Treatment-resistant epilepsy remains a major burden at both global and individual levels. About 1% of individuals have epilepsy and, in almost one-third of patients, antiseizure medications do not provide sufficient seizure control, which can result in dramatically impaired quality of life and increased mortality.

Nature Reviews Neurology is excited to publish this special Focus on Epilepsy, which highlights the important challenges and progress in epilepsy research and clinical practice. This focus issue brings together an ensemble of cutting-edge investigators from leading research institutes around the world.

The topics in this issue include global challenges in paediatric epilepsy, the genetic background of the epilepsies and its implications for genetic diagnosis and personalized medicine, prospects for gene therapy in epilepsy, brain stimulation in refractory epilepsy, and mechanisms of sudden unexpected death in epilepsy.

We thank UCB for their financial support for producing this Focus on Epilepsy issue. With the sponsor support, all of the Focus articles can be accessed for free until the end of October 2014 at With the exception of the Sponsor Feature and Adverts, the content of this supplement has been developed independently of UCB. Nature Publishing Group carries sole responsibility for the editorial content.


Epilepsy—burning questions and emerging therapies

Hemi Malkki


Nature Reviews Neurology 10, 243 (2014)

Research highlights

Epilepsy: Population-based study reinforces the link between autoimmune disease and epilepsy

Heather Wood


Nature Reviews Neurology 10, 240 (2014)

News and Views

Epilepsy: Preserving memory in temporal lobectomy—are networks the key?

Michael Duchowny & Sanjiv Bhatia


Nature Reviews Neurology 10, 245-246 (2014)

Epilepsy: Responsive neurostimulation—modulating the epileptic brain

Elinor Ben-Menachem & Gregory L. Krauss


Nature Reviews Neurology 10, 247-248 (2014)


The challenges and innovations for therapy in children with epilepsy

Jo M. Wilmshurst, Anne T. Berg, Lieven Lagae, Charles R. Newton & J. Helen Cross


Nature Reviews Neurology 10, 249-260 (2014)

Wilmshurst et al. discuss how appropriate terminology can aid in the diagnosis and treatment of paediatric epilepsies. Furthermore, they give an update on key changes to the organization and terminology of epilepsies by the International League Against Epilepsy and an overview of the challenges in implementing new guidelines to treat paediatric patients particularly in low-income countries.

Electrical brain stimulation for epilepsy

Robert S. Fisher & Ana Luisa Velasco


Nature Reviews Neurology10, 261-270 (2014)

The use of deep brain stimulation as a treatment for various refractory neurological disorders is increasing—perhaps faster than our understanding of this surgical technique. Electrical neuromodulation has been explored in people with epilepsy since the 1950s, and stimulation sites, parameters and results have varied. In this article, Fisher and Velasco review the use of neurostimulation as a treatment for epilepsy, from early experiments in animal models and humans to recent randomized controlled trials.

Mechanisms of sudden unexpected death in epilepsy: the pathway to prevention

Cory A. Massey, Levi P. Sowers, Brian J. Dlouhy & George B. Richerson


Nature Reviews Neurology 10, 271-282 (2014)

Sudden unexpected death in epilepsy (SUDEP) is cited as the cause of nearly 2,000 deaths per year in the USA alone, and accounts for as many as 15% of epilepsy-related deaths. Controversy prevails over the relative contributions of cardiac failure and respiratory arrest to SUDEP. Here, the authors discuss the mechanisms that cause cardiac, respiratory and arousal abnormalities during the ictal and postictal periods, and highlight possible preventive interventions that might reduce the risk of SUDEP.

The hidden genetics of epilepsy—a clinically important new paradigm

Rhys H. Thomas & Samuel F. Berkovic


Nature Reviews Neurology10, 283-292 (2014)

The aetiology of most epilepsies used to be regarded as unknown, but in the past few years, massively parallel gene-sequencing techniques and clinical genetic studies have revealed that many forms of epilepsy—including those formerly labelled as idiopathic or acquired—are likely to have a genetic basis. Increased understanding of the genetic architecture of epilepsies has important implications for genetic testing, treatment selection and counselling. Furthermore, understanding the genetic background of epilepsies can guide neurobiological research for novel therapies.


Genetic testing in the epilepsies—developments and dilemmas

Annapurna Poduri, Beth Rosen Sheidley, Sara Shostak & Ruth Ottman


Nature Reviews Neurology 10, 293-299 (2014)

Genetic testing has the potential to revolutionize care for individuals with epilepsy, but its advent is bringing to light important new issues, particularly surrounding the benefits and risks of testing, and the optimal provision of genetic services. Poduri and colleagues describe these challenges, and call for mechanisms to be established to address them.

Gene therapy in epilepsy—is it time for clinical trials?

Dimitri M. Kullmann, Stephanie Schorge, Matthew C. Walker & Robert C. Wykes


Nature Reviews Neurology 10, 300-304 (2014)

Kullmann et al. discuss the need for gene therapy in epilepsy and the challenges of translating experimental research into the clinic. Furthermore, they outline the potential for gene therapy strategies in pharmacoresistant epilepsy, ways to assess therapeutic efficacy, and the need to evaluate long-term safety data.


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Produced with financial support from UCB