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Aneurysmal subarachnoid hemorrhage is a devastating condition causing significant morbidity and mortality. While outcomes from subarachnoid hemorrhage have improved in recent years, there continues to be significant interest in identifying therapeutic targets for this disease. In particular, there has been a shift in emphasis toward secondary brain injury that develops in the first 72 hours after subarachnoid hemorrhage. This time period of interest is referred to as the early brain injury period and comprises processes including microcirculatory dysfunction, blood-brain-barrier breakdown, neuroinflammation, cerebral edema, oxidative cascades, and neuronal death. Advances in our understanding of the mechanisms defining the early brain injury period have been accompanied by improved imaging and nonimaging biomarkers for identifying early brain injury, leading to the recognition of an elevated clinical incidence of early brain injury compared with prior estimates. With the frequency, impact, and mechanisms of early brain injury better defined, there is a need to review the literature in this area to guide preclinical and clinical study.

Background and Purpose:Early brain injury may be a more significant contributor to poor outcome after aneurysmal subarachnoid hemorrhage (aSAH) than vasospasm and delayed cerebral ischemia. However, studying this process has been hampered by lack of a means of quantifying the spectrum of injury. Global cerebral edema (GCE) is the most widely accepted manifestation of early brain injury but is currently assessed only through subjective, qualitative or semi-quantitative means. Selective sulcal volume (SSV), the CSF volume above the lateral ventricles, has been proposed as a quantitative biomarker of GCE, but is time-consuming to measure manually. Here we implement an automated algorithm to extract SSV and evaluate the age-dependent relationship of reduced SSV on early outcomes after aSAH.Methods:We selected all adults with aSAH admitted to a single institution with imaging within 72 hours of ictus. Scans were assessed for qualitative presence of GCE. SSV was automatically segmented from serial CTs using a deep learning-based approach. Early SSV was the lowest SSV from all early scans. Modified Rankin Scale score of 4 to 6 at hospital discharge was classified as a poor outcome.Results:Two hundred forty-four patients with aSAH were included. Sixty-five (27%) had GCE on admission while 24 developed it subsequently within 72 hours. Median SSV on admission was 10.7 mL but frequently decreased, with minimum early SSV being 3.0 mL (interquartile range, 0.3–11.9). Early SSV below 5 mL was highly predictive of qualitative GCE (area under receiver-operating-characteristic curve, 0.90). Reduced early SSV was an independent predictor of poor outcome, with a stronger effect in younger patients.Conclusions:Automated assessment of SSV provides an objective biomarker of GCE that can be leveraged to quantify early brain injury and dissect its impact on outcomes after aSAH. Such quantitative analysis suggests that GCE may be more impactful to younger patients with SAH.

BACKGROUND Few studies use large, multi-institutional patient cohorts to examine the role of intraoperative magnetic resonance imaging (iMRI) in the resection of grade II gliomas. OBJECTIVE To assess the impact of iMRI and other factors on overall survival (OS) and progression-free survival (PFS) for newly diagnosed grade II astrocytomas and oligodendrogliomas. METHODS Retrospective analyses of a multicenter database assessed the impact of patient-, treatment-, and tumor-related factors on OS and PFS. RESULTS A total of 232 resections (112 astrocytomas and 120 oligodendrogliomas) were analyzed. Oligodendrogliomas had longer OS (P

Background Atherosclerotic vertebrobasilar disease is a significant etiology of posterior circulation stroke. The prospective observational VER i TAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) study demonstrated that distal hemodynamic status is a robust predictor of subsequent vertebrobasilar stroke risk. We sought to compare predictive models using thresholds for posterior circulation vessel flows standardized to age and vascular anatomy to optimize risk prediction. Methods and Results VER i TAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis/occlusion in vertebral and/or basilar arteries. Quantitative magnetic resonance angiography measured large‐vessel vertebrobasilar territory flow, and patients were designated as low or normal flow based on a prespecified empiric algorithm considering distal territory regional flow and collateral capacity. For the present study, post hoc analysis was performed to generate additional predictive models using age‐specific normalized flow measurements. Sensitivity, specificity, and time‐to‐event analyses were compared between the algorithms. The original prespecified algorithm had 50% sensitivity and 79% specificity for future stroke risk prediction; using a predictive model based on age‐normalized flows in the basilar and posterior cerebral arteries, standardized to vascular anatomy, optimized flow status thresholds were identified. The optimized algorithm maintained sensitivity and increased specificity to 84%, while demonstrating a larger and more significant hazard ratio for stroke on time‐to‐event analysis. Conclusions These results indicate that flow remains a strong predictor of stroke across different predictive models, and suggest that prediction of future stroke risk can be optimized by use of vascular anatomy and age‐specific normalized flows.

Background and Purpose: Given the benign natural history of intracranial low-grade dural arteriovenous fistulas (dAVFs), their routine treatment remains controversial. The aim of this study is to compare the outcomes of low-grade dAVF treatment to conservative management. Methods: We performed a retrospective review of dAVF patients derived from 12 institutions participating in the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR). Patients with low-grade (Borden I) dAVFs were included and categorized into treatment and observation cohorts. Primary outcome was defined as modified Rankin Scale (mRS) score at final follow-up. Secondary outcomes were rates of excellent (mRS 0-1) and good (mRS 0-2) functional outcomes, symptomatic improvement, mortality, and obliteration at final follow-up. Results: The treatment and observation cohorts comprised 230 and 112 patients, respectively. At last follow up, no difference in primary or secondary outcomes was observed between the two cohorts, with the exception of obliteration, which was higher in the treatment cohort (79.3% vs. 28.2%, p Conclusions: Low-grade dAVF treatment was not associated with increased functional disability compared to conservative management. Although higher obliteration rates were achieved in the treatment cohort, rates of symptomatic improvement were similar between the two cohorts. This study did not provide evidence to support the routine treatment of low-grade dAVFs.

BACKGROUND Perioperative steroid protocols for patients undergoing transsphenoidal surgery (TSS) for pituitary pathology vary by institution. OBJECTIVE To assess the safety of withholding glucocorticoids in patients undergoing TSS. METHODS Patients with an intact hypothalamic-pituitary-adrenal (HPA) axis undergoing TSS for a pituitary tumor at the same academic institution between 2012 and 2015 were randomized to either receive 100 mg of intravenous hydrocortisone followed by 0.5 mg of intravenous dexamethasone every 6 h for 4 doses (STER, n = 23) or to undergo surgery without steroids (NOSTER, n = 20). Postoperative cortisol levels were then used to determine the need for glucocorticoids after surgery. Data regarding postoperative cortisol levels, hospital stay length, and complications were collected. RESULTS Mean postoperative 8 am cortisol levels were higher in the NOSTER group compared to the STER group (745 ± 359 nmol/L and 386 ± 193 nmol/L, respectively, P = .001) and more patients were discharged on glucocorticoids in the STER group (42% vs 12%, P = .07). There was no difference in the incidence of postoperative complications, including hyperglycemia, diabetes insipidus, or permanent adrenal insufficiency. Permanent adrenal insufficiency occurred in 8% of patients. CONCLUSION Perioperative steroids can be safely withheld in patients with an intact HPA axis undergoing TSS. Although administration of perioperative glucocorticoids does not appear to increase the risk of complications, it may interfere with assessment of the HPA axis after surgery.

Background and Purpose— Several angiographic factors of dural arteriovenous fistulas (dAVFs) are associated with aggressive presentation and poor natural history. We examined the association of magnetic resonance imaging T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) hyperintensity with aggressive presentation. Methods— A cohort of dAVF patients from 2 centers was retrospectively examined. T2/FLAIR hyperintensity was determined by blinded, de-identified review and compared with angiographic grade and presenting symptoms. Results— T2/FLAIR hyperintensity was only identified in dAVF patients with cortical venous drainage (CVD). Among patients with CVD, those with T2/FLAIR hyperintensity were more likely to present with aggressive symptoms (20/23, 87.0%) than those without (6/21, 28.5%), P Conclusions— T2/FLAIR hyperintensity strongly correlates with aggressive presentation and CVD in dAVF patients, and may identify a subset that would benefit from early treatment.

Background and Purpose— Cerebral hypoperfusion symptoms (defined as symptoms related to change in position, effort or exertion, or recent change in antihypertensive medication) have been used in stroke studies as a surrogate for detecting hemodynamic compromise. However, the validity of these symptoms in identifying flow compromise in patients has not been well established. We examined whether hypoperfusion symptoms correlated with quantitative measurements of flow compromise in the prospective, observational VERiTAS study (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke). Methods— VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Hemodynamic status using vertebrobasilar large vessel flow was measured using quantitative magnetic resonance angiography, and patients were designated as low, borderline, or normal flow based on distal territory regional flow, incorporating collateral capacity. The presence of qualifying event hypoperfusion symptoms was assessed relative to the quantitatively determined flow status (normal versus borderline/low) and also examined as a predictor of subsequent stroke risk. Results— Of the 72 enrolled subjects, 66 had data on hypoperfusion symptoms available. On initial quantitative magnetic resonance angiography designation, 43 subjects were designated as normal flow versus 23 subjects designated as low flow (n=16) or borderline flow (n=7). Of these, 5 (11.6%) normal flow and 3 (13.0%) low/borderline flow subjects reported at least one qualifying event hypoperfusion symptom ( P =0.99, Fisher exact test). Hypoperfusion symptoms had a positive predictive value of 37.5% and negative predictive value of 65.5% for low/borderline flow status. Compared with flow status, which strongly predicted subsequent stroke risk, hypoperfusion symptoms were not associated with stroke outcome ( P =0.87, log-rank test). Conclusions— These results suggest that hypoperfusion symptoms alone correlate poorly with actual hemodynamic compromise as assessed by quantitative magnetic resonance angiography and subsequent stroke risk in vertebrobasilar disease, and are not a reliable surrogate for flow measurement. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00590980.

BACKGROUND Intraoperative magnetic resonance imaging (iMRI) is a powerful tool for guiding brain tumor resections, provided that it accurately discerns residual tumor. OBJECTIVE To use histopathology to assess how reliably iMRI may discern additional tumor for a variety of tumor types, independent of the indications for iMRI. METHODS A multicenter database was used to calculate the odds of additional resection during the same surgical session for grade I to IV gliomas and pituitary adenomas. The reliability of iMRI for identifying residual tumor was assessed using histopathology of tissue resected after iMRI. RESULTS Gliomas (904/1517 cases, 59.6%) were more likely than pituitary adenomas (176/515, 34.2%) to receive additional resection after iMRI (P

Approximately 795 000 strokes occur annually in the United States, and stroke remains a leading cause of major disability.1 Ischemic stroke accounts for ≈85% of cases, whereas the remaining 15% are attributable to hemorrhagic pathogeneses. Despite increased public awareness, improved prehospital triage and a greater focus on systems of care, intravenous tissue-type plasminogen activator, and endovascular intervention remain underutilized.2 Recent advances in endovascular technology, coupled with the positive results of at least 5 major clinical trials, support the efficacy of mechanical thrombectomy as a treatment of ischemic stroke.3–6 These studies emphasize that interventional capabilities are an essential element of stroke care. Before the completion of these interventional trials, several simultaneous efforts arose to provide a method of certifying institutions as being optimized for advanced cerebrovascular care, and these efforts were inclusive of ischemic and hemorrhagic disease. It is in the spirit of constant iterative improvement that the authors of this article call for a refinement of the requirements for the certification of hospitals as comprehensive stroke centers (CSCs). The certification process has the potential to serve an important function in improving the quality of care and patient outcomes by establishing criteria for certification of stroke centers. The Cerebrovascular Coalition (CVC), which represents all neuroscience-based physician professional societies in the United States (CVC member organizations include the American Academy of Neurology, American Association of Neurological Surgeons, Congress of Neurological Surgeons, Society of Vascular and Interventional Neurology, American Society of Neuroradiology, and the Society of NeuroInterventional Surgery) involved in the care of patients with acute stroke, embraces and applauds the need for greater access to acute stroke therapy. The CVC thinks that, in principle, a certification process for stroke centers can have a positive impact on patient care and outcomes. The Joint Commission (TJC), in partnership with the …

The purpose of neurosurgical education is to teach the clinical knowledge and surgical skills necessary to become a neurosurgeon. Another goal is to inculcate the principles of the scientific method. However, increasing expectations about attending involvement during surgery, duty hour requirements, and new curricular mandates have put programs under stress to ensure adequate training, in less time, in an environment of limited resident independence. More recently, the Accreditation Council for Graduate Medical Education has developed a new tracking process based on "milestones" or defined educational outcomes. At the same time, our healthcare system is undergoing a rapid socioeconomic transition in organization and payment models, which traditionally has not been a focus of formal teaching. A 2008 survey conducted by the Council of State Neurosurgical Societies found that graduating residents felt inadequately prepared in areas like contract negotiation, practice evaluation, and management.

Introduction: Hypoperfusion symptoms, defined as symptoms related to change in position (i.e. supine to seated), effort or exertion, or recent change in antihypertensive medication have been used in stroke studies as a surrogate for detecting hemodynamic compromise. However, the validity of these symptoms in identifying flow compromise in patients has not been well established. We examined whether hypoperfusion symptoms correlated with quantitative evaluation of flow compromise in the prospective observational Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study. Methods: VERiTAS enrolled patients with recent vertebrobasilar TIA or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries. Hemodynamic status using large vessel flow in the vertebrobasilar territory was measured using quantitative magnetic resonance angiography (QMRA), and patients were designated as low, borderline or normal flow based on distal territory regional flow, incorporating collateral capacity, as previously reported. The presence of qualifying event hypoperfusion symptoms was assessed relative to the quantitatively determined flow status (normal vs borderline/low), and also examined as a predictor of subsequent stroke risk. Results: Of the 72 enrolled subjects, 66 had data on hypoperfusion symptoms available. On initial QMRA designation, 43 subjects were designated as normal flow vs. 23 subjects designated as low flow (n=16) or borderline (n=7). Of these, 5 (11.6%) normal flow and 3 (13.0%) low/borderline flow subjects reported at least one qualifying event hypoperfusion symptom (p=0.99, Fisher’s exact test). Hypoperfusion symptoms had a positive predictive value of 37.5% and negative predictive value of 65.5% for low/borderline flow status. Compared to flow status, which strongly predicted subsequent stroke risk, hypoperfusion symptoms were not associated with stroke outcome (p=0.87, log rank test). Conclusions: These results suggest that hypoperfusion symptoms alone correlate poorly with actual hemodynamic compromise, and subsequent stroke risk in vertebrobasilar disease, and are not a reliable surrogate for flow measurement.

Purpose— The aim of this statement is to review the current data and to make suggestions for the diagnosis and management of both ruptured and unruptured brain arteriovenous malformations. Methods— The writing group met in person and by teleconference to establish search terms and to discuss narrative text and suggestions. Authors performed their own literature searches of PubMed, Medline, or Embase, specific to their allocated section, through the end of January 2015. Prerelease review of the draft statement was performed by expert peer reviewers and by the members of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee. Results— The focus of the scientific statement was subdivided into epidemiology; diagnosis; natural history; treatment, including the roles of surgery, stereotactic radiosurgery, and embolization; and management of ruptured and unruptured brain arteriovenous malformations. Areas requiring more evidence were identified. Conclusions— Brain arteriovenous malformations are a relatively uncommon but important cause of hemorrhagic stroke, especially in young adults. This statement describes the current knowledge of the natural history and treatment of patients with ruptured and unruptured brain arteriovenous malformations, suggestions for management, and implications for future research.

Objective: The purpose of this study was to determine the prevalence of bicuspid aortic valves (BAVs) and thoracic ascending aortic aneurysms (TAAs) in a retrospective cohort of patients treated for intracranial aneurysms (IAs). Methods: Patients treated for IA at our institution between 2002 and 2011 were identified and their clinical records reviewed. Those without an echocardiogram of sufficient quality to assess the aortic valve were excluded. The prevalence of BAVs and TAAs in this remaining cohort was determined based on echocardiography reports, medical records, and cross-sectional chest imaging. Results: Of 1,047 patients, 317 had adequate echocardiography for assessment of BAV. Of these, 82 also had cross-sectional chest imaging. Of the 317 patients, 2 had BAV and 15 had TAA. The prevalence of BAVs (0.6%, 95% confidence interval 0.2%–2.2%) was similar to population prevalence estimates for this condition; however, the prevalence of TAAs (4.7%, 95% confidence interval 2.9%–7.6%) was larger than expected in a normal age- and sex-matched population. Conclusions: Our data demonstrate an association between IA and TAA, but not independently for BAV.

Background and Purpose— We and others have shown that soluble amyloid β-peptide (Aβ) and cerebral amyloid angiopathy (CAA) cause significant cerebrovascular dysfunction in mutant amyloid precursor protein (APP) mice, and that these deficits are greater in aged APP mice having CAA compared with young APP mice lacking CAA. Amyloid β-peptide in young APP mice also increases infarction after focal cerebral ischemia, but the impact of CAA on ischemic brain injury is unknown. Methods— To determine this, we assessed cerebrovascular reactivity, cerebral blood flow (CBF), and extent of infarction and neurological deficits after transient middle cerebral artery occlusion in aged APP mice having extensive CAA versus young APP mice lacking CAA (and aged-matched littermate controls). Results— We found that aged APP mice have more severe cerebrovascular dysfunction that is CAA dependent, have greater CBF compromise during and immediately after middle cerebral artery occlusion, and develop larger infarctions after middle cerebral artery occlusion. Conclusions— These data indicate CAA induces a more severe form of cerebrovascular dysfunction than amyloid β-peptide alone, leading to intra- and postischemic CBF deficits that ultimately exacerbate cerebral infarction. Our results shed mechanistic light on human studies identifying CAA as an independent risk factor for ischemic brain injury.

Background and Purpose— The purpose of this statement is to delineate basic expectations regarding primary palliative care competencies and skills to be considered, learned, and practiced by providers and healthcare services across hospitals and community settings when caring for patients and families with stroke. Methods— Members of the writing group were appointed by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee and the American Heart Association’s Manuscript Oversight Committee. Members were chosen to reflect the diversity and expertise of professional roles in delivering optimal palliative care. Writing group members were assigned topics relevant to their areas of expertise, reviewed the appropriate literature, and drafted manuscript content and recommendations in accordance with the American Heart Association’s framework for defining classes and level of evidence and recommendations. Results— The palliative care needs of patients with serious or life-threatening stroke and their families are enormous: complex decision making, aligning treatment with goals, and symptom control. Primary palliative care should be available to all patients with serious or life-threatening stroke and their families throughout the entire course of illness. To optimally deliver primary palliative care, stroke systems of care and provider teams should (1) promote and practice patient- and family-centered care; (2) effectively estimate prognosis; (3) develop appropriate goals of care; (4) be familiar with the evidence for common stroke decisions with end-of-life implications; (5) assess and effectively manage emerging stroke symptoms; (6) possess experience with palliative treatments at the end of life; (7) assist with care coordination, including referral to a palliative care specialist or hospice if necessary; (8) provide the patient and family the opportunity for personal growth and make bereavement resources available if death is anticipated; and (9) actively participate in continuous quality improvement and research. Conclusions— Addressing the palliative care needs of patients and families throughout the course of illness can complement existing practices and improve the quality of life of stroke patients, their families, and their care providers. There is an urgent need for further research in this area.

Background Recent experimental evidence indicates that endogenous mechanisms against cerebral vasospasm can be induced via preconditioning. Objective To determine whether these vascular protective mechanisms are also present in vivo in humans with aneurysmal subarachnoid hemorrhage. Methods A multicenter retrospective cohort of patients with aneurysmal subarachnoid hemorrhage was examined for ischemic preconditioning stimulus: preexisting steno-occlusive cerebrovascular disease (CVD) and/or previous cerebral infarct. Generalized estimating equation models were performed to determine the effect of the preconditioning stimulus on the primary end points of radiographic vasospasm, symptomatic vasospasm, and vasospasm-related delayed cerebral infarction and the secondary end point of discharge modified Rankin Scale score. Results Of 1043 patients, 321 (31%) had preexisting CVD and 437 (42%) had radiographic vasospasm. Patients with preexisting CVD were less likely to develop radiographic vasospasm (odds ratio = 0.67; 95% confidence interval = 0.489-0.930; P = .02) but had no differences in other end points. In terms of the secondary end point, patients with preexisting CVD did not differ significantly from patients without preexisting CVD in mortality or unfavorable outcome in multivariate analyses, although patients with preexisting CVD were marginally more likely to die (P = .06). Conclusion This retrospective case-control study suggests that endogenous protective mechanisms against cerebral vasospasm-a preconditioning effect-may exist in humans, although these results could be the effect of atherosclerosis or some combination of preconditioning and atherosclerosis. Additional studies investigating the potential of preconditioning in aneurysmal subarachnoid hemorrhage are warranted.

BACKGROUND Changing landscapes in neurosurgical training and increasing use of endovascular therapy have led to decreasing exposure in open cerebrovascular neurosurgery. To ensure the effective transition of medical students into competent practitioners, new training paradigms must be developed. OBJECTIVE Using principles of pattern recognition, we created a classification scheme for middle cerebral artery (MCA) bifurcation aneurysms that allows their categorization into a small number of shape pattern groups. METHODS Angiographic data from patients with MCA aneurysms between 1995 and 2012 were used to construct 3-dimensional models. Models were then analyzed and compared objectively by assessing the relationship between the aneurysm sac, parent vessel, and branch vessels. Aneurysms were then grouped on the basis of the similarity of their shape patterns in such a way that the in-class similarities were maximized while the total number of categories was minimized. For each category, a proposed clip strategy was developed. RESULTS From the analysis of 61 MCA bifurcation aneurysms, 4 shape pattern categories were created that allowed the classification of 56 aneurysms (91.8%). The number of aneurysms allotted to each shape cluster was 10 (16.4%) in category 1, 24 (39.3%) in category 2, 7 (11.5%) in category 3, and 15 (24.6%) in category 4. CONCLUSION This study demonstrates that through the use of anatomic visual cues, MCA bifurcation aneurysms can be grouped into a small number of shape patterns with an associated clip solution. Implementing these principles within current neurosurgery training paradigms can provide a tool that allows more efficient transition from novice to cerebrovascular expert.

BACKGROUND Carotid endarterectomy (CEA) for symptomatic carotid artery stenosis and intravenous tissue-type plasminogen activator (IV-tPA) for acute ischemic stroke are proven therapies; however, the safety of CEA in stroke patients who recently received IV-tPA has not been established. OBJECTIVE To evaluate the safety of CEA in stroke patients who recently received IV-tPA. METHODS A retrospective review of patients who underwent CEA for symptomatic carotid artery stenosis was performed. The primary end point was postoperative symptomatic intracerebral hemorrhage (sICH). A univariate analysis of potential risk factors for sICH, including IV-tPA therapy, timing of CEA, degree of stenosis, and stroke severity, was performed. Factors with a value of P < .1 on univariate analysis were tested further. RESULTS Among 142 patients, 3 suffered sICH after CEA: 2 of 11 patients treated with IV-tPA (18.2%) and 1 of 131 patients not treated with IV-tPA (0.8%). Both IV-tPA patients suffering sICH underwent CEA within 3 days of tPA administration. On univariate analysis, IV-tPA (P = .02), female sex (P = .09), shorter time between ischemic event and CEA (P = .06), and lower mean arterial pressure during the first 48 hours of admission (P = .08) were identified as risk factors for sICH. On multivariate analysis, IV-tPA was the only significant risk factor (P = .002 by stepwise logistic regression; P = .03 by nominal logistic regression). CONCLUSION This study indicates that IV-tPA is an independent risk factor for sICH after CEA. This suggests that CEA should be pursued cautiously in patients who recently received IV-tPA. Early surgery may be associated with an increased risk for sICH. ABBREVIATIONS CEA, carotid endarterectomyIV-tPA, intravenous recombinant tissue-type plasminogen activatorMAP, mean arterial pressureNASCET, North American Symptomatic Carotid Endarterectomy TrialNIHSS, National Institutes of Health Stroke ScaleNINDS, National Institute of Neurological Disorders and StrokesICH, symptomatic intracerebral hemorrhageTIA, transient ischemic attack.

Background: Fractional flow across an atherosclerotic lesion measured with TOF-MRA signal intensity ratio (SIR) may be used to gauge hemodynamic severity and to predict subsequent stroke. The degree of flow impairment may also be ascertained by quantitative MRA (QMRA). We analyzed performance of these noninvasive imaging parameters to estimate risk of subsequent posterior circulation events in VERiTAS. Methods: TOF-MRA data and QMRA were simultaneously acquired in VERiTAS. SIR were derived from TOF source images and normalized for analysis with volume flow ratios (VFR) on QMRA at standard anatomical landmarks and across the maximal stenosis. Statistics analyzed the correlation between SIR and VFR, and the ability of each to predict clinical events. Results: 72 subjects (mean age 65.6±10.3 years, 32 (44%) women) with posterior circulation atherosclerosis were enrolled in VERiTAS. Posterior communicating artery (PCOMM) flow to the posterior circulation was detected in 85% on the right, in 86% on the left, with bilateral PCOMM flow in 78%. Fractional flow measures or SIR across the maximal stenotic lesion evident on TOF MRA was reduced in 43%, increased in 16%, with no change in 40%. SIR from the proximal to distal basilar artery segments increased in 62%, was unchanged in 33% and decreased in 4% of cases. SI and VFR exhibited limited correlation at corresponding arterial segments. QMRA VFR indicative of low distal flow status predicted subsequent clinical events, unlike SIR. Conclusions: Evaluation of hemodynamics in posterior circulation atherosclerosis reveals superiority of QMRA to SIR in prospectively predicting recurrent ischemia. Collateral circulation, tandem disease and unique aspects of vertebrobasilar atherosclerosis likely influence the utility of SIR on TOF MRA.

Introduction: Despite theoretical concerns regarding hypoperfusion in patients with large artery occlusive disease, strict blood pressure (BP) control has become adopted as a safe strategy for stroke risk reduction. We examined the relationship between BP control, flow, and risk of subsequent stroke in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) Study. Hypothesis: Strict BP control may be less efficacious and safe in flow compromised patients with symptomatic vertebrobasilar (VB) disease. Methods: VERiTAS enrolled patients with recent VB TIA or stroke and ≥50% atherosclerotic stenosis or occlusion of vertebral or basilar arteries. Hemodynamic status using large vessel flow in the VB territory was designated as low or normal flow using quantitative MRA. Patients underwent standard medical management and follow-up for primary outcome event of VB territory stroke. Mean SBP during follow-up ( Results: The 72 enrolled subjects had an average of 3.8±1.2 BP recordings over the 20 ±8 months of follow-up; 40 (56%) had mean SBP of Conclusion: Among a subgroup of patients with VB disease and low flow, strict BP control (SBP

Introduction: The role of regional hypoperfusion as an important contributor to stroke risk in atherosclerotic vertebrobasilar (VB) disease has recently been confirmed by the observational Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) Study. We examined the stability of hemodynamic status over time and relationship to stroke risk in patients followed in this prospective cohort. Methods: VERiTAS enrolled patients with recent VB TIA or stroke and ≥50% atherosclerotic stenosis or occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative MRA, and patients were designated as low flow or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of VB territory stroke. QMRA imaging was repeated at 6, 12 and 24 months. Flow status over time was examined relative to baseline, and relative to subsequent stroke risk using survival analysis. Results: Of 72 enrolled subjects, 50, 45 and 28 had follow-up QMRA at 6, 12 and 24 months respectively. 18 (25%) were characterized as low flow at baseline, 10% at 6 m, 20 % at 12m and 11% at 24m. Over 18±7months of follow-up, 7 of the 12 low flow patients (58%) with follow-up imaging had improved their flow status (low to normal) while only 3 of 44 normal flow patients (7%) had worsened. Baseline flow status has previously been demonstrated to be an independent stroke risk predictor; flow status at latest follow-up and prior to event remained a strong predictor of subsequent stroke (HR 4.9, CI 1.4 to16.9, p=0.01). Conclusions: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic VB disease; improvement, likely attributable to development of collateral supply, was evident more frequently than worsening, presumably due to progression of disease. Flow status, both at baseline and over time, remains a robust risk factor for subsequent stroke, thus serving as an important prognostic marker.

Background Cerebral vasospasm is an independent predictor of poor outcome after subarachnoid hemorrhage (SAH). The nitric oxide-cyclic guanosine monophosphate (NO-cGMP) vasodilatory pathway is strongly implicated in its pathophysiology. Preliminary studies suggest that phosphodiesterase 5 (PDE5), an enzyme that degrades cGMP, may play a role because the PDE5 inhibitor sildenafil was found to reduce vasospasm after SAH. However, several questions that are critical when considering translational studies remain unanswered. Objective To elucidate the mechanism of action of sildenafil against vasospasm and to assess whether sildenafil attenuates SAH-induced neuronal cell death, improves functional outcome after SAH, or causes significant physiological side effects when administered at therapeutically relevant doses. Methods SAH was induced via endovascular perforation in male C57BL6 mice. Beginning 2 hours later, mice received sildenafil citrate (0.7, 2 or 5 mg/kg orally twice daily) or vehicle. Neurological outcome was assessed daily. Vasospasm was determined on post-SAH day 3. Brain PDE5 expression and activity, cGMP content, neuronal cell death, arterial blood pressure, and intracranial pressure were examined. Results We found that PDE5 activity (but not expression) is increased after SAH, leading to decreased cGMP levels. Sildenafil attenuates this increase in PDE5 activity and restores cGMP levels after SAH. Post-SAH initiation of sildenafil was found to decrease vasospasm and neuronal cell death and markedly improve neurological outcome without causing significant physiological side effects. Conclusion Sildenafil, a US Food and Drug Administration-approved drug with a proven track record of safety in humans, is a promising new therapy for vasospasm and neurological deficits after SAH.

Background and importance Hemodynamic treatment of subarachnoid hemorrhage-induced vasospasm is associated with a number of systemic and cerebral risks. However, hypertensive encephalopathy has rarely been reported in the setting of induced hypertension. Recognition of this complication is nonetheless critical because failure to lower blood pressure may lead to worsening of deficits and even permanent injury. Clinical presentation This report details a case of unilateral hypertensive encephalopathy (also referred to as posterior reversible encephalopathy syndrome [PRES]) in a subarachnoid hemorrhage patient who was being treated with induced hypertension for symptomatic vasospasm affecting the contralateral hemisphere. This patient developed right hemispheric deficits associated with angiographic vasospasm of the right middle cerebral artery, which responded to induced hypertension. However, within 24 hours of raising blood pressure, the patient deteriorated with new left hemispheric deficits that paradoxically worsened when blood pressure was raised further in response. Computed tomography imaging was suspicious for evolving infarction in the left hemisphere, but on reevaluation, concern for PRES was raised. Magnetic resonance imaging confirmed left hemispheric PRES, and a dramatic neurological improvement occurred almost immediately after lowering blood pressure. Repeat CT showed resolution of the left hemispheric edema. Conclusion This is the first reported case of unilateral PRES in the setting of subarachnoid hemorrhage. It likely occurred because right-sided vasospasm attenuated ipsilateral distal perfusion pressures, leaving the left hemisphere vulnerable to the consequences of induced hypertension. Hypertensive encephalopathy should be considered in patients with unilateral or asymmetric vasospasm when neurological worsening occurs in the contralateral hemisphere during induced hypertension and/or the patient paradoxically worsens despite raising blood pressure.

BACKGROUND: The International Study of Intracranial Aneurysms found that for patients with no previous history of subarachnoid hemorrhage, small (< 7 mm) anterior circulation and posterior circulation aneurysms had a 0% and 2.5% risk of subarachnoid hemorrhage over 5 years, respectively. OBJECTIVE: To determine whether cerebral aneurysms shrink with rupture. METHODS: The clinical databases of 7 sites were screened for patients with imaging of cerebral aneurysms before and after rupture. Inclusion criteria included documented subarachnoid hemorrhage by imaging or lumbar puncture and intracranial imaging before and after cerebral aneurysm rupture. The patients were evaluated for aneurysm maximal height, maximal width, neck diameter, and other measurement parameters. Only a change of ≥ 2 mm was considered a true change. RESULTS: Data on 13 patients who met inclusion criteria were collected. The median age was 60, and 11 of the 13 patients (84.6%) were female. Only 5 patients had posterior circulation aneurysms. None of the aneurysms had a significant decrease in size. One aneurysm decreased by 1.8 mm in maximum size after rupture (7.7%). Six aneurysms had an increase in maximum size of at least 2 mm after rupture (46.2%) with a mean increase of 3.5 mm (± 0.5 mm). CONCLUSION: Unruptured aneurysms do not shrink when they rupture. The large percentage of ruptured small aneurysms in previous studies were likely small before they ruptured.

OBJECTIVE: The triad of acute spontaneous intracranial subarachnoid hemorrhage (SAH), hydrocephalus, and profound paraparesis in the absence of anterior cerebral artery vasospasm or ischemia has not been described previously. In this report, we present 6 patients presenting with this triad and provide a critical analysis of the clinical characteristics, radiographic workup, and long-term outcome for such patients. CLINICAL PRESENTATION: Six (0.9%) of 695 patients with nontraumatic SAH managed at Barnes-Jewish Hospital between January 2003 and January 2008 presented with profound paraparesis or paraplegia. All were Hunt and Hess Grade III or higher, and all had extensive SAH and ventriculomegaly on initial head computed tomography. Five patients underwent extensive spinal imaging, but no abnormality was identified. INTERVENTION: Five patients underwent surgical aneurysm obliteration, whereas 1 patient had no underlying aneurysm identified on multiple angiograms. All of the patients required urgent ventriculostomy for hydrocephalus, and 5 patients went on to require permanent shunt placement. Five of the 6 patients had gradual resolution of their presenting paraparesis over the course of 3 to 6 months. CONCLUSION: The clinical triad of SAH, hydrocephalus, and profound paraparesis has not been reported previously. In contrast to previous reports, these patients had aneurysms at varying sites, without evidence of vasospasm or ischemia. Interestingly, all required acute cerebrospinal fluid diversion, 5 of 6 patients required permanent shunting, and almost all demonstrated gradual and often complete resolution of their presenting paraparesis. The etiology of this syndrome remains to be defined, but a combined deleterious effect of SAH and acute ventricular distention on cerebral function is suggested.

Background and Purpose— To describe baseline clinical features and outcomes of adults with moyamoya phenomenon treated at a single North American institution. Methods— We identified 34 adults with moyamoya phenomenon by review of angiographic records. Clinical presentation and baseline stroke risk factors were obtained by chart review. Follow-up was obtained prospectively. A 5-year Kaplan-Meier stroke risk was calculated. Results— The median age was 42 (range 20 to 79) years. Twenty-five were women. The initial symptom was ischemia, hemorrhage, or asymptomatic in 24, 7, and 3 patients, respectively. Twenty-two had bilateral involvement and 12 had unilateral moyamoya vessels. Baseline stroke risk factors were similar between groups. The median follow-up in 31 living patients was 5.1 (range 0.2 to 19.6) years. Fourteen patients were treated with surgical revascularization (20 total hemispheres). In medically treated symptomatic hemispheres, the 5-year risk of recurrent ipsilateral stroke was 65% after the initial symptom and 27% after angiographic diagnosis. Patients with bilateral involvement presenting with ischemic symptoms were at the highest risk of subsequent stroke (n=17, 5-year risk of stroke with medical treatment after first symptom of 82%). In surgically treated hemispheres, the 5-year risk of perioperative or subsequent ipsilateral stroke or death was 17%. This was significantly different compared with medical treatment after first symptom ( P =0.02) but not after angiographic diagnosis. Conclusion— Moyamoya phenomenon in North American adults is associated with a high risk of recurrent stroke, particularly those with bilateral involvement and ischemic symptoms. These data suggest a potential benefit with surgery if diagnosis could be made earlier.

Background and Purpose—In light of recent evidence suggesting that an upregulation of K+efflux mediated by outward delayed rectifier (IK) channels promotes central neuronal apoptosis, we sought to test the possibility that blockers ofIKchannels might be neuroprotective against hypoxia/ischemia-induced neuronal death.Methods—Membrane currents were recorded with the use of patch clamp recordings in cultured murine cortical neurons. Protective effects of K+channel blockers were examined in rats subjected to transient middle cerebral artery occlusion followed by 14-day reperfusion.Results—The K+channel blocker tetraethylammonium (TEA) (5 mmol/L) selectively blockedIKwithout affectingN-methyl-d-aspartate receptor–mediated current or voltage-gated Ca2+currents. Both TEA and a lipophilic K+channel blocker, clofilium, attenuated neuronal apoptosis induced by hypoxia in vitro and infarct volume induced by ischemia in vivo.Conclusions—These data are consistent with the idea that K+channel–mediated K+efflux may contribute to ischemia-triggered apoptosis and suggest that preventing excessive K+efflux through K+channels may constitute a therapeutic approach for the treatment of stroke.

The purpose of neurosurgical education is to teach the clinical knowledge and surgical skills necessary to become a neurosurgeon. Another goal is to inculcate the principles of the scientific method. However, increasing expectations about attending involvement during surgery, duty hour requirements, and new curricular mandates have put programs under stress to ensure adequate training, in less time, in an environment of limited resident independence. More recently, the Accreditation Council for Graduate Medical Education has developed a new tracking process based on "milestones" or defined educational outcomes. At the same time, our healthcare system is undergoing a rapid socioeconomic transition in organization and payment models, which traditionally has not been a focus of formal teaching. A 2008 survey conducted by the Council of State Neurosurgical Societies found that graduating residents felt inadequately prepared in areas like contract negotiation, practice evaluation, and management.

Introduction: Atherosclerotic vertebrobasilar disease (VBD) is a significant etiology of posterior circulation stroke. In addition to thromboembolism, regional hypoperfusion is considered an important potential contributor to stroke risk. To examine the role of hemodynamic compromise in VBD, a prospective observational multi-center study, Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS), has recently been conducted. Here we report baseline features and vessel flow measurements from the study cohort. Methods: Baseline demographic and clinical data was collected in patients with recent vertebrobasilar TIA or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative MRA (QMRA). Results: The cohort (n=75, 56% male) had a mean age of 65.5 (range 40 to 90) years; two thirds presented with ischemic stroke. Hypertension (93%) and hyperlipidemia (79%) were the most prevalent vascular risk factors. Vertebral and basilar artery flows correlated negatively with degree of stenosis in the affected vessel, and positively to the minimal diameter at the site of stenosis (p Conclusions: Flow in stenotic posterior circulation vessels correlate with residual diameter and stenosis and drop significantly in the setting of tandem disease. However, distal flow status, incorporating collateral capacity, is not well predicted by the severity or location of the disease. Final clinical outcome results from the ongoing VERiTAS study will further clarify the relevance of anatomic stenosis and hemodynamic assessment to predicting stroke risk in patients with vertebrobasilar disease.

Introduction: The Nationwide Inpatient Sample (NIS) is the largest publicly available inpatient care database. Its use in subarachnoid hemorrhage (SAH) outcome studies, has been limited by an inability to control for SAH severity, and unverified outcome measures. To address this, we developed the NIS-SAH Severity Score (NIS-SSS) and NIS-SAH Outcome Measure (NIS-SOM). Methods: Three patient populations were used. Pop-I (N=148,958) and -II (N=147,395) were derived from the 1998-2009 NIS. Pop-III (N = 716) was derived from our institution. Using Pop-I, diagnosis codes likely to predict poor outcome were used to create the NIS-SOM. To create the NIS-SSS, diagnoses likely to predict SAH severity were entered into a regression model assessing poor outcome; model coefficients of significant factors were summed to generate the NIS-SSS. NIS-SOM was validated in Pop-III against modified Rankin Score (mRS) using inter-rater reliability; NIS-SSS was validated against Hunt-Hess (HH) grade using ANOVA; and the ability of NIS-SSS to predict poor outcome by mRS was analyzed using logistic regression. Using Pop-II, the ability of NIS-SSS to predict poor outcome was compared to other common measures of disease severity (APR-DRG, APS-DRG, and DRG). Results: A strong correlation between NIS-SOM and mRS was found, with agreement and Kappa statistic of 85% and 0.63 when poor outcome was defined by mRS > 2 and 95% and 0.84 when poor outcome was defined by mRS > 3. The NIS-SSS significantly correlated to HH grade (Fig. 1A) and strongly predicted poor outcome (Fig. 1B). When compared to APR-DRG, APS-DRG, and DRG, NIS-SSS was more accurate in predicting SAH outcome (AUC = 0.69, 0.71, 0.71, and 0.79, respectively). Conclusion: Our results indicate that: NIS-SOM is a valid measure for SAH outcome, NIS-SSS is a valid measure for SAH severity, and NIS-SSS outperforms other measures of disease severity in predicting SAH outcome. We believe NIS-SOM and NIS-SSS should be included in future NIS analyses.

INTRODUCTION: Prior studies have suggested an increased prevalence of intracranial aneurysms (ICA) in patients with bicuspid aortic valves (BAV) and thoracic ascending aortic aneurysms (TAA). We tested the hypothesis that if true, conversely, the prevalence of BAV and TAA should be increased in patients with ICA. METHODS: We identified and reviewed the clinical records of patients treated for an ICA at our institution between 2002 and 2011. Only those with an echocardiogram report in their clinical record were included for further analysis. The prevalence of BAV and TAA in this cohort was determined based on the echocardiogram reports, medical records, and, when available, cross-sectional chest imaging. Proportion confidence intervals were calculated and compared to population prevalence estimates. RESULTS: Of 1051 patients with ICA, 321 had available echocardiogram reports that included assessment of the aortic valve. Of these, 85 also had cross-sectional chest imaging. Of the 321 patients, 2 were reported to have a BAV (0.6%, 95% CI 0 - 2.5%), similar to population prevalence estimates for this condition. In this same cohort, there were 15 (4.7%, 95% CI 2.7 - 7.8%) patients with a TAA. Among the 85 patients with cross-sectional chest imaging, the prevalence of TAA exceeded that expected for a community age- and gender-matched population (see Figure, gray lines represent upper and lower limits of normal). CONCLUSIONS: This retrospective analysis suggests an increased prevalence of TAA, but not BAV, in patients with ICA.

INTRODUCTION:Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disease associated with high rates of mortality (40% at 1 month) and morbidity (only 50% of survivors return to work). Outcome depends critically on delayed cerebral ischemia (DCI), which includes cerebral vasospasm and microthro