Sudden unexpected death in epilepsy: ongoing challenges in finding mechanisms and prevention.

To summarize recent studies on the pathophysiology and preventive strategies for SUDEP. Databases and literature review. Patients with epilepsy have a significantly higher risk of death than the general population. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of sudden death among patients with epilepsy. Despite on-going research, there are still deficits in our knowledge about the mechanisms, genetic factors, and prevention of SUDEP. Current evidence suggests that cardiac arrhythmias, respiratory dysfunction, and brainstem arousal system dysfunction are the major mechanisms of SUDEP, and animal models support the role of neurotransmitters, especially serotonin and adenosine, in pathophysiology of SUDEP. Several mutations in the neurocardiogenic channelopathy genes have been identified as a possible cause of epilepsy and increased SUDEP risk. The lack of awareness that SUDEP can be a potential cause of premature death has been found in several surveys. In addition, medical legal cases demonstrate the need for more education about this condition. Several preventive strategies to reduce SUDEP have been proposed, including effective seizure control, nocturnal supervision, seizure monitoring, devices to protect the airway, and selective serotonin reuptake inhibitors. Further research is needed to determine the efficacy of these interventions. The major mechanisms of SUDEP include cardiac arrhythmias, respiratory dysfunction, and brainstem arousal system dysfunction. Effective control of seizures is the only effective strategy to prevent SUDEP. Other preventive interventions require more research.