PURPOSE: When epileptogenic regions encroach on eloquent brain, surgery may incur unacceptable deficits. Reversible cooling may control seizures while preserving function. We describe the effects of cooling kindled seizures in awake, freely moving rats. METHODS: We kindled rats after placement of a bipolar electrode and a copper cooling coil in dorsal hippocampus. Fully kindled animals (three consecutive grade 5 seizures) were cooled to one of two target temperatures (24 degrees or 27 degrees C) for 3 min preceding a kindling stimulation and 2 minutes after. We compared seizure score (0-5) and afterdischarge duration (ADD) with and without cooling. Target temperatures were confirmed in identical animals by using a needle thermocouple advanced to the kindling target while circulating coolant. RESULTS: Circulation of 16 degrees C and 8 degrees C coolant reliably achieved transcortical cooling of the hippocampal target to 27.0 +/- 1.2 degrees C and 23.8 +/- 2.0 degrees C, respectively, by 180 s. Cooling with 16 degrees C coolant (n = 5) significantly reduced seizure scores from 5 to 2.57 +/- 1.56, and ADD from 142 +/- 94.5 s to 45.7 +/- 20.5 s. Cooling with 8 degrees C coolant (n = 5) reduced seizure scores from 5 to 2.0 +/- 0.42, and ADD from 132.3 +/- 29.6 s to 55.5 +/- 25.9 s. In 33.3% of all cooled stimulations, grade 0 seizures resulted; grade 5 seizures recurred during subsequent stimulations when cooling was withheld. CONCLUSIONS: Fully kindled, tonic-clonic seizures can be suppressed or aborted with periictal cooling of the kindling target. Anticonvulsant activity occurred at temperatures well above those known to result in tissue injury or inhibition of normal neurologic function. These findings have important implications for the potential use of implantable cooling devices in humans with refractory epilepsies in or near eloquent cortex or dominant hippocampal formations.
PURPOSE: When epileptogenic regions encroach on eloquent brain, surgery may incur unacceptable deficits. Reversible cooling may control seizures while preserving function. We describe the effects of cooling kindled seizures in awake, freely moving rats. METHODS: We kindled rats after placement of a bipolar electrode and a copper cooling coil in dorsal hippocampus. Fully kindled animals (three consecutive grade 5 seizures) were cooled to one of two target temperatures (24 degrees or 27 degrees C) for 3 min preceding a kindling stimulation and 2 minutes after. We compared seizure score (0-5) and afterdischarge duration (ADD) with and without cooling. Target temperatures were confirmed in identical animals by using a needle thermocouple advanced to the kindling target while circulating coolant. RESULTS: Circulation of 16 degrees C and 8 degrees C coolant reliably achieved transcortical cooling of the hippocampal target to 27.0 +/- 1.2 degrees C and 23.8 +/- 2.0 degrees C, respectively, by 180 s. Cooling with 16 degrees C coolant (n = 5) significantly reduced seizure scores from 5 to 2.57 +/- 1.56, and ADD from 142 +/- 94.5 s to 45.7 +/- 20.5 s. Cooling with 8 degrees C coolant (n = 5) reduced seizure scores from 5 to 2.0 +/- 0.42, and ADD from 132.3 +/- 29.6 s to 55.5 +/- 25.9 s. In 33.3% of all cooled stimulations, grade 0 seizures resulted; grade 5 seizures recurred during subsequent stimulations when cooling was withheld. CONCLUSIONS: Fully kindled, tonic-clonic seizures can be suppressed or aborted with periictal cooling of the kindling target. Anticonvulsant activity occurred at temperatures well above those known to result in tissue injury or inhibition of normal neurologic function. These findings have important implications for the potential use of implantable cooling devices in humans with refractory epilepsies in or near eloquent cortex or dominant hippocampal formations.
Authors: Matthew D Smyth; Rowland H Han; Chester K Yarbrough; Edward E Patterson; Xiao-Feng Yang; John W Miller; Steven M Rothman; Raimondo D'Ambrosio Journal: Ther Hypothermia Temp Manag Date: 2015-04-22 Impact factor: 1.286
Authors: Raimondo D'Ambrosio; Clifford L Eastman; Felix Darvas; Jason S Fender; Derek R Verley; Federico M Farin; Hui-Wen Wilkerson; Nancy R Temkin; John W Miller; Jeffrey Ojemann; Steven M Rothman; Matthew D Smyth Journal: Ann Neurol Date: 2012-12-07 Impact factor: 10.422