Epilepsy research needs reach across the missions of multiple NIH Institutes and Centers and across many organizations outside the NIH. As the primary NIH Institute for epilepsy research, NINDS leads this working group, with broad representation from the NIH, other Federal agencies, and the research and patient advocacy communities. Annual meetings provide a forum for sharing information about ongoing and planned epilepsy research activities, highlighting advances and discussing needs and opportunities, and promoting increased collaboration toward common research goals.
Neuroscience Center (NSC) | Conference Room D
6001 Executive Blvd, Rockville, MD
Hosted by NINDS
Agenda and Presentations
|9:00 AM – 9:20 AM|
|9:20 AM – 9:45 AM||
Introduce new ICARE Members
|9:45 AM – 10:00 AM||Update on the Epilepsy Benchmarks(pdf, 222 KB)
Ray Dingledine, PhD, NINDS/AES Epilepsy Benchmarks Stewards Committee Chair
|Community-wide Epilepsy Research Portfolio Analysis(pdf, 663 KB)|
|10:00 AM – 10:25 AM||Methodology and Preliminary Results
Miriam Leenders, PhD, NINDS/NIH
|10:25 AM – 10:45 AM||Open Discussion, and future plans for ICARE portfolio analyses
Moderator: Brandy Fureman, PhD, NINDS/NIH
|10:45 AM – 11:00 AM||BREAK|
Collaborative Activities and Opportunities
|11:00 AM – 11:15 AM||Demonstration of the new Epilepsy Research Connection site(pdf, 4117 KB)
|11:15 AM – 11:30 AM|
|11:30 AM – 12:00 PM||
Open Discussion on collaborative opportunities
|12:00 PM – 1:15 AM||
Lunch (on your own/small group meetings)
|Scientific & Policy: Genetic Testing for the Epilepsies|
|1:15 PM – 1:35 PM||
Molecular Diagnosis for Epilepsies: The Impact on Patients and Families
|1:35 PM – 1:55 PM||
The Promise of Exome Sequencing in Epilepsy and the New Epilepsy Genetics Initiative (EGI)
|1:55 PM – 2:15 PM||State of the science in epilepsy genetics translation to clinical practice(pdf, 376 KB)
Dennis Dlugos, MD, Children’s Hospital of Philadelphia
|2:15 PM – 2:35 PM||Evidence development for clinical utility(pdf, 135 KB)
Suzanne Belinson, PhD, MPH, Blue Cross Blue Shield Association
|2:35 PM – 2:55 PM||
The Role of Education: Addressing the Challenges and Opportunities to Clinical Translation(pdf, 152 KB)
|2:55 PM – 3:30 PM||
|3:30 PM – 3:45 PM||Wrap-up and adjourn main meeting
Post-meeting Opportunities for small group meetings and networking
Tutorials/demonstrations: Room 3310 (NIH REPORTER, RCDC, and Epilepsy Resource Connection)
The ICARE group held its fifth annual meeting on April 13, 2015. Dr Walter Koroshetz, Acting Director, NINDS opened the meeting with highlights of accomplishments and collaborative opportunities from several ICARE member reports(pdf, 1170 KB) (submitted prior to the meeting).
- The Epilepsy Benchmark Stewards became a joint committee of the American Epilepsy Society (AES) and the NINDS, and the group plans to publish a mid-course progress report in Epilepsy Currents in 2016.
- The prior Vision 2020 organization adopted a new structure and name – the Epilepsy Leadership Council. The Epilepsy Leadership Council is a coalition of organizations representing individuals with epilepsy, professionals, and governmental organizations. The mission is to serve as a mechanism through which organizations can work on shared goals and projects that will have a positive impact on the lives of individuals with epilepsy, focusing on those areas where working together produces greater efficiency and impact than working independently.
- The AES launched a survey tool called Q-Pulse, which allows for a rapid way to collect data from a representative sampling of epilepsy specialists on current clinical practice. It can also be used in a number of other ways including determining the number of potential research subjects in a specific area or the availability of certain equipment in a given location.
- The CDC is supporting Project to Learn about Youth – Mental Health (PLAY-MH) is a set of cross-sectional epidemiologic studies within schools to characterize the underlying prevalence, diagnosed prevalence, and treated prevalence of children’s mental, emotional, and behavioral disorders. Epilepsy diagnosis and treatment is included in the questionnaires for this study. The CDC also continues to support the Managing Epilepsy Well Network which was established in 2007 to advance the science of epilepsy self-management by conducting research, collaborating with stakeholders to implement activities, and broadly disseminating research findings.
Dr Koroshetz also provided an update on the Federal budget outlook for the NIH and NINDS as well as some more specific details on the BRAIN initiative. One of the main goals of the BRAIN Initiative is to develop tools to help researchers better study how neural networks function, and thus this initiative will likely prove especially impactful on our understanding of the epilepsies.
Dr Koroshetz concluded his remarks by introducing several new representatives and members to ICARE, including Dr. Amy Brooks-Kayal (AES), Ms. Barbara Kroner (ELC), Dr. Anthony Pacifico (DOD, CDMRP), Ms. Abigail Hemani (Dravet Syndrome Foundation) as well as Drs. Glen Graham and Paul Rutecki representing the Department of Veterans Affairs.
Update on the Epilepsy Benchmarks
Dr. Ray Dingledine, Chair of the AES/NINDS Benchmark Stewards committee, described the new processes the Stewards are using to report progress made in the 2014 Benchmarks areas, which will be disseminated through publications in Epilepsy Currents in 2016 and 2019. He also highlighted some key recent advances, including 1) a new animal model of new-onset refractory status epilepticus (NORSE), 2) multi-lab replication of the epileptogenic roles of the mTOR, TRKB, and inflammatory pathways, and the transcriptional regulator REST, 3) the identification of a GRIN-specific mutation in a patient with refractory seizures, in vitro confirmation of memantine sensitivity of the affected channel, and N=1 efficacy of memantine to reduce seizure burden in the patient, and 4) new surveillance efforts and risk factor studies in Sudden Unexpected Death in Epilepsy (SUDEP).
Community-wide Epilepsy Portfolio Analysis
Dr. Miriam Leenders, NINDS, presented the first ICARE-wide research portfolio analysis. A working group of ICARE member volunteers developed the methodology and performed a small pilot study of the data collection approach, which was then extended to all ICARE organizations to analyze their research portfolios for 2013. The goals of the analysis included assessing progress made against epilepsy research priorities defined by the NINDS Epilepsy Benchmarks and the 2012 IOM Report “Epilepsy Across the Spectrum,” and also helping to guide future funding priorities by highlighting current gaps and opportunities. Major areas covered in the analysis included the breakdown of funding for epilepsy research by federal versus non-governmental sources, the types of research supported, and the specific research focus areas. Some general conclusions from the analysis included the finding that there was limited support for structured training (training grants, fellowships) in epilepsy research, and that research support is unevenly distributed between the Epilepsy Benchmark priorities. Significant discussion following the presentation focused on gaps in support for physician-scientists and other trainees wishing to pursue a career in epilepsy research.
Mr. Rob Moss, Seizure Tracker, shared the new Epilepsy Research Connection website developed by the Epilepsy Leadership Council. The purpose of the site is to provide researchers with a single search tool to identify epilepsy-related funding opportunities from public and not-for-profit organizations. Mr. Moss provided a demo of the site and search engine, and encouraged any organization funding epilepsy research to submit their funding opportunity announcements to the site. The site also allows researchers to set up profiles and perform more advanced funding opportunity searches on specific topics.
Dr. Brandy Fureman, NINDS, presented potential next steps and focus areas for ICARE. Dr. Fureman opened her presentation by reminding the committee of the purpose of ICARE, and that by working together we can make faster and further progress than any individual organization alone. As examples, Dr. Fureman highlighted how structured training and career development makes up a small proportion of ICARE funding from a limited number of organizations. She also showed a graphical representation of how funding from ICARE members is unevenly distributed across the Benchmark Areas, sometimes dramatically so. This may present opportunities for ICARE members with similar interests to work together, particularly when either organization alone could not bring sufficient resources to bear on the problem. Dr. Fureman introduced the ICARE collaboration request form(pdf, 128 KB)(pdf, 128 KB) (pdf, 126 kb) to initiate collaborations among ICARE members. Dr. Fureman presented strategies for ICARE to cooperate at multiple levels and also proposed setting up working groups to look into areas of shared interest, perhaps starting with training.
Scientific & Policy Session: Genetic Testing for the Epilepsies
Dr. Vicky Whittemore, NINDS, opened the afternoon session on genetic testing by setting out the goals of the session; to educate the organizations around the table about the state of genetic diagnosis for the epilepsies, and to discuss the evidence needed to establish the clinical utility of genetic testing in patients with severe epilepsy of unknown cause, particularly whole exome sequencing.
Ms. Beth Sheidley, Boston Children’s Hospital, spoke about the molecular diagnosis for epilepsies and the impact it can have for patients and families. She provided an overview of the process Boston Children’s uses to determine when genetic testing is appropriate as well as several example case studies of how genetic testing has been used successfully. Boston Children’s uses a committee to determine when exome sequencing is justified, evaluating cases based on when sequencing is medically necessary and whether there is an actionable outcome. Approximately 25% of cases that are recommended for sequencing by this committee are subsequently denied coverage by insurance providers, with private insurers providing almost no coverage for exome sequencing at present.
Dr. H. Steve White, CURE, provided an introduction and overview of CURE’s Epilepsy Genetics Initiative, or EGI, which is supported in partnership with NINDS. The cause of approximately 75% of epilepsy cases is unknown, although genetic lesions are increasingly being identified as causative in some rare epilepsies and are also likely to contribute to more prevalent forms. The goal of the EGI is to serve as a data repository for clinical exome and genome sequences from people with epilepsy. These sequences will be reanalyzed every 6 months to identify novel causative genetic mutations identified since the last analysis. Importantly, this information will then be communicated back to the patients via their doctor. This data will also be available for researchers and governed by a steering committee and several oversight and administrative committees, with participation from NINDS staff.
Dr. Dennis Dlugos, University of Pennsylvania/Children’s Hospital of Philadelphia, presented on the state and science of epilepsy genetics and translation to clinical practice. Dr. Dlugos began his presentation by discussing how genetic testing is already having an impact in the clinic, providing a diagnosis in a substantial number of cases and also often pointing towards better therapeutic choices to maximize benefit and minimize side effects. He also provided an example of one case where in vitro basic science work identified an FDA-approved drug that negated the effects of an epilepsy-causing mutation in a potassium channel. Giving this drug to an affected child resulted in a dramatic improvement in symptoms and cognitive function. Dr. Dlugos went on to describe the limitations of this study but also the promise of this type of approach, and how it could lead to more efficient and effective clinical trials guided by the precision afforded by genetic sequencing.
Dr. Suazanne Belinson, Blue Cross Blue Shield Association (BCBS), provided comments on the past, present and forward-looking views of genetic testing and reimbursement from the health insurance provider perspective. Within BCBS, the Center for Clinical Effectiveness within the Office of Clinical Affairs drafts policies for the BCBS system as a whole, although individual claim decisions are made on a case-by-case basis. The current overall policy of BCBS is that genetic testing for epilepsy is considered investigational except in the case of rare epilepsy syndromes where genetic testing may lead to changes in medication or management, changes in diagnostic testing, or lead to changes in reproductive decision making. The Center for Clinical Effectiveness reviews the scientific literature thoroughly in order to determine which procedures are supported by evidence and are likely to lead to medically actionable outcomes. BCBS is actively working to make this process transparent and efficient, and is also looking forward to new developments on the horizon such as pharmacogenomics applications that could have a significant impact on personalized patient care.
Dr. Michael Dougherty, American Society of Human Genetics, focused his presentation on the need to better prepare health care practitioners to use and interpret genetic information. Currently, there are few clinical guidelines on how best to use genomic medicine and there are additional hurdles in seeking reimbursement for these services as well as ensuring access to all patients. Non-genetic specialists will increasingly be called on to practice genomic medicine, especially in rural and underserved urban areas, so there is a need to start educating them now. The emphasis should be on skills over knowledge, such as the ability to gather family history information, communicate risk effectively with patients, and when to refer patients to specialists. Currently, educational material for genetic testing is often supplied by commercial vendors of such tests, but professional societies and academic centers are increasingly stepping in to better prepare medical personnel for the proper use of genetic testing and genomic medicine.
The meeting concluded with further discussion on how reimbursement decisions are made in genetic testing as well as discussion of plans to continue the portfolio analysis process and start a training working group of ICARE.
Member Update Reports(pdf, 1170 KB)