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

Solomon L. Moshé, M.D. (Albert Einstein College of Medicine)

Philip A. Schwartzkroin, Ph.D. (University of California -- Davis)

**Background of the benchmark goal:**

Epilepsy is relatively common in infants and babies. Some of the most
catastrophic epilepsy syndromes occur in the immature. Unfortunately,
there are few animal models of these early epilepsies. Models are needed
to carry out basic investigations of underlying mechanisms, for the
development of age-appropriate therapies, and for testing strategies to
prevent the development of an epileptic encephalopathy (static or
progressive).

**Current status of field:**

There is currently much interest and concern in pediatric seizure
issues. A significant focus of recent research has been on genetic
predisposition, and on events/trauma in early development that may lead
to an epileptic state - both during the first few years of life and also
much later on. But there have been few publications that describe models
within which we can study a specific form of pediatric epilepsy -
seizure or syndrome. Further, for the vast majority of the pediatric
epilepsies, there is no specific treatment (and no model within which to
develop a specific treatment).

**Activities update:**

An NIH-sponsored workshop was held in the spring of 2004. Investigators
actively involved in pediatric epilepsy research, as well as those
focused on pediatric research in related fields, attended and
contributed. A follow-up workshop was held at the 2004 American Epilepsy
Society Annual Meeting (Investigators\' Workshop session), to solicit
input from a larger audience. We are in the process of generating a
\"white paper,\" summarizing the discussion and recommendations of those
workshops. The \"white paper\" will be submitted to an epilepsy journal.

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

-   Develop appropriate models (especially for at least one form of
    catastrophic epilepsy)

-   Generate data bases for relevant clinical information regarding
    pediatric epilepsies, and for basic research investigations and
    available models

-   Develop age specific therapies/treatments (again, for at least one
    form of catastrophic epilepsy)

-   Encourage the development of experimental technologies that will
    facilitate studies on pediatric models (i.e., micro-techniques
    appropriate for studying baby rats and mice)

**Roadblocks to progress:**

-   There is a need for research focused specifically on pediatric
    epilepsy issues

-   Absence of effective inter-institutional networks for sharing
    clinical data (especially on rare forms of catastrophic epilepsies)

-   Need for collaborative cross-laboratory, multi-disciplinary
    approaches

-   Poorly-developed technologies/hardware applicable to immature
    animals (e.g., micro-imaging, EEG monitoring)

**References:**

Chan KF, Jia Z, Murphy PA, Burnham WM, Cortez MA, Snead OC 3rd (2004)
Learning and memory impairment in rats with chronic atypical absence
seizures. Exp. Neurol., 190:328-336.

Schwartzkroin PA, Roper SN, Wenzel HJ (2004) Cortical dysplasia and
epilepsy: animal models. Adv Exp Med Biol. 548:145-174.

Stables JP, Bertram EH, White HS, Coulter DA, Dichter MA, Jacobs MP,
Loscher W, Lowenstein DH, Moshe SL, Noebels JL, Davis M (2002) Models
for epilepsy and epileptogenesis: report from the NIH workshop,
Bethesda, Maryland. Epilepsia 43:1410-1420.

Jensen FE, Baram TZ (2000) Developmental seizures induced by common
early-life insults: short- and long-term effects on seizure
susceptibility. Ment Retard Dev Disabil Res Rev. 6:253-257.

Dube C, Marescaux C, Nehlig A (2000) A metabolic and neuropathological
approach to the understanding of plastic changes that occur in the
immature and adult rat brain during lithium-pilocarpine-induced
epileptogenesis. Epilepsia 41 (Suppl 6):S36-S43.

Anderson AE, Hrachovy RA, Antalffy BA, Armstrong DL, Swann JW (1999) A
chronic focal epilepsy with mossy fiber sprouting follows recurrent
seizures induced by intrahippocampal tetanus toxin injection in infant
rats. Neuroscience 92:73-82.

Kubova H, Moshe SL (1994) Experimental models of epilepsy in young
animals.

J Child Neurol. 9 (Suppl 1):S3-S11.

Pitkänen, A., Schwartzkroin, P., Moshé, S.L. (Eds), Models of Seizures
and Epilepsy, Elsevier (2005).