The influence of focal brain cooling on neurophysiopathology: validation for clinical application

Oku, Takayuki; Fujii, Masami; Tanaka, Nobuhiro; Imoto, Hirochika; Uchiyama, Joji; Oka, Fumiaki; Kunitsugu, Ichiro; Fujioka, Hikaru; Nomura, Sadahiro; Kajiwara, Koji; Fujisawa, Hironori; Kato, Shoichi; Saito, Takashi; Suzuki, Michiyasu

doi:10.3171/2009.1.jns08499

Cited by 35 publications

(34 citation statements)

References 45 publications

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“…Histopathologic analysis of FBC has already been conducted in animal models at 5°C . The concentration of extracellular glycerol was measured as an indicator of structural damage to neurons and glia, since glycerol is derived from glycophospholipids in the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, focal brain cooling (FBC) has been proposed as a method for treating refractory epilepsy, which in turn has promoted the development of implantable focal cooling devices . The effect of cooling on epilepsy has been demonstrated in various animal experiments; these report that epileptic discharges (EDs) can be terminated by FBC . However, the precise influence of cooling on the molecular basis of epilepsy needs to be explored to obtain the benefits and to understand the possible risks that may be linked to this form of treatment.…”

mentioning

confidence: 99%

“…[1][2][3][4] The effect of cooling on epilepsy has been demonstrated in various animal experiments; these report that epileptic discharges (EDs) can be terminated by FBC. 1,[4][5][6] However, the precise influence of cooling on the molecular basis of epilepsy needs to be explored to obtain the benefits and to understand the possible risks that may be linked to this form of treatment.…”

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confidence: 99%

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Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans

et al. 2014

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SUMMARYObjective: Recently, focal brain cooling (FBC) was proposed as a method for treating refractory epilepsy. However, the precise influence of cooling on the molecular basis of epilepsy has not been elucidated. Thus the aim of this study was to assess the effect of FBC on glutamate (Glu) concentration, cerebral blood flow (CBF), and glucose metabolism in patients with intractable epilepsy. Methods: Nine patients underwent FBC at 15°C for 30 min prior to cortical resection (n = 6) or hippocampectomy (n = 3). Measurement of metabolites and CBF, as well as electrocorticography (ECoG), was performed. Results: Epileptic discharge (ED), as observed by ECoG, disappeared in the cooling period and reappeared in the rewarming period. Glu concentrations were high during the precooling period and were reduced to 51.2% during the cooling period (p = 0.025). Glycerol levels showed a similar decrease (p = 0.028). Lactate concentration was high during the precooling period and was reduced during the cooling period (21.3% decrease; p = 0.005). Glucose and pyruvate levels were maintained throughout the procedure. Changes in CBF were parallel to those observed by ECoG. Significance: FBC reduced EDs and concentrations of Glu and glycerol. This demonstrates the neuroprotective effect of FBC. Our findings confirm that FBC is a reasonable and optimal treatment option for patients with intractable epilepsy.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans

et al. 2014

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“…A cooling device originally developed in our laboratory (Imoto et al., 2006; Oku et al., 2009; Fujioka et al., 2010) was used in the study. This device includes a cooling component and a heat‐processing component.…”

Section: Methodsmentioning

confidence: 99%

Cooling of the epileptic focus suppresses seizures with minimal influence on neurologic functions

et al. 2012

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SUMMARYPurpose: 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 freemoving 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. Key Findings: 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. Significance: 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.

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“…Therefore, we investigated the neuropathological consequences of focal cooling and changes in threshold temperature, which cause irreversible histological change in the neocortices of rats. 19) We concluded that focal cortical cooling at -59 C for 1 hour causes irreversible histological changes, which are coincident with the cryoinjury in the cooled cortex. However, focal brain cooling above 09 C for 1 hour did not cause motor dysfunction or histological damage (Fig.…”

Section: Influence Of Focal Cooling On Brain Tissuementioning

confidence: 99%

Application of Focal Cerebral Cooling for the Treatment of Intractable Epilepsy

Fujii

Fujioka

Oku

et al. 2010

Neurol. Med. Chir.(Tokyo)

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Epilepsy is usually treated with medication, but adequate seizure control is still not achieved in over 30% of epilepsy patients, even with the best available agents. Surgical treatment is also performed for such patients, but is not always successful. Focal cooling of the brain using a thermoelectric device has recently been evaluated as an alternative to epilepsy surgery. Brain cooling was first proposed approximately 50 years ago as an effective method for suppressing epileptic discharges (EDs). Recent studies indicate that focal cooling of the brain to a cortical surface temperature of 209 C to 259 C terminates EDs without inducing irreversible neurophysiological dysfunctions or neuronal damage in the brain tissue. Several mechanisms have been proposed for the antiepileptic effects of focal cooling, including reduction in neurotransmitter release, alternation of activation-inactivation kinetics in voltage-gated ion channels, and the slowing of catabolic processes. Developments in the implantable cooling device with closed-loop cooling systems for seizure detection and focal cooling have been promoted in the field of neuromodulation, but several aspects remain uncharacterized concerning the hardware. Recent advances in precision devices have enabled the optimization of the implantable local cooling system, which may become clinically applicable in the near future.

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The influence of focal brain cooling on neurophysiopathology: validation for clinical application

Cited by 35 publications

References 45 publications

Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans

Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans

Cooling of the epileptic focus suppresses seizures with minimal influence on neurologic functions

Application of Focal Cerebral Cooling for the Treatment of Intractable Epilepsy

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