Clinical Topics & News

Sudden Unexpected Death in Epilepsy: An Update


 

Pooja Patel, MD

Selim Benbadis, MD

Dr. Patel is a fourth year neurology resident at the University of South Florida and will begin an epilepsy fellowship at the University of South Florida in July.

Dr. Benbadis is Professor and Director of the Comprehensive Epilepsy Program at the University of South Florida and Tampa General Hospital in Tampa, Florida.

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with intractable epilepsy. SUDEP accounts for 7.5% to 17% of all deaths related to epilepsy and has an annual incidence of 3 to 9 per 1000 in the general epilepsy population. Even with such a high prevalence, epilepsy patients, their families, and even many physicians are unaware of the mortality and risk of SUDEP. SUDEP has recently received significant attention in the scientific literature due to its high prevalence and lack of well-defined mechanisms. Understanding the modifiable risk factors and pathophysiology of SUDEP is critically important to help delineate preventive strategies.

Several mechanisms have been proposed to play a role in the pathophysiology of SUDEP. Recent literature have included new insights derived from combined data from older and newer studies where clues were obtained from witnessed SUDEP cases, Epilepsy Monitoring Unit observation of SUDEP cases, physiological data obtained from nonfatal seizures, and animal models. Based on many cohort studies, the initial mechanism is thought to be due to hypoventilation or apnea resulting from the seizure itself. The prone position is thought to contribute to prolonged oxygen desaturation by causing loss of arousal and inability to sense increased carbon dioxide levels. This in turn can cause secondary cardiac arrhythmias that are fatal. The other proposed mechanism is primary cardiac arrhythmia resulting from autonomic dysfunction before, during, or after a seizure. Additionally, serotonergic neurons might contribute as well by causing combination of hypoventilation and seizure. Experts also have suggested that genetic mutations cause primary dysfunction leading to fatal seizures; however, this requires further research.

Based on recent findings about the pathophysiology of SUDEP, several preventive measures have been suggested. The critical preventive measure is still believed to be good control of seizures, as uncontrolled generalized tonic-clonic seizures continue to be the biggest risk factor of SUDEP. Good control of seizures can be difficult in chronic refractory epilepsy and early referral should be made to an epilepsy center. Several studies evaluating patients after epilepsy surgery have discovered that surgery reduces patients’ likelihood of SUDEP. A study done in 2000 evaluated vagus nerve stimulation (VNS) implantation and SUDEP risk, and concluded that during the first 2 years the risk of SUDEP was higher than isolated use of some of the antiepileptics. However, after a 2-year follow-up, the risk of SUDEP was remarkably lower. The initial higher rate was likely due to the fact that VNS was implanted in refractory patients who had failed antiepileptics and were candidates for surgery. Experts believe that VNS is likely protective toward SUDEP as it reduces the amount of generalized tonic-clonic seizures.

Sleep is considered to be high risk for SUDEP because of the higher number of seizures occurring in sleep and hormonal and autonomic changes occurring at nighttime, which increase SUDEP risk. Use of a bed where the head can be adjusted to be higher than the feet, a supine sleep position, a special pillow to prevent suffocation, and even supervision at night has been recommended to reduce the risk of SUDEP. Supervision at night, which includes a supervising person sharing the same bedroom, special precautions such as regular checks throughout the night, or use of a monitoring device, was associated with a decreased risk of SUDEP in a recent study. Medications such as alpha-blockers and beta-blockers might be considered as they can reduce sympathetic discharge and prevent cardiac arrhythmias. Selective serotonin reuptake inhibitors can also reduce ictal hypoxemia and can help prevent a potential mechanism leading to SUDEP.

SUDEP is a significant burden in the field of epilepsy because of its mortality, but it is a subject that is not known well among patients, family, and providers. A recent Australian study reported that only a minority of adult patients with epilepsy had heard about SUDEP from their neurologists. Due to limited experience and knowledge of SUDEP, some neurologists may be unable to provide the appropriate education to patients and their families. The first qualitative study to explore opinions of bereaved relatives on whether to discuss SUDEP with patients was recently performed in the United States. The study showed that 91% of parents of epilepsy patients and 89.5% of adults with epilepsy would have preferred to have information about SUDEP. These respondents would have liked their neurologists in particular to discuss SUDEP so that they could have focused on preventive techniques. Study results suggest a lack of knowledge and the need for more awareness of SUDEP among the epilepsy population. It should be the neurologists’ responsibility to discuss and inform patients and their families about SUDEP at an appropriate time based on their diagnosis.

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