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Summary: Purpose: Focal cerebral cooling has been shown to reduce epileptiform activity in animals. There are, however, few reports of this phenomenon in humans.
Methods: Electrocorticography was performed before resection of a right frontal tumor in a patient with partial seizures. Cold saline was applied to the interictal spike focus, and its effect on the epileptiform discharges was observed.
Results: Application of cold saline to the spike focus resulted in a transient, complete cessation of spiking. This effect was reproduced with a second application of cold saline. The motor threshold for electrical stimulation remained unchanged during the application of saline.
Conclusions: In this patient with tumor-related epilepsy, focal cooling of the cortex reproducibly abolished interictal epileptiform discharges without changing the motor threshold to electrical stimulation.
Cooling has been shown to deactivate the central nervous system reversibly (1,2). In addition, several in vivo and in vitro studies have demonstrated a reduction of epileptiform activity in models of epilepsy after gradual cooling (3–6). The mechanism by which this is achieved is not clearly understood, but there is evidence of interference with synaptic transmission and voltage-gated ion channels (7–9). There is some evidence that the antiseizure effect persists beyond acute abortion of seizure activity, with demonstration of a lasting effect on cortical irritability after two periods of cooling (5). There are, however, few accounts of the response of epileptiform activity in humans to cooling (10–12).
In 1969 the successful treatment of five of six patients with medically refractory, focal status epilepticus by using general hypothermia was reported (10). Similar accounts followed (11). More recently, there was a report of rapid termination of intraoperative stimulation-induced seizures and afterdischarges with the application of cold Ringer solution (12). We report the first evidence that focal cortical cooling by application of cold saline can abolish spontaneous epileptiform activity while maintaining intact cortical motor function.
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We report the first observation of reversible termination of spontaneous epileptiform activity in humans with focal application of cold saline. Cooling seemed to be effective without causing complete dysfunction of the involved cortex, as demonstrated by preservation of motor responses. Although the saline was cooled to 4°C, the cortical temperature was probably higher, given the observation that cooling to this temperature typically suppresses cortical function (2). Although the epileptiform activity suppressed by cooling was interictal, these findings suggest that focal cooling may be useful in treating human epilepsy. Animal investigation has suggested that focal cooling devices could be activated to abort evoked seizures (5). An implantable cooling device activated by a seizure-detection or -anticipation algorithm (13,14) might be a future alternative to resective surgery in humans, especially in patients with seizures arising from eloquent cortex. Additionally, cephalic cooling devices (15) may be developed to play a role in the management of medically refractory status epilepticus, likely with less chance of morbidity than with generalized hypothermia.