Current Best Practices in Clinical Management of Epilepsy

This edition of The Neurology Report focuses on the diagnosis and treatment of epilepsy in adults and children, including novel approaches to the clinical management of patients with refractory seizures.

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Gregory K. Bergey, MD
 Gregory K. Bergey, MD

Improvement in quality of life (QOL) is much more than a measure of physical and mental status—it represents a goal for practitioners and patients trying to optimally manage any disease state. For patients with epilepsy, improved QOL often is a function of prompt diagnosis and choice of appropriate drug therapy that minimizes side effects followed, if needed, by adjunctive treatments and, when appropriate, surgical intervention.

At the 69th Annual Meeting of the American Epilepsy Society (AES), held in Philadelphia, Pennsylvania, December 4–8, 2015, over 5,000 neurologists and other physicians, administrators, nurses, researchers, and allied health professionals participated in poster and platform presentations, symposia, special-interest meetings, general lectures, courses, and workshops to review the history of epilepsy management, evaluate current best practices in diagnosing and treating seizure disorders, and learn more about the disease to improve their skills in managing them. To create this issue of The Neurology Report, the authors attended last December's AES meeting and brought back with them important information on the clinical management of epilepsy and how management could be improved.

For over 150 years, research and clinical practice have greatly improved the diagnosis and treatment of epilepsy and our understanding of the disease. However, barriers to optimal management remain. To start off this issue of The Neurology Report, Pawan V. Rawal, MD, MHA, a neurologist at Baptist Memorial Health Care in Memphis, Tennessee, summarizes the "take home" messages from the 13th annual Judith Hoyer lecture in epilepsy, "Obstacles to Epilepsy Diagnosis: If You Don't Ask, They Won't Tell."

During her lecture, Jacqueline A. French, MD, reviewed the prevalence of epilepsy in the United States and focused on the reasons why some people with epilepsy are never diagnosed or are not properly diagnosed for a year or more after they began having seizures. Results from the Human Epilepsy Project showed that patients presenting with some seizure types were more likely to be treated promptly than others. Dr. French described the consequences of untreated epilepsy on the personal, professional, and social lives of people with seizure disorders and made several valuable proposals to raise awareness of the disease and the therapeutic options available.

James Thomas Houston, MD, a Clinical Neurophysiology Fellow at the University of Alabama at Birmingham, provides a well-organized, scholarly review of current best practices in managing epilepsy, based on a symposium held at the AES meeting. Physicians treating newly diagnosed patients must select an initial antiepileptic drug (AED) regimen appropriate to each patient's type and the patient's clinical history, keeping in mind that gender, age, genotype, comorbidities, previous reactions to other AEDs, concomitant illnesses, and other factors all may affect outcomes and the ultimate success or failure of the regimen finally chosen.

Dr. Houston goes on to discuss drug resistance and pseudoresistance as important obstacles to seizure control and the rational use of older and newer antiepileptic medications in combination for treating specific types of seizures, particularly in children. Nonpharmacologic treatment options (dietary therapy, responsive neurostimulation, vagal-nerve stimulation, and deep-brain stimulation) are reviewed as alternatives to drug therapy for treating patients who continue to have frequent seizures despite being treated with multiple AEDs or who cannot tolerate the side effects of these drugs and who are not candidates for seizure surgery. Lastly, Dr. Houston discusses the future potential of disease-modifying therapies and the many practical impediments (selection of appropriate study populations and "measuring sticks," the cost of conducting lengthy clinical trials, etc) to research in this area.

Christian M. Cabrera Kang, MD, a Clinical Neurophysiology Fellow at Emory University School of Medicine in Atlanta, describes the results of pivotal clinical trials and their follow-up studies showing perampanel—an AED with a unique mechanism of action on AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors—to be very useful in treating patients with partial seizures, with or without secondary generalization, as well as patients with primary generalized tonic-clonic seizures. Research studies stemming from these trials have helped to characterize these different responses, the efficacy of combining perampanel with other AEDs, and the influence of disease and treatment duration on patient response to the drug. Dr. Cabrera Kang also looks at the reports of use of perampanel in adolescents with partial seizures and Asian/Pacific Islanders. Lastly, he reviews recent research—much of it not yet published—on the risk of psychiatric and behavioral events, falls, long-term cognitive impairment, laboratory abnormalities, and impairment of adolescent growth and development in patients receiving perampanel.

Special Interest Groups (SIGs) provide intimate opportunities at the AES meetings for experts to get together and discuss specific topics related to different aspects of epilepsy. In the first of two reports for this issue of The Neurology Report, Deepti Anbarasan, MD, a Clinical Neurophysiology Fellow at The Neurological Institute of New York, Columbia University Medical Center, summarizes the importance of identifying psychiatric comorbidities in patients with seizure disorders, the pharmacologic issues that arise when psychotropic medications are used in combination with AEDs, and the potential risk of seizures and other adverse events arising from the use of antipsychotics in patients without epilepsy.

In her second report, Dr. Anbarasan recaps findings from a SIG on three interesting cognitive and behavioral interventions—acceptance and commitment therapy; progressive muscle relaxation; and HOBSCOTCH (Home-Based Self-management and COgnitive Training CHanges), a home-based, self-managed cognitive improvement program—in patients with epilepsy. Each intervention is discussed in terms of its efficacy, cost effectiveness, and ability to improve patient QOL. The HOBSCOTCH program, in particular, is a behavioral scheme that uses weekly telephone sessions with a "memory coach" and problem-solving carried out on a handheld Nintendo gaming device to improve memory and limit cognitive symptoms in patients with epilepsy.

To conclude this issue, Emily L. Johnson, MD, an Epilepsy Fellow at Johns Hopkins School of Medicine in Baltimore, reports what's new and hot in four different controversial areas of epilepsy management: (1) the usefulness of genetic testing in patients with epilepsy—and how to know which patients to send for testing; (2) the detection of autoimmune inflammation of the central nervous system and a practical approach to treating patients with autoimmune antibody–related seizure disorders; (3) the wisdom and safety of using valproate in women who are pregnant or may become pregnant; and (4) the current status of cannabis and cannabinoid derivatives in patients, especially children, with epilepsy.

We are grateful to these authors for providing an overview of some of the more interesting and potentially life-altering clinical and scientific presentations that were made during the 69th Annual Meeting of the AES. The study of seizure disorders in human subjects has produced tremendous insight into the optimal choice and sequencing of antiepileptic treatment. It also has delineated the safety and effectiveness of numerous medications with different mechanisms of action for treating epilepsy, as well as nonpharmacologic approaches to reduce seizure frequency and improve the QOL of patients with epilepsy when drug therapy alone is ineffectual. We look forward to future issues of The Neurology Report to see where all this research is taking us and our patients.

Dr. Bergey is Professor of Neurology, Director of the Johns Hopkins Epilepsy Center, and Co-Director of the Epilepsy Research Laboratory at Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland.

This activity is supported by an educational grant from Eisai Inc.