Epilepsy—Burning Questions and Emerging Therapies

FOCUS ONEDITORIAL EPILEPSY EDITORIAL

FOCUS CONTENTS Epilepsy—burning questions 245 Preserving memory in temporal lobectomy— are networks the key? and emerging therapies Michael Duchowny & Sanjiv Bhatia pilepsy imposes a major burden at both global nerve stimulation can reduce seizure frequency in 247 Responsive and individual levels. Worldwide, about 1% many patients with medically retractable epilepsy, neurostimulation Eof people have epilepsy, and nearly 4% will electrical brain stimulation has the potential to pro —modulating the experience epilepsy at some point during their lifetime. vide targeted and more-robust seizure control with epileptic brain In almost 30% of patients with epilepsy, antiseizure out adverse effects on the vocal apparatus. Robert Elinor Ben-Menachem medications do not provide sufficient seizure control. Fisher and Ana Luisa Velasco review the use of deep & Gregory L. Krauss Treatment-resistant epilepsy is a disabling disorder brain stimulation in epilepsy, highlighting the most 249 The challenges and that can dramatically impair quality of life, and is important knowledge gaps. innovations for therapy linked with severe morbidities and increased mortal- SUDEP remains the leading cause of mortality in children with epilepsy ity. Surgery is an option only for a minority of patients in patients with refractory epilepsy, with an esti- Jo M. Wilmshurst et al. with refractory epilepsy, and even in disorders amen mated lifetime risk of 35%, but the awareness of the 261 Electrical brain able to surgical intervention, such as temporal lobe increased risk of sudden death remains poor among stimulation for epilepsy epilepsy, there is a risk of cognitive impairment. Novel both patients and physicians. Cory Massey and co- Robert S. Fisher therapies for medication-resistant epilepsy are, thus, authors review the current knowledge of the mecha- & Ana Luisa Velasco in high demand. nisms of SUDEP, along with potential interventions 271 Mechanisms of sudden 2013 saw major breakthroughs in epilepsy research: and preventive treatments. unexpected death novel genes involved in epilepsy syndromes were dis- Over the past few years, an increasing number of in epilepsy: the pathway covered, the patterns underlying sudden unexpected epilepsies have been found to have a genetic contri- to prevention death in epilepsy (SUDEP) were elucidated, and bution. Rhys Thomas and Samuel Berkovic review Cory A. Massey et al. translational research paved the way to gene therapy the recent discoveries and urge clinicians to adopt a 283 The hidden genetics for epilepsy. new paradigm: the proportion of idiopathic epilep- of epilepsy—a clinically Nature Reviews Neurology is excited to publish sies is much smaller than previously thought, so the important new this special Focus on Epilepsy issue, which brings possibility of finding a genetic diagnosis should not paradigm together an ensemble of cutting-edge investigators be overlooked. Rhys H. Thomas from leading research institutes around the world to The bounty of newly discovered epilepsy-related & Samuel F. Berkovic highlight the important challenges and progress in genes, along with decreasing cost of whole-exome 293 Genetic testing epilepsy research and clinical practice. sequencing, means that genetic testing and personal in the epilepsies In the News & Views section, Michael Duchowny ized medicine are entering clinical practice. In the —developments and Sanjiv Bhatia discuss the prospects of optimiz- Perspectives section, Annapurna Poduri and col- and dilemmas ing surgical intervention in temporal lobe epilepsy leagues discuss the ethical dilemmas related to genetic Annapurna Poduri et al. to minimize adverse effects on verbal memory, and testing in the epilepsies. 300 Gene therapy in Elinor Ben-Menachem and Gregory Krauss comment Increasing our understanding of the genetic back- epilepsy—is it time on a new follow-up study that assessed the safety and ground of epilepsy is just a starting point in finding a for clinical trials? efficacy of an implantable, responsive neurostimu- cure for this condition. In their Perspectives article, Dimitri M. Kullmann lation device—a treatment approved by the FDA in Dimitri Kullmann and colleagues expand the horizon et al. 2013—in patients with medically intractable epilepsy. of epilepsy therapies by outlining a roadmap towards Efficient management of epilepsy is particularly clinical trials. important in paediatric patients because of the pos- We thank UCB for their financial support for pro- sible detrimental effects of the uncontrolled seizures ducing this Focus on Epilepsy issue. With the sponsor on the developing brain. In the Reviews section of this support, all of the Focus articles can be accessed for issue, Jo Wilmshurst and colleagues outline the most free until the end of October 2014 at www.nature.com/ important challenges in treating infants and children nrneurol/focus/epilepsy. With the exception of the with epilepsy. The scarcity of Class I evidence in Sponsor Feature and Adverts, the content of this sup- Hemi Malkki is an Associate paediatric epilepsies remains a problem, and many plement has been developed independently of UCB. Editor of Nature Reviews Neurology. standard practices are not based on clinical evidence. Nature Publishing Group carries sole responsibility In 2013, the American Academy of Neurology for the editorial content. Competing interests The author declares no published an evidence-based guideline update for competing interests. chronic vagus nerve stimulation. Although vagus doi:10.1038/nrneurol.2014.63