Deep Brain Stimulation for Seizure Control in Drug-resistant Epilepsy

Neil Klinger, MD; Sandeep Mittal, MD, FRCSC


Neurosurg Focus. 2018;45(2):e4 

In This Article

Abstract and Introduction


Antiepileptic drugs prevent morbidity and death in a large number of patients suffering from epilepsy. However, it is estimated that approximately 30% of epileptic patients will not have adequate seizure control with medication alone. Resection of epileptogenic cortex may be indicated in medically refractory cases with a discrete seizure focus in noneloquent cortex. For patients in whom resection is not an option, deep brain stimulation (DBS) may be an effective means of seizure control. Deep brain stimulation targets for treating seizures primarily include the thalamic nuclei, hippocampus, subthalamic nucleus, and cerebellum. A variety of stimulation parameters have been studied, and more recent advances in electrical stimulation to treat epilepsy include responsive neurostimulation. Data suggest that DBS is effective for treating drug-resistant epilepsy.


Epilepsy has an estimated lifetime prevalence of 7.6 cases per 1000 persons and an incidence of 68 cases per 100,000 individuals internationally.[19] In the 2010 Global Burden of Disease Study, epilepsy was found to have a worldwide burden second only to migraine headaches among neurological disorders.[48] The International League Against Epilepsy defines drug-resistant epilepsy as a failure to achieve sustained seizure freedom after two appropriately chosen, tolerated, and scheduled antiepileptic drugs (AEDs), whether they are given as monotherapy or in combination.[35] Estimates of patients with drug-resistant epilepsy are as high as 30% but vary depending on the resistance criteria used and are generally slightly lower in more developed countries.[53]

The mechanism by which the disorder is resistant to AEDs remains incompletely understood. The most prevalent explanations include the "target hypothesis" and the "transporter hypothesis." In the target hypothesis, it is thought that changes in the AED targets, such as ion channels, lead to decreased drug efficacy. In contrast, in the transporter hypothesis, efflux pumps are thought to restrict AED movement into cells and to be overexpressed in patients resistant to AEDs.[61] P-glycoprotein (Pgp) is one such multidrug transporter that has been implicated in drug-resistant epilepsy. Significantly increased levels of Pgp have been found in patients with medically refractory epilepsy.[18] Among patients with drug-resistant epilepsy, adding surgical treatment is four times more likely to result in seizure freedom than medical treatment alone.[58] A meta-analysis of long-term (≥ 5 years) seizure freedom after epilepsy surgery revealed that 66% of patients who underwent temporal lobe resections were seizure free, though this figure was lower among patients requiring extratemporal resection.[62] A review of nine systematic reviews and two large case series of patients with intractable epilepsy revealed a median 62.4% of patients to be seizure free after epilepsy surgery; however, surgery was found to be less effective for epilepsy not associated with structural pathology and/or extratemporal lesions.[31] Better surgical outcomes were reported when seizures were associated with hippocampal sclerosis and benign tumors. Mortality with epilepsy surgery was reported to be 0.1%–0.5%, and surgery is effective and safe for correctly selected patients.

In general, contraindications to epilepsy surgery include the lack of a discrete seizure focus, seizure foci involving eloquent cortex, or significant comorbidities such that the patient is not medically stable for resective surgery. For patients whose epilepsy is refractory to medical therapy and who are not good candidates for resective epilepsy surgery, other treatment options are available. Nonsurgical therapies that may reduce seizures in appropriately selected patients include the administration of a ketogenic diet and, to a lesser degree, the use of cannabidiol, although current data are conflicting as to their efficacies.[17,49,72] Vagus nerve stimulation is less invasive than resective surgery and improves seizure control in carefully selected individuals.[16,25,47] Deep brain stimulation (DBS) is another promising treatment modality that has shown efficacy in decreasing seizure frequency in patients with refractory epilepsy.