Harry Meinardi

This paper gives an account of the global evolution of (neuro-)chemistry in epileptology with an emphasis on the role of the International League Against Epilepsy (ILAE), which declared in its constitution a mission "to make the epilepsy-problem the object of special study and to make practical use of the results of such study." As Epilepsia is the scientific journal of the ILAE, the review emphasizes papers published in the journal.

Summary: This article is a summary of a workshop held by the ILAE concerning the issue of the epilepsy treatment gap in developing countries. The gap is defined in terms of those people with epilepsy who are not being appropriately treated and is the result of an array of medical, political, social, economic, and cultural factors. The situation regarding the treatment gap for various countries is reviewed, along with some of its causes. Although the overall gap is estimated to be large, a number of recent projects and interventions have been effective in delivering appropriate treatment to people with epilepsy in underresourced countries of the developing world. It is hoped that these may be transferable elsewhere and that, combined with the ILAE/IBE/WHO Global Campaign against Epilepsy and increased support from the worldwide epilepsy community, the treatment gap will begin to be bridged.

Summary: Purpose: When monotherapy with antiepileptic drugs (AEDs) fails, combination therapy is tried in an attempt to improve effectiveness by improving efficacy, tolerability, or both. We reviewed the available studies (both animal and human) on AED polytherapy to determine whether AEDs can be selected for combination therapy based on their mechanisms of action, and if so, which combinations are associated with increased effectiveness. Because various designs and methods of analysis were used in these studies, it was also necessary to evaluate the appropriateness of these approaches. Methods: Published papers reporting on AED polytherapy in animals or humans were identified by Medline search and by checking references cited in these papers. Results: Thirty‐nine papers were identified reporting on two‐drug AED combinations. Several combinations were reported to offer improved effectiveness, but no uniform approach was used in either animal or human studies for the evaluation of pharmacodynamic drug interactions; efficacy was often the only end point. Conclusions: There is evidence that AED polytherapy based on mechanisms of action may enhance effectiveness. In particular, combining a sodium channel blocker with a drug enhancing GABAergic inhibition appears to be advantageous. Combining two GABA mimetic drugs or combining an AMPA antagonist with an NMDA antagonist may enhance efficacy, but tolerability is sometimes reduced. Combining two sodium channel blockers seems less promising. However, given the incomplete knowledge of the pathophysiology of seizures and indeed of the exact mechanisms of action of AEDs, an empirical but rational approach for evaluating AED combinations is of fundamental importance. This would involve appropriate testing of all possible combinations in animal models and subsequent evaluation of advantageous combinations in clinical trials. Testing procedures in animals should include the isobologram method, and the concept of drug load should be the basis of studies in patients with epilepsy.

Article abstract-We compared the treatment policy for patients with epilepsy in six Dutch cities, comprising 302,149 inhabitants, with the treatment policies of a secondary referral center (a university hospital) and tertiary referral centers (outpatient departments of epilepsy centers). By comparing the prevalence of individuals receiving antiepileptic drugs in the six cities with the epidemiologic data for epilepsy in Rochester, Minnesota, we concluded that prescription data offer a suitable means by which to estimate the prevalence of epilepsy in a community. To compare prescriptions in cases of polytherapy, we normalized data by using defined daily doses published by the WHO Collaborating Center for Drugs Statistics Methodology and the Nordic Council on Medicines and concluded that the defined daily doses of antiepileptic drugs should be further elaborated. There is a need to obtain complete dose-response curves of equivalent antiepileptic drugs in humans. The trend of drug use found in the six cities, the university hospital, and the epilepsy centers is, however, in accord with the expectations regarding primary, secondary, and tertiary referral centers. NEUROLOGY 1996;46: 62-67

The treatment of generalized convulsive status epilepticus according to a protocol, including a time schedule, prevents unnecessary delay and improves outcome. Based on a literature study and our own clinical experiences a treatment protocol is discussed with special emphasis on medical complications, choice of antiepileptic drugs, route of administration and a proper time schedule.