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VBCN - April 2016 Volume 3, No 1 - Epilepsy Update
Wayne Kuznar

A team of neurologists and population health scientists from New York University (NYU) has issued a call to action to reduce deaths from epilepsy. They call for educational interventions and public health campaigns targeting medication adherence, psychiatric comorbidity, and other modifiable risk factors (Devinsky O, et al. Neurology. 2016;86:779-786).

“Epilepsy-related mortality remains underappreciated and public health interventions are inadequate,” stated Orrin Devinsky, MD, Director of the NYU Comprehensive Epilepsy Center, and colleagues. Devinsky and colleagues argue that epilepsy-related mortality must first be defined and its frequency assessed.

The investigators noted that although sudden unexpected death in epilepsy (SUDEP) is the most common cause of deaths associated with epilepsy, and patients with epilepsy have 27-fold higher rates of sudden death compared with the general population, SUDEP may account for <50% of all deaths directly caused by seizures. Other common causes of death from epilepsy include status epilepticus, drownings, suicides, and fatal unintentional injuries.

Classifying Epilepsy-Related Deaths

The inability to accurately quantify epilepsy-related deaths is a major bottleneck to the development and assessment of preventive interventions, according to Devinsky and colleagues. They propose a classification system for epilepsy-related mortality that would comprise 4 categories:

  • Deaths directly caused by epilepsy (ie, SUDEP, status epilepticus)
  • Deaths caused by acute symptomatic seizures
  • Deaths indirectly caused by epilepsy (ie, aspiration pneumonia, suicide)
  • Deaths caused by underlying neurologic diseases.
“SUDEP is infrequently classified as the COD [cause of death] despite the absence of another credible explanation,” noted Devinsky and colleagues. Cardiovascular disease or arrhythmia is often the assumed cause of death in otherwise healthy patients with epilepsy, ignoring the 27-fold increase in the rate of sudden death in this patient population.

Furthermore, if a patient with epilepsy dies, “and there are other potential contributing factors, such as excessive recent alcohol use, the COD may be attributed solely to that factor,” the researchers noted. “Similarly, if a seizure causes aspiration pneumonia, and pneumonia is lethal, the COD may be listed as pneumonia, ignoring how epilepsy initiated the causal chain leading to death.”

Understanding Sudden Death in Epilepsy

The concept of SUDEP may need to be expanded to include mild and severe ends of the spectrum of epilepsy. For example, “a person who dies immediately after a first seizure is not classified as SUDEP since a single seizure is not epilepsy,” the researchers wrote. “We exclude cases of status epilepticus (>30 minutes duration) from SUDEP, yet ≥5 minutes of continuous seizure activity is the current practical definition for status epilepticus.”

The pathophysiology of SUDEP could be better elucidated by studying the temporal pattern of physiologic changes during seizures. Prolonged seizures may be the most informative about the mechanisms of SUDEP, and excluding them will ensure that barriers to understanding these mechanisms will remain.

“We should study how seizure intensity, duration, and number interact with an individual’s environmental, medical, neurologic, genetic, and epigenetic background to modify risk of death,” the investigators wrote.

A Call to Action

Despite teachings that tonic-clonic seizures are only dangerous if prolonged or if they cause physical injury, recent or frequent tonic-clonic seizures are the most significant risk factors for SUDEP. However, information on how recurrent seizures directly cause severe morbidities is lacking from medical, nursing, and patient education. Physicians need to be well-informed about SUDEP and educate their patients accordingly.

Addressing potentially modifiable risk factors for epilepsy-related mortality, including psychiatric illnesses, is paramount. Devinsky and colleagues encourage effective management of epilepsy through lifestyle changes, medication, and, when appropriate, dietary or surgical therapy to prevent seizures. Near-perfect adherence to antiepileptic medications is required for seizure control—a goal established by the World Health Organization.

Epilepsy-related mortality is especially prevalent in socioeconomically poor patients with epilepsy, who would benefit from reducing healthcare disparities and improving outcomes, as has been done with stroke.

Public surveillance data and awareness education are lacking for epilepsy-­related mortality, Devinsky and colleagues emphasized.

“We have done too little for too long. Far too many have died who could have been saved by information. It is time to act,” they concluded.

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