(SAH). Data challenge vasospasm as the sole cause of ischemia and suggest other factors, such as dysfunctional cerebral autoregulation. We tested the hypothesis that early autoregulatory failure, detected using near-infrared spectroscopy, TOxa index, and transcranial Doppler based, Sxa index, can predict DCI. We analyzed the relationship between indices and the transient hyperemic response test (THRT) which uses a blood pressure stimulus. METHODS: In this prospective observational study we enrolled consecutive patients within ,5 days of onset from aneurysmal SAH. The primary end-point was occurrence of DCI at 21 days post-ictus. The predictive value of autoregulatory disturbances in the first 5 days was assessed using Cox proportional hazards and multivariate models. The benefit of using multiple indices was analyzed. RESULTS: 98 patients were included. Cox analysis demonstrated increased odds of DCI with early autoregulation failure (Odds Ratio (OR): 7.46, 95%CI: 3.03-18.40 and OR: 4.52, 95%CI: 1.84-11.07 for Sxa and TOxa respectively) but not vasospasm (OR: 1.36, 95%CI: 0.56- 3.33). Sxa and TOxa remained independent predictors of DCI in multivariate analysis (OR: 12.66, 95%CI: 2.97-54.07 and OR: 5.34, 95%CI: 1.25-22.84 for Sxa and TOxa respectively). Sxa and TOxa showed good accuracy in predicting impaired autoregulation evidenced by a negative THRT (area under the curve (AUC): 0.788, 95% CI: 0.723 to 0.854 and AUC: 0.827, 95% CI: 0.769 to 0.885, respectively). 100% specificity was seen for combined monitoring, with 13/13 patients with impaired autoregulation in all 3 methods developing DCI. CONCLUSION: Disturbed autoregulation in the first 5 days post- SAH predicts DCI. Although colinearities exist between the assessed methods, multimodal monitoring of cerebral autoregulation can aid in predicting DCI. 190 Critical Role of TNF-a in Cerebral Aneurysm Formation and Rupture Robert M. Starke, MD, MSc; Nohra Chalouhi; Muhammad S. Ali, MD; Pascal Jabbour, MD; Stavropoula I. Tjoumakaris, MD; L. Fernando Gonzalez, MD; Robert H. Rosenwasser, MD, FACS, FAHA; Gary Owens, PhD; Nigel H. Greig, PhD; Aaron S. Dumont, MD INTRODUCTION: Alterations in TNF-a expression have been associated with cerebral aneurysms, but a direct role in aneurysm formation and rupture has not been established. METHODS: Aneurysms were induced in mice by a combination of induced hypertension and a single stereotactic injection of elastase into the right basal cistern. To test the role of TNF-a in aneurysm formation, aneurysms were induced in TNF-a knock-out mice and mice pretreated with the synthesized TNF-a inhibitor 3,6’dithiothalidomide (DTH). Aneurysmal rupture was detected by alteration of neurological symptoms and confirmed by the presence of intracranial aneurysms with sub- arachnoid hemorrhage. TNF-a expression was assessed through real-time PCR and with immunofluorence staining. RESULTS: Cerebral aneurysm formation occurred in 18 of 22 (81.8%) animals receiving only vehicle as compared to 3 of 12 TNF-a knock-out mice receiving vehicle (25%, P ¼ .002) and 4 of 12 mice (33%, P ¼ .008) treated with DTH. TNF-a knock-out mice were 12.4 times (95% CI 1.6-94.2, P ¼ .015) and those treated with DTH were 4.1 times (95% CI 1.2-14.1, P ¼ .028) less likely to have aneurysm rupture as compared to those receiving vehicle only. As compared with untreated mice, TNF-a expression was not significantly different in TNF-a knock- out mice or those pre-treated with DTH, but was significantly elevated in unruptured and furthermore ruptured aneurysms. CONCLUSION: These data suggest a critical role of TNF-a in the formation and rupture of aneurysms in a model of cerebral aneurysm formation. Inhibitors of TNF-a could be beneficial in preventing aneurysm rupture. 191 Heme Induces Microglial CXCL2 Release-A Mechanism of Neutrophil-Mediated Injury After Intracerebral Hemorrhage David B. Kurland, BA; Volodymyr Gerzanich, MD, PhD; J. Marc Simard, MD INTRODUCTION: Neutrophils recruited into the CNS after in- tracerebral hemorrhage (ICH) are an important source of secondary injury. Chemokines are released following ICH, which act as chemoattractants for neutrophils and other inflammatory cells. In the setting of ICH in rodents, the neutrophil-specific chemokine CXCL2 is upregulated and is associated with severity of injury. CXCL2 signals via interaction with CXCR2, the same binding partner of CXCL8/IL-8, the most important neutrophil chemokine in humans. Heme, present in high concentrations locally after ICH, has recently been characterized as an endogenous ligand for Toll-like Receptor 4 (TLR4). TLR4 is well-known as the receptor for LPS and is critical in initiating the innate inflammatory response to bacterial infection. Additionally, TLR4 activation is upstream of CXCL2 production. METHODS: Intrastriatal injection of whole blood, heme or CXCL2 was performed under stereotactic guidanace. Isolation of resting adult microglia was performed using percoll gradients. An ELISA kit was utilized in the measurement of CXCL2 in cell culture supernatant. Behavioral testing was recorded using the 5-Choice-Serial-Reaction-Time-Test apparatus. Standard immunolabeling procedures for CXCL2 and TLR4 were employed. RESULTS: Here we report results from in vivo experiments showing that physiological concentrations of heme lead to upregulation of CXCL2 by IHC. Furthermore, in cultures of freshly isolated microglia from adult rat hippocampus, application of heme results in significant release of CXCL2 as measured by ELISA. Finally, intrastriatal injection of CXCL2 leads to acute accumulation of neutrophils and produces complex neurobehavioral deficits in rats trained in the 5-Choice Serial Reaction Time task. CONCLUSION: We conclude that microglial release of CXCL2 may play a role in neutrophil-mediated injury after ICH. Therapeutic intervention aimed at disrupting this chemokine signal may prove to be beneficial in treating this devastating injury. 192 Pediatric Head Injury During Operations Iraqi Freedom and Enduring Freedom Paul Klimo, MD, MPH; Brian T. Ragel, MD; Rocco Armonda, MD; Shalece Kofford, Randall R. McCafferty, MD INTRODUCTION: Children are the inevitable and unfortunate victims of armed conflicts throughout history. The operations in Afghanistan (Operation Enduring Freedom) and Iraq (Operation Iraqi Freedom) were no different. METHODS: Using the Joint Theater Trauma Registry (JTTR), which is the largest injury database in existence, we searched for all children (,18 ORAL PRESENTATIONS Ó 2013 The Congress of Neurological Surgeons 183 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited.