Anticonvulsant properties of hypothermia in experimental status epilepticus.
Status epilepticus in patients often does not respond to first-line anticonvulsants, and subsequent treatment escalation with continuous intravenous anesthetics may be associated with significant side-effects. Therefore, alternative treatment regimens are urgently needed. Hypothermia has been shown to reduce excitatory transmission and may thus serve as an interesting adjunct in the management of status epilepticus. In the current experiments, three treatment groups were compared. Animals with self-sustaining status epilepticus were treated with external cooling for 3 h, with low-dose diazepam, or with a combination of both. The effect of these regimens on epileptic activity was compared with untreated controls. Animals that underwent cooling were rewarmed, and all animals were monitored for 5 h to assess occurrence and severity of motor seizures and frequency and amplitude of spontaneous epileptic discharges. Cooling alone significantly reduced number and severity of motor seizures but did not alter epileptic discharges. Cooling in addition to low-dose diazepam significantly diminished amplitudes and frequencies of epileptic discharges, while diazepam alone had only a minor reducing effect on discharge amplitudes. However, at later stages of status epilepticus, diazepam significantly reduced motor seizures. Following rewarming, the discharge frequency tended to increase again, suggesting partial reversibility. The current experiments show that in status epilepticus hypothermia exhibits anticonvulsant effects which are most pronounced if co-administered with low-dose diazepam. The results still require confirmation in other animal models and also clinical studies are urgently needed. However, our data indicate that cooling could well become a future adjunct in the treatment of status epilepticus in patients.
Schmitt
F C
FC
Department of Neurology, Charité-Universitätsmedizin Berlin, Schumannstr. 20/21, 10117 Berlin, Germany.
Buchheim
K
K
Meierkord
H
H
Holtkamp
M
M
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D001831:Body Temperature / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D003080:Cold Temperature; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007036:Hypothermia, Induced / Q000379:methods* / Q000592:standards / Q000639:trends; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D013226:Status Epilepticus / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000927:Anticonvulsants; D003975:Diazepam