Pharmacoresistance occurs in up to 30% of patients with epilepsy, and is most commonly associated with epilepsy of structural or metabolic origin, abnormal findings on brain imaging or examination, and failure to respond to the first two antiepileptic drugs. However, in patients presumed to have difficult to treat epilepsy, factors that might result in apparent treatment resistance (misdiagnosis of epilepsy, incorrect drug and/or dose, and lifestyle issues) must first be excluded and the diagnosis re-examined. Epilepsy is commonly misdiagnosed, especially in patients with syncope and psychogenic events. The initial steps in confirming the diagnoses of both epilepsy and pharmacoresistance are to obtain a detailed, reliable history and to conduct a careful review of all prior trials of antiepileptic drug therapy. Once the diagnoses of epilepsy and pharmacoresistance are confirmed, the seizure type, epilepsy syndrome, and expected course of the disorder dictate its medical and surgical management. Epilepsy surgery should be considered promptly in these patients, since few interventions are as effective as brain surgery in this setting, particularly in patients with focal pharmacoresistant epilepsy. This Review discusses the concept of pharmacoresistance and describes the approach to management of the patient with difficult to treat epilepsy, focusing on the important role of epilepsy surgery.
About 25% of patients identified as having difficult to treat epilepsy do not have pharmacoresistance and/or epilepsy
Pharmacoresistance occurs in up to 30% of patients with epilepsy, and is usually identified after patients fail to respond to two antiepileptic drugs
The diagnosis of pharmacoresistant epilepsy should be confirmed and acted on promptly to control seizures
Surgery is a highly effective treatment for pharmacoresistant epilepsy—65% of patients with pharmacoresistant focal epilepsy achieve sustained seizure remission after surgical therapy
Despite robust evidence of its efficacy and safety, surgical treatment for epilepsy remains underutilized
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S. Wiebe has received grants from the Canadian Institutes of Health Research, the National Institutes of Neurological Disorders and Stroke, the Public Health Agency of Canada, Alberta Innovates Health Solutions, Alberta Health Services, the University of Calgary Faculty of Medicine and Hotchkiss Brain Institute. N. Jette holds a Population Health Investigator Award from Alberta Innovates Health Solutions and a Canada Research Chair Tier 2 in Neuroscience Health Services Research. She has received grants or research support from the Canadian Institutes of Health Research, the Public Health Agency of Canada, Alberta Innovates Health Solutions, Alberta Health Services, the University of Calgary Faculty of Medicine and Hotchkiss Brain Institute and Alberta Health and Wellness. The authors thank Dr Elaine Wirrell for giving permission to use some of her data from a literature review written with N. Jette on predictors of remission and intractability in patients with epilepsy.
The authors declare no competing financial interests.
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Wiebe, S., Jette, N. Pharmacoresistance and the role of surgery in difficult to treat epilepsy. Nat Rev Neurol 8, 669–677 (2012). https://doi.org/10.1038/nrneurol.2012.181
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