Neurostimulation as a promising epilepsy therapy

The revolution in theory, swift technological developments, and invention of new devices have driven tremendous progress in neurostimulation as a third‐line treatment for epilepsy. Over the past decades, neurostimulation took its place in the field of epilepsy as an advanced treatment technique and opened up a new world. Numerous animal studies have proven the physical efficacy of stimulation of the brain and peripheral nerves. Based on this optimistic fundamental research, new advanced techniques are being explored in clinical practice. Over the past century, drawing on the benefits brought about by vagus nerve stimulation for the treatment of epilepsy, various new neurostimulation modalities have been developed to control seizures. Clinical studies including case reports, case series, and clinical trials have been booming in the past several years. This article gives a comprehensive review of most of these clinical studies. In addition to highlighting the advantages of neurostimulation for the treatment of epilepsy, concerns with this modality and future development directions are also discussed. The biggest advantage of neurostimulation over pharmacological treatments for epilepsy is the modulation of the epilepsy network by delivering stimuli at a specific target or the “hub.” Conversely, however, a lack of knowledge of epilepsy networks and the mechanisms of neurostimulation may hinder further development. Therefore, theoretical research on the mechanism of epileptogenesis and epilepsy networks is needed in the future. Within the multiple modalities of neuromodulation, the final choice should be made after full discussion with a multidisciplinary team at a presurgical conference. Furthermore, the establishment of a neurostimulation system with standardized parameters and rigorous guidelines is another important issue. To achieve this goal, a worldwide collaboration of epilepsy centers is also suggested in the future.

[1]  J. Jankovic,et al.  Deep Brain Stimulation Hardware Complications in Patients with Movement Disorders: Risk Factors and Clinical Correlations , 2012, Stereotactic and Functional Neurosurgery.

[2]  S. Noohi,et al.  History, Studies and Specific Uses of Repetitive Transcranial Magnetic Stimulation (rTMS) in Treating Epilepsy , 2016, Iranian journal of child neurology.

[3]  S. Krahl,et al.  Deep Brain Stimulation of the Subthalamic Nucleus as Adjunct Treatment for Refractory Epilepsy , 2006, Epilepsia.

[4]  T. Harmony,et al.  Repetitive transcranial magnetic stimulation decreases the number of seizures in patients with focal neocortical epilepsy , 2008, Seizure.

[5]  M. Velasco,et al.  Electrical Stimulation of the Hippocampal Epileptic Foci for Seizure Control: A Double‐Blind, Long‐Term Follow‐Up Study , 2007, Epilepsia.

[6]  M. Galanda,et al.  Some observations in treatment stimulation of epilepsy. , 1976, Acta neurochirurgica.

[7]  Sung-chul Lim,et al.  Reply to “Recruitment responses have no localizing value” , 2015, Clinical Neurophysiology.

[8]  Katherine Nickels,et al.  Evidence-based guideline update: Vagus nerve stimulation for the treatment of epilepsy , 2013, Neurology.

[9]  C. Heck,et al.  Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy , 2013, Neurology.

[10]  Dae Won Seo,et al.  Antiepileptic effects of low-frequency repetitive transcranial magnetic stimulation by different stimulation durations and locations , 2007, Clinical Neurophysiology.

[11]  Dirk Van Roost,et al.  Deep Brain Stimulation in Patients with Refractory Temporal Lobe Epilepsy , 2007, Epilepsia.

[12]  L. F. Levy,et al.  Chronic Cerebellar Stimulation in the Treatment of Epilepsy , 1979, Epilepsia.

[13]  E. Ben-Menachem,et al.  Complications and safety of vagus nerve stimulation: 25 years of experience at a single center. , 2016, Journal of neurosurgery. Pediatrics.

[14]  J. Öhman,et al.  Outcome based definition of the anterior thalamic deep brain stimulation target in refractory epilepsy , 2016, Brain Stimulation.

[15]  M Velasco,et al.  Subacute Electrical Stimulation of the Hippocampus Blocks Intractable Temporal Lobe Seizures and Paroxysmal EEG Activities , 2000, Epilepsia.

[16]  Gregor Thut,et al.  A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy , 2006, Annals of neurology.

[17]  Á. Pascual-Leone,et al.  Exploring the efficacy of a 5-day course of transcranial direct current stimulation (TDCS) on depression and memory function in patients with well-controlled temporal lobe epilepsy , 2016, Epilepsy & Behavior.

[18]  Hongbo Jin,et al.  Hippocampal deep brain stimulation in nonlesional refractory mesial temporal lobe epilepsy , 2016, Seizure.

[19]  R. Davis,et al.  Cerebellar stimulation for seizure control: 17-year study. , 1992, Stereotactic and functional neurosurgery.

[20]  EEG driving response during low-frequency stimulation of anterior thalamic nucleus: Is it a good predictor of the correct location of DBS electrode? , 2014, Clinical Neurophysiology.

[21]  M Velasco,et al.  Electrocortical and behavioral responses produced by acute electrical stimulation of the human centromedian thalamic nucleus. , 1997, Electroencephalography and clinical neurophysiology.

[22]  Y. Shon,et al.  Chronic deep brain stimulation of subthalamic and anterior thalamic nuclei for controlling refractory partial epilepsy. , 2006, Acta neurochirurgica. Supplement.

[23]  W. Marks,et al.  Cost‐Effectiveness of Deep Brain Stimulation for Advanced Parkinson's Disease in the United States , 2016, Neuromodulation : journal of the International Neuromodulation Society.

[24]  Á. Pascual-Leone,et al.  Study and modulation of human cortical excitability with transcranial magnetic stimulation. , 1998, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[25]  Jean-Lon Chen,et al.  Long-term anterior thalamus stimulation for intractable epilepsy. , 2008, Chang Gung medical journal.

[26]  A. Barker,et al.  NON-INVASIVE MAGNETIC STIMULATION OF HUMAN MOTOR CORTEX , 1985, The Lancet.

[27]  Sophie Dupont,et al.  Vagus nerve stimulation therapy in partial epilepsy: a review , 2016, Acta Neurologica Belgica.

[28]  Philippe Kahane,et al.  Deep brain stimulation in epilepsy with particular reference to the subthalamic nucleus. , 2002, Epileptic disorders : international epilepsy journal with videotape.

[29]  S. Wiebe,et al.  Hippocampal electrical stimulation in mesial temporal lobe epilepsy , 2006, Neurology.

[30]  F. Fregni,et al.  Transcranial direct current stimulation in adolescent and adult Rasmussen's encephalitis , 2011, Epilepsy & Behavior.

[31]  Dirk Van Roost,et al.  Long‐term Deep Brain Stimulation for Refractory Temporal Lobe Epilepsy , 2005, Epilepsia.

[32]  Ana Luisa Velasco,et al.  Double‐blind, Randomized Controlled Pilot Study of Bilateral Cerebellar Stimulation for Treatment of Intractable Motor Seizures , 2005, Epilepsia.

[33]  Claudio Pollo,et al.  High and low frequency electrical stimulation in non-lesional temporal lobe epilepsy , 2007, Seizure.

[34]  L. Guoming,et al.  Treatment of mesial temporal lobe epilepsy with amygdalohippocampal stimulation: A case series and review of the literature , 2013, Experimental and therapeutic medicine.

[35]  J. Zabara Inhibition of Experimental Seizures in Canines by Repetitive Vagal Stimulation , 1992, Epilepsia.

[36]  R A Wennberg,et al.  Long-term follow-up of patients with thalamic deep brain stimulation for epilepsy , 2006, Neurology.

[37]  Ferdinando Rodriguez y Baena,et al.  Microtextured surfaces for deep-brain stimulation electrodes: a biologically inspired design to reduce lead migration. , 2012, World neurosurgery.

[38]  Felipe Fregni,et al.  Transcranial Direct Current Stimulation in Epilepsy , 2015, Brain Stimulation.

[39]  Alan Lai,et al.  Cortical Hyperexcitability: A New Biomarker in Generalized Epilepsy Syndromes , 2013 .

[40]  Zhang,et al.  Effects of low-frequency repetitive transcranial magnetic stimulation on electroencephalogram and seizure frequency in 15 patients with temporal lobe epilepsy following dipole source localization , 2008 .

[41]  B. Jobst,et al.  Critical review of the responsive neurostimulator system for epilepsy , 2015, Medical devices.

[42]  G. Worrell,et al.  Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial , 2014, Epilepsia.

[43]  Somsak Tiamkao,et al.  Transcranial Direct Current Stimulation for Treatment of Refractory Childhood Focal Epilepsy , 2013, Brain Stimulation.

[44]  Lippincott Williams Wilkins,et al.  A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures , 1995, Neurology.

[45]  Damianos E. Sakas,et al.  Surgical and hardware complications of deep brain stimulation. A seven-year experience and review of the literature , 2010, Acta Neurochirurgica.

[46]  R P Lesser,et al.  Placebo‐Controlled Pilot Study of Centromedian Thalamic Stimulation in Treatment of Intractable Seizures , 1992, Epilepsia.

[47]  Edward F. Chang,et al.  Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy , 2015, Neurosurgery.

[48]  Á. Pascual-Leone,et al.  Transcranial magnetic stimulation for refractory focal status epilepticus in the intensive care unit , 2013, Seizure.

[49]  Liang Qiao,et al.  TMS: A Tailored Method of Stimulation for Refractory Focal Epilepsy? , 2013, Epilepsy currents.

[50]  P. Doshi Long-Term Surgical and Hardware-Related Complications of Deep Brain Stimulation , 2011, Stereotactic and Functional Neurosurgery.

[51]  Claudio Pollo,et al.  Electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy , 2013, Seizure.

[52]  A. Cukiert,et al.  Intraoperative neurophysiological responses in epileptic patients submitted to hippocampal and thalamic deep brain stimulation , 2011, Seizure.

[53]  P. Bonanni,et al.  Anterior thalamic nucleus deep brain Stimulation (DBS) for drug-resistant complex partial seizures (CPS) with or without generalization: long-term evaluation and predictive outcome , 2015, Acta Neurochirurgica.

[54]  A. Cukiert,et al.  Centro-median stimulation yields additional seizure frequency and attention improvement in patients previously submitted to callosotomy , 2009, Seizure.

[55]  L. Cohen,et al.  Transcranial magnetic stimulation for the treatment of seizures: A controlled study , 2002, Neurology.

[56]  Sabine Rona,et al.  Chronic High‐Frequency Deep Brain Stimulation of the STN/SNr for Progressive Myoclonic Epilepsy , 2007, Epilepsia.

[57]  A. Parent,et al.  Single‐axon tracing and three‐dimensional reconstruction of centre médian‐parafascicular thalamic neurons in primates , 2005, The Journal of comparative neurology.

[58]  W. Tatum,et al.  Trigeminal stimulation , 2013, Neurology.

[59]  K. Meador,et al.  Quality of life and mood in patients with medically intractable epilepsy treated with targeted responsive neurostimulation , 2015, Epilepsy & Behavior.

[60]  Steve S. Chung,et al.  Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy , 2015, Neurology.

[61]  Mojgan Hodaie,et al.  Chronic Anterior Thalamus Stimulation for Intractable Epilepsy , 2002, Epilepsia.

[62]  Li Liping,et al.  A controlled trial of transcutaneous vagus nerve stimulation for the treatment of pharmacoresistant epilepsy , 2014, Epilepsy & Behavior.

[63]  A. Cukiert,et al.  Seizure outcome after hippocampal deep brain stimulation in a prospective cohort of patients with refractory temporal lobe epilepsy , 2014, Seizure.

[64]  Tatsuya Tanaka,et al.  Anti-convulsant effect of electrical stimulation and lesioning of the anterior thalamic nucleus on kainic acid-induced focal limbic seizure in rats , 2007, Epilepsy Research.

[65]  S. Wiebe,et al.  Bilateral hippocampal stimulation for intractable temporal lobe epilepsy: Impact on seizures and memory , 2010, Epilepsia.

[66]  W. Doyle,et al.  Long-term Expectations of Vagus Nerve Stimulation: A Look at Battery Replacement and Revision Surgery. , 2016, Neurosurgery.

[67]  R. Wennberg,et al.  Dravet syndrome and deep brain stimulation: Seizure control after 10 years of treatment , 2009, Epilepsia.

[68]  Y. Shon,et al.  Clinical Outcome of Patients with Deep Brain Stimulation of the Centromedian Thalamic Nucleus for Refractory Epilepsy and Location of the Active Contacts , 2016, Stereotactic and Functional Neurosurgery.

[69]  Peng Wu,et al.  Transcutaneous vagus nerve stimulation for refractory epilepsy: a randomized controlled trial. , 2014, Clinical science.

[70]  F. Fregni,et al.  Feasibility of focal transcranial DC polarization with simultaneous EEG recording: Preliminary assessment in healthy subjects and human epilepsy , 2012, Epilepsy & Behavior.

[71]  E. Pralong,et al.  Chronic deep brain stimulation in mesial temporal lobe epilepsy , 2011, Seizure.

[72]  Steve S. Chung,et al.  Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy , 2010, Epilepsia.

[73]  Alan Lai,et al.  Capturing the epileptic trait: cortical excitability measures in patients and their unaffected siblings. , 2013, Brain : a journal of neurology.

[74]  Brian Litt,et al.  Electrical Stimulation of the Anterior Nucleus of the Thalamus for the Treatment of Intractable Epilepsy , 2004, Epilepsia.

[75]  J. Naegele,et al.  Cortical GABAergic Interneuron/Progenitor Transplantation as a Novel Therapy for Intractable Epilepsy , 2018, Front. Cell. Neurosci..

[76]  Sung-chul Lim,et al.  Cognitive improvement after long-term electrical stimulation of bilateral anterior thalamic nucleus in refractory epilepsy patients , 2012, Seizure.

[77]  Danny T M Chan,et al.  Complications of deep brain stimulation: a collective review. , 2009, Asian journal of surgery.

[78]  E. Pralong,et al.  Effects of amygdala–hippocampal stimulation on interictal epileptic discharges , 2012, Epilepsy Research.

[79]  I. Cooper,et al.  Chronic cerebellar stimulation in epilepsy. Clinical and anatomical studies. , 1976, Archives of neurology.

[80]  C. Elger,et al.  Cardiac-based vagus nerve stimulation reduced seizure duration in a patient with refractory epilepsy , 2015, Seizure.

[81]  D. Terney,et al.  Transcranial direct current stimulation in refractory continuous spikes and waves during slow sleep: A controlled study , 2011, Epilepsy Research.

[82]  R. Raedt,et al.  The Effect of Vagus Nerve Stimulation on CSF Monoamines and the PTZ Seizure Threshold in Dogs , 2015, Brain Stimulation.

[83]  S. Rossi,et al.  Slow Repetitive TMS for Drug‐resistant Epilepsy: Clinical and EEG Findings of a Placebo‐controlled Trial , 2007, Epilepsia.

[84]  D. Mclellan,et al.  A double-blind trial of chronic cerebellar stimulation in twelve patients with severe epilepsy. , 1984, Journal of neurology, neurosurgery, and psychiatry.

[85]  M. Morrell Responsive cortical stimulation for the treatment of medically intractable partial epilepsy , 2011, Neurology.

[86]  C. Heck,et al.  A prospective long-term study of external trigeminal nerve stimulation for drug-resistant epilepsy , 2015, Epilepsy & Behavior.

[87]  Ivan Osorio,et al.  High Frequency Thalamic Stimulation for Inoperable Mesial Temporal Epilepsy , 2007, Epilepsia.

[88]  Miron Šramka,et al.  Electrophysiological effects and clinical results of direct brain stimulation for intractable epilepsy , 2004, Clinical Neurology and Neurosurgery.

[89]  P. Kwan,et al.  The Effects of Cathodal Transcranial Direct Current Stimulation in a Patient with Drug-Resistant Temporal Lobe Epilepsy (Case Study) , 2016, Brain Stimulation.

[90]  Tony Wu,et al.  Electrical Stimulation of the Anterior Nucleus of the Thalamus for Intractable Epilepsy: A Long‐term Follow‐up Study , 2007, Epilepsia.

[91]  J. V. Van Buren,et al.  Preliminary evaluation of cerebellar stimulation by double-blind stimulation and biological criteria in the treatment of epilepsy. , 1978, Journal of neurosurgery.

[92]  A. Hamberger,et al.  Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures , 1995, Epilepsy Research.

[93]  W. Hauser,et al.  Likelihood of seizure remission in an adult population with refractory epilepsy , 2007, Annals of neurology.

[94]  M. Thordstein,et al.  Possibly lifesaving, noninvasive, EEG‐guided neuromodulation in anesthesia‐refractory partial status epilepticus , 2012, Epilepsy & Behavior.

[95]  M. Nitsche,et al.  Can epilepsies be improved by repetitive transcranial magnetic stimulation?--interim analysis of a controlled study. , 2003, Supplements to Clinical neurophysiology.

[96]  R. Wennberg,et al.  Anterior Nucleus Deep Brain Stimulation for Refractory Epilepsy: Insights Into Patterns of Seizure Control and Efficacious Target. , 2016, Neurosurgery.

[97]  M. Velasco,et al.  Neuromodulation of the Centromedian Thalamic Nuclei in the Treatment of Generalized Seizures and the Improvement of the Quality of Life in Patients with Lennox–Gastaut Syndrome , 2006, Epilepsia.

[98]  A. Upton,et al.  Effects of cerebellar stimulation on epilepsy, the EEG and cerebral palsy in man. , 1978, Electroencephalography and clinical neurophysiology. Supplement.

[99]  Á. Pascual-Leone,et al.  Technology Insight: noninvasive brain stimulation in neurology—perspectives on the therapeutic potential of rTMS and tDCS , 2007, Nature Clinical Practice Neurology.

[100]  L. T. Rutledge,et al.  Prevention of supersensitivity in partially isolated cerebral cortex. , 1967, Electroencephalography and clinical neurophysiology.

[101]  S. Lee,et al.  Low and High Frequency Hippocampal Stimulation for Drug‐Resistant Mesial Temporal Lobe Epilepsy , 2016, Neuromodulation : journal of the International Neuromodulation Society.

[102]  M Velasco,et al.  Predictors in the treatment of difficult-to-control seizures by electrical stimulation of the centromedian thalamic nucleus. , 2000, Neurosurgery.

[103]  S. Aksu,et al.  The effect of transcranial direct current stimulation on seizure frequency of patients with mesial temporal lobe epilepsy with hippocampal sclerosis , 2016, Clinical Neurology and Neurosurgery.

[104]  A. Schulze-Bonhage Brain stimulation as a neuromodulatory epilepsy therapy , 2017, Seizure.

[105]  M. Nitsche,et al.  Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation , 2000, The Journal of physiology.

[106]  S. Cash,et al.  Long-term treatment with responsive brain stimulation in adults with refractory partial seizures , 2015, Neurology.

[107]  Kristl Vonck,et al.  Long‐term amygdalohippocampal stimulation for refractory temporal lobe epilepsy , 2002, Annals of neurology.

[108]  T. Hirfanoğlu,et al.  Long term effect of vagus nerve stimulation in pediatric intractable epilepsy: an extended follow-up , 2016, Child's Nervous System.

[109]  W. van Paesschen,et al.  Randomized crossover sham‐controlled clinical trial of targeted low‐frequency transcranial magnetic stimulation comparing a figure‐8 and a round coil to treat refractory neocortical epilepsy , 2016, Epilepsia.

[110]  Kook Jin Ahn,et al.  Effect of Chronic Deep Brain Stimulation of the Subthalamic Nucleus for Frontal Lobe Epilepsy: Subtraction SPECT Analysis , 2005, Stereotactic and Functional Neurosurgery.

[111]  Á. Pascual-Leone,et al.  A Controlled Clinical Trial of Cathodal DC Polarization in Patients with Refractory Epilepsy , 2006, Epilepsia.

[112]  Narong Auvichayapat,et al.  Transcranial Direct Current Stimulation for Treatment of Childhood Pharmacoresistant Lennox–Gastaut Syndrome: A Pilot Study , 2016, Front. Neurol..

[113]  M. Scerrati,et al.  Chronic bilateral subthalamic stimulation after anterior callosotomy in drug-resistant epilepsy: Long-term clinical and functional outcome of two cases , 2012, Epilepsy Research.

[114]  R. Raedt,et al.  A Decade of Experience with Deep Brain Stimulation for patients with Refractory Medial Temporal Lobe epilepsy , 2013, Int. J. Neural Syst..

[115]  P. Kotagal Neurostimulation: vagus nerve stimulation and beyond. , 2011, Seminars in pediatric neurology.

[116]  M. Ko,et al.  Suppression of Seizure by Cathodal Transcranial Direct Current Stimulation in an Epileptic Patient - A Case Report - , 2011, Annals of rehabilitation medicine.

[117]  G. Alarcón,et al.  Intracranial stimulation for children with epilepsy. , 2017, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[118]  J D Norrie,et al.  Patterns of treatment response in newly diagnosed epilepsy , 2012, Neurology.

[119]  Antonio Valentín,et al.  Deep brain stimulation of the centromedian thalamic nucleus for the treatment of generalized and frontal epilepsies , 2013, Epilepsia.

[120]  L. Cohen,et al.  Transcranial direct current stimulation: State of the art 2008 , 2008, Brain Stimulation.

[121]  B. Uthman,et al.  Vagus nerve stimulation therapy for partial-onset seizures , 1998, Neurology.

[122]  V. Mok,et al.  Cost-effectiveness of subthalmic nucleus deep brain stimulation for the treatment of advanced Parkinson disease in Hong Kong: a prospective study. , 2014, World neurosurgery.

[123]  R. Wennberg,et al.  Rhythmic cortical EEG synchronization with low frequency stimulation of the anterior and medial thalamus for epilepsy , 2006, Clinical Neurophysiology.

[124]  Y. Shon,et al.  Long-Term Outcome of Anterior Thalamic Nucleus Stimulation for Intractable Epilepsy , 2012, Stereotactic and Functional Neurosurgery.

[125]  A. Korczyn,et al.  [Vagus nerve stimulation for partial seizures]. , 1995, Harefuah.

[126]  W. Hauser,et al.  Seizure remission and relapse in adults with intractable epilepsy: A cohort study , 2008, Epilepsia.

[127]  Y. Shon,et al.  Relationship between Postoperative EEG Driving Response and Lead Location in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus for Refractory Epilepsy , 2016, Stereotactic and Functional Neurosurgery.