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Focal Cooling for Drug-Resistant EpilepsyA Review

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Abstract

Importance  Epilepsy affects at least 1.2% of the population, with one-third of cases considered to be drug-resistant epilepsy (DRE). For these cases, focal cooling therapy may be a potential avenue for treatment, offering hope to people with DRE for freedom from seizure. The therapy leverages neuroscience and engineering principles to deliver a reversible treatment unhindered by pharmacology.

Observations  Analogous to (but safer than) the use of global cooling in postcardiac arrest and neonatal ischemic injury, extensive research supports the premise that focal cooling as a long-term treatment for epilepsy could be effective. The potential advantages of focal cooling are trifold: stopping epileptiform discharges, seizures, and status epilepticus safely across species (including humans).

Conclusions and Relevance  This Review presents the most current evidence supporting focal cooling in epilepsy. Cooling has been demonstrated as a potentially safe and effective treatment modality for DRE, although it is not yet ready for use in humans outside of randomized clinical trials. The Review will also offer a brief overview of the technical challenges related to focal cooling in humans, including the optimal device design and cooling parameters.

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Article Information

Accepted for Publication: May 20, 2022.

Published Online: July 25, 2022. doi:10.1001/jamaneurol.2022.1936

Corresponding Author: Daniel M. Goldenholz, MD, PhD, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Baker 5, Boston, MA 02215 (daniel.goldenholz@bidmc.harvard.edu).

Author Contributions: Drs Goldenholz and Niesvizky-Kogan had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Niesvizky-Kogan, D. Goldenholz.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Niesvizky-Kogan, Bass.

Critical revision of the manuscript for important intellectual content: Niesvizky-Kogan, S. Goldenholz, D. Goldenholz.

Obtained funding: D. Goldenholz.

Administrative, technical, or material support: Niesvizky-Kogan, Bass, D. Goldenholz.

Supervision: D. Goldenholz.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was funded in part by the National Institutes of Health (grant KL2 5KL2TR002542).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Wilson  JV , Reynolds  EH .  Texts and documents: translation and analysis of a cuneiform text forming part of a Babylonian treatise on epilepsy.   Med Hist. 1990;34(2):185-198. doi:10.1017/S0025727300050651PubMedGoogle ScholarCrossref
2.
Zack  MM , Kobau  R .  National and state estimates of the numbers of adults and children with active epilepsy: United States, 2015.   MMWR Morb Mortal Wkly Rep. 2017;66(31):821-825. doi:10.15585/mmwr.mm6631a1PubMedGoogle ScholarCrossref
3.
Institute of Medicine (US) Committee on the Public Health Dimensions of the Epilepsies, England MJ, Liverman CT, Schultz AM, Strawbridge LM, eds.  Epilepsy Across the Spectrum: Promoting Health and Understanding. National Academies Press; 2012. doi:10.17226/13379
4.
Sander  JWAS .  ILAE Commission Report: the epidemiology of the epilepsies: future directions. International League Against Epilepsy.   Epilepsia. 1997;38(5):614-618. doi:10.1111/j.1528-1157.1997.tb01148.xPubMedGoogle ScholarCrossref
5.
Kwan  P , Brodie  MJ .  Early identification of refractory epilepsy.   N Engl J Med. 2000;342(5):314-319. doi:10.1056/NEJM200002033420503PubMedGoogle ScholarCrossref
6.
Hamilton  P , Soryal  I , Dhahri  P ,  et al.  Clinical outcomes of VNS therapy with AspireSR® (including cardiac-based seizure detection) at a large complex epilepsy and surgery centre.   Seizure. 2018;58:120-126. doi:10.1016/j.seizure.2018.03.022PubMedGoogle ScholarCrossref
7.
Heck  CN , King-Stephens  D , Massey  AD ,  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.   Epilepsia. 2014;55(3):432-441. doi:10.1111/epi.12534PubMedGoogle ScholarCrossref
8.
Razavi  B , Rao  VR , Lin  C ,  et al.  Real-world experience with direct brain-responsive neurostimulation for focal onset seizures.   Epilepsia. 2020;61(8):1749-1757. doi:10.1111/epi.16593PubMedGoogle ScholarCrossref
9.
Fisher  R , Salanova  V , Witt  T ,  et al; SANTE Study Group.  Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy.   Epilepsia. 2010;51(5):899-908. doi:10.1111/j.1528-1167.2010.02536.xPubMedGoogle ScholarCrossref
10.
Neves  GS , Lunardi  MS , Lin  K , Rieger  DK , Ribeiro  LC , Moreira  JD .  Ketogenic diet, seizure control, and cardiometabolic risk in adult patients with pharmacoresistant epilepsy: a review.   Nutr Rev. 2021;79(8):931-944. doi:10.1093/nutrit/nuaa112PubMedGoogle ScholarCrossref
11.
Cervenka  MC , Henry  BJ , Felton  EA , Patton  K , Kossoff  EH .  Establishing an adult epilepsy diet center: experience, efficacy and challenges.   Epilepsy Behav. 2016;58:61-68. doi:10.1016/j.yebeh.2016.02.038PubMedGoogle ScholarCrossref
12.
Solli  E , Colwell  NA , Say  I ,  et al.  Deciphering the surgical treatment gap for drug-resistant epilepsy (DRE): a literature review.   Epilepsia. 2020;61(7):1352-1364. doi:10.1111/epi.16572PubMedGoogle ScholarCrossref
13.
Health Quality Ontario.  Epilepsy surgery: an evidence summary.   Ont Health Technol Assess Ser. 2012;12(17):1-28.PubMedGoogle Scholar
14.
Malmgren  K , Edelvik  A .  Long-term outcomes of surgical treatment for epilepsy in adults with regard to seizures, antiepileptic drug treatment and employment.   Seizure. 2017;44:217-224. doi:10.1016/j.seizure.2016.10.015PubMedGoogle ScholarCrossref
15.
Weber  J , Gustafsson  C , Malmgren  K ,  et al.  Evaluation for epilepsy surgery: why do patients not proceed to operation?   Seizure. 2019;69(February):241-244. doi:10.1016/j.seizure.2019.05.004PubMedGoogle ScholarCrossref
16.
Grant  MJ , Booth  A .  A typology of reviews: an analysis of 14 review types and associated methodologies.   Health Info Libr J. 2009;26(2):91-108. doi:10.1111/j.1471-1842.2009.00848.xPubMedGoogle ScholarCrossref
17.
Remba  SJ , Varon  J , Rivera  A , Sternbach  GL .  Dominique-Jean Larrey: the effects of therapeutic hypothermia and the first ambulance.   Resuscitation. 2010;81(3):268-271. doi:10.1016/j.resuscitation.2009.11.010PubMedGoogle ScholarCrossref
18.
Mark  VH , Chato  JC , Eastman  FG , Aronow  S , Ervin  FR .  Localized cooling in the brain.   Science. 1961;134(3489):1520-1521. doi:10.1126/science.134.3489.1520PubMedGoogle ScholarCrossref
19.
Benson  DW , Williams  GR  Jr , Spencer  FC , Yates  AJ .  The use of hypothermia after cardiac arrest.   Anesth Analg. 1959;38:423-428. doi:10.4213/tvp4576PubMedGoogle ScholarCrossref
20.
Hypothermia after Cardiac Arrest Study Group.  Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest.   N Engl J Med. 2002;346(8):549-556. doi:10.1056/NEJMoa012689PubMedGoogle ScholarCrossref
21.
Song  SS , Lyden  PD .  Overview of therapeutic hypothermia.   Curr Treat Options Neurol. 2012;14(6):541-548. doi:10.1007/s11940-012-0201-xPubMedGoogle ScholarCrossref
22.
Legriel  S , Lemiale  V , Schenck  M ,  et al; HYBERNATUS Study Group.  Hypothermia for neuroprotection in convulsive status epilepticus.   N Engl J Med. 2016;375(25):2457-2467. doi:10.1056/NEJMoa1608193PubMedGoogle ScholarCrossref
23.
Shankaran  S , Laptook  AR , Ehrenkranz  RA ,  et al; National Institute of Child Health and Human Development Neonatal Research Network.  Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy.   N Engl J Med. 2005;353(15):1574-1584. doi:10.1056/NEJMcps050929PubMedGoogle ScholarCrossref
24.
Dankiewicz  J , Cronberg  T , Lilja  G ,  et al; TTM2 Trial Investigators.  Hypothermia versus normothermia after out-of-hospital cardiac arrest.   N Engl J Med. 2021;384(24):2283-2294. doi:10.1056/NEJMoa2100591PubMedGoogle ScholarCrossref
25.
Sartorius  CJ , Berger  MS .  Rapid termination of intraoperative stimulation-evoked seizures with application of cold Ringer’s lactate to the cortex: technical note.   J Neurosurg. 1998;88(2):349-351. doi:10.3171/jns.1998.88.2.0349PubMedGoogle ScholarCrossref
26.
Karkar  KM , Garcia  PA , Bateman  LM , Smyth  MD , Barbaro  NM , Berger  M .  Focal cooling suppresses spontaneous epileptiform activity without changing the cortical motor threshold.   Epilepsia. 2002;43(8):932-935. doi:10.1046/j.1528-1157.2002.03902.xPubMedGoogle ScholarCrossref
27.
Soriano  J , Kubo  T , Inoue  T ,  et al.  Differential temperature sensitivity of synaptic and firing processes in a neural mass model of epileptic discharges explains heterogeneous response of experimental epilepsy to focal brain cooling.   PLoS Comput Biol. 2017;13(10):e1005736. doi:10.1371/journal.pcbi.1005736PubMedGoogle ScholarCrossref
28.
Gartside  IB , Lippold  OCJ .  The production of persistent changes in the level of neuronal activity by brief local cooling of the cerebral cortex of the rat.   J Physiol. 1967;189(3):475-487. doi:10.1113/jphysiol.1967.sp008180PubMedGoogle ScholarCrossref
29.
He  Y , Inoue  T , Nomura  S ,  et al.  Limitations of local brain cooling on generalized motor seizures from unknown foci in awake rats.   Neurol Med Chir (Tokyo). 2019;59(4):147-153. doi:10.2176/nmc.oa.2018-0112PubMedGoogle ScholarCrossref
30.
Filipchenko  RE , Pevzner  LZ , Slonim  AD .  RNA content in the neurons and glia of the hypothalamic nuclei after intermittent cooling.   Neurosci Behav Physiol. 1976;7(1):69-71. doi:10.1007/BF01148751PubMedGoogle ScholarCrossref
31.
Nomura  S , Fujii  M , Inoue  T ,  et al.  Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans.   Epilepsia. 2014;55(5):770-776. doi:10.1111/epi.12600PubMedGoogle ScholarCrossref
32.
Nomura  S , Inoue  T , Imoto  H ,  et al.  Effects of focal brain cooling on extracellular concentrations of neurotransmitters in patients with epilepsy.   Epilepsia. 2017;58(4):627-634. doi:10.1111/epi.13704PubMedGoogle ScholarCrossref
33.
Volgushev  M , Vidyasagar  TR , Chistiakova  M , Yousef  T , Eysel  UT .  Membrane properties and spike generation in rat visual cortical cells during reversible cooling.   J Physiol. 2000;522 pt 1(pt 1):59-76. doi:10.1111/j.1469-7793.2000.0059m.xGoogle ScholarCrossref
34.
Volgushev  M , Vidyasagar  TR , Chistiakova  M , Eysel  UT .  Synaptic transmission in the neocortex during reversible cooling.   Neuroscience. 2000;98(1):9-22. doi:10.1016/S0306-4522(00)00109-3PubMedGoogle ScholarCrossref
35.
Moriyama  H , Nomura  S , Kida  H ,  et al.  Suppressive effects of cooling compounds icilin on penicillin G-induced epileptiform discharges in anesthetized rats.   Front Pharmacol. 2019;10(JUN):652. doi:10.3389/fphar.2019.00652PubMedGoogle ScholarCrossref
36.
Adey  WR .  Biophysical and metabolic bases of cooling effects on cortical membrane potentials in the cat.   Exp Neurol. 1974;42(1):113-140. doi:10.1016/0014-4886(74)90011-9PubMedGoogle ScholarCrossref
37.
Banerjee  A , Egger  R , Long  MA .  Using focal cooling to link neural dynamics and behavior.   Neuron. 2021;109(16):2508-2518. doi:10.1016/j.neuron.2021.05.029PubMedGoogle ScholarCrossref
38.
Hill  MW , Wong  M , Amarakone  A , Rothman  SM .  Rapid cooling aborts seizure-like activity in rodent hippocampal-entorhinal slices.   Epilepsia. 2000;41(10):1241-1248. doi:10.1111/j.1528-1157.2000.tb04601.xPubMedGoogle ScholarCrossref
39.
Aihara  H , Okada  Y , Tamaki  N .  The effects of cooling and rewarming on the neuronal activity of pyramidal neurons in guinea pig hippocampal slices.   Brain Res. 2001;893(1-2):36-45. doi:10.1016/S0006-8993(00)03285-6PubMedGoogle ScholarCrossref
40.
Javedan  SP , Fisher  RS , Eder  HG , Smith  K , Wu  J .  Cooling abolishes neuronal network synchronization in rat hippocampal slices.   Epilepsia. 2002;43(6):574-580. doi:10.1046/j.1528-1157.2002.40101.xPubMedGoogle ScholarCrossref
41.
Fujii  M , Inoue  T , Nomura  S ,  et al.  Cooling of the epileptic focus suppresses seizures with minimal influence on neurologic functions.   Epilepsia. 2012;53(3):485-493. doi:10.1111/j.1528-1167.2011.03388.xPubMedGoogle ScholarCrossref
42.
Vastola  EF , Homan  R , Rosen  A .  Inhibition of focal seizures by moderate hypothermia: a clinical and experimental study.   Arch Neurol. 1969;20(4):430-439. doi:10.1001/archneur.1969.00480100106015PubMedGoogle ScholarCrossref
43.
Smyth  MD , Rothman  SM .  Focal cooling devices for the surgical treatment of epilepsy.   Neurosurg Clin N Am. 2011;22(4):533-546, vii. doi:10.1016/j.nec.2011.07.011PubMedGoogle ScholarCrossref
44.
Shibasaki  K , Yamada  K , Miwa  H ,  et al.  Temperature elevation in epileptogenic foci exacerbates epileptic discharge through TRPV4 activation.   Lab Invest. 2020;100(2):274-284. doi:10.1038/s41374-019-0335-5PubMedGoogle ScholarCrossref
45.
Motamedi  GK , Gonzalez-Sulser  A , Dzakpasu  R , Vicini  S .  Cellular mechanisms of desynchronizing effects of hypothermia in an in vitro epilepsy model.   Neurotherapeutics. 2012;9(1):199-209. doi:10.1007/s13311-011-0078-5PubMedGoogle ScholarCrossref
46.
Kida  H , Fujii  M , Inoue  T ,  et al.  Focal brain cooling terminates the faster frequency components of epileptic discharges induced by penicillin G in anesthetized rats.   Clin Neurophysiol. 2012;123(9):1708-1713. doi:10.1016/j.clinph.2012.02.074PubMedGoogle ScholarCrossref
47.
Motamedi  GK , Salazar  P , Smith  EL ,  et al.  Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models.   Epilepsy Res. 2006;70(2-3):200-210. doi:10.1016/j.eplepsyres.2006.05.001PubMedGoogle ScholarCrossref
48.
Hou  KC , Chang  CW , Chiou  JC , Huang  YH , Shaw  FZ .  Wireless and batteryless biomedical microsystem for neural recording and epilepsy suppression based on brain focal cooling.   IET Nanobiotechnol. 2011;5(4):143-147. doi:10.1049/iet-nbt.2011.0017PubMedGoogle ScholarCrossref
49.
Oku  T , Fujii  M , Tanaka  N ,  et al.  The influence of focal brain cooling on neurophysiopathology: validation for clinical application.   J Neurosurg. 2009;110(6):1209-1217. doi:10.3171/2009.1.JNS08499PubMedGoogle ScholarCrossref
50.
Fujioka  H , Fujii  M , Koizumi  H ,  et al.  An implantable, automated focal cerebral-cooling system suppresses epileptic seizures in free-moving, spontaneously epileptic rats.   Neurosurgery. 2008;62(6):1420. doi:10.1227/01.NEU.0000333515.26840.EFGoogle ScholarCrossref
51.
Smyth  MD , Han  RH , Yarbrough  CK ,  et al.  Temperatures achieved in human and canine neocortex during intraoperative passive or active focal cooling.   Ther Hypothermia Temp Manag. 2015;5(2):95-103. doi:10.1089/ther.2014.0025PubMedGoogle ScholarCrossref
52.
Iaichnikov  IK .  [Changes in the EEG of rabbits induced by local cooling or heating of the central thermosensory area].   Fiziol Zh SSSR Im I M Sechenova. 1979;65(2):224-229.PubMedGoogle Scholar
53.
Cheng  H , Shi  J , Zhang  L , Zhang  Q , Yin  H , Wang  L .  Epidural cooling for selective brain hypothermia in porcine model.   Acta Neurochir (Wien). 2006;148(5):559-564. doi:10.1007/s00701-006-0735-3PubMedGoogle ScholarCrossref
54.
Inoue  T , Fujii  M , He  Y ,  et al.  Development of a focal cerebral cooling system for the treatment of intractable epilepsy: an experimental study in cats and non-human primates.  2011 IEEE International Conference on Systems, Man, and Cybernetics. Accessed June 15, 2022. doi:10.1109/ICSMC.2011.6083721
55.
Lomber  SG , Payne  BR , Horel  JA .  The cryoloop: an adaptable reversible cooling deactivation method for behavioral or electrophysiological assessment of neural function.   J Neurosci Methods. 1999;86(2):179-194. doi:10.1016/S0165-0270(98)00165-4PubMedGoogle ScholarCrossref
56.
Fukuda  M , Ono  T , Nakamura  K .  Functional relations among inferotemporal cortex, amygdala, and lateral hypothalamus in monkey operant feeding behavior.   J Neurophysiol. 1987;57(4):1060-1077. doi:10.1152/jn.1987.57.4.1060PubMedGoogle ScholarCrossref
57.
Ablah  E , Tran  MP , Isaac  M , Kaufman  DAS , Moufarrij  N , Liow  K .  Effect of cortical cooling on interictal epileptiform activities.   Seizure. 2009;18(1):61-63. doi:10.1016/j.seizure.2008.06.005PubMedGoogle ScholarCrossref
58.
Schaumburg  H , Byck  R , Herman  R , Rosengart  C .  Peripheral nerve damage by cold.   Arch Neurol. 1967;16(1):103-109. doi:10.1001/archneur.1967.00470190107013PubMedGoogle ScholarCrossref
59.
Govindaraju  SR , Curry  BD , Bain  JLW , Riley  DA .  Effects of temperature on vibration-induced damage in nerves and arteries.   Muscle Nerve. 2006;33(3):415-423. doi:10.1002/mus.20478PubMedGoogle ScholarCrossref
60.
Bakken  HE , Kawasaki  H , Oya  H , Greenlee  JDW , Howard  MA  III .  A device for cooling localized regions of human cerebral cortex: technical note.   J Neurosurg. 2003;99(3):604-608. doi:10.3171/jns.2003.99.3.0604PubMedGoogle ScholarCrossref
61.
Nomura  S , Kida  H , Hirayama  Y ,  et al.  Reduction of spike generation frequency by cooling in brain slices from rats and from patients with epilepsy.   J Cereb Blood Flow Metab. 2019;39(11):2286-2294. doi:10.1177/0271678X18795365PubMedGoogle ScholarCrossref
62.
Sourek  K , Trávnícek  V .  General and local hypothermia of the brain in the treatment of intractable epilepsy.   J Neurosurg. 1970;33(3):253-259. doi:10.3171/jns.1970.33.3.0253PubMedGoogle ScholarCrossref
63.
Rothman  SM .  The therapeutic potential of focal cooling for neocortical epilepsy.   Neurotherapeutics. 2009;6(2):251-257. doi:10.1016/j.nurt.2008.12.002PubMedGoogle ScholarCrossref
64.
Fujii  M , Fujioka  H , Oku  T ,  et al.  Application of focal cerebral cooling for the treatment of intractable epilepsy.   Neurol Med Chir (Tokyo). 2010;50(9):839-844. doi:10.2176/nmc.50.839PubMedGoogle ScholarCrossref
65.
Yang  XF , Kennedy  BR , Lomber  SG , Schmidt  RE , Rothman  SM .  Cooling produces minimal neuropathology in neocortex and hippocampus.   Neurobiol Dis. 2006;23(3):637-643. doi:10.1016/j.nbd.2006.05.006PubMedGoogle ScholarCrossref
66.
Liu  Z , Gatt  A , Mikati  M , Holmes  GL .  Effect of temperature on kainic acid-induced seizures.   Brain Res. 1993;631(1):51-58. doi:10.1016/0006-8993(93)91185-UPubMedGoogle ScholarCrossref
67.
Yang  XF , Duffy  DW , Morley  RE , Rothman  SM .  Neocortical seizure termination by focal cooling: temperature dependence and automated seizure detection.   Epilepsia. 2002;43(3):240-245. doi:10.1046/j.1528-1157.2002.33301.xPubMedGoogle ScholarCrossref
68.
Kowski  AB , Kanaan  H , Schmitt  FC , Holtkamp  M .  Deep hypothermia terminates status epilepticus: an experimental study.   Brain Res. 2012;1446:119-126. doi:10.1016/j.brainres.2012.01.022PubMedGoogle ScholarCrossref
69.
D’Ambrosio  R , Eastman  CL , Darvas  F ,  et al.  Mild passive focal cooling prevents epileptic seizures after head injury in rats.   Ann Neurol. 2013;73(2):199-209. doi:10.1002/ana.23764PubMedGoogle ScholarCrossref
70.
Csernyus  B , Szabó  Á , Fiáth  R ,  et al.  A multimodal, implantable sensor array and measurement system to investigate the suppression of focal epileptic seizure using hypothermia.   J Neural Eng. 2021;18(4). doi:10.1088/1741-2552/ac15e6PubMedGoogle ScholarCrossref
71.
Benita  M .  [A new device for localized cooling of nerve structures].   Electroencephalogr Clin Neurophysiol. 1972;32(1):90-94. doi:10.1016/0013-4694(72)90233-7PubMedGoogle ScholarCrossref
72.
Chang  C-W , Hou  K-C , Chou  L-C ,  et al.  Miniaturized cortex cooling device and system for hypothermia therapy application on freely moving rat.  2012 IEEE Sensors. Accessed June 15, 2022. doi:10.1109/ICSENS.2012.6411273
73.
Nemoto  EM , Jungreis  C , Jovin  T ,  et al. Safety of direct local cooling (15° C) of the cerebral cortex with the Chillerstrip during focal cerebral ischemia in monkeys. In:  Oxygen Transport to Tissue XXVII. Springer US; 2006:317-322. doi:10.1007/0-387-29540-2_50
74.
Tokiwa  T , Zimin  L , Ishiguro  H ,  et al.  A palm-sized cryoprobe system with a built-in thermocouple and its application in an animal model of epilepsy.   IEEE Trans Biomed Eng. 2019;66(11):3168-3175. doi:10.1109/TBME.2019.2901530PubMedGoogle ScholarCrossref
75.
Yang  XF , Chang  JH , Rothman  SM .  Long-lasting anticonvulsant effect of focal cooling on experimental neocortical seizures.   Epilepsia. 2003;44(12):1500-1505. doi:10.1111/j.0013-9580.2003.23003.xPubMedGoogle ScholarCrossref
76.
Ryvlin  P , Rheims  S , Hirsch  LJ , Sokolov  A , Jehi  L .  Neuromodulation in epilepsy: state-of-the-art approved therapies.   Lancet Neurol. 2021;20(12):1038-1047. doi:10.1016/S1474-4422(21)00300-8PubMedGoogle ScholarCrossref
77.
Wang  H , Wang  B , Normoyle  KP ,  et al.  Brain temperature and its fundamental properties: a review for clinical neuroscientists.   Front Neurosci. 2014;8(SEP):307. doi:10.3389/fnins.2014.00307PubMedGoogle ScholarCrossref
78.
Guerra  RA , Carey  V , Rubinsky  B ,  et al. Characterization of the focal cooling necessary to suppress spontaneous epileptiform activity. In: 7th ASME/JSME Thermal Engineering Conference/Summer Heat Transfer Conference. Am Soc Mechanical Engineers; 2007:375-384.
79.
Guilliams  K , Rosen  M , Buttram  S ,  et al.  Hypothermia for pediatric refractory status epilepticus.   Epilepsia. 2013;54(9):1586-1594. doi:10.1111/epi.12331PubMedGoogle ScholarCrossref
80.
Assis  FR , Narasimhan  B , Ziai  W , Tandri  H .  From systemic to selective brain cooling: methods in review.   Brain Circ. 2019;5(4):179-186. doi:10.4103/bc.bc_23_19PubMedGoogle ScholarCrossref
81.
Adams  T .  A method for local heating and cooling of the brain.   J Appl Physiol. 1964;19:338-340. doi:10.1152/jappl.1964.19.2.338Google ScholarCrossref
82.
Cooke  DF , Goldring  AB , Yamayoshi  I ,  et al.  Fabrication of an inexpensive, implantable cooling device for reversible brain deactivation in animals ranging from rodents to primates.   J Neurophysiol. 2012;107(12):3543-3558. doi:10.1152/jn.01101.2011PubMedGoogle ScholarCrossref
83.
Hata  K , Fujiwara  K , Kano  M ,  et al. Design of focal brain cooling system for suppressing epileptic seizures. Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society. Accessed June 15, 2022. doi:10.1109/EMBC.2017.8036817
84.
Hata  K , Fujiwara  K , Inoue  T ,  et al.  Epileptic seizure suppression by focal brain cooling with recirculating coolant cooling system: modeling and simulation.   IEEE Trans Neural Syst Rehabil Eng. 2019;27(2):162-171. doi:10.1109/TNSRE.2019.2891090PubMedGoogle ScholarCrossref
85.
Abe  T , Fujiwara  K , Inoue  T ,  et al.  Optimal design of neuroprotective focal brain cooling device using surrogate model approach.   IEEE Transactions on Medical Robotics and Bionics. 2020;2(4):681-691. doi:10.1109/TMRB.2020.3020687Google ScholarCrossref
86.
Csernyus  B , Szabó  Á , Zátonyi  A ,  et al.  Recent antiepileptic and neuroprotective applications of brain cooling.   Seizure. 2020;82(April):80-90. doi:10.1016/j.seizure.2020.09.018PubMedGoogle ScholarCrossref
87.
Reed  DJ , Miller  AD .  Thermoelectric Peltier device for local cortical cooling.   Physiol Behav. 1978;20(2):209-211. doi:10.1016/0031-9384(78)90077-XPubMedGoogle ScholarCrossref
90.
Imoto  H , Fujii  M , Uchiyama  J ,  et al.  Use of a Peltier chip with a newly devised local brain-cooling system for neocortical seizures in the rat: technical note.   J Neurosurg. 2006;104(1):150-156. doi:10.3171/jns.2006.104.1.150PubMedGoogle ScholarCrossref
91.
Tanaka  N , Fujii  M , Imoto  H ,  et al.  Effective suppression of hippocampal seizures in rats by direct hippocampal cooling with a Peltier chip.   J Neurosurg. 2008;108(4):791-797. doi:10.3171/JNS/2008/108/4/0791PubMedGoogle ScholarCrossref
92.
Faghri  A .  Heat Pipe Science and Technology. Global Digital Press; 2016.
93.
Uchiyama  J , Fujii  M , Imoto  H ,  et al.  Suppressive effect of a new focal cooling device with a heat pipe on epileptiform discharges in an experimental seizure model.   Epilepsia. 2007;48:94-95.Google Scholar
94.
Cattaneo  G , Schumacher  M , Maurer  C ,  et al.  Endovascular cooling catheter for selective brain hypothermia: an animal feasibility study of cooling performance.   AJNR Am J Neuroradiol. 2016;37(5):885-891. doi:10.3174/ajnr.A4625PubMedGoogle ScholarCrossref
95.
Al-Senani  FM , Graffagnino  C , Grotta  JC ,  et al.  A prospective, multicenter pilot study to evaluate the feasibility and safety of using the CoolGard System and Icy catheter following cardiac arrest.   Resuscitation. 2004;62(2):143-150. doi:10.1016/j.resuscitation.2004.02.016PubMedGoogle ScholarCrossref
96.
Attaluri  A , Zhongping  H , Liang  Z .  Evaluation of an interstitial cooling device for carotid arterial cooling using a tissue equivalent gel phantom.   J Therm Sci Eng Appl. 2010;2(1):11007. doi:10.1115/1.4002196Google ScholarCrossref
97.
Behringer  W , Safar  P , Wu  X ,  et al.  Veno-venous extracorporeal blood shunt cooling to induce mild hypothermia in dog experiments and review of cooling methods.   Resuscitation. 2002;54(1):89-98. doi:10.1016/S0300-9572(02)00046-1PubMedGoogle ScholarCrossref
98.
Choi  JH , Marshall  RS , Neimark  MA ,  et al.  Selective brain cooling with endovascular intracarotid infusion of cold saline: a pilot feasibility study.   AJNR Am J Neuroradiol. 2010;31(5):928-934. doi:10.3174/ajnr.A1961PubMedGoogle ScholarCrossref
99.
Dinis  H , Fernandes  J , Mendes  PM . Slot antenna design for a wirelessly powered implantable microcooler for neuronal applications. 11th European Conference on Antennas and Propagation (EUCAP). Accessed June 15, 2022. https://ieeexplore.ieee.org/document/7928775
100.
Fernandes  J , Vendramini  E , Miranda  AM ,  et al.  Design and performance assessment of a solid-state microcooler for thermal neuromodulation.   Micromachines (Basel). 2018;9(2):E47. doi:10.3390/mi9020047PubMedGoogle ScholarCrossref
101.
Hilderbrand  JK , Peterson  GP , Rothman  SM .  Development of phase change heat spreader for treatment of intractable neocortical epilepsy.   Heat Transf Eng. 2007;28(4):282-291. doi:10.1080/01457630601117872Google ScholarCrossref
102.
Humphrey  GL , Orman  SS .  Removable, conforming device for cooling the cortical surface.   Brain Res Bull. 1979;4(6):871-872. doi:10.1016/0361-9230(79)90026-1PubMedGoogle ScholarCrossref
103.
Yamakawa  T , Niwayama  M , Inoue  T ,  et al. Implantable electronics for diagnosis and treatment of intractable epilepsy. 6th International Conference on Electronics, Computers and Artificial Intelligence (ECAI); 2014.
104.
Cook  MJ , O’Brien  TJ , Berkovic  SF ,  et al.  Prediction of seizure likelihood with a long-term, implanted seizure advisory system in patients with drug-resistant epilepsy: a first-in-man study.   Lancet Neurol. 2013;12(6):563-571. doi:10.1016/S1474-4422(13)70075-9PubMedGoogle ScholarCrossref
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