Faculty Bibliography

OBJECTIVE: Stereotactic radiosurgery has been shown in small clinical series to reduce or abolish seizures in patients with lesion-related or idiopathic epilepsy. The radiation dose necessary to eliminate epileptogenesis is unknown, and the histological and metabolic effects of radiosurgery remain undefined. We hypothesized that in a rat model of kainic acid-induced hippocampal epilepsy, radiosurgery could provide a significant reduction in seizure frequency while limiting biochemical and structural histological damage to the brain. METHODS: Kainic acid (8 g) was injected into the rat hippocampus using stereotactic 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 of 20, 40, 60, or 100 Gy (8-9 animals per group) were administered. Over a 42-day period, seizure frequency was determined by direct observation for 8 hours per week. Scalp EEG was performed weekly in all animals. Magnetic resonance imaging (MRI) studies (T1- and T2-weighted water-proton and quantitative sodium images) were obtained on Days 7, 21, and 42. RESULTS: As compared with the control group, treated animals showed significant 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 seizures observed in the latter half of the study (Weeks 4-6), we found a significant 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 animals. Increasing doses of radiosurgery correlated with higher percentages of rats that became seizure-free by EEG criteria. MRI-determined total sodium concentration in the injected hippocampus was 49.8+/-3 mmol/L, compared with 42.8 mmol/L on the contralateral side (within normal limits). This significant increase in sodium concentration was present in control rats (because of the kainic acid) and did not change with increasing radiosurgery dose. 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 hippocampal injury from kainic acid by proton MRI and histological examination. CONCLUSION: In this rat hippocampal epilepsy model, stereotactic radiosurgery 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 assessed by proton and sodium MRI or histological examination. The role of radiosurgery as a new, nondestructive surgical therapy for idiopathic epilepsy warrants further investigation.

Image guidance promotes safe and effective surgical management of a wide array of intracranial diseases. To better define the historical importance of image guidance and to assess the relative contribution of each imaging modality to the safety and efficacy of selected procedures, we reviewed our 20-year experience at a single institution. A retrospective review of our departmental surgical records was performed to identify patients who underwent brain surgery with image guidance between January 1979 and January 1999. We identified the use of intraoperative fluoroscopy, endoscopy, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and angiography in 7,388 patients. During this 20-year interval, advances in neuroimaging were translated into the operating room environment. Fluoroscopic guidance received the highest overall rating and was deemed critical for the performance of successful transsphenoidal surgery (n = 436) and effective percutaneous trigeminal neuralgia management (n = 1,121). Ultrasound and angiography both had limited roles; the latter was important to successful outcomes in 64 patients undergoing aneurysm management (n = 64) and arteriovenous malformation Gamma Knife radiosurgery (n = 786). Endoscopy also had a small role but had limited cost. Beginning in 1982, a dedicated operating room CT scanner was used during both morphologic and functional stereotactic surgery (n = 1,749). After 1986, MRI was used increasingly in the management of selected functional and tumor cases (n = 337); despite great versatility for patients undergoing Gamma Knife radiosurgery, the costs were relatively high. Frameless neuronavigation (n = 263) had excellent versatility and was relatively low in cost. During the last 20 years, image guidance techniques have facilitated minimally invasive brain surgery at our institution. The relative merits of all these imaging tools depended mostly on their versatility and relative costs. Major centers currently contemplating the incorporation of image guidance into routine brain surgery need not reproduce our own learning curve.

OBJECTIVE: To assess the effectiveness of stereotactic radiosurgery in achieving tumor control and improving survival in patients with hemangioblastoma, we evaluated results from patients who were managed at the University of Pittsburgh and the Mayo Clinic. PATIENTS AND METHODS: Twenty-seven patients with 29 hemangioblastomas had stereotactic radiosurgery over a 10 year interval. The mean patient age was 32 years (range, 14-75 years). The tumor volumes varied from 0.36 to 27 ml (mean, 3.2 ml), and the mean tumor margin dose was 16 Gy (range, 11.7-20). Clinical and neuroimaging follow-up was obtained for all patients between 0.5 and 9 years (mean, 4 years) after radiosurgery. RESULTS: At this assessment, 21 patients (79%) were alive and six (21%) had died. The median survival after radiosurgery was 6.5 years (actuarial 5 year survival = 75.1 +/- 11.5%). The median survival from the initial diagnosis was 15 years. Twenty two of 29 evaluable tumors were controlled locally. The two-year actuarial control rate was 84.5 +/- 7.1% and at five years, 75.2 +/- 8.9%. Multivariate testing of factors affecting good outcome indicated that smaller tumor volume and higher radiosurgical dose (> 18 Gy) were significant. CONCLUSION: For small to moderate size hemangioblastomas, multiple or recurrent tumors, and for patients who are not surgical candidates, radiosurgery is a safe and effective option to control disease and improve survival.