SUDEP and PAME

Prevention of SUDEP, by Orrin Devinsky, MD

Research findings during the past several decades have identified a number of risk factors for SUDEP that can be modified and suggest strategies to help prevent SUDEP. Seizure control is a primary focus of prevention. Complete seizure control – especially for generalized tonic-clonic seizures (GTCS) - is the goal but this must be balanced against side effects of antiepileptic drugs (AEDs) and quality-of-life.  Often, seizures cannot be fully controlled despite the best medical care. Other modifiable risk factors include AED drug polytherapy and alcohol abuse. Although lamotrigine is a risk factor for SUDEP in some studies, meta-analyses that control for GTCS frequency found no increased risk with lamotrigine.   A meta-analysis of randomized AED clinical trials found that an adjunctive AED at an efficacious dose was associated with a 10-fold reduction in SUDEP compared to placebo. Although these clinical trials were short-term and cannot be generalized to routine clinical care, they provide compelling evidence that improved seizure control reduces the rate of SUDEP, at least in the short-term.

Evidence from epidemiological studies, cases of SUDEP witnessed in the community and recorded on video EEG all suggest that seizures, most often GTCS, precede the majority of SUDEPs.  In many patients, GTCS cannot be fully controlled with AEDs and patient education on AED adherence, sleep deprivation, etc. In these cases, what can be done to prevent SUDEP after a GTCS or another seizure type?  Nothing is proven to prevent SUDEP. However, several studies found that epilepsy patients are more likely to fall victim to SUDEP when they are unsupervised, especially at night, as compared to those who are supervised during sleep with a monitoring device (e.g., sound monitor) or observer who can reposition them. Recent unpublished observations suggest that intervention by nurses in an epilepsy monitoring unit (Bateman, unpublished) may shorten seizure duration and the severity and duration of postictal hypoxemia. We need more studies to address the role of repositioning, specific forms of stimulation, and the use of oxygen. We also need to understand why some seizures that occur in medical settings are followed by SUDEP despite prompt resuscitative measures.

Accumulating evidence that many SUDEPs follow GTCS, especially in sleep and that patients are found prone. Together with data that unsupervised patients are at higher risk of SUDEP, this suggests that devices to detect seizures and alarm caregivers could potentially prevent SUDEP. A variety of seizure detection devices have been or are being developed. Studies on these devices remains limited and none are approved in the United States for seizure detection and their role in preventing SUDEP remains unproven. Although EEG based devices can offer high sensitivity and specificity, they are limited by difficulty with application and patient compliance.  Most available devices are motion detectors, and include accelerometers (e.g., SmartWatch*, EpiLert (watch), EpDetect phone app*), mattress sensory (e.g., Medpage MP5*, Emfit Movement Detector*), or video motion detectors. They are inexpensive and noninvasive but detect only convulsive seizures and may have limited specificity.  Several multimodal devices are in development that detect combinations of motion, electrodermal skin response, heart rate, and respiratory rate (e.g., MIT-Boston Children’s Hospital and RTI). In addition, lattice pillows that allow airflow even if a patient’s face is flush against the surface, are a Class I medical device in the United Kingdom but have never been tested and remain unproven. Finally, seizure detection devices are limited by the availability of a nearby caregiver who can respond. We need to address systems that can detect seizures and prevent progression to SUDEP for those who live alone.

Education may be the most effective current tool to combat SUDEP. Many SUDEPs occur in young adults, a population at high risk for non-adherence to AED therapy, sleep deprivation, and intermittent consumption of excess alcohol. In addition, many epilepsy patients are unaware of the dangers of seizures, which extend beyond SUDEP. We need to better identify educational strategies that reduce seizure activity in different populations.

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PAME, by Daniel Friedman, MD

The first Partners in Mortality Against Epilepsy (PAME) Conference took place June 21-24, 2012 in Evanston, Illinois and FACES was a proud co-sponsor of the event, along with the Epilepsy Therapy Project. This conference was unique in that it brought together clinicians, clinical and basic science researchers, advocacy groups, patients, and family members to discuss mortality in epilepsy. It has been known for some time that people with epilepsy have an elevated risk of dying compared to the general population. Epidemiological studies have shown that most of the excess mortality in people with epilepsy occurs in the first 40 years of life and within the first decade of diagnosis. While some of these deaths can be explained by progressive causes of epilepsy such as brain tumors or neurodegenerative conditions, epilepsy itself is associated with increased mortality. Epilepsy-related causes of death include accidents, suicide and sudden unexpected death in epilepsy (SUDEP). These deaths typically affect people in the prime of their lives. If conceptualized in terms of years of potential life lost, the public health burden of epilepsy-related death is higher than that of more common diseases that affect the elderly such as Alzheimer disease or Parkinson diseases.

The meeting brought together a diverse set of speakers from all over the world across many disciplines to discuss our current understanding of why some people with epilepsy die earlier than expected and to review the research that will lead to strategies to reduce this mortality. Discussions interspersed laboratory findings, clinical research, advocacy and education. Speakers addressed the epidemiology of epilepsy mortality and strategies that public-health officials can employ to get more accurate reporting, especially of SUDEP, which is unrecognized by many coroners and medical examiners. Other researchers reviewed the factors that may elevate SUDEP risk such as ongoing seizures, especially generalized tonic-clonic seizures (GTCS), and the presence of neurologic deficits. Basic scientists described elegant studies showing how seizures may interact with the heart and breathing centers in animal models and have identified possible targets for intervention. Other scientists examined the role of genetics in predisposing some individuals to both seizures and heart arrhythmias. Speakers also discussed current strategies for prevention of SUDEP such as seizure treatment, improving compliance and targeted education, as well as the future role of medical devices. Finally, and perhaps, most poignantly, family members affected by SUDEP and people living with epilepsy shared their experiences. Their testimony and the stories of others who lost loved ones to epilepsy helped provide a sense of common purpose to the diverse audience and will likely ensure that the next PAME meeting will be even larger.