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Objective: Endothelial damage and intimal proliferation occur in vasospastic cerebral arteries after subarachnoid hemorrhage (SAH). In the peripheral vasculature, endothelial damage increases intimal matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) levels, causing neointimal proliferation. We hypothesized that serum von Willebrand factor (vWF) (a marker of endothelial cell death), MMP-9, and VEGF levels could serve as prognostic markers in predicting the occurrence of cerebral vasospasm., Methods: Venous serum vWF, MMP-9, and VEGF levels were prospectively measured daily, for 12 days or until the onset of vasospasm, for 45 consecutive patients admitted with SAH (n = 38) or admitted for elective aneurysm clipping (control subjects, n = 7). The development of transcranial Doppler flow velocities of more than 180 cm/s and/or new focal neurological deficits with angiographically confirmed vasospasm was considered the onset of vasospasm. To establish whether these markers were specific for vasospasm versus ischemia, blood samples were obtained from a concurrent group of 42 patients within 24 hours after stroke onset unrelated to SAH., Results: Fifty-seven percent of patients (22 of 38 patients) developed vasospasm, 4 to 11 days after SAH (median, 7 d). Mean peak serum vWF, MMP-9, and VEGF levels were increased in the SAH prevasospasm cohort, compared with the SAH nonvasospasm cohort (vWF, 5526 +/- 929 versus 4934 +/- 599 ng/ml, P = 0.01; MMP-9, 705 +/- 338 versus 438 +/- 154 ng/ml, P = 0.006; VEGF, 0.12 +/- 0.06 versus 0.06 +/- 0.06 ng/ml, P = 0.023). Mean peak vWF, MMP-9, and VEGF levels for the focal ischemia cohort (vWF, 4645 +/- 875 ng/ml, P = 0.01; MMP-9, 250 +/- 308 ng/ml, P = 0.001; VEGF, 0.03 +/- 0.04 ng/ml, P = 0.001) were markedly lower in comparison with the SAH prevasospasm cohort and were unchanged in comparison with the control cohort. vWF levels of more than 5500 ng/ml, VEGF levels of more than 0.12 ng/ml, and MMP levels of more than 700 ng/ml each independently increased the odds of subsequent vasospasm (18-, 20-, and 25-fold, respectively)., Conclusion: The development of cerebral vasospasm after SAH was preceded by increases in serum vWF, MMP-9, and VEGF levels. Increased serum vWF, MMP-9, and VEGF levels could accurately predict the onset of cerebral vasospasm after SAH. These factors were not elevated by SAH alone or in a separate cohort of patients with ischemic stroke, suggesting that these factors might play a role in the pathogenesis of human cerebral vasospasm.

Background and Purpose: Subarachnoid hemorrhage (SAH) increases production of vascular extracellular superoxide anion (*O2-). We examined whether overexpression of murine extracellular superoxide dismutase (EC-SOD) alters SAH-induced cerebral vasospasm, oxidative stress, and neurological outcome., Methods: Mice exhibiting a 2-fold increase in vascular EC-SOD and wild-type (WT) littermates were subjected to sham surgery or SAH by perforation of the right anterior cerebral artery. Neurological deficits were scored 72 hours later. Middle cerebral artery (MCA) diameter was measured or immunohistochemically stained for nitrotyrosine., Results: MCA diameter (mean+/-SD) was greater in EC-SOD versus WT mice after SAH but not sham surgery (EC-SOD SAH=56+/-10 microm; WT SAH=38+/-13 microm [P<0.01]; EC-SOD sham=99+/-16 microm; WT sham=100+/-15 microm). SAH decreased median (range) neurological score (scoring scale, 9 to 39; no deficit=39) versus shams, but there was no difference between EC-SOD and WT groups (EC-SOD SAH=26 [23 to 30]; WT SAH=23 [19 to 29] [P=0.27]; EC-SOD sham=39 [39]; WT sham=39 [39]). Sensory-motor deficits correlated with MCA diameter (P<0.001) but worsened primarily between 60 and 50 micro m, plateauing below this threshold. The percentage of mice with MCA nitrotyrosine staining increased after SAH in WT (sham=29%; SAH=100% [P<0.05]) but not EC-SOD (sham=33%; SAH=44% [P=0.80]) mice., Conclusions: Endogenous overexpression of EC-SOD attenuated vasospasm and oxidative stress but failed to reduce neurological deficits after SAH. Extracellular *O2- likely plays a direct role in the etiology of vasospasm.

The transgenic mouse has been used to study subarachnoid hemorrhage (SAH) induced delayed cerebral vasospasm (DCV). Methodological parameters have not been analyzed to validate this model and associated neurological deficits have not been described. We introduce a technique to quantify DCV and associated neurological deficits. C57BL/6J mice were subjected to SAH or sham surgery. Seventy-two hours later, the vasculature was cast in situ with India ink/gelatin at perfusion pressures of 40-60, 60-80, or 100-120 mmHg. Mice were perfused with and without microfiltration. Additional mice underwent grading of SAH size, measurement of vascular diameters, and neurological examination (score range 5-27; 27= normal). When cast at 60-80 mmHg, SAH was associated with an intraluminal cross-sectional diameter reduction in 3 of 7 ipsilateral vascular segments. At 40-60 mmHg, the diameter of only one segment was reduced. No changes were observed at 100-120 mmHg. Emboli prevented adequate perfusion of vascular segments in the absence of microfiltration. Median (interquartile range) neurologic score was reduced after SAH (sham, 27(27); SAH 11(7-17)). Deficits correlated with middle cerebral artery (MCA) diameter and SAH grade. MCA diameter also correlated with SAH grade. Only when utilizing microfiltration, controlling for hemorrhage size, and casting at perfusion pressures of 60-80 mmHg does India ink/gelatin vascular casting demonstrate consistent DCV that correspnds to neurological deficits. This allows measurement of both anatomical and clinical DCV in the mouse.

Adjuvant use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers with surgical resection is becoming common for the treatment of malignant gliomas. Cyst formation in the tumor resection cavity is a recently described complication associated with the use of BCNU wafers. There is currently no report in which successful management of this complication without additional surgical intervention is described. The authors describe four patients in whom postoperative cysts developed in the tumor resection cavity after placement of BCNU wafers. These include a 38-year-old man with a left frontoparietal tumor, a 48-year-old man with a right frontal lobe tumor, a 78-year-old man with a left parietooccipital tumor, and a 61-year-old woman with a left frontotemporal tumor. Histopathological studies of biopsy samples revealed malignant glioma in each patient. All four patients had unremarkable perioperative courses, were discharged within 3 to 8 days of surgery, and subsequently returned with acute neurological deterioration. Follow-up magnetic resonance (MR) imaging demonstrated cyst formation with significant mass effect at the previous resection site. Three patients were treated with high-dose dexamethasone and returned to their neurological baseline over an 8-day period. The fourth patient improved after surgical drainage and biopsy sampling of the cyst, which revealed no evidence of infection or recurrent tumor, but again sought medical care 2 weeks later with cyst recurrence necessitating high-dose steroid therapy. On MR images at least a 30% reduction in cyst size was demonstrated in all four patients, each of whom remained clinically stable at 2, 6, 6, and 4 months of follow-up review. Neurosurgeons should be aware of the potential for postoperative cyst formation accompanied by clinically significant mass effect after BCNU wafer implantation, as well as the potential for successful nonsurgical management leading to clinical and radiological improvement.

Background: Innovations in shunt technology and neuroendoscopy have been increasingly applied to shunt management. However, the relative life span of shunts and the etiology of shunt failure have not been characterized recently., Methods: We reviewed the records of all shunting procedures at our institution between January 1992 and December 1998. Independent predictors of shunt failure were analyzed via multivariate Cox regression analysis in 836 shunting procedures. Independent predictors of the etiology of failure (infection, proximal obstruction, distal malfunction) were analyzed via multivariate logistic regression analysis in the 383 shunts which failed., Results: A total of 353 pediatric patients underwent 308 shunt placements and 528 revisions. The risk (hazard ratio; HR) of shunt failure decreased as a function of time in both primary placements and revised shunts. In failed shunts, the odds of infection decreased 4-fold per year of shunt function, while the odds of distal malfunction increased 1.45-fold per year. Increasing number of shunt revisions (HR 1.31, p < 0.05), decreasing patient age in years (HR 1.04, p < 0.001), gestational age <40 weeks (HR 2.15, p < 0.001) but not the etiology of hydrocephalus were associated with an increased risk of shunt failure. Revisions versus primary placements, Dandy-Walker cysts and gestational age <40 weeks were independently associated with proximal, distal and infectious causes of failure, respectively., Conclusions: The long-term shunt revision rates observed here are similar to those reported over the past 2 decades. Shunt life span remains poorer in shunt revisions and in younger patients. Patient characteristics may suggest a specific risk and mechanism of failure, aiding in the long-term management of shunted hydrocephalus., (Copyright 2002 S. Karger AG, Basel)

Background: Use of intraoperative myelography as a radiologic guidance for percutaneous cervical cordotomy (PCC) has been superseded by more modern imaging. The only significant advancement in cordotomy techniques over the last 30 years has been CT-guided PCC. The goal of this study was to demonstrate the feasibility of an MRI-guided frameless technique in high cervical cordotomy., Methods: We describe 6 patients with intractable pain treated using a frameless, MRI-guided, stereotactic, PCC technique in combination with standard physiological localization procedures. Results were compared with those from 32 patients who underwent PCC in the last 5 years using physiological localizing techniques only., Results: Six patients (100%) who underwent the frameless technique had excellent pain relief postoperatively. Patients in the non-stereotactic group, on average, required a higher number of lesions (2.5 vs. 1.2, p < 0.005), and 7 (22%) of these patients had unsatisfactory pain relief following PCC (p = 0.21). Five patients in the non-stereotactic group had weakness postoperatively and 1 had changes in bladder function. Postoperative weakness occurred in 1 patient undergoing the frameless technique. At an average of 6 months of follow-up (range 5-11), excellent pain relief was achieved in 83% (5/6) of MRI frameless PCC patients and 55% (16/29) of standard PCC patients (p = 0.20)., Conclusions: Intraoperative frameless stereotaxy provides surgeons with accurate information that helps to guide the operative approach and precisely tailor the trajectory and depth of the electrode, potentially increasing the safety and efficacy of the operation., (Copyright 2003 S. Karger AG, Basel)

Background: Spinal cord injury affects approximately 10,000 new persons each year in the United States. Motor vehicle crashes, violence, and falls are the most common causes. The purpose of this review is to provide a rational management strategy for treating acute cervical spinal cord injuries., Review Summary: History-taking in these patients should focus on a few key points. Physical examination consists of determining the level of the lesion by a tailored motor, sensory, and reflex examination. An algorithm for the judicious use of plain radiographs, computed tomography scans, and emergent magnetic resonance imaging is presented. Management goals include protection of uninjured tissue, restoration of reversibly injured tissue, and achieving alignment and permanent spinal stability. The role of early surgery and high-dose steroids are discussed., Conclusion: Maximizing neurological function after cervical spinal cord injuries relies on rapid diagnosis and appropriate management. Although prognosis generally remains poor, recent advances in the basic sciences offer hope for the future.