Sudden unexpected death in epilepsy: An overview

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Sudden unexpected death in epilepsy An overview

• Maromi Nei, M.D.
• Department of Neurology
• Jefferson Medical College
• Philadelphia, PA

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SUDEP

• Sudden unexpected death in epilepsy sudden,
  unexpected, witnessed or unwitnessed,non-traumatic
  and non-drowning death in epilepsy, with or
  without evidence for a seizure and excluding
  documented status epilepticus, in which the
  post-mortem examination does not show a
  toxicological or anatomic cause for death
  (Nashef, 1995)

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Epidemiology

• Epilepsy overall mortality 2-3 times that of
  general population
• SUDEP 2-18 of deaths in patients with epilepsy
• Risk of sudden unexpected death is 24 40 times
  that in the general population, depending on
  population of epilepsy

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Series SUDEP rate Comments Dashieff 1991 1/108
person-yrs Refractory Sperling 1996 1/150
person-yrs Post TL surgery Hennessy 1999 1/455
person-yrs Post TL surgery Walczak
2001 1.21/1000 person-yrs prospective, epil
epsy ctrs
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SUDEP population-based study (Ficker 1998)

• All deaths in persons with epilepsy between
  1935-1994 in Rochester, MN
• SUDEP 1.7 of all deaths (8.6 of deaths in
  persons 15-44 yrs of age)
• Sudden death rate was 24 times higher than
  expected

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Epilepsy control and risk for SUDEP

• Risk for SUDEP appears to be closely related to
  seizure control
• Patients with refractory epilepsy are at highest
  risk for SUDEP
• Patients who become seizure-free after epilepsy
  surgery reduce their risk for SUDEP (Hennessy
  1999, Sperling1996, Sperling 2005)

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Who is at risk? Age, Sex

• Children to elderly reported
• Most are between 20 40 yrs of age
• Men and women affected No clear male or female
  predominance

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SUDEP associations

• Poor seizure control
• GTC szs
• AED polytherapy
• Mental retardation
• Recent seizure
• Refractory epilepsy
• Often die in sleep
• Earlier onset epilepsy

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Possible contributing factors

• Positioning prone position
• Low AEDs
• Seizure in sleep
• Specific AED ?CBZ
• Structural lesions
• Psychotropic drugs
• Lack of stimulation post-ictally

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Seizure frequency
Adapted from Nilsson, et al., 1999 Increased
relative risk of SUDEP with increased seizure
frequency (total SUDEP n 57)
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Seizures and risk

• A preceding GTC sz is reported in most witnessed
  cases of SUDEP
• In many other cases, the patient is found in bed
  with evidence of a recent seizure (tongue
  laceration, etc.)
• There are rare reports of SUDEP without a
  preceding seizure

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Other circumstances of death

• 30 50 patients are found dead in bed
• Often patients are found in the prone position
• 12/15 witnessed SUDEP cases associated with
  respiratory difficulties (Langan, 2000)

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Case series SUDEP circumstances
Adapted from Nashef, 1995
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Types of seizures, timing of seizures

• Generalized tonic-clonic seizures most often
  associated with higher risk for SUDEP
• ? Nocturnal seizures
• ? Seizure clusters

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• SUDEP
• ? Cardiac
• ? Pulmonary
• ? AEDs
• ? multifactorial

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AEDS and SUDEP

• No definite association between any specific AED
  and SUDEP
• Some data suggests that carbamazepine may alter
  autonomic function - ? Role in SUDEP
• One study found a higher percentage of SUDEP
  patients on carbamazepine, as compared with other
  patients with epilepsy - ? possible association
  (Timmings, 1998)

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Respiratory data
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Observations

• Patients with SUDEP often found lying in prone
  position - ? Suffocation
• Autopsy data reveals pulmonary edema in many cases

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Observations, continued

• Seizures are often associated with apnea
• Decreased risk of SUDEP in patients of a
  supervised residential school while at the center
  than outside the residence (? more stimulation
  after seizures in the residence) (Nashef, 1995)

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Animal data

• Sheep model and hypoventilation Sudden death
  associated with induced seizures in unventilated
  sheep resulted in pulmonary edema (Johnston,
  1995)
• Mouse model audiogenic seizures produce
  respiratory arrest, but mice can survive with
  oxygenation (Venit, 2004) serotonin may also
  play a role in protecting against respiratory
  arrest (Tupal, 2006)

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Near-SUDEP central apnea

• 20 yo woman underwent video-EEG
• 56 second convulsive sz
• Persistent apnea
• EKG unimpaired for 10 seconds, then gradually
  slowed and ceased 57 seconds later
• CPR successful

So, 2000
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Cardiac Data in epilepsy
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Epilepsy and cardiac function

• Seizures can affect cardiac rate and rhythm
• Unexplained myocardial injury in epilepsy
• Altered autonomic function in the ictal and
  interictal states in patients with epilepsy

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Sinus tachycardia during a left temporal seizure
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Seizures and cardiac rhythm

• Partial epilepsy
• Up to 39 of seizures are associated with
  abnormal cardiac rhythm (Nei 2000, Opherk, 2002)
• Occur in the the ictal and post-ictal periods
• Abnormal rhythm may outlast the seizure duration
  by minutes to hours (Tigaran,1998)

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Common ictal abnormalities

• Atrial premature depolarizations
• Ventricular premature depolarizations
• Marked sinus arrhythmia

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Uncommon ictal abnormalities

• Atrial fibrillation
• Atrial triplets, couplets
• Ventricular bigeminy
• Supraventricular tachycardia
• Junctional rhythm
• Asystole, bradycardia

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Ictal asystole
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Uncommon ictal/post-ictal EKG abnormalities
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(No Transcript)
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Cardiac rhythm prior to death in SUDEP

• Junctional rhythm which failed to return to NSR
  after cardioversion
• Ventricular arrhythmia
• Ventricular fibrillation, then asystole

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Cardiac data in SUDEP

• 12-lead interictal EKG data unrevealing
• Post-mortem microscopic myocardial injury no
  coronary artery disease
• Ictal cardiac rate and rhythm abnormalities - ?
  role in SUDEP
• No evidence of gross structural heart disease

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Summary

• SUDEP is an important cause of death in patients
  with epilepsy
• While the etiology is not known, accumulating
  data suggests that seizures themselves may play a
  role, and perhaps respiratory and/or cardiac
  abnormalities may contribute

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SUDEP Can it be prevented?

• Kelly Caravetta, CRNP
• Jefferson Comprehensive Epilepsy Center

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SUDEP Prevention

• Best recommendation to reduce SUDEP is to get
  seizures under control
• When seizures are not controlled, additional
  evaluation (e.g., video-EEG) may be valuable in
  directing correct therapy
• Epilepsy surgery should be considered in
  appropriate candidates with refractory epilepsy

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Epilepsy surgery and SUDEP

• 5-years post temporal lobectomy reduced
  mortality in seizure-free individuals as compared
  with those with any seizures, and no SUDEP
  patients were seizure-free (Sperling, 1996)
• 305 pts post temporal lobectomy reduced
  mortality after surgery as compared with SUDEP
  rate in similar groups of patients with
  refractory epilepsy who had not undergone
  epilepsy surgery (Hennessy, 1999)

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Case Scenerio

• 38 year old man with refractory epilepsy is seen
  in the office. He has frequent generalized
  tonic-clonic and tonic seizures. He has tried 9
  AEDs in the past but continues to experience
  frequent seizures (average 5/month). Currently
  he is being treated with carbamazepine, 800
  mg/daily, clonazepam 1.5 mg/daily, topiramate 600
  mg/daily, and olanzapine, 10 mg/daily.

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You recognize that he has multiple risk factors
for SUDEP, including all except which one of the
following?

• Age of 38 years
• Male sex
• C) AED polytherapy
• D) History of generalized tonic-clonic seizures
• E) Refractory epilepsy

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Which of the following may aid in the possibly
reducing his risk for SUDEP?
A) Taper the carbamazepine B) Send him for a
full pulmonary evaluation to assess for
underlying respiratory dysfunction C) Stress to
the patient and caretakers the need for good
medication compliance D) Recommend a regular
exercise regimen
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In educating the patients caregiver, which of
the following would you be least likely to
recommend in preventing SUDEP?

• Video/Audio Monitor
• The Sleep Safe Pillow
• Stimulation after seizures
• Proper positioning in sleep

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What are some things to consider prior to
discussing SUDEP with the patient and his
caregiver?

• His quality of life
• His autonomy
• His degree of medication compliance
• All of the above

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When to discuss SUDEP with patients

• No clear consensus
• Some clinicians and patient advocate groups
  suggest that the possibility of SUDEP should be
  discussed with all patients
• Consider in patients with refractory epilepsy
  e.g., weighing pros/cons of surgery
• Consider discussing in patients with poor
  compliance with medical treatment

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Discussion with family after SUDEP has occurred

• When a patient dies due to SUDEP, direct
  communication with the family is important
• A discussion regarding SUDEP is often helpful in
  family members through the grieving process. They
  frequently ask, Could we have prevented this?

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Conclusions/Suggestions

• Cardiac evaluation in patients with significant
  ictal arrhythmias
• Stimulation of patients after seizures may be
  important
• ?Role of oxygenation during seizures
• Identification of nocturnal seizures may be more
  important than has been generally recognized

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• Prevention of seizure clusters, particularly when
  nocturnal - ? Decrease risk of SUDEP
• Role of pacemaker uncertain at this time May
  want to consider pacemaker implantation in
  patients with refractory seizures associated with
  asystole
• May want to expedite surgical evaluation for
  refractory patients, especially when ictal
  arrhythmias/prolonged apnea are present