Treating Drug-resistant Epilepsy – Why are we Waiting?

Abstract

Drug-resistant epilepsy (DRE) has been defined by the ad hoc Task Force of the International League Against Epilepsy (ILAE) Commission on Therapeutic Strategies as the failure of two appropriately chosen and tolerated anti-epileptic drugs (AEDs) (whether as monotherapy or in combination) to control seizures when used for an adequate period of time. The difference between the number of patients with DRE and the number of these patients who do not get access to adequate treatment is defined as the 'treatment gap', which is considered to be substantial.There are multiple possible causes that underlie the treatment gap in DRE: economic costs, natural history of epilepsy, deficiencies in health service provision, social stigma and other as yet unidentified causes. Factors affecting quality of life in DRE include depression and anxiety, raised risk of mortality and morbidity, increased healthcare utilisation and increased risk of adverse events with long-term use of AEDs, cognitive and memory impairment, seizure-related injuries, impaired ability to achieve educational and vocational goals, to drive, establish families and benefit from social relationships. Among the reasons for the greater risk of premature death are the raised risk of suicide in those patients with comorbid psychiatric disease and the increased incidence of sudden unexpected death among those with epilepsy. Managing epilepsy well involves more than just seizure reduction and when freedom from seizures cannot be achieved, addressing quality of life is likely to be more beneficial than interventions aimed at seizure reduction alone. Options exist for patients with DRE who are not candidates for epilepsy surgery, including dietary treatments, further attempts with AEDs and non-pharmacological interventions with devices. Further, non-invasive modalities are emerging, creating a more hopeful picture that the treatment gap for patients with DRE may be narrowed or even closed.

Current Status and Future Objectives of Surgical Therapies for Epilepsy in Japan

“…It has been reported that the prevalence of epilepsy in the general population is approximately 1%, approximately 30-40% of patients with epilepsy are drug resistant, and epilepsy surgery is safe and effective for these patients. [8][9][10] However, only 36% of patients with drug-resistant epilepsy undergo a comprehensive epilepsy evaluation 11) and less than 1% of patients with epilepsy are referred to full-service epilepsy centers to be assessed for surgical eligibility. [11][12][13] Furthermore, it has been reported that only 1-2% of patients with drug-resistant epilepsy ultimately undergo surgery, and some of them are referred to low-volume, non-academic hospitals where treatment outcomes are worse and complication rates are higher.…”

“…[8][9][10] However, only 36% of patients with drug-resistant epilepsy undergo a comprehensive epilepsy evaluation 11) and less than 1% of patients with epilepsy are referred to full-service epilepsy centers to be assessed for surgical eligibility. [11][12][13] Furthermore, it has been reported that only 1-2% of patients with drug-resistant epilepsy ultimately undergo surgery, and some of them are referred to low-volume, non-academic hospitals where treatment outcomes are worse and complication rates are higher. 14) Therefore, one study recommended that in order to provide many more patients with refractory epilepsy with safe and effective surgical therapy, the number of referrals to full-service epilepsy centers offering specialized diagnosis and other alternative treatments, as well as psychosocial support, should be increased.…”

Selected flavonoids and their role in the treatment of epilepsy – a review of the latest reports from experimental studies

“…Sudden unexpected death in epilepsy (SUDEP) is the main cause of death in patients with DRE and accounts for up to 50% documented causes of death in this group of patients (Opeskin and Berkovic 2003;Tomson et al, 2008;Surges et al, 2009;Shorvon and Tomson, 2011). Therefore, the main goal of DRE therapy is to extend the seizure control period, minimize side effects and improve quality of life (Boon et al, 2015). Currently, a number of scientific studies include the use of natural substances with antiepileptic properties as adjuncts to standard antiepileptic drugs in the DRE treatment and flavonoids and may be a potential group of natural drugs that increase the effects of commonly used anticonvulsants.…”