Curing epilepsy: Progress and future directions

Abstract

During the past decade, substantial progress has been made in delineating clinical features of the epilepsies and the basic mechanisms responsible for these disorders. Eleven human epilepsy genes have been identified and many more are now known from animal models. Candidate targets for cures are now based upon newly identified cellular and molecular mechanisms that underlie epileptogenesis. However, epilepsy is increasingly recognized as a group of heterogeneous syndromes characterized by other conditions that co-exist with seizures. Cognitive, emotional and behavioral co-morbidities are common and offer fruitful areas for study. These advances in understanding mechanisms are being matched by the rapid development of new diagnostic methods and therapeutic approaches. This article reviews these areas of progress and suggests specific goals that once accomplished promise to lead to cures for epilepsy.

Epilepsy research 150 years after Darwin's theory of evolution

“…Because epilepsy is a complex disease, genetic influences as causal factors of the epilepsies can point the way to new treatment strategies. On the basis of these facts, an elegant study recently reviewed the progress in this area and suggested specific goals that once accomplished promise to lead to cures for epilepsy 11 . Thus, at least 11 genes have now been described for human epilepsy and over 50 more genes have been identified in animal models of epilepsy [11][12][13] .…”

“…On the basis of these facts, an elegant study recently reviewed the progress in this area and suggested specific goals that once accomplished promise to lead to cures for epilepsy 11 . Thus, at least 11 genes have now been described for human epilepsy and over 50 more genes have been identified in animal models of epilepsy [11][12][13] . Alternatively, the specialists believe that the progress in understanding epilepsies of complex genetic origin will require not only identification of individual susceptibility alleles and analysis of gene to gene interactions, but also the study of gene-environment interactions 11 .…”

“…Clinical and experimental evidence supports these considerations. To begin with, it has been demonstrated that family members of individuals with acquired epilepsy are at higher risk of seizures compared with the general population 11,14,15 , and that common genetic features affect kainic acid-induced seizure susceptibility in rodent models 11,16 . The individual responsiveness and tolerance to antiepileptic drugs are the other important consequences of gene-environment interactions in epilepsy syndromes 11 .…”

“…To begin with, it has been demonstrated that family members of individuals with acquired epilepsy are at higher risk of seizures compared with the general population 11,14,15 , and that common genetic features affect kainic acid-induced seizure susceptibility in rodent models 11,16 . The individual responsiveness and tolerance to antiepileptic drugs are the other important consequences of gene-environment interactions in epilepsy syndromes 11 . This topic is supported by a recent study demonstrating that the HLA-B*1502 gene could contribute to the pathogenesis of Stevens-Johnson syndrome and toxic epidermal necrolysis in Asian patients, and that genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions is phenotype-specific 17 .…”

“…In these circumstances, pharmacogenetic approaches to epilepsy are already beginning to produce clinically important resolutions in the treatment of patients with epilepsy. For instance, the US Food and Drug Administration (FDA) has recently expanded an alert on the commonly used carbamazepine where a newly developed genetic test for risk of severe skin reactions is recommended 11 .…”