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Epilepsy Research Benchmarks
The 2007 Epilepsy Research Benchmarks are now available

In March 2000, a historic milestone in epilepsy research was reached. Scientists, clinicians, people with epilepsy, family members, public policy makers, and committed volunteers came together at the National Institutes of Health to discuss what it would take to reach a cure for epilepsy, defined as the prevention of epilepsy in people at risk, and by effective and safe therapy ("no seizures, no side effects") for those with the disorder. Co-sponsored by the NINDS, American Epilepsy Society, Citizens United for Research in Epilepsy, Epilepsy Foundation, and National Association of Epilepsy Centers, the White House-initiated conference integrated advances in neuroscience, imaging, genetics, and clinical research to better understand the mechanisms of epileptogenesis, and to apply this knowledge toward developing new treatments and cures.

NINDS has developed a Research Agenda for Epilepsy. Based on the three major topic areas of the Conference:1) interrupting and monitoring epileptogenesis; 2) genetic strategies; and 3) developing new therapies, a series of goals and benchmarks were developed and are listed below:

I. Understanding basic mechanisms of epileptogenesis.

A. Discover the range of anatomical, physiological, and molecular substrates associated with the epilepsies; define unambiguous markers of epileptogenicity.

A1. Specific Benchmark:
Successfully develop a non-invasive, dynamic imaging system or physiological monitoring system that reliably identifies an epileptogenic region in at least one form of human epilepsy.
2005 Benchmark Steward Report [Word | PDF]

A2. Specific Benchmark:
a. Create a large-scale imaging database comprised of high-resolution MRI studies of patients with epilepsy (analyzing both cross-sectional and longitudinal populations) including demographic, historical and phenotypic data, and analyze this information in light of the normative database developed by the International Consortium for Brain Mapping (ICBM).
b. Use a portion of the imaging database and co-register the anatomical information with functional studies (e.g. fMRI, MEG, MRS, SPECT, PET, EEG, and cutting edge modalities), to identify potential structure-function relationships.
2005 Benchmark Steward Report [Word | PDF]

A3. Specific Benchmark:
Establish a collaborative network that enables investigators to compare results of gene-chip analyses arising from different models of epileptogenesis and epilepsy.
2005 Benchmark Steward Report [Word]

B. Continue the progress of identifying the genes predisposing to epilepsy.

B1. Specific Benchmark:
Create and enhance national research collaborations between physicians, human geneticists, and families to identify and clone the gene of pedigrees with monogenic epilepsy syndromes.
2005 Benchmark Steward Report [Word]

B2. Specific Benchmark:
Create a national consortium aimed at identifying new epilepsy susceptibility genes through a large-scale genotype:phenotype screen. Initiate this effort with a consensus conference that prioritizes phenotypes, develops implementation strategies, and defines endpoints.
2005 Benchmark Steward Report [Word]

C. Validate and apply models of epileptogenesis and epilepsy as biological test systems for novel therapy.

C1. Specific Benchmark:
Design a strategy for validating models of epileptogenesis, and determine the efficacy of a limited number of proposed antiepileptic treatments in validated models of epileptogenesis. The strategic approach will include arriving at a consensus on the current models of epileptogenesis, and identifying a scientific approach for validating the potential utility of future models for the study of human epilepsy.
2005 Benchmark Steward Report [Word]

C2. Specific Benchmark:
Characterize and develop new models for epileptogenesis and epilepsy in the developing brain, and therapy resistant epilepsy.
2005 Benchmark Steward Report [Word]

C3. Specific Benchmark:
Identify and characterize potential surrogate markers of epileptogenesis and epilepsy, and use these markers to carry out a high throughput screen for anti-epileptogenic compounds in animal models.
2005 Benchmark Steward Report [Word]

II. Create and implement new therapies aimed at the prevention of epilepsy in patients at risk (anti-epileptogenesis therapy in humans).

A. Specific Benchmark:
Use markers of epileptogenicity (see IA1) to successfully identify a potential epileptogenic region that responds to preventive intervention.

B. Specific Benchmark:
Complete at least 2 major, multi-center trials that test the effectiveness of potential neuroprotective or anti-epileptogenesis compounds in patients at highest risk for developing epilepsy. Successfully plan for the design and implementation of these trials before the availability of the intervention (rather than waiting until after the therapy appears).
2005 Benchmark Steward Report [Word]

III. Create and implement new therapies free of side effects that are aimed at the cessation of seizures in patients with epilepsy.

A. Specific Benchmark:
Assess the potential efficacy of therapies in individual patients by examining effects on markers of epileptogenicity. Aim at developing highly individualized treatments that take into account the maturational state of the brain and other factors proven to be relevant, such as hormonal status.
2005 Benchmark Steward Report [Word]

B. Specific Benchmark:
Develop a genetic fingerprint diagnostic test to: 1) identify patients who are likely to respond to a specific therapy; 2) identify patients likely to become refractory to therapy; 3) identify risk factors for abnormal metabolism or potential adverse effects for specific AEDs in individual patients.
2005 Benchmark Steward Report [Word]

C. Specific Benchmark:
Define the extent of diffuse seizure suppressing systems that may be dysfunctional in multifocal epilepsies. Define methods of activating these systems to ameliorate or even suppress seizures.
2005 Benchmark Steward Report [Word]

D. Specific Benchmark:
Achieve a complete cure for a genetic form of epilepsy by developing a rational approach to therapy that is based on an understanding of the functional effects of a mutation or acquired aberration, and is validated in a mouse model.

E. Specific Benchmark:
Successfully use a biosensor device (comprised of a biodetector, mini-pump, microstimulator, or other detector systems) that reliably anticipates or identifies seizures, and apply targeted treatment to abort seizures in at least one form of epilepsy.
2005 Benchmark Steward Report [Word]

F. Specific Benchmark:
Widen the use of epilepsy surgery including its use as a form of early intervention. Develop new surgical approaches such as the use of robotic arms.
2005 Benchmark Steward Report [Word]

G. Specific Benchmark:
Successfully use an entirely new therapeutic strategy such as cell transplantation or vaccination to significantly reduce seizure frequency in at least one form of epilepsy.

To ask questions or comment on the Benchmarks, please contact epilepsybenchmarks@ninds.nih.gov.

Related documents are available on the Epilepsy Research Web

Links to Co-Sponsors:

Last updated November 28, 2007