OBJECTIVE: To evaluate which presentation indices, demographics, and clinical information predict 12-month outcome in poor-grade aneurysmal subarachnoid hemorrhage (SAH), and to provide a preoperative index of prognosis. METHODS: Data were obtained on all patients with poor-grade (Hunt and Hess Grades IV and V) aneurysmal SAH from a prospectively maintained SAH database and health outcomes project. Demographics, medical history, presenting clinical condition, and health outcomes were analyzed. Survival analysis was performed and Kaplan-Meier curves were generated. Multivariable logistic regression analysis was used to identify significant predictors of poor outcome at 12 months after hemorrhage, as measured by the modified Rankin disability scale. RESULTS: Survival curves for open surgery and endovascular treatment did not differ significantly. Overall, 40% of the 98 definitively treated patients had a favorable outcome at 12 months. Multivariable analysis identified patient age older than 65 years (P < 0.001), hyperglycemia (P < 0.03), worst preoperative Hunt and Hess Grade V (P < 0.0001), and aneurysm size of at least 13 mm (P < 0.002) as significant predictors of poor outcome. These variables were weighted and used to compute a poor-grade aneurysmal SAH Prognosis Score (hereafter, Prognosis Score) for each patient. A Prognosis Score of 0 was associated with a 90% favorable outcome; Prognosis Score of 1 with 83%; Prognosis Score of 2 with 43%; Prognosis Score of 3 with 8%; Prognosis Score of 4 with 7%; and a Prognosis Score of 5 with 0%. CONCLUSION: Outcome in poor-grade aneurysmal SAH is strongly predicted by patient age, worst preoperative Hunt and Hess clinical grade, and aneurysm size. Hyperglycemia on admission after poor-grade aneurysmal SAH increases the likelihood of poor outcome, and is a potentially modifiable risk factor. The Prognosis Score is a useful tool for preoperatively assessing the likelihood of a favorable outcome for poor-grade aneurysmal SAH patients.

Glioblastoma Multiforme (GBM) is the most common and lethal form of primary brain tumor in adults. Following standard treatment of surgery, radiation and chemotherapy, patients are expected to survive 12–14 months. Theorized cause of disease recurrence in these patients is tumor cell repopulation through the proliferation of treatment-resistant cancer stem cells. Current research has revealed curcumin, the principal ingredient in turmeric, can modulate multiple signaling pathways important for cancer stem cell self-renewal and survival. Following resection, tumor specimens were dissociated and glioblastoma stem cells (GSCs) were propagated in neurosphere media and characterized via immunocytochemistry. Cell viability was determined with MTS assay. GSC proliferation, sphere forming and colony forming assays were conducted through standard counting methods. Reactive oxygen species (ROS) production was examined using the fluorescent molecular probe CM-H2DCFA. Effects on cell signaling pathways were elucidated by western blot. We evaluate the effects of curcumin on patient-derived GSC lines. We demonstrate a curcumin-induced dose-dependent decrease in GSC viability with an approximate IC50 of 25 μM. Treatment with sub-toxic levels (2.5 μM) of curcumin significantly decreased GSC proliferation, sphere forming ability and colony forming potential. Curcumin induced ROS, promoted MAPK pathway activation, downregulated STAT3 activity and IAP family members. Inhibition of ROS with the antioxidant N-acetylcysteine reversed these effects indicating a ROS dependent mechanism. Discoveries made in this investigation may lead to a non-toxic intervention designed to prevent recurrence in glioblastoma by targeting glioblastoma stem cells.

Background and Purpose— ε-Aminocaproic acid (EACA) is an antifibrinolytic agent used to prevent rebleeding in aneurysmal subarachnoid hemorrhage. Although studies have found that a decrease in rebleeding with long-term antifibrinolytic therapy is offset by an increase in ischemic deficits, more recent studies have indicated that early, short-term therapy may be beneficial. Methods— We instituted a protocol for acute EACA administration starting at diagnosis and continued for a maximum duration of 72 hours after subarachnoid hemorrhage onset. We compared 73 patients treated with EACA with 175 non–EACA-treated patients. We sought to identify differences in the occurrence of rebleeding, side effects, and outcome. Results— Baseline characteristics were similar in the 2 groups. There was a significant decrease in rebleeding in EACA-treated patients (2.7%) versus non-EACA patients (11.4%). There was no difference in ischemic complications between cohorts. There was a significant 8-fold increase in deep venous thrombosis in the EACA group but no increase in pulmonary embolism. There was a nonsignificant 76% reduction in mortality attributable to rebleeding, a 13.3% increase in favorable outcome in good-grade EACA-treated patients, and a 6.8% increase in poor-grade patients. Conclusions— When used acutely, short-term EACA treatment resulted in decreased rebleeding without an increase in serious side effects in our selected group of patients. Randomized placebo-controlled trials are needed to determine whether acute antifibrinolytic therapy should be accepted as the standard of care in all patients.

Object: The object of this study was to report the clinical features, surgical treatment, and long-term outcomes in adults with moyamoya phenomenon treated at a single institution in the US. Methods: Forty-three adult patients with moyamoya disease (mean age 40 ± 11 years [SD], range 18–69 years) were treated with encephaloduroarteriosynangiosis (EDAS). Neurologists examined patients pre- and postoperatively. Follow-up was obtained in person or by structured telephone interview (median 41 months, range 4–126 months). The following outcomes were collected: transient ischemic attack (TIA), infarction, graft collateralization, change in cerebral perfusion, and functional level according to the modified Rankin scale (mRS). Kaplan-Meier estimates of infarction risk were calculated for comparison of surgically treated and contralateral hemispheres. Results: The majority of patients were women (65%), were Caucasian (65%), presented with ischemic symptoms (98%), and had bilateral disease (86%). Nineteen patients underwent unilateral and 24 patients bilateral EDAS (67 treated hemispheres). Collateral vessels developed in 50 (98%) of 52 hemispheres for which imaging was available and there was evidence of increased perfusion on SPECT scans in 41 (82%) of the 50 hemispheres evaluated. Periprocedural infarction (< 48 hours) occurred in 3% of the hemispheres treated. In the follow-up period patients experienced 10 TIAs, 6 infarctions, and 1 intracranial hemorrhage. Although the hemisphere selected for surgery was based upon patients' symptoms and severity of pathology, the 5-year infarction-free survival rate was 94% in the surgically treated hemispheres versus < 36% in the untreated hemispheres (p = 0.007). After controlling for age and sex, infarction was 89% less likely to occur in the surgically treated hemispheres than in the contralateral hemispheres (hazard ratio 0.11, 95% CI 0.02–0.56). Thirty-eight (88%) of 43 patients had preserved or improved mRS scores, relative to baseline status. Conclusions: In this mixed-race population of North American patients, indirect bypass promoted adequate pial collateral development and increased perfusion in the majority of adult patients with moyamoya disease. Patients had low rates of postoperative TIAs, infarction, and hemorrhage, and the majority of patients had preserved or improved functional status.