Case Reports Focal Cooling Suppresses Spontaneous Epileptiform Activity without Changing the Cortical Motor Threshold *Kameel M. Karkar, *Paul A. Garcia, *Lisa M. Bateman, †Matthew D. Smyth, †Nicholas M. Barbaro, and †Mitchel Berger Departments of *Neurology and †Neurological Surgery, University of California, San Francisco, San Francisco, California, U.S.A. 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 resec- tion 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, fo- cal cooling of the cortex reproducibly abolished interictal epi- leptiform discharges without changing the motor threshold to electrical stimulation. Key Words: Cerebral cooling— Epileptiform—Motor threshold. Cooling has been shown to deactivate the central ner- vous 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 inter- ference with synaptic transmission and voltage-gated ion channels (7–9). There is some evidence that the antisei- zure effect persists beyond acute abortion of seizure ac- tivity, 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 us- ing general hypothermia was reported (10). Similar ac- counts 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. CASE REPORT History A 41 year-old man was in good health until 6 years before surgery, when he had a focal motor seizure in- volving his left arm that progressed to a secondarily gen- eralized tonic–clonic seizure. Magnetic resonance imaging (MRI) revealed a right frontal mass, later deter- mined on biopsy to be a grade II oligoastrocytoma. The patient subsequently underwent resection of the tumor, followed by external beam radiation treatment. He con- tinued to have frequent brief focal motor seizures involv- ing the left arm and leg that proved to be medically intractable. Three months before surgery, a MRI showed no progression of the residual tumor in the right poste- rior–superior frontal lobe. Nevertheless, because of the intractable seizures, surgery was performed to remove the tumor and to resect adjacent epileptogenic tissue. Operating room Electrodes were placed on the cortical surface in four rows of four, as shown in Fig. 1. Recording from these electrodes revealed a back- Accepted March 30, 2002. Address correspondence and reprint requests to Dr. K.M. Karkar at Department of Neurology, University of California at San Francisco, San Francisco, CA, U.S.A. E-mail: karkark@itsa.ucsf.edu Epilepsia, 43(8):932–935, 2002 Blackwell Publishing, Inc. © International League Against Epilepsy 932