Focal cooling: An alternative treatment for drug-resistant epilepsy in a mesial temporal lobe epilepsy primate model-A preliminary study.
hippocampal sclerosis
implantable device
neuromodulation
seizure detection
seizure reduction
sensors
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
25 May 2024
25 May 2024
Historique:
revised:
01
05
2024
received:
25
10
2023
accepted:
01
05
2024
medline:
25
5
2024
pubmed:
25
5
2024
entrez:
25
5
2024
Statut:
aheadofprint
Résumé
Focal cooling is emerging as a relevant therapy for drug-resistant epilepsy (DRE). However, we lack data on its effectiveness in controlling seizures that originate in deep-seated areas like the hippocampus. We present a thermoelectric solution for focal brain cooling that specifically targets these brain structures. A prototype implantable device was developed, including temperature sensors and a cannula for penicillin injection to create an epileptogenic zone (EZ) near the cooling tip in a non-human primate model of epilepsy. The mesial temporal lobe was targeted with repeated penicillin injections into the hippocampus. Signals were recorded from an sEEG (Stereoelectroencephalography) lead placed 2 mm from the EZ. Once the number of seizures had stabilized, focal cooling was applied, and temperature and electroclinical events were monitored using a customized detection algorithm. Tests were performed on two Macaca fascicularis monkeys at three temperatures. Hippocampal seizures were observed 40-120 min post-injection, their duration and frequency stabilized at around 120 min. Compared to the control condition, a reduction in the number of hippocampal seizures was observed with cooling to 21°C (Control: 4.34 seizures, SD 1.704 per 20 min vs Cooling to 21°C: 1.38 seizures, SD 1.004 per 20 min). The effect was more pronounced with cooling to 17°C, resulting in an almost 80% reduction in seizure frequency. Seizure duration and number of interictal discharges were unchanged following focal cooling. After several months of repeated penicillin injections, hippocampal sclerosis was observed, similar to that recorded in humans. In addition, seizures were identified by detecting temperature variations of 0.3°C in the EZ correlated with the start of the seizures. In epilepsy therapy, the ultimate aim is total seizure control with minimal side effects. Focal cooling of the EZ could offer an alternative to surgery and to existing neuromodulation devices.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
Références
Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Estimation of the burden of active and life‐time epilepsy: a meta‐analytic approach: estimation of the burden of epilepsy. Epilepsia. 2010;51:883–890.
Cockerell OC, Johnson AL, Sander JW, Hart YM, Shorvon SD. Remission of epilepsy: results from the National General Practice Study of epilepsy. Lancet. 1995;346:140–144.
Annegers JF, Hauser WA, Elveback LR. Remission of seizures and relapse in patients with epilepsy. Epilepsia. 1979;20:729–737.
Téllez‐Zenteno JF, Dhar R, Wiebe S. Long‐term seizure outcomes following epilepsy surgery: a systematic review and meta‐analysis. Brain. 2005;128:1188–1198.
Englot DJ, Wang DD, Rolston JD, Shih TT, Chang EF. Rates and predictors of long‐term seizure freedom after frontal lobe epilepsy surgery: a systematic review and meta‐analysis: clinical article. J Neurosurg. 2012;116:1042–1048.
Englot DJ, Chang EF. Rates and predictors of seizure freedom in resective epilepsy surgery: an update. Neurosurg Rev. 2014;37:389–405.
Englot DJ, Rolston JD, Wright CW, Hassnain KH, Chang EF. Rates and predictors of seizure freedom with Vagus nerve stimulation for intractable epilepsy. Neurosurgery. 2016;79:345–353.
Morrell MJ. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology. 2011;77:1295–1304.
Hartshorn A, Jobst B. Responsive brain stimulation in epilepsy. Ther Adv Chronic Dis. 2018;9:135–142.
Fisher R, Salanova V, Witt T, Worth R, Henry T, Gross R, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010;51:899–908.
Salanova V, Witt T, Worth R, Henry TR, Gross RE, Nazzaro JM, et al. Long‐term efficacy and safety of thalamic stimulation for drug‐resistant partial epilepsy. Neurology. 2015;84:1017–1025.
Simpson HD, Schulze‐Bonhage A, Cascino GD, Fisher RS, Jobst BC, Sperling MR, et al. Practical considerations in epilepsy neurostimulation. Epilepsia. 2022;63:2445–2460.
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;88:349–351.
Brooks VB. Study of brain function by local, reversible cooling. Reviews of physiology, biochemistry and pharmacology, Volume 95. Berlin, Heidelberg: Springer Berlin Heidelberg; 1983. p. 1–109. https://doi.org/10.1007/BFb0034097
Yang X‐FA, Ouyang YA, Kennedy BRA, Rothman SMAB. Cooling blocks rat hippocampal neurotransmission by a presynaptic mechanism: observation using 2‐photon microscopy. J Physiol. 2005;567:215–224.
Ren G, Yan J, Tao G, Gan Y, Li D, Yan X, et al. Rapid focal cooling attenuates cortical seizures in a primate epilepsy model. Exp Neurol. 2017;295:202–210.
Tanaka N, Fujii M, Imoto H, Uchiyama J, Nakano K, Nomura S, et al. Effective suppression of hippocampal seizures in rats by direct hippocampal cooling with a Peltier chip: laboratory investigation. J Neurosurg. 2008;108:791–797.
Wallace BA, Ashkan K, Heise CE, Foote KD, Torres N, Mitrofanis J, et al. Survival of midbrain dopaminergic cells after lesion or deep brain stimulation of the subthalamic nucleus in MPTP‐treated monkeys. Brain. 2007;130:2129–2145.
Darlot F, Moro C, el Massri N, Chabrol C, Johnstone DM, Reinhart F, et al. Near‐infrared light is neuroprotective in a monkey model of Parkinson disease. Ann Neurol. 2016;79:59–75.
Martin RF, Bowden DM. A stereotaxic template atlas of the macaque brain for digital imaging and quantitative neuroanatomy. NeuroImage. 1996;4:119–150.
Smith EH, Liou JY, Merricks EM, Davis T, Thomson K, Greger B, et al. Human interictal epileptiform discharges are bidirectional traveling waves echoing ictal discharges. elife. 2022;11:e73541.
Mukhopadhyay S, Ray GC. A new interpretation of nonlinear energy operator and its efficacy in spike detection. IEEE Trans Biomed Eng. 1998;45:180–187.
Hjorth B. EEG analysis based on time domain properties. Electroencephalogr Clin Neurophysiol. 1970;29:306–310.
Janssen FEM, Leeuwen GMJV, Steenhoven AAV. Modelling of temperature and perfusion during scalp cooling. Phys Med Biol. 2005;50:4065–4073.
Fiala D, Lomas KJ, Stohrer M. A computer model of human thermoregulation for a wide range of environmental conditions: the passive system. J Appl Physiol. 1999;87:1957–1972.
Gotoh M, Nagasaka K, Nakata M, Takashima I, Yamamoto S. Brain temperature alters contributions of excitatory and inhibitory inputs to evoked field potentials in the rat frontal cortex. Front Cell Neurosci. 2020;14:1–13.
Kida H, Fujii M, Inoue T, He Y, Maruta Y, Nomura S, et al. Focal brain cooling terminates the faster frequency components of epileptic discharges induced by penicillin G in anesthetized rats. Clin Neurophysiol. 2012;123:1708–1713.
Ablah E, Tran MP, Isaac M, Kaufman DAS, Moufarrij N, Liow K. Effect of cortical cooling on interictal epileptiform activities. Seizure. 2009;18:61–63.
Nomura S, Fujii M, Inoue T, He Y, Maruta Y, Koizumi H, et al. Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans. Epilepsia. 2014;55:770–776.
Niesvizky‐Kogan I, Bass M, Goldenholz SR, Goldenholz DM. Focal cooling for drug‐resistant epilepsy: a review. JAMA Neurol. 2022;79:937–944.
Yang X‐F, Duffy DW, Morley RE, Rothman SM. Neocortical seizure termination by focal cooling: temperature dependence and automated seizure detection. Epilepsia. 2002;43:240–245.
Yang X‐F, Chang JH, Rothman SM. Intracerebral temperature alterations associated with focal seizures. Epilepsy Res. 2002;52:97–105.
Dymond AM, Crandall PH. Intracerebral temperature changes in patients during spontaneous epileptic seizures. Brain Res. 1973;60:249–254.
Johnson DW et al. Xenon/CT cerebral blood flow studies during continuous depth electrode monitoring in epilepsy patients. 1993.
Federico P, Abbott DF, Briellmann RS, Harvey AS, Jackson GD. Functional MRI of the pre‐ictal state. Brain J Neurol. 2005;128:1811–1817.
Sherdil A, Chabardès S, Guillemain I, Michallat S, Prabhu S, Pernet‐Gallay K, et al. An on demand macaque model of mesial temporal lobe seizures induced by unilateral intra hippocampal injection of penicillin. Epilepsy Res. 2018;142:20–28.
Blümcke I, Thom M, Aronica E, Armstrong DD, Bartolomei F, Bernasconi A, et al. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a task force report from the ILAE commission on diagnostic methods. Epilepsia. 2013;54:1315–1329.
Motamedi GK, Salazar P, Smith EL, Lesser RP, Webber WRS, Ortinski PI, et al. Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models. Epilepsy Res. 2006;70:200–210.