**2005 Report submitted by Benchmark Steward(s):**

Marc A. Dichter, M.D., Ph.D. (University of Pennsylvania)

**Background of the benchmark goal:**

Almost unique in the field of neurology, or in medicine itself, for more
than a century physicians have focused almost exclusively on treating
the symptoms of epilepsy after it has developed, rather than on trying
to prevent the disease from occurring. This state of affairs applies
most obviously to acquired epilepsy (such as occurs after brain trauma
or intracerebral hemorrhage) where a normal individual develops epilepsy
after a known risk. However, it can also apply to genetic epilepsy, as
most forms of these disorders have a developmental pattern allowing for
prophylactic intervention, if such an intervention were available.

**Current Status of Field:**

At the time the original CURING EPILEPSY meeting was held, there was
only one ongoing, randomized double blind study of epilepsy prevention
in man occurring on the planet. This was the third in a series of such
studies initiated at the University of Washington and sponsored by the
NINDS. This group had been shown previously that neither phenytoin nor
valproate were capable of preventing epilepsy after traumatic brain
injury, and a very recent report indicates that their third study, using
MgSO4 was also negative. Other, non-blinded or non-randomized studies
had been performed with other "older" AEDs and also failed to show
efficacy at reducing epilepsy.

**Activities update**:

In the past year, 3 pilot clinical studies have been launched to try to
prevent epilepsy after either TBI (2) or intracerebral hemorrhage (1).
Dr. Pavel Klein at the Washington Center (DC) received a pilot grant
from the NINDS to study the use of levetiracetam to prevent epilepsy
after TBI. Dr. Marc Dichter received a pilot clinical trial grant from
the USArmy/DOD to study the use of topiramate to prevent epilepsy after
moderate to severe TBI (in a civilian population). Dr. Marc Dichter also
received a pilot grant from UCB Pharma to study the use of levetiracetam
to prevent epilepsy after lobar intracerebral hemorrhage. Both of the
latter two studies will employ continuous surface EEG recordings for 7
days to evaluate the presence of early subclinical seizures and to
compare the ability of the trial drugs to suppress early clinical and
subclinical seizures. Functional outcomes and imaging analyses will also
be performed on all patients to determine if the treatments result in a
"neuroprotective" outcome. In addition, attempts will be made to develop
other surrogate markers for epileptogenesis in man.

**Top priorities for next 5-10 years:**

-   Complete the three pilot programs. Determine feasibility for larger
    definitive studies.

-   Begin definitive studies based on any promising results in the pilot
    studies.

-   Develop a paradigm for early clinical evaluation of promising
    neuroprotective or antiepileptogenic compounds/strategies.

-   Develop surrogate markers for epileptogenesis in man.

**Roadblocks to progress:**

-   These studies are very complex and labor intensive.

-   These studies are very expensive.

-   There is no "gold standard" against which to compare any new agent
    or any new protocol

-   More animal studies are needed in parallel with the clinical trials

-   Clinical trial infrastructure needs to be stable so it can be
    sequentially implemented, rather than having to start each new study
    "from scratch".