Sudden Unexpected Death in Epilepsy

Sudden Unexpected Death in Epilepsy

is a fatal complication of epilepsy.It is defined as the sudden and unexpected , non-traumatic and non-drowning death of a person with epilepsy, without a toxicological or anatomical cause of death detected during the post-mortem examination. While the mechanisms underlying SUDEP are still poorly understood, it is possibly the most common cause of death as a result of complications from epilepsy, accounting for between 7.5 to 17% of all epilepsy related deaths and 50% of all deaths in refractory epilepsy. The causes of SUDEP seem to be multifactorial and include respiratory, cardiac and cerebral factors, as well as the severity of epilepsy and seizures. Proposed pathophysiologicalmechanisms include seizure-induced cardiac and respiratory arrests.Instances of death as a result of prolonged seizures (status epilepticus) are not classified as SUDEP.

Risk factors

Consistent risk factors include:

  • Severity of seizures, increased refractoriness of epilepsy and presence of generalized tonic-clonic seizures: the most consistent risk factor is an increased frequency of tonic–clonic seizures.
  • Poor compliance. Lack of therapeutic levels of anti epileptic drugs, non adherence to treatment regimens, and frequent changes in regimens are risk factors for sudden death.[5]
  • Young age, and early age of seizures onset.
  • Male gender
  • Poly-therapy of epilepsy. If this is an independent risk factor or a surrogate marker for severity of epilepsy remains unclear.
  • The use of lamotrigine in idiopathic generalized epilepsy cases
  • Being asleep during a seizure is likely to favour SUDEP occurrence.


The mechanisms underlying SUDEP are not well understood but probably involve several pathophysiological mechanisms and circumstances. The most commonly involved are seizure-induced hypoventilation and cardiac arrhythmias but different mechanisms may be involved in different individuals, and more than one mechanism may be involved in any one individual.

  • Cardiac factors: cardiac arrhythmias and other cardiac events are known to be involved in some cases of SUDEP.Such arrhythmias are defined as ictal arrhythmias and include the ictal asystole which is a rare occurrence mostly in people that have temporal lobe epilepsy.
  • Respiratory factors: impaired respiration and seizure induced pulmonary dysfunction as well as central apnea as a result of brain-stem respiratory centers suppression are known to play a role in some cases of SUDEP.
  • Cerebral and autonomic nervous system dysregulation: cardiac arrhythmia and respiratory failure as a result of seizure related changes to brain function and dysfunction of the autonomic nervous system have been described in cases of SUDEP. These include cases of post-ictal generalized EEG suppression described as cerebral shutdown, but its significance remains unclear.
  • Genetic factors: mutations in several genes have been associated with an increased susceptibility to SUDEP. Over 33% of these are related to mutations which lead to increased susceptibility for arrhythmia. Genes involved include the hyperpolarization-activated cyclic nucleotide-gated channels genes (HCN1, HCN2, HCN3, and HCN4).
  • Anti epileptic drugs: most evidence suggests that antiepileptic drugs are not associated with an increased risk for SUDEP, but rather reduce its incidence. Some studies however indicate that some antiepileptic drugs such as lamotrigine and carbamazepine, may increase the risk of SUDEP in certain individuals. It is unclear if this is because of the potential cardio-respiratory adverse effects such as lengthening of the QT interval and reduction of heart rate known to be associated with these drugs under certain circumstances,[9] or because a high drug dosage could be a surrogate marker for poor seizure control.
  • Vagal nerve stimulation: concerns have been raised that vagal nerve stimulation may induce bradycardia or cardiac arrest, and may exacerbate sleep apnoea common in people with epilepsy.


The lack of generally recognized clinical recommendations available are a reflection of the dearth of data on the effectiveness of any particular clinical strategy,[9] but on the basis of present evidence, the following may be relevant:

  • Epileptic seizure control with the appropriate use of medication and lifestyle counseling is the focus of prevention.
  • Reduction of stress, participation in physical exercises, and night supervision might minimize the risk of SUDEP.
  • Knowledge of how to perform the appropriate first-aid responses to seizure by persons who live with epileptic people may prevent death.
  • People associated with arrhythmias during seizures should be submitted to extensive cardiac investigationwith a view to determining the indication for on-demand cardiac pacing.
  • Successful epilepsy surgery may reduce the risk of SUDEP, but this depends on the outcome in terms of seizure control.
  • The use of anti suffocation pillows have been advocated by some practitioners to improve respiration while sleeping, but their effectiveness remain unproven because experimental studies are lacking.
  • Providing information to individuals and relatives about SUDEP is beneficial.

Sudden Unexpected Death in Epilepsy1


  • Approximately 50,000 people die each year in the USA from status epilepticus (prolonged seizures), SUDEP, and other seizure-related causes. SUDEP accounts for 8-17% of deaths in people with epilepsy.
  • The risk of sudden death in young adults with epilepsy is increased 24-fold compared to the general population.
  • SUDEP is the number one cause of epilepsy related death in people with pharmaco-resistant epilepsy.
  • Children with epilepsy have a cumulative risk of dying suddenly of 7% within 40 years.
  • In children, SUDEP accounts for 34% of all sudden deaths.