Epilepsy is a significant health problem. Ten percent of people living a normal lifespan will experience at least one epileptic seizure and one third will develop a chronic epileptic condition. At any given time, 0.5% to 1% of the world's population has active epilepsy, amounting to over 40 million people. A World Health Organization-sponsored study determined that epilepsy accounts for 1% of the global burden of disease, measured as disability-adjusted life years equivalent to the global burden of lung cancer in men and to breast cancer in women. Disability-adjusted life years measure years of productivity lost as a result of disability or death, which is relatively high for epilepsy because this condition often begins in childhood. The cost of epilepsy in the United States has been estimated at $12.5 billion/year, and 80% of this cost is borne by the 30% of patients whose seizures are not controlled.

The cost of uncontrolled epileptic seizures to society, and to individuals with epilepsy and their families, is measured not only in economic terms, but also in terms of human suffering. In this month's first article, Michael R. Sperling, MD, who has authored seminal papers on consequences of epilepsy, provides evidence that epilepsy is not a benign disorder; that early control of epileptic seizures is important to avoid irreversible disability due to the development of psychological and social disturbances and progressive cerebral dysfunction, as well as epilepsy-related death. The burden imposed on society and on individuals by uncontrolled epileptic seizures is all the more tragic because many suffer needlessly. For a significant number of adults who have had recurrent seizures since infancy, childhood, or adolescence, more aggressive early intervention might have rescued them from a lifetime of disability. Consequently, the goal of therapy today should be no seizures and no side effects, as soon as possible.

The consequences of epilepsy can be quite severe and include shortened lifespan, excessive bodily injury, neuropsychological and psychiatric impairment, and social disability. There is evidence that seizures cause brain injury, including neuronal death and physiological dysfunction. Mortality rates are 4—7 times higher in people with medically refractory seizures, and injury rates are substantial, ranging from one per 20 person-years to as much as one per 3 person-years. Quality of life is impaired in epilepsy, and relates to seizure control. Psychosocial disabilities, including lower social interaction with reduced marriage rates and reduced employment levels, are more common in people with refractory seizures. Complete seizure control is desirable, since seizures potentially constitute a serious threat to health and well-being. Therefore, satisfactory seizure control should be defined as having no seizures. Treatment should be directed to preventing seizures whenever possible and achieving control early in the course of illness. The risks of uncontrolled seizures outweigh the risks of aggressive medical or surgical therapy.

Although modern community-based studies have shown that a majority of people with newly diagnosed epilepsy will enter long-term remission, seizures remain refractory to treatment in a substantial proportion of this population—perhaps as much as 40%. A consensus is being reached that, for operational purposes, pharmacoresistance can be suspected when two appropriately chosen, well-tolerated, first-line antiepileptic drugs (AEDs) or one monotherapy and one combination regimen have failed due to lack of efficacy. Poor prognostic factors include lack of response to the first AED, specific syndromes, symptomatic etiology, family history of epilepsy, psychiatric comorbidity, and high frequency of seizures. These observations suggest that prognosis can often be determined early in the course of the disorder. We propose a management paradigm that aims to maximize the chance of successful AED therapy, including the early use of “rational polytherapy” for patients not responding to monotherapy, and to identify efficiently patients suitable for “curative” resective surgery, in particular those with mesial temporal lobe epilepsy. An orderly approach to each epilepsy syndrome will optimize the chance of perfect seizure control and help more patients achieve a fulfilling life.

Evidence from a recent randomized controlled trial of surgical versus medical therapy of temporal lobe epilepsy proves that antero'mesial resection is safe and more effective than medical therapy. The number of patients needed to treat for one patient to become free of disabling seizures is two, which is superior to most interventions in neurology. A meta-analysis of non-randomized trials gives almost identical results; about two-thirds of patients become seizure-free, compared with only 8% with medical therapy. The results are remarkably similar among studies from different parts of the world. Quality of life improves early after epilepsy surgery, the improvements are both statistically and clinically significant, and they are sustained. Surgical morbidity with clinically important permanent sequelae is 2%. Epilepsy surgery remains underutilized in developed countries and it does not exist in all but a few developing countries. Current randomized trials are underway to explore the effect of early surgery versus optimum medical therapy on the prevention of disability in patients with mesial temporal lobe epilepsy, and to examine the effectiveness of novel interventions, such as minimally invasive surgery and brain stimulation.

Intractable temporal lobe epilepsy that is surgically treated in adulthood is a disorder whose onset frequently occurs during childhood and early adolescence. The average duration of epilepsy prior to surgery is on the order of 20 years. The long delay between onset and surgery has at least two components: time from onset to intractability and time from evidence of intractability to surgery. The first interval is prolonged >10 years especially if the onset is during childhood. This suggests a complex natural history that we have not fully appreciated as well as a potential window of opportunity for early secondary intervention. The second interval is also prolonged, especially if onset was during childhood. Reasons for this are not fully clear but may include a reluctance to consider surgery and perhaps difficulty deciding whether seizures are sufficiently intractable to warrant surgery especially after what may have been a relatively benign initial course. Factors involved in the second delay need to be better understood so that surgical interventions can be appropriately targeted early rather than late, thereby reducing serious social, psychological, and educational consequences associated with uncontrolled seizures.

It is estimated that only a small proportion of patients with surgically remediable intractable epilepsy receive surgical treatment. There are multiple reasons why this is the case. Patients with intractable epilepsy are sometimes severely disabled and disability can create barriers to getting recommended care. Patients with epilepsy are not well informed about their condition and the available treatments. The incidence of epilepsy is similar in minority populations, and surgically remediable epilepsy frequently presents in adolescence. Nevertheless, these vulnerable populations have specific barriers to receiving epilepsy care, which are often not addressed. In addition, despite scientific evidence for the benefits of the surgical treatment of epilepsy, many healthcare providers do not recommend or adequately discuss surgery with patients. Solutions to these barriers will require interventions that result in informed and capable patients who actively participate in their care and healthcare providers who practice culturally sensitive, recommended care.