe treatments appropriate for your type of epilepsy.  Each patient is different.   Your dosage/frequency may be different than a friend on the same medication.

   Well-controlled seizures is one key to preventing SUDEP.
2. A management plan should be established ensuring regular review of seizure control, accuracy of diagnosis, medication, side effects and impact on lifestyle.  Your physician/specialist should review over this list with you to ensure you are getting the best possible treatment.
3. Trigger factors for seizures should be identified and avoided.
4. Adherence with medication is important and avoiding sudden changes in the taking of medication
5. Reduce/avoid alcohol and recreational drugs.  If you must drink, limit how much you consume.  Binge drinking (even for people without illnesses) is never a safe thing to do.
6. Before deciding to become pregnant, women should consult their physician/specialist for more information regarding seizures during pregnancy as well as how their AEDs will affect the developing foetus.
7. Where seizures are nocturnal - it may be preferable to have a futon or other bed, which is low on the ground. A solid foam pillow with air holes may be advised, although these have not been tested.
8. Do your family and friends know what to do if you have a seizure? Make sure family and carers are informed of what to do during and following a seizure.  In particular, carers should be advised to stay with a person for 15-20 minutes after the seizure to ensure they are breathing easily and to watch that they are not turning blue. An ambulance should be called if the seizure lasts more than five minutes or they are unduly concerned.
9. Where risk factors of SUDEP are present carers should have a basic knowledge of resuscitation techniques

The benefits of healthy living including regular sleep and diet and reduction of stress can make a serious impact on the quality of life of an epileptic patient.

While a cure is still unknown, these simple preventative measures can help epileptic patients live full lives.  The above tips are hardly restricting and are beneficial for not only people with epilepsy but also everyone in general.

Areas of Research:

esearchers are looking into different areas that may be involved in the mechanism of SUDEP.  While there is no definite source, they have noticed some similarities between patients.

Current research is focusing on several areas:

1. Case control studies
2. Pathophysiological research.  

The result: the exact event triggering SUDEP may vary from patient to patient.

Acknowledgements:

Dr. Elizabeth Donner, Hospital for Sick Children, Ontario

Dr. Neelan Pillay, University of Calgary, Foothills Medical Centre, Calgary Alberta

References:

Opeskin K, Berkovic SF. Risk factors for sudden unexpected death in epilepsy: a controlled prospective study based on coroners cases. Seizure. 2003 Oct;12(7):456-464.

Donner EJ, Smith CR, Snead OC III. Sudden unexplained death in children with epilepsy. Neurology. 2001 Aug 14;57(3):430-4.

Epilepsy: Safety, Excess Mortality, and Sudden Death.
Epilepsia. 2003 Sep;44 Suppl 6:19-20. No abstract available.

Annegers JF, Coan SP. SUDEP: overview of definitions and review of incidence data.
Seizure. 1999 Sep;8(6):347-52. Review.

Kloster R, Engelskjon T. Sudden unexpected death in epilepsy (SUDEP): a clinical perspective and a search for risk factors. J Neurol Neurosurg Psychiatry. 1999 Oct;67(4):439-44.

Nilsson L, Farahmand BY, Persson PG, Thiblin I, Tomson T. Risk factors for sudden unexpected death in epilepsy: a case-control study. Lancet. 1999 Mar 13;353(9156):888-93.

Langan Y, Nashef L, Sander JW. Sudden unexpected death in epilepsy: a series of witnessed deaths. J Neurol Neurosurg Psychiatry. 2000 Feb;68(2):211-3.

Nilsson L, Bergman U, Diwan V, Farahmand BY, Persson PG, Tomson T. Antiepileptic drug therapy and its management in sudden unexpected death in epilepsy: a case-control study. Epilepsia. 2001 May;42(5):667-73.

Lhatoo SD, Sander JW. Sudden unexpected death in epilepsy. Hong Kong Med J. 2002 Oct;8(5):354-8. Review.