Abstracts

RATIONALE: Focal neocortical seizures can be intractable to anticonvulsant therapy and difficult to surgically localize and resect. We have previously shown that rapid, focal cooling with a small Peltier device can abruptly terminate rodent neocortical seizures without damaging underlying cortex (Yang and Rothman, Ann. Neurol. 2001, 49: in press). We needed to expand our earlier results to identify the temperature decrement required for seizure control.
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 artificial CSF). We used monopolar EEG recording to verify that the site of seizure generation was within 2 mm of the injection site. When seizures were detected by bipolar EEG,we manually activated a Peltier device (3.5 mm x 7.0 mm) in direct contact with the pial surface. A copper rod connected to the Peltier device acted as both holder and heat sink. Temperature at the interface between the Peltier and pia was regulated by a feedback circuit.
RESULTS: When the temperature at the interface was 20[degree] or 22 [degree]C, seizures terminated in 5.6[plusminus]1.3 and 7.5[plusminus]2.0 seconds, respectively, compared to 76.2[plusminus]12.9 seconds in normothermic controls (n=5 animals in each group; p[lt]0.01). At 24[degree]C, seizure duration was variably affected (29.3[plusminus]34.2 sec), and at 26[degree]C there was no effect of cooling (76.9[plusminus]22.8 seconds). When the pial surface is maintained at 20[degree]C, there is a steep temperature gradient across the cortex, with temperature rising to 24.3[degree], 25.4[degree], and 31.3[degree] at 1, 2 and 4 mm below the cortical surface. The devices, therfore, only cool a restricted volume of cortex. Interestingly, when we monitor uncooled seizures, we detect a temperature increase of 0.1[degree]-0.2[degree]C, indicating that seizure activity has a small effect on brain temperature.
CONCLUSIONS: Our results suggest the pial surface temperature must be lowered below 22[degree]C to significantly alter the duration of neocortical seizures. This level of cooling, however, would not be expected to produce cortical damage. Peltier devices could be incorporated into currently available recording grids for neocortical mapping. When improved heat dissipation techniques are developed, Peltier devices might be permanently implanted and linked to seizure anticipation software for chronic seizure control.
Support: Supported by NIH P01 NS14834 and a grant from CURE