Closed-Loop Brain Stimulation for Drug-Resistant Epilepsy: Towards an Evidence-Based Approach to Personalized Medicine

Overview

Journal Neurotherapeutics

Specialty Neurology

Date 2018 Nov 1

PMID 30378004

Citations 32

Authors

Nathaniel D Sisterson

Thomas A Wozny

Vasileios Kokkinos

Alexander Constantino

R Mark Richardson

Affiliations

Soon will be listed here.

Abstract

Closed-loop brain stimulation is one of the few treatments available for patients who are ineligible for traditional surgical resection of the epileptogenic zone, due to having generalized epilepsy, multifocal epilepsy, or focal epilepsy localized to an eloquent brain region. Due to its clinical efficacy and potential to delivery personalized therapy based on an individual's own intracerebral electrophysiology, this treatment is becoming an important part of clinical practice, despite a limited understanding of how to program detection and stimulation parameters for optimal, patient-specific benefit. To bring this challenge into focus, we review the evolution of neural stimulation for epilepsy, provide a technical overview of the RNS System (the only FDA-approved closed-loop device), and discuss the major challenges of working with a closed-loop device. We then propose an evidence-based solution for individualizing therapy that is driven by a bottom-up informatics approach.

Citing Articles

Advancements in Surgical Therapies for Drug-Resistant Epilepsy: A Paradigm Shift towards Precision Care.

Zhong C, Yang K, Wang N, Yang L, Yang Z, Xu L Neurol Ther. 2025; 14(2):467-490.

PMID: 39928287 PMC: 11906941. DOI: 10.1007/s40120-025-00710-4.

A Comprehensive Review of Recent Trends in Surgical Approaches for Epilepsy Management.

Sabzvari T, Aflahe Iqbal M, Ranganatha A, Daher J, Freire I, Shamsi S Cureus. 2024; 16(10):e71715.

PMID: 39553057 PMC: 11568833. DOI: 10.7759/cureus.71715.

Closing the Loop for Precise Seizure Control.

Gu B Epilepsy Curr. 2024; 24(2):135-137.

PMID: 39280057 PMC: 11394418. DOI: 10.1177/15357597241233221.

The bidirectional relationship between the cerebellum and seizure networks: a double-edged sword.

Streng M Curr Opin Behav Sci. 2024; 54.

PMID: 38800711 PMC: 11126210. DOI: 10.1016/j.cobeha.2023.101327.

The role of neuromodulation in the management of drug-resistant epilepsy.

Salama H, Salama A, Oscher L, Jallo G, Shimony N Neurol Sci. 2024; 45(9):4243-4268.

PMID: 38642321 DOI: 10.1007/s10072-024-07513-9.

References

Lipski W, DeStefino V, Stanslaski S, Antony A, Crammond D, Cameron J . Sensing-enabled hippocampal deep brain stimulation in idiopathic nonhuman primate epilepsy. J Neurophysiol. 2014; 113(4):1051-62. DOI: 10.1152/jn.00619.2014. View

Jobst B, Kapur R, Barkley G, Bazil C, Berg M, Bergey G . Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas. Epilepsia. 2017; 58(6):1005-1014. DOI: 10.1111/epi.13739. View

Banerjee P, Filippi D, Hauser W . The descriptive epidemiology of epilepsy-a review. Epilepsy Res. 2009; 85(1):31-45. PMC: 2696575. DOI: 10.1016/j.eplepsyres.2009.03.003. View

Feldwisch-Drentrup H, Staniek M, Schulze-Bonhage A, Timmer J, Dickten H, Elger C . Identification of preseizure States in epilepsy: a data-driven approach for multichannel EEG recordings. Front Comput Neurosci. 2011; 5:32. PMC: 3133837. DOI: 10.3389/fncom.2011.00032. View

Kinoshita M, Ikeda A, Matsumoto R, Begum T, Usui K, Yamamoto J . Electric stimulation on human cortex suppresses fast cortical activity and epileptic spikes. Epilepsia. 2004; 45(7):787-91. DOI: 10.1111/j.0013-9580.2004.60203.x. View

Motamedi G, Lesser R, Miglioretti D, Mizuno-Matsumoto Y, Gordon B, Webber W . Optimizing parameters for terminating cortical afterdischarges with pulse stimulation. Epilepsia. 2002; 43(8):836-46. DOI: 10.1046/j.1528-1157.2002.24901.x. View

Huang L, Luijtelaar G . The effects of acute responsive high frequency stimulation of the subiculum on the intra-hippocampal kainic acid seizure model in rats. Brain Behav. 2012; 2(5):532-40. PMC: 3489806. DOI: 10.1002/brb3.70. View

Yamamoto T . Vagus nerve stimulation therapy: indications, programing, and outcomes. Neurol Med Chir (Tokyo). 2015; 55(5):407-15. PMC: 4628168. DOI: 10.2176/nmc.ra.2014-0405. View

Brinkmann B, Wagenaar J, Abbot D, Adkins P, Bosshard S, Chen M . Crowdsourcing reproducible seizure forecasting in human and canine epilepsy. Brain. 2016; 139(Pt 6):1713-22. PMC: 5022671. DOI: 10.1093/brain/aww045. View

10.

Kossoff E, Ritzl E, Politsky J, Murro A, Smith J, Duckrow R . Effect of an external responsive neurostimulator on seizures and electrographic discharges during subdural electrode monitoring. Epilepsia. 2004; 45(12):1560-7. DOI: 10.1111/j.0013-9580.2004.26104.x. View

11.

Salanova V, Witt T, Worth R, Henry T, Gross R, Nazzaro J . Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015; 84(10):1017-25. PMC: 4352097. DOI: 10.1212/WNL.0000000000001334. View

12.

Durand D . Control of seizure activity by electrical stimulation: effect of frequency. Annu Int Conf IEEE Eng Med Biol Soc. 2009; 2009:2375. DOI: 10.1109/IEMBS.2009.5334993. View

13.

Bergey G, Morrell M, Mizrahi E, Goldman A, King-Stephens D, Nair D . Long-term treatment with responsive brain stimulation in adults with refractory partial seizures. Neurology. 2015; 84(8):810-7. PMC: 4339127. DOI: 10.1212/WNL.0000000000001280. View

14.

Han C, Hu W, Stead M, Zhang T, Zhang J, Worrell G . Electrical stimulation of hippocampus for the treatment of refractory temporal lobe epilepsy. Brain Res Bull. 2014; 109:13-21. DOI: 10.1016/j.brainresbull.2014.08.007. View

15.

Schuele S, Luders H . Intractable epilepsy: management and therapeutic alternatives. Lancet Neurol. 2008; 7(6):514-24. DOI: 10.1016/S1474-4422(08)70108-X. View

16.

Laxpati N, Kasoff W, Gross R . Deep brain stimulation for the treatment of epilepsy: circuits, targets, and trials. Neurotherapeutics. 2014; 11(3):508-26. PMC: 4121455. DOI: 10.1007/s13311-014-0279-9. View

17.

Chen Z, Brodie M, Liew D, Kwan P . Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study. JAMA Neurol. 2017; 75(3):279-286. PMC: 5885858. DOI: 10.1001/jamaneurol.2017.3949. View

18.

Kinoshita M, Ikeda A, Matsuhashi M, Matsumoto R, Hitomi T, Begum T . Electric cortical stimulation suppresses epileptic and background activities in neocortical epilepsy and mesial temporal lobe epilepsy. Clin Neurophysiol. 2005; 116(6):1291-9. DOI: 10.1016/j.clinph.2005.02.010. View

19.

Wozny T, Lipski W, Alhourani A, Kondylis E, Antony A, Richardson R . Effects of hippocampal low-frequency stimulation in idiopathic non-human primate epilepsy assessed via a remote-sensing-enabled neurostimulator. Exp Neurol. 2017; 294:68-77. DOI: 10.1016/j.expneurol.2017.05.003. View

20.

Sun F, Morrell M, Wharen Jr R . Responsive cortical stimulation for the treatment of epilepsy. Neurotherapeutics. 2008; 5(1):68-74. PMC: 5084128. DOI: 10.1016/j.nurt.2007.10.069. View