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).
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 2)
Identifying factors involved in the development of drug resistant epilepsy (DRE) remains a challenge. Candidate gene studies have shown modulation of resistance to drugs by various multidrug resistance proteins in DRE. However the resistance to drugs in DRE could be more complex and multifactorial involving molecules in different pharmacokinetic processes.
A study for the first time analyzed the relative expression of four molecules with different drug resistance mechanisms in two most common DRE pathologies, mesial temporal lobe epilepsy (MTLE) and focal cortical dysplasia (FCD) with respect to each other and also with different non-epileptic controls.
Upregulation of breast cancer resistance protein (BCRP) and major vault protein (MVP) is associated with MTLE and FCD and these molecules not only may have the potential to predict pathology specific phenotypes but may also have therapeutic potential as adjunct treatment in these pathologies. 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).
Up to one third of epilepsy patients develop pharmacoresistant seizures and many benefit from resective surgery. However, patients with non-lesional focal epilepsy often require intracranial monitoring to localize the seizure focus. Intracranial monitoring carries operative morbidity risk and does not always succeed in localizing the seizures, making the benefit of this approach less certain.
Intracranial monitoring is favored over VNS and medical management in young and elderly patients over a wide, clinically-relevant range of pertinent model variables such as the chance of localizing the seizure focus and the surgical morbidity rate 5).