Abstracts

Different procedures of deep brain and cortical stimulation have been proposed in the treatment of drug resistant epilepsy, including electrical stimulation of the epileptogenic zone proper, such as the hippocampus, without consensus regarding their respective efficacy. One of the major limitations in designing such study and defining the optimal stimulation parameters is the paucity of experimental data. The aim of this study was to evaluate various parameters which could influence the anti-epileptic efficacy of brief electrical stimulation applied to the limbic structures of kindled rats. Forty Sprague-Dawley rats were used in this study.
Experiment 1: Ten rats received a fully complete stage 5 hippocampal kindling. They then underwent 60 additional stimulation-induced seizures at 3 days interval, during which a second brief electrical pulse (50 ms duration, intensity twice that of after-discharge threshold) was applied 5 seconds after the end of the first stimulation. In each animal, this pulse was either applied to the hippocampus, to the entorhinal cortex, or was replaced by sham stimulation.
Experiment 2: Thirty rats were fully kindled in the amygdala, and then also underwent additional stimulation-induced seizures during which a brief electrical stimulation was applied in the same amygdala 5 seconds later. Animals were distributed in 5 groups: G1: stimulation with a single pulse of 50 ms, G2: stimulation with a single pulse of 130 ms, G3: 50 Hz stimulation during 1 second, G4: 130 Hz stimulation during 1 second, G5: sham stimulation.
The duration of after-discharges was used as the endpoint measure in both experiments. Experiment 1: A significant reduction of hippocampal after-discharges duration was associated with the delivery of brief electrical pulse in the hippocampus (96 [plusmn] 22 sec, p[lt]0.01), but not in the entorhinal cortex (103 [plusmn] 27 sec ), as compared to controls (113 [plusmn] 28 sec).
Experiment 2: Two types of brief electrical stimulation were associated with a significant reduction of the duration of amygdala after-discharge, i.e. single pulse of 130 ms duration (101[plusmn] 8 sec, p[lt]0.0001), and 50 Hz stimulation of 1 second duration (89 [plusmn] 14 sec,p[lt]0.00001) as compared to sham stimulation (114 [plusmn] 11sec ). In the kindling model of epilepsy, brief electrical stimulations delivered after the onset of stimulation-induced after-discharge can reduce the duration of the latter. This proved to be more effective when applied to the site of seizure onset than to a connected distant site, with 50 Hz rather 130 Hz 1 second duration train, and with 130 ms rather than 50 ms duration single pulse. (Supported by Universite Claude Bernard Lyon 1)