Abstracts

Rationale: Resection of epileptogenic tissue is a standard method in the surgical treatment of epilepsy. However, respective surgery is not recommended when the epileptogenic lesion overlaps functionally eloquent area. For such cases, non-resective surgical treatments, such as multiple subpial transection or vagal nerve stimulation, are considered although its efficacy is fairly inferior to respective surgery. Thus, a new method for non-resective control of epileptic lesion is highly awaited. Convection-enhanced delivery (CED) is a method of delivering drugs from thin catheter tip directly into brain parenchyma with slow infusion rate. This method can achieve larger drug distribution volume and less damage than bolus injection. CED is already in clinical use for treatment of malignant brain tumors. Levetiracetam (LEV) is characterized by its hydrophilic character which is suitable for long-lasting distribution in the interstitial space of brain. In this study, we evaluated the safety and efficacy of LEV-CED for rat epilepsy model. Methods: Hippocampal epilepsy model was prepared by injecting 50ng tetanus toxin into the right ventral hippocampus of Wister rat (n=5). After the development of spontaneous seizures, LEV was delivered by CED (concentration: 100?M, injection rate: 0.5?l/min, total injection volume: 5?l) to the epileptic hippocampus under the anesthesia with ketamine and xylazine. Local field potentials were simultaneously recorded from depth electrode inserted to the hippocampus. The average number of spikes in 10 minutes were statistically compared between pre- and post-CED. Toxicity of LEV-CED was examined histologically for various concentrations (32, 100, 320, 1000?M) using normal Wister rat (n=3 for each group). Results: The average number of spikes decreased after LEV-CED with statistical significance (Figure, p<0.001). No tissue damage was observed histologically in any group. Conclusions: LEV-CED has significant suppressive effect to epileptic discharges in rat tetanus toxin model and no histological damage was observed in any concentrations tested. CED can be a candidate of new method for non-resective surgical treatment of intractable epilepsy.