Vagus nerve stimulation (VNS) for epilepsy is a well established and effective treatment for medically intractable epilepsy. VNS is indicated if resective epilepsy surgery is unsuccessful or is not an option. About 50% of patients with VNS have a seizure reduction greater than 50%, but less than 10% become seizure-free. VNS also has an alerting effect on patients and may allow a reduction in sedating medications. The major adverse event is hoarseness, but treatment is generally well tolerated. The therapeutic effect can be delayed: patients may improve several months after VNS implantation. Direct brain stimulation (DBS) is an emerging treatment for epilepsy. Scheduled stimulation is similar to brain stimulation in Parkinson’s disease. Only the anterior thalamic nucleus has been studied in a larger randomized, controlled trial, in which patients with the stimulator turned on had a significantly reduced seizure frequency. Responsive stimulation applies an electrical stimulus at the site of seizure onset to terminate the seizure if one occurs. The seizure-onset zone must be well defined before implantation. Responsive stimulation requires seizure detection and application of a stimulus online. A large pivotal trial showed a significant reduction in seizure frequency. Both DBS and responsive neurostimulation are well tolerated, but there has been some concern about depression with DBS. Infection, hemorrhage, and lead breakage are adverse events possible with any type of stimulator. None of the brain stimulation devices have been approved by the US Food and Drug Administration, but final approval is expected soon. These devices are indicated for patients with bilateral seizure onset or seizure onset in eloquent areas. Although the initial trials of brain stimulation do not show overwhelming improvement in seizure frequency, the technology will improve with time as we continue to learn about the use of brain stimulation for epilepsy. Optimization of VNS has been going on for 10 years, and we need to ensure that brain stimulation is similarly developed further. In addition, sophisticated devices such as responsive neurostimulators can greatly enhance our understanding of the pathophysiology of epilepsy.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Jobst BC: Treatment algorithms in refractory partial epilepsy. Epilepsia 2009, 50(Suppl 8):51–56.
Jobst B: Brain stimulation for surgical epilepsy. Epilepsy Res 2010, 89(1):154–161. This is a recent review of case series of brain stimulation for epilepsy.
Fisher RS, Handforth A: Reassessment: vagus nerve stimulation for epilepsy: a report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 1999, 53(4):666–669.
Heck C, Helmers SL, DeGiorgio CM: Vagus nerve stimulation therapy, epilepsy, and device parameters: scientific basis and recommendations for use. Neurology 2002, 59(6 Suppl 4):S31–S37.
Ben-Menachem E, Mañon-Espaillat R, Ristanovic R, et al.: Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia 1994, 35(3):616–626.
Handforth A, DeGiorgio CM, Schachter SC, et al.: Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 1998, 51(1):48–55.
DeGiorgio CM, Schachter SC, Handforth A, et al.: Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia 2000, 41(9):1195–1200.
Ghaemi K, Elsharkawy AE, Schulz R, et al.: Vagus nerve stimulation: outcome and predictors of seizure freedom in long-term follow-up. Seizure 2010, 19(5):264–268.
Kuba R, Brázdil M, Kalina M, et al.: Vagus nerve stimulation: longitudinal follow-up of patients treated for 5 years. Seizure 2009, 18(4):269–274.
Alexopoulos AV, Kotagal P, Loddenkemper T, et al.: Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy. Seizure 2006, 15(7):491–503.
Majoie HJ, Berfelo MW, Aldenkamp AP, et al.: Vagus nerve stimulation in patients with catastrophic childhood epilepsy, a 2-year follow-up study. Seizure 2005, 14(1):10–18.
Spanaki MV, Allen LS, Mueller WM, Morris 3rd GL: Vagus nerve stimulation therapy: 5-year or greater outcome at a university-based epilepsy center. Seizure 2004, 13(8):587–590.
Vonck K, Thadani V, Gilbert K, et al.: Vagus nerve stimulation for refractory epilepsy: a transatlantic experience. J Clin Neurophysiol 2004, 21(4):283–289.
Amar AP, Apuzzo ML, Liu CY: Vagus nerve stimulation therapy after failed cranial surgery for intractable epilepsy: results from the vagus nerve stimulation therapy patient outcome registry. Neurosurgery 2004, 55(41):1086–1093.
Holmes MD, Silbergeld DL, Drouhard D, et al.: Effect of vagus nerve stimulation on adults with pharmacoresistant generalized epilepsy syndromes. Seizure 2004, 13(41):340–345.
Helmers SL, Wheless JW, Frost M, et al.: Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study. J Child Neurol 2001, 16(11):843–848.
De Herdt V, Boon P, Ceulemans B, et al.: Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. Eur J Paediatr Neurol 2007, 11(41):261–269.
Hallböök T, Lundgren J, Stjernqvist K, et al.: Vagus nerve stimulation in 15 children with therapy resistant epilepsy; its impact on cognition, quality of life, behaviour and mood. Seizure 2005, 14(7):504–513.
Boon P, Raedt R, de Herdt V, et al.: Electrical stimulation for the treatment of epilepsy. Neurotherapeutics 2009, 6(2):218–227.
Vonck K, De Herdt V, Bosman T, et al.: Thalamic and limbic involvement in the mechanism of action of vagus nerve stimulation, a SPECT study. Seizure 2008, 17(8):699–706.
Marzec M, Edwards J, Sagher O, et al.: Effects of vagus nerve stimulation on sleep-related breathing in epilepsy patients. Epilepsia 2003, 44(7):930–935.
Nei M, O’Connor M, Liporace J, Sperling MR: Refractory generalized seizures: response to corpus callosotomy and vagal nerve stimulation. Epilepsia 2006, 47(1):115–122.
Ben-Menachem E, Hellstrom K, Verstappen D: Analysis of direct hospital costs before and 18 months after treatment with vagus nerve stimulation therapy in 43 patients. Neurology 2002, 59(6 Suppl 4):S44–S47.
Fisher R, Salanova V, Witt T, et al.: Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 2010, 51(5):899–908. This is a report of a randomized controlled trial of stimulation of the anterior nucleus of the thalamus.
Boon P, Vonck K, De Herdt V, et al.: Deep brain stimulation in patients with refractory temporal lobe epilepsy. Epilepsia 2007, 48(8):1551–1560. This recent trial assessed hippocampal stimulation.
Velasco F, Velasco M, Jimenez F, et al.: Stimulation of the central median thalamic nucleus for epilepsy. Stereotact Funct Neurosurg 2001, 77:228–232.
Chabardès S, Kahane P, Minotti L, et al.: Deep brain stimulation in epilepsy with particular reference to the subthalamic nucleus. Epileptic Disord 2002, 4(Suppl 3):S83–S93.
Chkhenkeli SA, Sramka M, Lortkipanidze GS, et al.: Electrophysiological effects and clinical results of direct brain stimulation for intractable epilepsy. Clin Neurol Neurosurg 2004, 106(4):318–329.
Cooper IS, Upton AR: Effects of cerebellar stimulation on epilepsy, the EEG and cerebral palsy in man. Electroencephalogr Clin Neurophysiol Suppl 1978, 34:349–354.
Wright GD, McLellan DL, Brice JG: A double-blind trial of chronic cerebellar stimulation in twelve patients with severe epilepsy. J Neurol Neurosurg Psychiatry 1984, 47(8):769–774.
Velasco AL, Velasco F, Velasco M, et al.: Electrical stimulation of the hippocampal epileptic foci for seizure control: a double-blind, long-term follow-up study. Epilepsia 2007, 48(10):1895–1903. This is another study showing that hippocampal stimulation is probably effective in controlling seizures.
Lado FA: Chronic bilateral stimulation of the anterior thalamus of kainate-treated rats increases seizure frequency. Epilepsia 2006, 47(1):27–32.
Hamani C, Hodaie M, Chiang J, et al.: Deep brain stimulation of the anterior nucleus of the thalamus: effects of electrical stimulation on pilocarpine-induced seizures and status epilepticus. Epilepsy Res 2008, 78(2–3):117–123.
Wyckhuys T, Raedt R, Vonck K, et al.: Comparison of hippocampal Deep Brain Stimulation with high (130 Hz) and low frequency (5 Hz) on afterdischarges in kindled rats. Epilepsy Res 2010, 88(2–3):239–246.
Kenney C, Simpson R, Hunter C, et al.: Short-term and long-term safety of deep brain stimulation in the treatment of movement disorders. J Neurosurg 2007, 106(4):621–625.
Tomaszewski KJ, Holloway RG: Deep brain stimulation in the treatment of Parkinson’s disease: a cost-effectiveness analysis. Neurology 2001, 57(4):663–671.
Pivotal Trial Data Demonstrate NeuroPace RNS® System Reduced Seizures in People with Epilepsy [news release]. Mountain View, CA: NeuroPace; 2009. http://www.neuropace.com/about/news/091207.html. Accessed June 15, 2010.
Osorio I, Overman J, Giftakis J, Wilkinson SB: High frequency thalamic stimulation for inoperable mesial temporal epilepsy. Epilepsia 2007, 48(8):1561–1571. This interesting study used a somewhat different stimulation paradigm.
Lesser RP, Kim SH, Beyderman L, et al.: Brief bursts of pulse stimulation terminate afterdischarges caused by cortical stimulation. Neurology 1999, 53(9):2073–2081.
Motamedi GK, Lesser RP, Miglioretti DL, et al.: Optimizing parameters for terminating cortical afterdischarges with pulse stimulation. Epilepsia 2002, 43(8):836–846.
Morrell M, Hirsch L, Bergey G, et al.: Long-term safety and efficacy of the RNS™ system in adults with medically intractable partial onset seizures [abstract B.01]. Presented at the American Epilepsy Society 62nd Annual Meeting. Seattle, WA; December 8, 2008.
Spanaki MV, Greene D, Smith BJ, et al.: Chronic measurement of increased epileptiform activity over multiple menstrual cycles in two patients using the responsive neurostimulator system (RNS) [abstract 4.125]. Presented at the American Epilepsy Society Meeting. San Diego, CA; 2006.
Anderson CT, Sun F, Tcheng T: Circadian patterns of epileptiform activity in 65 patients with an intracranial responsive neurostimulator for epilepsy (the NeuroPace RNS system) [abstract]. Presented at the American Epilepsy Society 62nd Annual Meeting. Seattle, WA; December 5–9, 2008. Available at http://www.neuropace.com/about/news/0812.html#2. Accessed June 15, 2010.
Majoie HJ, Berfelo MW, Aldenkamp AP, et al.: Vagus nerve stimulation in children with therapy-resistant epilepsy diagnosed as Lennox-Gastaut syndrome: clinical results, neuropsychological effects, and cost-effectiveness. J Clin Neurophysiol 2001, 18(41):419–428.
Florczak JW, Roberts DW, Morse RP, et al.: Deep brain stimulation (DBS) for the treatment of epileptic encephalopathy [abstract 1.093]. Epilepsia 2006, 47(Suppl 4):119–204.
Dr. Jobst has received research support from NeuroPace, Inc. and is one of the investigators of the NeuroPace pivotal and long-term treatment trial.
About this article
Cite this article
Jobst, B.C. Electrical Stimulation in Epilepsy: Vagus Nerve and Brain Stimulation. Curr Treat Options Neurol 12, 443–453 (2010). https://doi.org/10.1007/s11940-010-0087-4