Epilepsy

Epileptologists have been fortunate in the past decade. Developments in diagnostic technology translate to fewer cases of "idiopathic" epilepsy. Expanding treatment options include eight new antiepileptic drugs (AEDs) since 1993, the first (but not last) device approved for the treatment of epilepsy, and improved efficacy and safety of epilepsy surgical procedures.

At the same time, more than 30% of persons with epilepsy continue to have seizures, and a similar number experience medication-associated side effects that limit quality of life. It appears that therapy advances have not achieved the treatment goal of no seizures and no side effects for all persons with epilepsy. This treatment gap implies that presently available therapies are not sufficient for more than 30% of persons with epilepsy, that some persons with epilepsy do not have access to new therapies, that patient/physician expectations about a good treatment response may be lower than is necessary, or all of the above. Finally, while we work towards better seizure suppression with well-tolerated therapies, we do not yet have an intervention that alters epileptogenesis. In other words, we cannot prevent epilepsy, nor can we cure epilepsy.

In this issue, a group of epileptologists expands the concept of treating epilepsy. Our treatment goal goes beyond suppressing seizures with medications, to maintaining health and enhancing over-all well being.

A successful treatment plan requires an understanding of the seizure type and epilepsy syndrome. The concept of epilepsy syndromes goes beyond a phenomenological description of seizure semiology. The epilepsy syndrome incorporates expected seizure types with presumed etiology, likely prognosis, and expected response to particular therapies. The epilepsy syndrome classification directs the clinician towards treatment options and permits the scientist to define groups with shared phenotypes. Ultimately this will facilitate development of therapies targeted to the molecular or network defect underlying the specific syndrome. Dr. Joseph Sirven provides a comprehensive and clear review of our current understanding of seizures and of epilepsy syndromes. This information provides a framework for the neurologist to describe seizures and epilepsies, to understand the epilepsy syndrome pathophysiology, and to select among therapies.

Pharmacologic therapy of epilepsy has never offered so many options. More than a dozen AEDs are in wide use. The clinician finds that selection of a particular agent requires familiarity with efficacy of each AED for specific types of seizures as well as pharmacokinetic characteristics, and immediate, dose-related, and long-term side effects. Having so many AED options also challenges the clinician to consider changing AED therapy if seizures are not controlled, or if the patient experiences medication-related side effects. A review of the individual AEDs in common use is supplemented with information about how to start AED therapy as well as when to consider stopping therapy.

Antiepileptic medications provide seizure control in most, but not all, persons with epilepsy. Concerns about acute and long-term side effects of antiepileptic medications contribute to the growing interest in nonpharmacological therapies. While early attempts to control seizures with electrical stimulation were disappointing, experience with implanted electrical stimulation devices for pain and movement disorders have renewed interest in this therapeutic approach for epilepsy. Dr. Steven Karceski reviews current experience with devices for epilepsy and provides a detailed discussion of the vagus nerve stimulator, which is the first, but certainly not last, FDA-approved device to treat epilepsy.

Epilepsy surgery is the only currently available therapy that is curative for some forms of epilepsy. Improved localization of the epileptogenic focus with computer assisted video-electroencephalogram monitoring and new generation neuroimaging permits identification of candidates with a greater than 80% chance of seizure freedom after cortical resective surgery. The first prospective randomized trial assessing the efficacy and tolerability of continued medical therapy versus surgical therapy in persons with medial temporal lobe epilepsy demonstrates clear superiority of epilepsy surgery. Continued enhancements in surgical technique and better understanding of surgically remedial epilepsy syndromes contribute to better safety and efficacy. Dr. Guy McKhann II discusses the rationale behind the surgical treatment of epilepsy as well as surgical approaches and outcomes. Although surgery is the only option for complete seizure control for many persons with localization-related epilepsy, few eligible candidates are so treated. Providers of health care for persons with epilepsy should consider referring a patient with localization-related epilepsy for an epilepsy surgery evaluation after two to three antiepileptic drugs have failed. Candidates for epilepsy surgery can therefore be identified within 1 to 2 years of diagnosis.

Much of the success of epilepsy surgery can be attributed to advances in brain imaging. Magnetic resonance imaging (MRI) has elucidated the anatomic basis of some epilepsies and helped to illuminate the pathophysiology of epilepsy syndromes. Functional imaging techniques using MRI, positron emission tomography, and single photon emission computed tomography visualize the brain's workings. These modalities provide dynamic portrayal of the epileptic focus and are essential tools for the scientist investigating epileptogenesis. The applications of neuroimaging technology in the clinic and the laboratory are expertly reviewed by one of the leaders in applying imaging technology to epilepsy, Dr. Ruben Kuzniecky.

Epilepsy is often a chronic condition, and many women must deal with the consequences of seizures and of taking AEDs during the childbearing years. While there was not much information concerning issues of concern for women with epilepsy even a decade ago, so much information has become available recently that this topic deserves two independent discussions. Dr. Alison Pack discusses physiological concerns of the woman with epilepsy, including the effect of ovarian steroid hormones on seizures, the impact of epilepsy and AEDs on fertility, reproductive hormones and ovarian function, and the adverse effects of AEDs on bone health.

Dr. Page Pennell follows with a thorough discussion of the association between AEDs and adverse pregnancy outcome. Fetal malformations and anomalies are increased in women receiving AEDs. Several straightforward interventions will enhance the prenatal detection of malformations and should lessen the teratogenic potential of these agents.

The elderly represent the fastest growing population of persons with epilepsy. Yet, until recently, very little attention was paid to the unique treatment needs of this population. Thanks to clinician/investigators like Dr. Ilo Leppik, this is no longer true. Dr. Leppik discusses the special needs of the elderly with epilepsy. This includes adjustments in antiepileptic medication dosage to compensate for differences in pharmacokinetics and reduced tolerability. The elderly are more likely to have comorbid medical conditions that must be considered as part of overall management. The elderly are at higher risk for drug-drug interactions that must be considered when selecting the antiepileptic medication. While these concerns complicate management, the clinician will be gratified to know that response to treatment may be better in this group.

We close this issue with a review of sleep and epilepsy by Dr. Carl Bazil. Dr. Bazil is one of the investigators who have described the association between sleep disturbances and epilepsy. Persons with epilepsy are often in a vicious cycle: seizures and AEDs disrupt sleep architecture and impair sleep quality, while poor sleep quality promotes more seizures. Daytime lethargy and fatigue often encountered in persons with epilepsy does not always represent a side effect of antiepileptic medication. These symptoms may be the presentation of a sleep disorder. Until we consider the quality of sleep, we cannot address our patient's overall well being.

I cannot close this preface without making all readers aware of a tremendous resource for health care providers treating persons with epilepsy (and a resource for persons with epilepsy as well). The Epilepsy Foundation is the national voluntary health care agency that represents persons with epilepsy through advocacy, research, and information and services. The Epilepsy Foundation maintains a web site, www.epilepsyfoundation.org, which contains a wealth of information about epilepsy, as well as links to other high-quality sites relevant to this neurological disorder. Please take the opportunity to inform each and every patient about this resource. Well-informed patients serve as effective self advocates in a health care system increasingly less sympathetic to the needs of persons with chronic neurological disease.