Abstracts

Rationale: Local delivery of anti-epileptic substances may be an alternative treatment option for patients with refractory epilepsy. Adenosine has proven anti-epileptic effects, but can not be given systemically because of side effects. We evaluated the efficacy of continuous local delivery of adenosine in the hippocampi in rats with spontaneous seizures. Methods: Male Sprague-Dawley rats (n=7, 175-200g) were injected intraperitoneally with kainic acid to evoke a status epilepticus. Following a latent period, spontaneous seizures occurred. A cannula-electrode complex was implanted bilaterally in the hippocampi, which was connected with osmotic minipumps in order to continuously infuse a solution in the hippocampi at a flow rate of 0.23 µl/hr. During the first 2 weeks (baseline period), the rats received continuous saline infusion, followed by 2 weeks of local delivery of adenosine (6µg/µl in saline). During both periods video-EEG monitoring was performed to evaluate seizure frequency and duration. Results: In 6 out of 7 rats, daily seizure frequency during adenosine treatment was reduced compared to seizure frequency during baseline period (respectively 21 ± 8 seizures/day and 30 ± 7 seizures/day; p <0.05). No significant effect of local adenosine delivery on seizure duration could be demonstrated. The mean seizure duration was 61 ± 4 sec during the baseline period and 59 ± 9 sec during adenosine treatment. Conclusions: Continuous delivery of adenosine in the hippocampi of the intraperitoneal kainic acid model can lead to a significant reduction of seizure frequency. (A. Van Dycke is supported by a grant (‘aspirant’) from the FWO-Flanders)