title: Cooling of the epileptic focus suppresses seizures with minimal influence on neurologic functions.
abstract: OBJECTIVE
  Focal brain cooling is effective for suppression of epileptic seizures, but it is unclear if seizures can be suppressed without a substantial influence on normal neurologic function. To address the issue, a thermoelectrically driven cooling system was developed and applied in free-moving rat models of focal seizure and epilepsy.
  
  
  METHODS
  Focal seizures limited to the unilateral forelimb were induced by local application of a penicillin G solution or cobalt powder to the unilateral sensorimotor cortex. A proportional integration and differentiation (PID)-controlled, thermoelectrically driven cooling device (weight of 11 g) and bipolar electrodes were chronically implanted on the eloquent area (on the epileptic focus) and the effects of cooling (20, 15, and 10°C) on electrocorticography, seizure frequency, and neurologic changes were investigated.
  
  
  RESULTS
  Cooling was associated with a distinct reduction of the epileptic discharges. In both models, cooling of epileptic foci significantly improved both seizure frequency and neurologic functions from 20°C down to 15°C. Cooling to 10°C also suppressed seizures, but with no further improvement in neurologic function. Subsequent investigation of sensorimotor function revealed significant deterioration in foot-fault tests and the receptive field size at 15°C.
  
  
  CONCLUSIONS
  Despite the beneficial effects in ictal rats, sensorimotor functions deteriorated at 15°C, thereby suggesting a lower limit for the therapeutic temperature. These results provide important evidence of a therapeutic effect of temperatures from 20 to 15°C using an implantable, hypothermal device for focal epilepsy.
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan. masfujii@yamaguchi-u.ac.jp
authors.forename: Masami
authors.initials: M
authors.lastname: Fujii
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Nomura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Maruta
authors.forename: Yeting
authors.initials: Y
authors.lastname: He
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Koizumi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shirao
authors.forename: Yuji
authors.initials: Y
authors.lastname: Owada
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kunitsugu
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Yamakawa
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Tokiwa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishizuka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamakawa
authors.forename: Michiyasu
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000502:physiology; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology; D003035:Cobalt / Q000633:toxicity; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004582:Electronics, Medical / Q000295:instrumentation / Q000379:methods; D004828:Epilepsies, Partial / Q000503:physiopathology* / Q000628:therapy*; D004827:Epilepsy / Q000503:physiopathology* / Q000628:therapy*; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology*; D010400:Penicillin G / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003292:Convulsants; D003035:Cobalt; D010400:Penicillin G