The treatment of many human epileptic syndromes remains unsatisfactory. While anticonvulsant medications allow about 75% of epileptics to achieve excellent seizure control, the remaining 25% of patients suffer from a combination of continued seizures and medication toxicity. It is unlikely that a single medical breakthrough will provide a cure for all of these refractory patients. Focal neocortical epilepsies have proven particularly difficult to manage. While some respond to anticonvulsants, a large fraction remains intractable to medical therapy. This group can respond to cortical resection, but surgical management is problematic. Exact identification of the epileptogenic focus can be complicated and there is a risk of unanticipated, irreversible neurological deficits after resection. Focal cortical cooling has the potential to improve the evaluation and treatment of this epileptic subgroup.
The aims of the experiments described in this application are to investigate the potential of focal cooling with thermoelectric (Peltier) chips to rapidly terminate chronic seizure discharges, determine the degree of cooling required to stop these seizures, determine whether cooling can prevent seizures, and develop computer programs that recognize and anticipate seizures in """"""""real time"""""""". In addition, the potential pathological consequences of cortical cooling will be determined. These experiments represent a necessary first step toward utilizing these techniques for the therapy of human epilepsy. These experiments will utilize models of acute and chronic rodent neocortical seizures and small Peltier devices developed for the microelectronics industry. If Peltier devices can control focal seizures in our models, they will be refined for future experiments to investigate their potential role in mapping and controlling epileptogenic neocortex in man. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS042936-04
Application #
7033931
Study Section
Special Emphasis Panel (ZRG1-BDCN-1 (01))
Program Officer
Fureman, Brandy E
Project Start
2003-04-01
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
4
Fiscal Year
2006
Total Cost
$265,185
Indirect Cost
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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D'Ambrosio, Raimondo; Eastman, Clifford L; Darvas, Felix et al. (2013) Mild passive focal cooling prevents epileptic seizures after head injury in rats. Ann Neurol 73:199-209
Smyth, Matthew D; Rothman, Steven M (2011) Focal cooling devices for the surgical treatment of epilepsy. Neurosurg Clin N Am 22:533-46, vii
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Rothman, Steven M (2009) The therapeutic potential of focal cooling for neocortical epilepsy. Neurotherapeutics 6:251-7
Xu, Lin; Rensing, Nicholas; Yang, Xiao-Feng et al. (2008) Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents. J Clin Invest 118:272-80
Rothman, Steven M; Perry, Gavin; Yang, Xiao-Feng et al. (2007) Optical suppression of seizure-like activity with an LED. Epilepsy Res 74:201-9
Zeng, Ling-Hui; Xu, Lin; Rensing, Nicholas R et al. (2007) Kainate seizures cause acute dendritic injury and actin depolymerization in vivo. J Neurosci 27:11604-13
Yang, Xiao-Feng; Weisenfeld, Aryan; Rothman, Steven M (2007) Prolonged exposure to levetiracetam reveals a presynaptic effect on neurotransmission. Epilepsia 48:1861-9

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