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drug_resistant_epilepsy

Drug resistant epilepsy

Definition

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).

Epidemiology

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)

Etiology

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. 4).

Risk Factor

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 5).

Diagnosis

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 6).

Treatment

Case series

1)
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.
2)
Kabat J, Król P. Focal cortical dysplasia - review. Pol J Radiol. 2012 Apr;77(2):35-43. PubMed PMID: 22844307; PubMed Central PMCID: PMC3403799.
3)
Golyala A, Kwan P. Drug development for refractory epilepsy: the past 25 years and beyond. Seizure. 2017;44:147-156.
4)
Banerjee Dixit A, Sharma D, Srivastava A, Banerjee J, Tripathi M, Prakash D, Sarat Chandra P. Upregulation of breast cancer resistance protein and major vault protein in drug resistant epilepsy. Seizure. 2017 Feb 27;47:9-12. doi: 10.1016/j.seizure.2017.02.014. [Epub ahead of print] PubMed PMID: 28273590.
5)
Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. PubMed PMID: 10660394.
6)
Hotan GC, Struck AF, Bianchi MT, Eskandar EN, Cole AJ, Westover MB. Decision analysis of intracranial monitoring in non-lesional epilepsy. Seizure. 2016 Jun 18;40:59-70. doi: 10.1016/j.seizure.2016.06.010. [Epub ahead of print] PubMed PMID: 27348062.
drug_resistant_epilepsy.txt · Last modified: 2018/10/16 08:56 by administrador