Neuroprotection and antiepileptogenesis

The stated goal of the community of physicians and scientists who treat and study epilepsy, as articulated at an NIH-sponsored consensus conference in 2000, is “no seizures, no side effects.” The conference report, however, makes clear that suppression of the symptoms of epilepsy, i.e., seizures per se, is not sufficient. Additional efforts must focus on preventing the development of epilepsy in individuals at risk and preventing the negative consequences of seizures when they occur (see http://www.ninds.nih.gov/about_ninds/epilepsybenchmarks.htm). This holistic approach to epilepsy, which emphasizes disease modification in addition to symptomatic relief, represents nothing less than a paradigm shift for the discoverers, developers, prescribers, and users of epilepsy therapeutics. Gowers recognized that “seizures beget seizures” over a century ago. Using the tools of clinical observation alone, however, it was impossible to determine whether seizures were epileptogenic or whether both the initial seizure and subsequent seizures a patient experienced were the result of a common pathology or genetic predisposition. Recent studies using animal models strongly support the notion that an otherwise normal individual can develop epilepsy as the result of an initial seizure.1,2⇓ These studies used chemoconvulsants to induce status epilepticus and then documented the occurrence or spontaneous recurrent seizures weeks to months later. It remains unclear whether a single …