Abstracts

RATIONALE: Because we have previously shown that rapid, focal cooling with a small Peltier device can abruptly terminate neocortical seizures, we wished to investigate the possibility that focal cooling could attenuate or prevent seizures when applied [italic]prior[/italic] to seizure onset.
METHODS: Experiments were performed on halothane-anesthetized rats. Seizures were induced by a neocortical microinjection of the potassium channel blocker 4-aminopyridine (4-AP; 0.5 [mu]l of a 25 mM solution in ACSF). We placed two screw electrodes symmetrically over each hemisphere and separately recorded the electroencephalogram (EEG) between the two. Cortical cooling was accomplished with a Peltier device, which made direct contact with the pial surface and maintained a temperature of 20[degree]C at the interface between Peltier and cortex. We measured seizure duration, frequency, and power in a control (uncooled) group and two experimental groups: the intermittent cooling group was cooled for 30 sec every 2 minutes starting 15 minutes after 4-AP; the pre-cooling experimental group was cooled for 30 min prior to 4-AP injection using the same 30 second cooling cycle. Seizures were quantified in 30 min observation periods for 2 hours.
RESULTS: During the first 30 min observation period, seizures in the control group lasted 91.72 [plusminus] 33.09 sec; in the intermittent cooling group seizures were 36.97 [plusminus] 10.43 sec; and in the pre-cooled group seizures were 19.39 [plusminus] 2.09 sec. During the second 30 min observation period, seizure durations were 69.36 [plusminus] 21.68 sec, 23.92 [plusminus] 11.52 sec and 17.85 [plusminus] 1.63 sec in the control, intermittent cooling, and pre-cooling groups, respectively (N=5 animals in each group; p[lt]0.001). Seizure frequency in the three groups did not differ during the first thirty minutes after initial seizure onset. The seizure frequency significantly dropped to 4.6 [plusminus] 2.7 and 4.5 [plusminus] 4.95 in the intermittent cooling and pre-cooling groups in the second thirty minutes, but it stayed constant at 15.2 [plusminus] 4.32 in control group (p[lt]0.001). The ratio of seizure power to baseline power was significantly higher in control seizures, compared to seizures in either of the cooling groups (4.62 [plusminus] 2.36 at control, 1.78 [plusminus] 0.46 at intermittent cooling, and 0.91[plusminus] 0.17 at pre-cooling group, p[lt]0.001). While seizures persisted in the control group for the second hour of observation, no seizures were seen in the intermittent cooling and pre-cooling groups during this period. Histological examination of the cortex after cooling and pre-cooling has shown no evidence of neuronal injury.
CONCLUSIONS: These results demonstrate that focal cooling not only terminates neocortical seizures, but also has long-lasting antiepileptic effects. These results, achieved in a particularly severe model of acute, neocortical epilepsy, might be even more impressive in a model of focal epilpsy that more closely modeled the human condition. When improved heat-pipes and seizure prediction algorithms become more widely available, it may be possible to permanently implant Peltier devices to prevent clinical seizures in patients with refractory neocortical epilepsy.
[Supported by: This research was supported by a grant from Citizens United for Research in Epilepsy, Inc. (CURE), the Stein Fund for Pediatric Neurology Research, and NS14834 from the NIH.]