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Advances in Surgical Options for Medically Refractory Epilepsy

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Published Online: May 15th 2012 European Neurological Review, 2012;7(2):140-4 DOI:
Authors: Paul R Gigante, Robert R Goodman
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The evolution of surgical treatment for medically refractory epilepsy (MRE) has been influenced over the last decade by substantial advancements in imaging- and device-related technology, as well as an expanding assemblage of prospective data that support the utilisation of surgery for MRE. These data, which have grown to include randomised trials and long-term follow up for established surgery, as well as large series for investigational procedures, have demonstrated safe, efficacious results with proper patient selection. Prospective randomised trials of three surgically implanted neuromodulatory devices, vagus nerve stimulators, deep brain stimulators and responsive neurostimulators have demonstrated safety and significant seizure frequency reduction. Numerous studies have provided strong evidence for the efficacy and safety of temporal lobe resective surgery and recent studies have focused on applying alternative approaches to open resective surgery for patients presumed to have a medial temporal seizure focus. These alternatives include stereotactic radiosurgery, radiofrequency ablation and a magnetic resonance imaging (MRI)-guided laser technique for thermal ablation. Current evidence for these new surgical options for the treatment of medically refractory epilepsy will be presented and discussed.


Epilepsy, deep brain stimulation, surgery, neurostimulation, neurostimulator, neuromodulation, refractory, radiosurgery, vagus, temporal lobe epilepsy, responsive


Neuromodulation Devices
Vagus Nerve Stimulation
Vagus nerve stimulation (VNS), first used for seizure treatment in the 1880s, was approved by the US Food and Drug Administration (FDA) in 1997 after decades of animal studies demonstrating reduction of chemically induced seizures,1,2 and subsequent promising human trials beginning in the early 1990s. Since FDA approval, VNS technology has been improved, with smaller neurostimulator/battery and simplified wire and connection. After exposure of the left vagus nerve distal to the recurrent laryngeal nerve, two bipolar electrodes are placed around the nerve and connected to a subcutaneously implanted, programmable stimulation device below the level of the clavicle. Stimulation is typically at high frequency and cycles between periods on (typically 30 seconds) and off (typically several minutes). To date, the physiological mechanism of VNS on seizure activity remains incompletely understood. As identified broadly in neuronal networks involved in seizure pathophysiology, VNS studies indicate that stimulation influences activity in the thalamus and limbic structures, alters cerebral blood flow and influences neurotransmitter and amino acid concentrations.3–5

Initially, two blinded, randomised controlled trials comparing high and low VNS amplitude stimulation in patients over 12 years old with partial seizures demonstrated a significantly greater reduction in seizure frequency in the high-stimulation (25–28 %) group compared to the low-stimulation (6–15 %) group.6,7 Multiple prospective and retrospective series followed, reporting seizure reduction outcomes in variable epilepsy populations.

Recently, the first meta-analysis of VNS trials identified 74 clinical studies containing outcomes data, of which 15 studies produced Class I, II, or III evidence. In a pooled analysis of 2,634 patients, the authors determined the efficacy of VNS to be a ≥50 % reduction in seizure frequency in 50.6 % of patients; a ≥90 % seizure reduction in 12.2 %; and seizure freedom in 4.6 % of patients. The mean seizure frequency reduction was 44.6 % amongst 1,789 patients with available percentage reduction data. Despite a large volume of pooled data, the wide variability in follow-up, ranging from three months to five years, and non-controlled variables such as medication changes, indicate the continued need for a randomised controlled trial with long-term follow-up.

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Article Information:

Paul R Gigante has no conflicts of interest to declare. Robert R Goodman serves as a consultant for NeuroPace, Inc.


Paul R Gigante, Department of Neurological Surgery, Columbia University Medical Center, 710 West 168th street, 4th floor, New York, NY 10032, US. E:




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