Epilepsy
Update and Overview of the International League Against Epilepsy Consensus Definition of Drug-resistant Epilepsy
Xiao-Ting Hao, MD1 and Patrick Kwan, MD, PhD2
1. Doctorate Student, Division of Neurology, Department of Neurology, West China Hospital, Sichuan University School of Medicine; 2. Associate Consultant, Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital
Abstract
Drug-resistant epilepsy remains a major clinical challenge. Diverse criteria have been used to define drug resistance by different researchers, making it difficult or even impossible to compare the results across different studies. To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) recently proposed a consensus definition to define drug-resistant epilepsy. This is the failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This article outlines the framework of the consensus definition, explains how to apply it in practice, and discusses the future development of its use.
Keywords Epilepsy, seizures, drug resistant, refractory, pharmacoresistance, antiepileptic drugs (AEDs), definition, International League Against Epilepsy (ILAE)
Disclosure: Xiao-Ting Hao, MD, has no conflicts of interest to declare. Patrick Kwan, MD, PhD, is lead author of the report on the International League Against Epilepsy definition of drug-resistant epilepsy. He has received speaker’s or consultancy fees and/or research grants from Eisai, Johnson & Johnson, Pfizer and UCB Pharma. Received: October 7, 2010 Accepted: December 2, 2010 Citation: US Neurology, 2010;6(2):122–4 Correspondence: Patrick Kwan, MD, PhD, Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong. E:
patrickkwan@cuhk.edu.hk
Approximately 50 million people have epilepsy worldwide,1
up to
Diverse criteria have been used to define drug resistance by different researchers, making it difficult or even impossible to compare the results across different studies. To improve patients’ care and facilitate clinical research, the International League Against Epilepsy (ILAE) recently proposed a consensus definition of drug-resistant epilepsy. Given that most patients are initially managed by general physicians or general neurologists, it is hoped that the definition framework will provide clear and simple guidance in identifying patients with pharmacoresistance for early referral to specialist centers for evaluation.3
one-third of whom continue to experience seizures despite drug treatment.2
This article outlines the framework of the consensus definition, explains how to apply it in practice and discusses the future development of its use.
The Burden of Drug-resistant Epilepsy Recurrent seizures are associated with a range of deleterious consequences. Seizure-related deaths may account for up to 40% of all deaths in patients with chronic epilepsy. The rate of sudden unexpected death, which accounts for 7–17% of deaths among epilepsy patients, is estimated to be up to 27-fold higher in those with ongoing seizures compared to those who are seizure free.4,5 Uncontrolled seizures restrict patients’ social activities, reducing their ability to hold a driving license or keep a job. Refractory epilepsy places substantial stress on the patient’s family members and caregivers. It is also a great economic burden for society, through expenditures
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in healthcare and unemployment. In a study of the cost of epilepsy in the US, it was reported that the average montly cost per individual in the patient-based analysis was $1,490, whereas the average annual cost per individual in the population-based analysis was $1,510 with average yearly costs between $1,480 and $1,740.6
In patients whose epilepsy
failed to respond to several antiepileptic drugs (AEDs), the chance of significant benefit from a further AED change is estimated to be <5% per year.7
For these patients, resective surgery is a potential therapeutic option.8
Early diagnosis of drug resistance using a universally-accepted definition can facilitate the selection of patients for such non-drug therapies and potentially alleviate the medicosocial and economic burden of refractory epilepsy.
The International League Against Epilepsy Consensus Definition Definition Framework
The proposal defines drug-resistant epilepsy as failure of adequate trials of two (or more) tolerated, appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. The overall framework of the definition comprises two ‘hierarchical’ levels. Level 1 provides a general template or scheme to categorize the outcome to each therapeutic intervention (whether pharmacological or non-pharmacological). To categorize the outcome accurately, a minimum dataset of details of the AED history, including the dose and duration the drug was used for, must be available. This is the most important factor in determining whether
© TOUCH BRIEFINGS 2010
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