Effects of stereotactic radiosurgery on an animal model of hippocampal epilepsy

OBJECTIVE: Stereotactic radiosurgery has been shown in small clinical serie s to reduce or abolish seizures in patients with lesion-related or idiopath ic epilepsy. The radiation dose necessary to eliminate epileptogenesis is u nknown, and the histological and metabolic effects of radiosurgery remain u ndefined. We hypothesized that in a vat model of kainic acid-induced hippoc ampal epilepsy, radiosurgery could provide a significant reduction in seizu re frequency while limiting biochemical and structural histological damage to the brain. METHODS: Kainic acid (8 g) was injected into the rat hippocampus using ster eotactic targeting. Focal seizures so generated were identified with scalp and depth electroencephalography (EEG). Epileptic rats were randomized to a control group (n = 20) and to radiosurgery groups in which maximum doses o f 20, 40, 60, or 100 Gy (8-9 animals per group) were administered. Over a 4 2-day period, seizure frequency was determined by direct observation for 8 hours per week. Scalp EEG was performed weekly in all animals. Magnetic res onance imaging (MRI) studies (T1- and T2-weighted water-proton and quantita tive sodium images) were obtained on Days 7, 21, and 42. RESULTS: As compared with the control group, treated animals showed signifi cant reductions in the number of seizures during each successive week after 20-Gy radiosurgery (P = 0.01-0.002). When we combined the number of seizur es observed in the latter half of the study (Weeks 4-6), we found a signifi cant reduction in seizures after 20-Gy (P = 0.007), 40-Gy (P = 0.03), 60-Gy (P = 0.03), and 100-Gy (P = 0.03) radiosurgery as compared with control an imals. Increasing doses of radiosurgery correlated with higher percentages of rats that became seizure-free by EEC criteria. MRI-determined total sodi um concentration in the injected hippocampus was 49.8 +/- 3 mmol/L, compare d with 42.8 mmol/L on the contralateral side (within normal limits). This s ignificant increase in sodium concentration was present in control rats (be cause of the kainic acid) and did not change with increasing radiosurgery d ose. No parenchymal effects from radiosurgery were identified after 20, 40, and 60 Gy, and only two rats had necrosis at 100 Gy. All animals showed hi ppocampal injury from kainic acid by proton MRI and histological examinatio n. CONCLUSION: In this rat hippocampal epilepsy model, stereotactic radiosurge ry was followed by a significant dose-dependent reduction in the frequency of observed and EEG-defined seizures. These effects were not accompanied by increased radiation-induced structural or metabolic brain injury as assess ed by proton and sodium MRI or histological examination. The role of radios urgery as a new, nondestructive surgical therapy for idiopathic epilepsy wa rrants further investigation.