Abstracts

Rationale: We performed tissue immunostaining for iron, oxidant stress and inflammatory mediators using tissues around the cavernous angioma removed during epileptogenic focal excision to further elucidate the mechanism of epilepsy pathogenesis in the tissues around the cavernous angioma. Methods: We examined the cavernous angioma and the surrounding brain tissues of eight patients(male 4: female 4, mean 33.1yo, temporal 7,frontal 1) who underwent epilepsy surgery at the Neurosurgery Department of Juntendo University. After identifying the epileptogenic focus based on the preoperative EEG findings, the focus of the angioma was resected including the brain cortex in which the focal epileptic discharge was observed on intracranial ECoG. The specimen was fixed in formalin, and iron staining was performed together with immune-histo-staining for MAP-2, GFAP and CD68 as markers for neurons, astrocytes and microglia, respectively. Immunostaining was performed using TLR4, HMGB1 and IL-1β for inflammatory mediators, and 4-HNE as an oxidation stress marker. Results: In the vicinity of the cavernoma, we identified some grid electrode locations with intense high frequency band (80-150Hz) activity. We included those locations in the resection specimen. In all patients who underwent focal resection, no postoperative symptomatic epilepsy was noted. When iron staining was performed for the obtained tissues around the cavernous angioma, four patients showed less iron deposition in the tissue around the angioma, while the other four patients showed iron diffusing throughout the tissue. The immunoreaction for oxidant stress was confirmed in many sites surrounded by iron, as well as in sites with no iron. In the samples in which many iron depositions were confirmed in the tissues, the amounts of reactive astrocytes and microglia, which phagocytize iron, were increased, as indicated by the expression of HMGB1 and TLR4. Furthermore, there were neurons showing HMGB1 and TLR4 expression in the cells of the brain cortex located far from the angioma. Throughout the brain cortex, IL-1β expression was confirmed. However, even in the tissues with unclear iron diffusion, HMGB1 and TLR4-positive astrocytes, microglia and neurons were confirmed. Conclusions: In the sites around the cavernous angioma, in which spikes were identified based on ECoG and high frequency firing, oxidant stress and inflammatory mediators were confirmed throughout the brain tissue samples, suggesting a relationship with epilepsy pathogenesis. In addition, the appropriate range of focal resection by sufficient electrophysiological evaluation should be determined for surgical treatment of the cavernous angioma in patients with epilepsy.