Faculty Bibliography

Determining the prognosis of patients when they first present with epilepsy is a difficult task. Several clinical studies have shed light on this very important topic. Potential predictors of the refractory state, including seizure etiology, duration of epilepsy before treatment, and epilepsy type, have not been successful indicators of long-term outcome. One predictor of the refractory state appears to be early response to AED therapy. Inadequate seizure control after initial treatment is a poor prognostic sign. Recent research into genetic causes of the refractory state has included investigation of the multiple drug resistance gene, and polymorphisms at drug targets. More work is needed to determine the causes and predictors of drug resistance

About a third of the patients diagnosed with epilepsy will not be fully controlled with antiepileptic drugs (AEDs), and many of them will have frequent and disabling seizures. These patients will undergo multiple drug trials, most often without complete seizure remission. Moreover, refractory epilepsy is associated with increased morbidity (from seizures and medications), social isolation, unemployment, and overall reduced quality of life. There is evidence that refractory epilepsy can be a progressive disorder, which, if controlled early, might never develop into a full syndrome with all of its associated sequelae. The difficulty lies in identifying at an early stage patients who are likely to progress to intractability. No currently known markers enable clinicians to make this identification with confidence. Advances in pharmacogenomics and our understanding of pharmacologic responsiveness in epilepsy may change this situation. Even now, we are able to identify many patients with a poor prognosis earlier than before, particularly in the pediatric population, in which syndromic classification may provide an approach to predict intractability. The early initiation of aggressive therapy may improve outcome and overall quality of life