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Treating Drug-resistant Epilepsy – Why are we Waiting?

European Neurological Review, 2015;10(2):171–5 DOI: http://doi.org/10.17925/ENR.2015.10.02.171

Abstract:

Drug-resistant epilepsy (DRE) has been defined by the ad hoc Task Force of the International League Against Epilepsy (ILAE) Commission on Therapeutic Strategies as the failure of two appropriately chosen and tolerated anti-epileptic drugs (AEDs) (whether as monotherapy or in combination) to control seizures when used for an adequate period of time. The difference between the number of patients with DRE and the number of these patients who do not get access to adequate treatment is defined as the ‘treatment gap’, which is considered to be substantial. There are multiple possible causes that underlie the treatment gap in DRE: economic costs, natural history of epilepsy, deficiencies in health service provision, social stigma and other as yet unidentified causes. Factors affecting quality of life in DRE include depression and anxiety, raised risk of mortality and morbidity, increased healthcare utilisation and increased risk of adverse events with long- term use of AEDs, cognitive and memory impairment, seizure-related injuries, impaired ability to achieve educational and vocational goals, to drive, establish families and benefit from social relationships. Among the reasons for the greater risk of premature death are the raised risk of suicide in those patients with comorbid psychiatric disease and the increased incidence of sudden unexpected death among those with epilepsy. Managing epilepsy well involves more than just seizure reduction and when freedom from seizures cannot be achieved, addressing quality of life is likely to be more beneficial than interventions aimed at seizure reduction alone. Options exist for patients with DRE who are not candidates for epilepsy surgery, including dietary treatments, further attempts with AEDs and non-pharmacological interventions with devices. Further, non-invasive modalities are emerging, creating a more hopeful picture that the treatment gap for patients with DRE may be narrowed or even closed.
Keywords: Drug-resistant epilepsy, vagus nerve stimulation, deep brain stimulation, epilepsy surgery, closed loop neurostimulation, AspireSR®
Disclosure: Paul Boon has received support from Cyberonics, Medtronic, Sorin and UCB for lecture and consultancy fees and for educational grants through his institution. Philippe Ryvlin have received speaker or consulting fees from Cyberonics, UCB Pharma and Eisai Pharmaceuticals. James W Wheless has received grants from NIH, Shainberg Foundation, Questcor, Novartis, GW Pharma and INSYS Inc. He has received a grant, is on the speaker’s bureau and is a consultant for Lundbeck. He is on the speaker’s bureau for Cyberonics. He is on the speaker’s bureau and is a consultant for Eisai and Supernus. He has received a grant from, and is a consultant for Upsher- Smith, and is a consultant for UCB. Kensuke Kawai has received lecture honorarium from Cyberonics, Nihon Koden, Otsuka Pharmaceutical, and GlaxoSmithKline.
Acknowledgments: Editorial assistance was provided by Catherine Amey at Touch Medical Media, London and funded by Cyberonics BVBA. This article reports the proceedings of a sponsored satellite symposium and as such has not been subject to the journal’s usual peer-review process
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.
Received: November 03, 2015 Accepted: December 04, 2015
Correspondence: Paul Boon, Sint-Pietersnieuwstraat 25, Ghent, B-9000, Belgium. E: paul.boon@ugent.be
Support: The publication of this article was supported by Cyberonics (Subsidiary of Livanova PLC). The views and opinions expressed are those of the authors and not necessarily those of Cyberonics.

Epilepsy is one of the most common serious neurological conditions, has no geographic, social or racial boundaries and can affect people of all ages.1 It is frequently associated with co-morbidities, not just seizures, and is a condition that is linked with a high rate of premature death compared with that in the general population.1 The consensus proposal by the ad hoc Task Force of the International League Against Epilepsy (ILAE) Commission on Therapeutic Strategies defined drugresistant epilepsy (DRE) as the failure of two appropriately chosen and tolerated anti-epileptic drugs (AEDs) (whether as monotherapy or in combination) to control seizures when used for an adequate period of time.2,3 The ideal goal for treating newly diagnosed epilepsy is to eliminate seizures while having minimal side-effects; however, in DRE, the treatment goals are required to be more modest.2,4,5 These involve: optimizing long-term seizure control, maximising quality of life (QoL), minimising side effects, maximising adherence and decreasing seizure severity and the postictal period.

The consequences of DRE have significant QoL implications for patients. These include: depression and anxiety;5–7 raised risk of mortality and morbidity;6,8–10 increased healthcare utilisation;4,11,14 more adverse events (AEs) with long-term use of AEDs;5–7,13 cognitive and memory impairment;6,7,14 seizure-related injuries;6,7 and impaired ability to obtain educational and work goals; to drive; establish families; and develop and maintain social relations.7,13 Out of a population in Europe of 850 million people, a conservative estimate of people with active epilepsy is 6 million (prevalence of 8.2/1000).15 Of these 6 million people, epilepsy is well controlled with AEDs in 70 %.15 In the remaining 30 % with DRE, onequarter to one-third (450 000–600 000 people) are potential candidates for epilepsy surgery.15 Two-thirds to three-quarters of the people with DRE (approximately 1.4 million) are candidates for other therapies such as vagus nerve stimulation (VNS) Therapy, ketogenic diet, deep brain stimulation (DBS) or experimental AEDs. According to a recent survey of epilepsy clinicians who were asked about the DRE treatment gap, around 40 % of DRE patients have undergone a comprehensive evaluation and, of this 40 %, the proportion who had not received VNS Therapy or epilepsy surgery was 83 %.16

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Keywords: Drug-resistant epilepsy, vagus nerve stimulation, deep brain stimulation, epilepsy surgery, closed loop neurostimulation, AspireSR®