A Sudden, Scary Side to Epilepsy

Editor's Note:

Neurologist Andrew Wilner, MD, discusses the first Partners Against Mortality in Epilepsy (PAME) conference with conference co-chairs Jeffrey Buchholter, MD, PhD, Pediatric Neurologist and Epileptologist at the Barrow Neurologic Institute in Phoenix, Arizona, and Gardiner Lapham, RN, MPH, Member of the Board of Directors of CURE: Citizens United for Research in Epilepsy. The meeting took place June 21-24, 2012, in Evanston, Illinois, and brought together a diverse group of scientists, clinicians, families, and others interested in advancing efforts aimed at preventing sudden death in people with epilepsy.

Dr. Wilner: The first PAME conference was cosponsored by several organizations including the Centers for Disease Control and Prevention (CDC), the American Epilepsy Society (AES), CURE, the Epilepsy Foundation of America, the Epilepsy Therapy Project/FACES (Finding a Cure for Epilepsy and Seizures), the National Institute of Neurologic Disorders and Stroke, Intractable Childhood Epilepsy Alliance, SUDEP (Sudden Unexplained Death in Epilepsy) Aware, and RTI International. What was the purpose of this meeting? How did it come about, and what were its goals?

Dr. Buchholter: The reality that death can be associated with epilepsy is well known and has been in the scientific literature for 20 or 30 years. But it was only in the mid-2000s that organizations such as the AES, the Epilepsy Foundation, and CURE decided it was time to have a more focused effort [at prevention]. We found a great deal of interest in this topic among basic scientists, clinicians, and advocacy organizations, and that interest required an avenue for more participation. To address this, we came up with the idea of having this unique meeting. The purpose of the PAME conference was to bring together clinical scientists, basic scientists, individuals interested in research advocacy, and the bereaved community and families to discuss the reality of death in epilepsy.

Dr. Wilner: One of the areas for which research has increased is SUDEP. What is SUDEP?

Dr. Buchholter: The core definition of SUDEP that we have come to accept was described by Dr. Lina Nashef in the mid-'90s as sudden, unexpected, witnessed or unwitnessed, nontraumatic and nondrowning death in a patient with epilepsy, with or without evidence of a seizure and excluding documented status epilepticus. Those are the core features. What has been added to that in the last 10 or 15 years is the importance of obtaining an autopsy to exclude other causes of death.

Dr. Wilner: It is well recognized that people with epilepsy can die from status epilepticus or accidents related to seizures, but the concept of SUDEP, that one could die for a cause outside of a seizure, is what is new. Ten years ago, when this concept was becoming more well known, many doctors were explaining this to patients with epilepsy and their families, and I have to admit that I had mixed feelings because SUDEP is a rare occurrence but nonetheless becomes one more thing for someone with epilepsy to worry about. What is the value of explaining this to families and patients?

Dr. Buchholter: The 2 primary benefits represent the spectrum of people living with epilepsy. The first is that, for those individuals with intractable epilepsy not responsive to antiepileptic drugs, which is 30% of our large population of individuals with epilepsy, the risk of dying can be as high as 1 in 100. In any busy clinic, that means several people will die every year. At the other end of the spectrum are those individuals with an extremely low risk of dying. For those individuals and their families, they should receive the reassurance that although this does happen, they or their loved ones are at low risk, although not zero.

Dr. Wilner: It is important to educate patients and families about where they are on the spectrum. In my own practice, for the patients who are at high risk, the risk for sudden death is an argument for better adherence to a regimen and more aggressive treatment. For example, some patients are afraid of the dangers of surgery, but if those patients could be cured by surgery, they would no longer have the risk for SUDEP and that may be persuasive.

Dr. Buchholter: Yes, exactly.

Dr. Wilner: What were your roles at the conference?

Ms. Lapham: Dr. Buchholter and I served as co-chairs of the conference steering committee. As an MD PhD and child epileptologist, Dr. Buchholter represented the professionals. As a mother who has lost a child to SUDEP and a CURE board member, I represented the bereaved and advocacy communities. The committee itself was noteworthy in that it was made up of scientists, clinicians, family members, and advocates. Individuals came from a range of medical centers, epilepsy advocacy organizations, funding organizations, government agencies, and the AES. The spirit of the meeting was very much one of partnership. What made the meeting unique was this diversity and strength of its network.

Dr. Wilner: The last time I researched this topic, it was still unknown whether SUDEP is primarily a cardiac event or primarily a respiratory event or whether more than one type of pathophysiology is contributing. What is our current understanding of the pathophysiology?

Dr. Buchholter: We have champions for each of the mechanisms you mentioned. Right now, the thinking is that multiple causes are likely responsible and that it may be multifactorial. Whether it is primarily a disorder of respiration, cardiac dysfunction, or something intrinsic in the brain is unknown. That is the focus of a lot of the basic research.

Dr. Wilner: How helpful is this mix of interested parties? Researchers are working as hard as they can and family members want everything done. Was it helpful to have everyone together?

Ms. Lapham: We did not have separate tracks. The whole meeting was composed of plenary sessions, so everyone sat through everything. Although the science soared over the heads of most of the lay participants, what I heard from families was that they were just happy to know that this science is being pursued. When you lose a loved one suddenly, unexpectedly, it is quite difficult to get your mind around it. You feel very alone in this field, and no one talks about it. To come to a meeting like this, to meet other family members, and then to connect with scientists and clinicians who are doing something [to prevent these deaths] is very powerful. But it was a 2-way street. Many of the scientists said that they had never met anyone who had lost someone to SUDEP. So it made the problem that much more real to these scientists and put faces on the problem. I think this added a new urgency to finding a solution. The epidemiologists who participated brought new understanding to some of the mortality numbers and framed the problem in a novel and urgent light. We often seem to think this is very, very rare so we do not need to talk about it.

Dr. Wilner: One other aspect of the meeting that impressed me is the proliferation of nonprofit societies for epilepsy, such as CURE and the Epilepsy Foundation, the Epilepsy Therapy Project, SUDEP Aware. I have been concerned that this would result in a dilution of the energy. But to see all the organizations come together and work together at this conference had a very positive effect.

Ms. Lapham: I agree. We tried very hard not to allow one organization to own the meeting or to celebrate just one group or one person. This was very much a team effort. Everyone approached it that way.

Dr. Buchholter: I agree. We always worry about the issue of dilution of effort, but the state of the art right now is the grassroots efforts, which are driving the whole process. Whether it be CURE or newer organizations, it has involved a remarkable group of people who are united to try to do something they all believe is very important and feel with great passion.

Dr. Wilner: Ms. Lapham, as a parent who has lost a child because of epilepsy and sudden death, what needs to happen [to improve our response and awareness] going forward?

Ms. Lapham: Keeping this momentum going is critical so that the government agencies and nongovernmental organizations like CURE will continue to invest in the science. The grassroots efforts need to stay active and engaged to continue to promote awareness. We have a long way to go before this is a mainstream issue that clinicians feel comfortable talking about. This is a multifaceted issue that we need to keep emphasizing.

Dr. Wilner: Did any actionable items come out of the meeting? What is going to happen next?

Dr. Buchholter: There were several, and these were core components of the meeting. The first was a renewed interest and focus on research and registries, both national and international, because without good phenotypic data and autopsy-based materials we will not be able to take the next step. The second was agreement that we need a greater focus on professional education, particularly education of physicians, to get the message out and discuss this with our patients and families exactly because of the reason you mentioned earlier. Bringing it out in the open is a key component of prevention, and first-line prevention is adherence to medication regimens, surgical therapy if needed, vagus nerve stimulator if needed, ketogenic diet -- all to prevent seizures. The third was the proliferation of innovative devices being developed to warn families of an impairment of respiration, heart rate, or the presence of a seizure. The challenge now is to test those devices in a responsible fashion and not [have questionable devices] flood the market. We will see a great deal of progress in all 3 of those areas in the next few years.

Dr. Wilner: Will another meeting be scheduled for the future?

Dr. Buchholter: We just received the results of a survey of the meeting participants, and it was remarkable in 2 regards. First, the response rate to the survey was in the range of 30%-40%, which is several orders of magnitude greater than typical survey response rates. The other was that the enthusiasm for the meeting was in the 80%-90% range, with the vast majority saying we should definitely do this again and have the same kind of format where everyone is talking to each other directly. The meeting will definitely happen again. We are beginning the planning for 2014.

Dr. Wilner: Is there a SUDEP section or something similar at the AES?

Dr. Buchholter: Yes. The SUDEP Task Force has a Webpage that can be accessed from the AES site. You also will see information regarding future meetings on the CURE site, on the Epilepsy Therapy Project site, CDC, etc., so that the community at large will know about this.

Ms. Lapham: An audio version of the conference will be available on the AES Website along with most of the slides that were presented at the meeting. So if people would like to get more in-depth knowledge of what occurred, that will be available soon.

Dr. Wilner: Thanks to both of you for bringing me up to date on the PAME conference. It was a pleasure speaking with you, and I look forward to a lot of progress in this area.