Drug-resistant epilepsy

Seizures sometimes are not controlled with antiepileptic drugs. A number of different terms may be used to describe these including: “uncontrolled,” “intractable,” “refractory,” or “drug resistant.”

The International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two “hierarchical” levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as 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 definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided 1).

Focal cortical dysplasia is a malformation of cortical development, which is the most common cause of drug resistant epilepsy in the pediatric population 2).

In a study, roughly one-third of patients (64.0%) had continued seizures despite AED management, and failure of first or second line therapies correlated with an increased likelihood to develop refractory (or drug-resistant) epilepsy. Over the ensuing 2 decades since this study, AEDs with novel mechanisms of action have expanded treatment options and many are thought to be safer with similar clinical efficacy, when used as monotherapy or as adjunctive agents 3).

Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy 4).

Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshé SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010 Jun;51(6):1069-77. doi: 10.1111/j.1528-1167.2009.02397.x. Epub 2009 Nov 3. Erratum in: Epilepsia. 2010 Sep;51(9):1922. PubMed PMID: 19889013.
Kabat J, Król P. Focal cortical dysplasia - review. Pol J Radiol. 2012 Apr;77(2):35-43. PubMed PMID: 22844307; PubMed Central PMCID: PMC3403799.
Golyala A, Kwan P. Drug development for refractory epilepsy: the past 25 years and beyond. Seizure. 2017;44:147-156.
Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. PubMed PMID: 10660394.
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