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The human cerebrovascular system is responsible for maintaining neural function through oxygenation, nutrient supply, filtration of toxins, and additional specialized tasks. While the cerebrovascular system has resilience imparted by elaborate redundant collateral circulation from supportive tertiary structures, it is not infallible, and is susceptible to developing structural vascular abnormalities. The causes of this class of structural cerebrovascular diseases can be broadly categorized as 1) intrinsic developmental diseases resulting from genetic or other underlying aberrations (arteriovenous malformations and cavernous malformations) or 2) extrinsic acquired diseases that cause compensatory mechanisms to drive vascular remodeling (aneurysms and arteriovenous fistulae). Cerebrovascular diseases of both types pose significant risks to patients, in some cases leading to death or disability. The drivers of such diseases are extensive, yet inflammation is intimately tied to all of their progressions. Central to this inflammatory hypothesis is the role of peripheral macrophages; targeting this critical cell type may lead to diagnostic and therapeutic advancement in this area. Here, we comprehensively review the role that peripheral macrophages play in cerebrovascular pathogenesis, provide a schema through which macrophage behavior can be understood in cerebrovascular pathologies, and describe emerging diagnostic and therapeutic avenues in this area., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AKV has received teaching and speaker fees from Penumbra.

Objective: To identify factors, including the use of intraoperative magnetic resonance imaging (iMRI), impacting overall survival (OS) and progression-free survival (PFS) after resections of newly diagnosed intracranial grade II ependymomas performed across 4 different institutions., Methods: Analyses of a multicenter mixed retrospective/prospective database assessed the impact of patient, treatment, and tumor characteristics on OS and PFS. iMRI workflow and logistics were also outlined., Results: Forty-three patients were identified (mean age 25.4 years, mean follow-up 52.8 months). The mean OS was 52.8 ± 44.7 months. Univariate analyses failed to identify prognostic factors associated with OS, likely due to relatively shorter follow-up time for this less aggressive glioma subtype. The mean PFS was 43.7 ± 39.8 months. Multivariate analyses demonstrated that gross-total resection was associated with prolonged PFS compared to both subtotal resection (STR) (P = 0.005) and near-total resection (P = 0.01). Infratentorial location was associated with improved PFS compared to supratentorial location (P = 0.04). Log-rank analyses of Kaplan-Meier survival curves showed that increasing extent of resection (EOR) led to improved OS specifically for supratentorial tumors (P = 0.02) and improved PFS for all tumors (P < 0.001). Thirty cases (69.8%) utilized iMRI, of which 12 (27.9%) involved additional resection after iMRI. Of these, 8/12 (66.7%) resulted in gross-total resection, while 2/12 (16.7%) were near-total resection and 2/12 (16.7%) were subtotal resection. iMRI was not an independent prognosticator of PFS (P = 0.72)., Conclusions: Greater EOR and infratentorial location were associated with increased PFS for grade II ependymomas. Greater EOR was associated with longer OS only for supratentorial tumors. A longer follow-up is needed to establish prognostic factors for this cohort, including use of iMRI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Recent investigations of the meninges have highlighted the importance of the dura layer in central nervous system immune surveillance beyond a purely structural role. However, our understanding of the meninges largely stems from the use of pre-clinical models rather than human samples., Methods: Single-cell RNA sequencing of seven non-tumor-associated human dura samples and six primary meningioma tumor samples (4 matched and 2 non-matched) was performed. Cell type identities, gene expression profiles, and T cell receptor expression were analyzed. Copy number variant (CNV) analysis was performed to identify putative tumor cells and analyze intratumoral CNV heterogeneity. Immunohistochemistry and imaging mass cytometry was performed on selected samples to validate protein expression and reveal spatial localization of select protein markers., Results: In this study, we use single-cell RNA sequencing to perform the first characterization of both non-tumor-associated human dura and primary meningioma samples. First, we reveal a complex immune microenvironment in human dura that is transcriptionally distinct from that of meningioma. In addition, we characterize a functionally diverse and heterogenous landscape of non-immune cells including endothelial cells and fibroblasts. Through imaging mass cytometry, we highlight the spatial relationship among immune cell types and vasculature in non-tumor-associated dura. Utilizing T cell receptor sequencing, we show significant TCR overlap between matched dura and meningioma samples. Finally, we report copy number variant heterogeneity within our meningioma samples., Conclusions: Our comprehensive investigation of both the immune and non-immune cellular landscapes of human dura and meningioma at single-cell resolution builds upon previously published data in murine models and provides new insight into previously uncharacterized roles of human dura., (© 2022. The Author(s).)

Purpose: Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA., Methods: A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS., Results: Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified., Conclusions: Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively.

Objective: To assess the impact of intraoperative magnetic resonance imaging (iMRI), extent of resection (EOR), and other factors on overall survival (OS) and progression-free survival (PFS) for patients with newly diagnosed grade I gliomas., Methods: A multicenter database was queried to identify patients with grade I gliomas. Retrospective analyses assessed the impact of patient, treatment, and tumor characteristics on OS and PFS., Results: A total of 284 patients underwent treatment for grade I gliomas, including 248 resections (205 with iMRI, 43 without), 23 biopsies, and 13 laser interstitial thermal therapy treatments. Log-rank analyses of Kaplan-Meier plots showed improved 5-year OS (P = 0.0107) and PFS (P = 0.0009) with increasing EOR, and a trend toward improved 5-year OS for patients with lower American Society of Anesthesiologists score (P = 0.0528). Greater EOR was associated with significantly increased 5-year PFS for pilocytic astrocytoma (P < 0.0001), but not for ganglioglioma (P = 0.10) or dysembryoplastic neuroepithelial tumor (P = 0.57). Temporal tumors (P = 0.04) and location of "other" (P = 0.04) were associated with improved PFS, and occipital/parietal tumors (P = 0.02) were associated with decreased PFS compared with all other locations. Additional tumor resection was performed after iMRI in 49.7% of cases using iMRI, which produced gross total resection in 64% of these additional resection cases., Conclusions: Patients with grade I gliomas have extended OS and PFS, which correlates positively with increasing EOR, especially for patients with pilocytic astrocytoma. iMRI may increase EOR, indicated by the rate of gross total resection after iMRI use but was not independently associated with increased OS or PFS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose: Impaired cerebrovascular reactivity has been associated with decreased cortical thickness in patients with arterial occlusive diseases. This study tests the hypothesis that severe hemodynamic impairment, indicated by increased oxygen extraction fraction ratios on positron-emission tomography with 15 O tracers, is associated with decreased cortical thickness in patients with Moyamoya phenomenon., Materials and Methods: Patients with unilateral or bilateral idiopathic Moyamoya phenomenon were recruited. Oxygen extraction fraction ratio maps were generated from cerebral images of O[ 15 O] counts divided by H 2 [ 15 O] counts with normalization by corresponding cerebellar counts. The normal range of the oxygen extraction fraction ratio was estimated from historically available healthy control subjects. Cortical thickness was estimated from T1-weighted MR imaging and FreeSurfer. Regional samples of oxygen extraction fraction ratios and cortical thicknesses were drawn using FreeSurfer parcellations, retaining only parcellations from the vascular territory of the middle cerebral artery., Results: Complete MR imaging and PET datasets were available in 35 subjects, including 23 women; the mean age at scanning was 44 years. Patients with Moyamoya phenomenon had a significantly increased regional oxygen extraction fraction ratio compared with 15 healthy control subjects ( P < .001). Regional oxygen extraction fraction ratio and age were significant predictors of cortical thickness ( P < .001 for each) in a generalized linear mixed-effects model. Using hemisphere averages and patient averages, we found that only age was a significant predictor of cortical thickness ( P < .001)., Conclusions: Chronic hemodynamic impairment, as indicated by a higher regional oxygen extraction fraction ratio, was significantly predictive of reduced cortical thickness in mixed-effects analysis of FreeSurfer regions. This phenomenon may be related to reversible metabolic down-regulation., (© 2018 by American Journal of Neuroradiology.)

We report a case of renal cell carcinoma (RCC) metastasis to the calvarium and describe a strategy for percutaneous embolization of hypervascular calvarial tumors with intracranial extension. An elderly patient with history of RCC presented with left-sided weakness. Imaging studies showed a large right frontoparietal calvarial mass with intra- and extracranial extension. The tumor was devascularized by direct puncture tumor embolization using Onyx 18, allowing subsequent operative resection without significant blood loss or the need for flap reconstruction of the scalp. Compared to more common endovascular approaches, direct-needle puncture embolization of transcalvarial masses may offer lower risk of injury to scalp vessels and underlying brain parenchyma.

The authors propose a novel bibilometric index, the reverberation index (r-index), as a comparative assessment tool for use in determining differential reverberation between scientific fields for a given scientific entity. Conversely, this may allow comparison of 2 similar scientific entities within a single scientific field. This index is calculated using a relatively simple 3-step process. Briefly, Thompson Reuters' Web of Science is used to produce a citation report for a unique search parameter (this may be an author, journal article, or topical key word). From this citation report, a list of citing journals is retrieved from which a weighted ratio of citation patterns across journals can be calculated. This r-index is then used to compare the reverberation of the original search parameter across different fields of study or wherever a comparison is required. The advantage of this novel tool is its ability to transcend a specific component of the scientific process. This affords application to a diverse range of entities, including an author, a journal article, or a topical key word, for effective comparison of that entity's reverberation within a scientific arena. The authors introduce the context for and applications of the r-index, emphasizing neurosurgical topics and journals for illustration purposes. It should be kept in mind, however, that the r-index is readily applicable across all fields of study.

OBJECTIVE Despite persisting questions regarding its appropriateness, 30-day readmission is an increasingly common quality metric used to influence hospital compensation in the United States. However, there is currently insufficient evidence to identify which patients are at highest risk for readmission after aneurysmal subarachnoid hemorrhage (SAH). The objective of this study was to identify predictors of 30-day readmission after SAH, to focus preventative efforts, and to provide guidance to funding agencies seeking to risk-adjust comparisons among hospitals. METHODS The authors performed a case-control study of 30-day readmission among aneurysmal SAH patients treated at a single center between 2003 and 2013. To control for geographic distance from the hospital and year of treatment, the authors randomly matched each case (30-day readmission) with approximately 2 SAH controls (no readmission) based on home ZIP code and treatment year. They evaluated variables related to patient demographics, socioeconomic characteristics, comorbidities, presentation severity (e.g., Hunt and Hess grade), and clinical course (e.g., need for gastrostomy or tracheostomy, length of stay). Conditional logistic regression was used to identify significant predictors, accounting for the matched design of the study. RESULTS Among 82 SAH patients with unplanned 30-day readmission, the authors matched 78 patients with 153 nonreadmitted controls. Age, demographics, and socioeconomic factors were not associated with readmission. In univariate analysis, multiple variables were significantly associated with readmission, including Hunt and Hess grade (OR 3.0 for Grade IV/V vs I/II), need for gastrostomy placement (OR 2.0), length of hospital stay (OR 1.03 per day), discharge disposition (OR 3.2 for skilled nursing vs other disposition), and Charlson Comorbidity Index (OR 2.3 for score ≥ 2 vs 0). However, the only significant predictor in the multivariate analysis was discharge to a skilled nursing facility (OR 3.2), and the final model was sensitive to criteria used to enter and retain variables. Furthermore, despite the significant association between discharge disposition and readmission, less than 25% of readmitted patients were discharged to a skilled nursing facility. CONCLUSIONS Although discharge disposition remained significant in multivariate analysis, most routinely collected variables appeared to be weak independent predictors of 30-day readmission after SAH. Consequently, hospitals interested in decreasing readmission rates may consider multifaceted, cost-efficient interventions that can be broadly applied to most if not all SAH patients.

As healthcare delivery shifts from fee-for-service, episodic care to pay for performance and population health, both hospitals and physicians are looking for new forms of integration. A number of regulations and restrictions govern physician relationships with hospitals. In this paper, we review the legal basis for such relationships and the options available. We also survey neurosurgeons and hospital executives to gain their perspective on the current situation and likely future. Two series of structured interviews were conducted with 10 neurosurgeons who work in a range of situations in diverse markets, and with Memorial Hermann Healthcare System senior executive leadership. Their responses form the basis for the subsequent discussion. Neurosurgeons can be independent, join a confederation such as an Independent Physician Association or another type of "clinically integrated" network, or be employed by a hospital, medical school, or physician group. With varying levels of integration comes the strength of size, management expertise, negotiating leverage, economies of scale, and possibly financial advantages, but with impact on autonomy and independence. Constructive alignment can lead to a win-win situation for both the individual physician and the organization, but options vary widely due to heterogeneous local conditions. This paper reviews possible relationships, moving along a spectrum from no financial integration to full integration. Concepts such as physician leasing, professional service agreements, "clinical integration," and employment are presented. This paper offers a practical reference that might be useful to a new graduate, independent neurosurgeon considering integration, or employed physicians considering alternatives., (Copyright © 2016 by the Congress of Neurological Surgeons.)

Background and Purpose: The purpose was to test the hypothesis that increased oxygen extraction fraction (OEF), a marker of severe hemodynamic impairment measured by positron emission tomography, is an independent risk factor for subsequent ischemic stroke in this population., Methods: Adults with idiopathic moyamoya phenomena were recruited between 2005 and 2012 for a prospective, multicenter, blindly adjudicated, longitudinal cohort study. Measurements of OEF were obtained on enrollment. Subjects were followed up for the occurrence of ipsilateral ischemic stroke at 6-month intervals. Patients were censored at the time of surgical revascularization or at last follow-up. The primary analysis was time to ischemic stroke in the territory of the occlusive vasculopathy., Results: Forty-nine subjects were followed up during a median of 3.7 years. One of 16 patients with increased OEF on enrollment had an ischemic stroke and another had an intraparenchymal hemorrhage. Three of 33 patients with normal OEF had an ischemic stroke. On a per-hemisphere basis, 21 of 79 hemispheres with moyamoya vasculopathy had increased OEF at baseline. No ischemic strokes and one hemorrhage occurred in a hemisphere with increased OEF (n=21). Sixteen patients (20 hemispheres), including 5 with increased OEF at enrollment, were censored at a mean of 5.3 months after enrollment for revascularization surgery., Conclusions: The risk of new or recurrent stroke was lower than expected. The low event rate, low prevalence of increased OEF, and potential selection bias introduced by revascularization surgery limit strong conclusions about the association of increased OEF and future stroke risk., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00629915., (© 2017 American Heart Association, Inc.)

OBJECTIVE Colloid cysts are rare, histologically benign lesions that may result in obstructive hydrocephalus and death. Understanding the natural history of colloid cysts has been challenging given their low incidence and the small number of cases in most reported series. This has complicated efforts to establish reliable prognostic factors and surgical indications, particularly for asymptomatic patients with incidental lesions. Risk factors for obstructive hydrocephalus in the setting of colloid cysts remain poorly defined, and there are no grading scales on which to develop standard management strategies. METHODS The authors performed a single-center retrospective review of all cases of colloid cysts of the third ventricle treated over nearly 2 decades at Washington University. Univariate analysis was used to identify clinical, imaging, and anatomical factors associated with 2 outcome variables: symptomatic clinical status and presentation with obstructive hydrocephalus. A risk-prediction model was defined using bootstrapped logistic regression. Predictive factors were then combined into a simple 5-point clinical scale referred to as the Colloid Cyst Risk Score (CCRS), and this was evaluated with receiver-operator characteristics. RESULTS The study included 163 colloid cysts, more than half of which were discovered incidentally. More than half of the incidental cysts (58%) were followed with surveillance neuroimaging (mean follow-up 5.1 years). Five patients with incidental cysts (8.8%) progressed and underwent resection. No patient with an incidental, asymptomatic colloid cyst experienced acute obstructive hydrocephalus or sudden neurological deterioration in the absence of antecedent trauma. Nearly half (46.2%) of symptomatic patients presented with hydrocephalus. Eight patients (12.3%) presented acutely, and there were 2 deaths due to obstructive hydrocephalus and herniation. The authors identified several factors that were strongly correlated with the 2 outcome variables and defined third ventricle risk zones where colloid cysts can cause obstructive hydrocephalus. No patient with a lesion outside these risk zones presented with obstructive hydrocephalus. The CCRS had significant predictive capacity for symptomatic clinical status (area under the curve [AUC] 0.917) and obstructive hydrocephalus (AUC 0.845). A CCRS ≥ 4 was significantly associated with obstructive hydrocephalus (p < 0.0001, RR 19.4). CONCLUSIONS Patients with incidentally discovered colloid cysts can experience both lesion enlargement and symptom progression or less commonly, contraction and symptom regression. Incidental lesions rarely cause acute obstructive hydrocephalus or sudden neurological deterioration in the absence of antecedent trauma. Nearly one-half of patients with symptomatic colloid cysts present with obstructive hydrocephalus, which has an associated 3.1% risk of death. The CCRS is a simple 5-point clinical tool that can be used to identify symptomatic lesions and stratify the risk of obstructive hydrocephalus. External validation of the CCRS will be necessary before objective surgical indications can be established. Surgical intervention should be considered for all patients with CCRS ≥ 4, as they represent the high-risk subgroup.

Background: Ruptured intracranial dissecting aneurysms must be secured quickly to prevent re-hemorrhage. Endovascular sacrifice of the diseased segment is a well-established treatment method, however postoperative outcomes of symptomatic stroke and re-hemorrhage rates are not well reported, particularly for the perforator-rich distal vertebral artery or proximal posterior inferior cerebellar artery (PICA)., Methods: We retrospectively reviewed cases of ruptured distal vertebral artery or PICA dissecting aneurysms that underwent endovascular treatment. Diagnosis was based on the presence of subarachnoid hemorrhage on initial CT imaging and of a dissecting aneurysm on catheter angiography. Patients with vertebral artery aneurysms were selected for coil embolization of the diseased arterial segment based on the adequacy of flow to the basilar artery from the contralateral vertebral artery. Patients with PICA aneurysms were generally treated only if they were poor surgical candidates. Outcomes included symptomatic and asymptomatic procedure-related cerebral infarction, recurrent aneurysm rupture, angiographic aneurysm recurrence, and estimated modified Rankin Scale (mRS)., Results: During the study period, 12 patients with dissecting aneurysms involving the distal vertebral artery (n=10) or PICA (n=2) were treated with endovascular sacrifice. Two patients suffered an ischemic infarction, one of whom was symptomatic (8.3%). One patient (8.3%) died prior to hospital discharge. No aneurysm recurrence was identified on follow-up imaging. Ten patients (83%) made a good recovery (mRS ≤2). Median clinical and imaging follow-up periods were 41.7 months (range 0-126.4 months) and 14.3 months (range 0.03-88.6 months), respectively., Conclusions: In patients with good collateral circulation, endovascular sacrifice may be the preferred treatment for acutely ruptured dissecting aneurysms involving the distal vertebral artery., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

We investigated in cerebral penetrating arterioles the signaling mechanisms and dose-dependency of extracellular magnesium-induced vasodilation and also its vasodilatory effects in vessels preconstricted with agonists associated with delayed cerebral vasospasm following SAH. Male rat penetrating arterioles were cannulated. Their internal diameters were monitored. To investigate mechanisms of magnesium-induced vasodilation, inhibitors of endothelial function, potassium channels and endothelial impairment were tested. To simulate cerebral vasospasm we applied several spasmogenic agonists. Increased extracellular magnesium concentration produced concentration-dependent vasodilation, which was partially attenuated by non-specific calcium-sensitive potassium channel inhibitor tetraethylammonium, but not by other potassium channel inhibitors. Neither the nitric oxide synthase inhibitor L-NNA nor endothelial impairment induced by air embolism reduced the dilation. Although the magnesium-induced vasodilation was slightly attenuated by the spasmogen ET-1, neither application of PF2α nor TXA2 analog effect the vasodilation. Magnesium induced a concentration- and smooth muscle cell-dependent dilation in cerebral penetrating arterioles. Calcium-sensitive potassium channels of smooth muscle cells may play a key role in magnesium-induced vasodilation. Magnesium also dilated endothelium-impaired vessels as well as vessels preconstricted with spasmogenic agonists. These results provide a fundamental background for the clinical use of magnesium, especially in treatment against delayed cerebral ischemia or vasospasm following SAH., (Copyright © 2015 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.)

Objective: Hospital readmission is a common but controversial quality measure increasingly used to influence hospital compensation in the US. The objective of this study was to evaluate the causes for 30-day hospital readmission following aneurysmal subarachnoid hemorrhage (SAH) to determine the appropriateness of this performance metric and to identify potential avenues for improved patient care., Methods: The authors retrospectively reviewed the medical records of all patients who received surgical or endovascular treatment for aneurysmal SAH at Barnes-Jewish Hospital between 2003 and 2013. Two senior faculty identified by consensus the primary medical/surgical diagnosis associated with readmission as well as the underlying causes of rehospitalization., Results: Among 778 patients treated for aneurysmal SAH, 89 experienced a total of 97 readmission events, yielding a readmission rate of 11.4%. The median time from discharge to readmission was 9 days (interquartile range 3-17.5 days). Actual hydrocephalus or potential concern for hydrocephalus (e.g., headache) was the most frequent diagnosis (26/97, 26.8%), followed by infections (e.g., wound infection [5/97, 5.2%], urinary tract infection [3/97, 3.1%], and pneumonia [3/97, 3.1%]) and thromboembolic events (8/97, 8.2%). In most cases (75/97, 77.3%), we did not identify any treatment lapses contributing to readmission. The most common underlying causes for readmission were unavoidable development of SAH-related pathology (e.g., hydrocephalus; 36/97, 37.1%) and complications related to neurological impairment and immobility (e.g., thromboembolic event despite high-dose chemoprophylaxis; 21/97, 21.6%). The authors determined that 22/97 (22.7%) of the readmissions were likely preventable with alternative management. In these cases, insufficient outpatient medical care (for example, for hyponatremia; 16/97, 16.5%) was the most common shortcoming., Conclusions: Most readmissions after aneurysmal SAH relate to late consequences of hemorrhage, such as hydrocephalus, or medical complications secondary to severe neurological injury. Although a minority of readmissions may potentially be avoided with closer medical follow-up in the transitional care environment, readmission after SAH is an insensitive and likely inappropriate hospital performance metric.

Objective: Studies show that phosphodiesterase-V (PDE-V) inhibition reduces cerebral vasospasm (CVS) and improves outcomes after experimental subarachnoid hemorrhage (SAH). This study was performed to investigate the safety and effect of sildenafil (an FDA-approved PDE-V inhibitor) on angiographic CVS in SAH patients., Methods: A2-phase, prospective, nonrandomized, human trial was implemented. Subarachnoid hemorrhage patients underwent angiography on Day 7 to assess for CVS. Those with CVS were given 10 mg of intravenous sildenafil in the first phase of the study and 30 mg in the second phase. In both, angiography was repeated 30 minutes after infusion. Safety was assessed by monitoring neurological examination findings and vital signs and for the development of adverse reactions. For angiographic assessment, in a blinded fashion, pre- and post-sildenafil images were graded as "improvement" or "no improvement" in CVS. Unblinded measurements were made between pre- and post-sildenafil angiograms., Results: Twelve patients received sildenafil; 5 patients received 10 mg and 7 received 30 mg. There were no adverse reactions. There was no adverse effect on heart rate or intracranial pressure. Sildenafil resulted in a transient decline in mean arterial pressure, an average of 17% with a return to baseline in an average of 18 minutes. Eight patients (67%) were found to have a positive angiographic response to sildenafil, 3 (60%) in the low-dose group and 5 (71%) in the high-dose group. The largest degree of vessel dilation was an average of 0.8 mm (range 0-2.1 mm). This corresponded to an average percentage increase in vessel diameter of 62% (range 0%-200%)., Conclusions: The results from this Phase I safety and proof-of-concept trial assessing the use of intravenous sildenafil in patients with CVS show that sildenafil is safe and well tolerated in the setting of SAH. Furthermore, the angiographic data suggest that sildenafil has a positive impact on human CVS.

Background: The pathogenesis of human intracranial arteriovenous malformations (AVMs) is not well understood; this study aims to quantitatively assess cortical folding in patients with these lesions., Methods: Seven adult participants, 4 male and 3 female, with unruptured, surgically unresectable intracranial AVMs were prospectively enrolled in the study, with a mean age of 42.1 years and Spetzler-Martin grade range of II-IV. High-resolution brain MRI T1 and T2 sequences were obtained. After standard preprocessing, segmentation and registration techniques, three measures of cortical folding, the depth difference index (DDI), coordinate distance index (CDI) and gyrification index (GI)), were calculated for the affected and unaffected hemispheres of each subject as well as a healthy control subject set., Results: Of the three metrics, CDI, DDI and GI, used for cortical folding assessment, none demonstrated significant differences between the participants and previously studied healthy adults. There was a significant negative correlation between the DDI ratio between affected and unaffected hemispheres and AVM volume (correlation coefficient r = -0.74, p = 0.04)., Conclusion: This study is the first to quantitatively assess human brain cortical folding in the presence of intracranial AVMs and no significant differences between AVM-affected versus unaffected hemispheres were found in a small dataset. We suggest longitudinal, larger human MRI-based cortical folding studies to assess whether AVMs are congenital lesions of vascular development or de novo , dynamic lesions.

Background and Purpose: Cerebral arterial vasospasm (CVS) is a common complication of aneurysmal subarachnoid hemorrhage strongly associated with neurological deterioration and delayed cerebral ischemia (DCI). The utility of screening for CVS as a surrogate for early detection of DCI, especially in patients without clinical signs of DCI, remains uncertain., Methods: We performed a retrospective analysis of 116 aneurysmal subarachnoid hemorrhage patients who underwent screening digital subtraction angiography to determine the association of significant CVS and subsequent development of DCI. Patients were stratified into 3 groups: (1) no symptoms of DCI before screening, (2) ≥1 episodes of suspected DCI symptoms before screening, and (3) unable to detect symptoms because of poor examination., Results: Patients asymptomatic before screening had significantly lower rates of CVS (18%) compared with those with transient symptoms of DCI (60%; P<0.0001). None of the 79 asymptomatic patients developed DCI after screening, regardless of digital subtraction angiography findings, compared with 56% of those with symptoms (P<0.0001). Presence of CVS was significantly associated with DCI in those with transient symptoms and in those whose examinations did not permit clear assessment (odds ratio 16.0, 95% confidence interval 2.2-118.3, P=0.003)., Conclusions: Patients asymptomatic before screening have low rates of CVS and seem to be at negligible risk of developing DCI. Routine screening of asymptomatic patients seems to have little utility. Screening may still be considered in patients with possible symptoms of DCI or those with examinations too poor to clinically detect symptoms because finding CVS may be useful for risk stratification and guiding management., (© 2015 American Heart Association, Inc.)

Perforating arteries rarely project from the fundus of an aneurysm. We present the case of a 35-year-old woman who was found to have a right posterior communicating artery (PCOM) aneurysm via catheter angiography. Superselective microcatheter angiography revealed that perforating arteries arose from the aneurysm fundus that supplied the anterolateral thalamus. Microsurgical exploration confirmed several small perforating arteries arising from the aneurysm dome as well as an atretic distal PCOM artery. Given the complex anatomy, the lesion was unsuitable for clipping. We propose that this aneurysm represents a developmental variant whereby the proximal PCOM artery becomes atretic and terminates in PCOM perforators. The video can be found here: http://youtu.be/iDcp9fsDjq4.

Background: North American and Asian forms of moyamoya have distinct clinical characteristics. Asian adults with moyamoya are known to respond better to direct versus indirect revascularization. It is unclear whether North American adults with moyamoya have a similar long-term angiographic response to direct versus indirect bypass., Methods: A retrospective review of surgical revascularization for adult moyamoya phenomenon was performed. Preoperative and postoperative cerebral angiograms underwent consensus review, with degree of revascularization quantified as extent of new middle cerebral artery (MCA) territory filling., Results: Late angiographic follow-up was available in 15 symptomatic patients who underwent 20 surgical revascularization procedures. In 10 hemispheres treated solely with indirect arterial bypass, 3 had 2/3 revascularization, 4 had 1/3 revascularization, and 3 had no revascularization of the MCA territory. In the 10 hemispheres treated with direct arterial bypass (8 as a stand-alone procedure and 2 in combination with an indirect procedure), 2 had complete revascularization, 7 had 2/3 revascularization, and 1 had 1/3 revascularization. Direct bypass provided a higher rate of "good" angiographic outcome (complete or 2/3 revascularization) when compared with indirect techniques (P = .0198)., Conclusions: Direct bypass provides a statistically significant, more consistent, and complete cerebral revascularization than indirect techniques in this patient population. This is similar to that reported in the Asian literature, which suggests that the manner of presentation (ischemia in North American adults versus hemorrhage in Asian adults) is likely not a contributor to the extent of revascularization achieved after surgical intervention., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Multiple national initiatives seek to curb spending to address increasing healthcare costs in the United States. The Choosing Wisely initiative is a popular initiative that focuses on reducing healthcare spending by setting guidelines to limit tests and procedures requested by patients and ordered by physicians. To reduce spending on neuroimaging, the Choosing Wisely initiative and other organizations have offered guidelines to limit neuroimaging for headaches. Although the intentions are laudable, these guidelines are inconsistent with the neurosurgeon's experience with patients with brain tumor. If adopted by governing or funding organizations, these guidelines threaten to negatively affect the care and outcomes of patients with brain tumors, who frequently present with minimal symptoms or isolated headaches syndromes. As physicians grapple with the difficult conflict between evidence-based cost-cutting guidelines and individualized patient-tailored medicine, they must carefully balance the costs and benefits of discretionary services such as neuroimaging for headaches. By participating in the development of validated clinical decision rules on neuroimaging for headaches, neurosurgeons can advocate for their patients and improve their patients' outcomes.

Object: Most patients with asymptomatic intracranial aneurysms treated with endovascular methods are closely observed overnight in an intensive care unit setting for complications, including ischemic and hemorrhagic stroke, cardiac dysfunction, and groin access complications. The purpose of this study was to analyze the timing, nature, and rate of in-house postoperative events., Methods: Patients who underwent endovascular treatment or retreatment of unruptured cerebral aneurysms from March 2002 to June 2012 were identified from a prospective case log and their medical records were reviewed. The presentation, patient characteristics, aneurysm size and location, and method of endovascular treatment of each cerebral aneurysm were recorded. Patients with adverse intraprocedural events including perforation and thromboembolism were excluded from this analysis. Overnight postprocedural monitoring was performed in a neurological intensive care unit or postanesthesia care unit for all patients, with discharge planned for postoperative Day 1. Postprocedural events occurring during hospitalization were categorized as intracranial hemorrhage, ischemic stroke, groin hematoma resulting in additional treatment or prolonged hospital stay, retroperitoneal hematoma, and cardiac events. The time from the completion of the procedure to event discovery was recorded., Results: A total of 687 endovascular treatments of unruptured cerebral aneurysms were performed. Nine treatments were excluded from our analysis due to intraprocedural events. Endovascular procedures included coiling alone, stent-assisted coiling, balloon-assisted coiling, balloon-assisted embolization with a liquid embolic agent, and placement of a flow diversion device with or without coiling. Twenty-seven treatments (4.0%) resulted in postprocedural complications: 3 intracranial hemorrhages, 6 ischemic strokes, 4 cardiac events, 5 retroperitoneal hematomas, and 9 groin hematomas. The majority (20 [74.0%]) of these 27 complications were detected within 4 hours from the procedure. These included 1 hemorrhage, 4 ischemic strokes, 4 cardiac events, 2 retroperitoneal hematomas, and 9 groin hematomas. All cardiac events and groin hematomas were detected within 4 hours. Four (14%) of the 27 complications were detected between 4 and 12 hours, 1 (3.7%) between 12 and 24 hours, and 2 (7.4%) more than 24 hours after the procedure. The complications detected more than 4 hours from the conclusion of the procedure included 2 minor intracranial hemorrhages causing headache and resulting in no permanent deficits, 2 mild ischemic strokes, and 3 asymptomatic retroperitoneal hematomas identified by falling hematocrit levels that required no further intervention or treatment., Conclusions: The large majority of significant postprocedural events after uncomplicated endovascular aneurysm intervention occur within the first 4 hours; these events become less frequent with increasing time. Transfer to a floor bed after 4-12 hours for further observation is reasonable to consider in some patients.

Object: Studies using the Nationwide Inpatient Sample (NIS), a large ICD-9-based (International Classification of Diseases, Ninth Revision) administrative database, to analyze aneurysmal subarachnoid hemorrhage (SAH) have been limited by an inability to control for SAH severity and the use of unverified outcome measures. To address these limitations, the authors developed and validated a surrogate marker for SAH severity, the NIS-SAH Severity Score (NIS-SSS; akin to Hunt and Hess [HH] grade), and a dichotomous measure of SAH outcome, the NIS-SAH Outcome Measure (NIS-SOM; akin to modified Rankin Scale [mRS] score)., Methods: Three separate and distinct patient cohorts were used to define and then validate the NIS-SSS and NIS-SOM. A cohort (n = 148,958, the "model population") derived from the 1998-2009 NIS was used for developing the NIS-SSS and NIS-SOM models. Diagnoses most likely reflective of SAH severity were entered into a regression model predicting poor outcome; model coefficients of significant factors were used to generate the NIS-SSS. Nationwide Inpatient Sample codes most likely to reflect a poor outcome (for example, discharge disposition, tracheostomy) were used to create the NIS-SOM. Data from 716 patients with SAH (the "validation population") treated at the authors' institution were used to validate the NIS-SSS and NIS-SOM against HH grade and mRS score, respectively. Lastly, 147,395 patients (the "assessment population") from the 1998-2009 NIS, independent of the model population, were used to assess performance of the NIS-SSS in predicting outcome. The ability of the NIS-SSS to predict outcome was compared with other common measures of disease severity (All Patient Refined Diagnosis Related Group [APR-DRG], All Payer Severity-adjusted DRG [APS-DRG], and DRG). RESULTS The NIS-SSS significantly correlated with HH grade, and there was no statistical difference between the abilities of the NIS-SSS and HH grade to predict mRS-based outcomes. As compared with the APR-DRG, APSDRG, and DRG, the NIS-SSS was more accurate in predicting SAH outcome (area under the curve [AUC] = 0.69, 0.71, 0.71, and 0.79, respectively). A strong correlation between NIS-SOM and mRS was found, with an agreement and kappa statistic of 85% and 0.63, respectively, when poor outcome was defined by an mRS score > 2 and 95% and 0.84 when poor outcome was defined by an mRS score > 3., Conclusions: Data in this study indicate that in the analysis of NIS data sets, the NIS-SSS is a valid measure of SAH severity that outperforms previous measures of disease severity and that the NIS-SOM is a valid measure of SAH outcome. It is critically important that outcomes research in SAH using administrative data sets incorporate the NIS-SSS and NIS-SOM to adjust for neurology-specific disease severity.

Background: Concerns regarding preparation of residents for independent surgical practice are widespread and support for junior surgeons entering practice is variable across institutions and practices. The American College of Surgeons (ACS) Division of Education partnered with the Accreditation Council for Graduate Medical Education (ACGME) to convene a National Invitational Conference to define key issues relating to the transition to practice and develop recommendations to address various challenges., Outcomes of the National Invitational Conference: Leaders from ACS, ACGME, certifying boards, residency review committees, program director organizations, and professional societies representing the breadth of surgical specialties, along with other key stakeholders, were invited to participate in the 1.5-day conference in July 2012. Key recommendations generated during the conference included the need to focus on the transition to practice within the context of the continuum of professional development; definition of specific levels of knowledge and skills expected of graduating surgery residents; development and adoption of competency-based methods for training, assessment, and advancement of residents; implementation of special interventions during the chief resident year to prepare residents for practice; robust evaluations of residents before graduation; intake assessments of junior surgeons during the onboarding processes; and effective mentorship for junior surgeons as they enter practice. Recommendations also highlighted major regulatory, legal, and financial issues. The key role of ACS and other national organizations in implementing the recommendations was underscored., Conclusion: The recommendations from the conference should be of great help in addressing various challenges associated with the transition from surgery residency to independent practice., (Copyright © 2014 Mosby, Inc. All rights reserved.)

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: 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.

Moyamoya is a rare disorder that involves steno-occlusive arterial changes of the anterior circulation, along with proliferative development of basal arterial collaterals. It is either idiopathic (called moyamoya disease) or the result of a specific underlying condition such as atherosclerosis, radiation therapy, or sickle cell disease (called moyamoya syndrome or phenomenon). In recent years, numerous insights into and advances in the understanding, evaluation, and management of moyamoya patients have occurred. This article briefly reviews the spectrum of moyamoya conditions and then provides a synopsis of numerous recent investigations that shed light on various aspects of the disease, including its clinical characteristics, natural history, underlying pathology, imaging, surgical techniques, and long-term patient outcome.

Background and Purpose: Spontaneous idiopathic subarachnoid hemorrhage (SAH) with a perimesencephalic bleeding pattern is usually associated with a benign course, whereas a diffuse bleeding pattern has been associated with a higher risk of vasospasm and disability. We evaluated whether volume of bleeding explains this disparity., Methods: Pattern and amount of bleeding (by Hijdra and intraventricular hemorrhage scores) were assessed in 89 patients with nonaneurysmal SAH. Outcomes included angiographic vasospasm, delayed cerebral ischemia, and functional outcome at 1 year., Results: Diffuse bleeding was associated with significantly higher Hijdra and intraventricular hemorrhage scores than perimesencephalic SAH, P≤0.003. Angiographic vasospasm was more likely in diffuse versus perimesencephalic SAH (45% versus 27%; odds ratio, 2.9; P=0.08), but adjustment for greater blood burden only partially attenuated this trend (adjusted odds ratio, 2.2; 95% confidence interval, 0.69-7.2; P=0.18); delayed cerebral ischemia was only seen in those with diffuse bleeding. Patients with diffuse bleeding were less likely to be discharged home (68% versus 90%; P=0.01) and tended to have more residual disability (modified Rankin scale, 3-6; 20% versus 6%; P=0.18)., Conclusions: Nonaneurysmal SAH can still result in vasospasm and residual disability, especially in those with diffuse bleeding. This disparity is only partially accounted for by greater cisternal or intraventricular blood, suggesting that the mechanism and distribution of bleeding may be as important as the amount of hemorrhage in patients with idiopathic SAH.

Assessing the academic impact and output of scientists and physicians is essential to the academic promotion process and has largely depended on peer review. The inherent subjectivity of peer review, however, has led to an interest to incorporate objective measures into more established methods of academic assessment and promotion. Journal impact factor has been used to add objectivity to the process but this index alone does not capture all aspects of academic impact and achievement. The "h" index and its variants have been designed to compensate for these shortcomings, and have been successfully used in the fields of physics, mathematics, and biology, and more recently in medicine. Leaders in academic neurosurgery should be aware of the advantages offered by each of these indices, as well as of their individual shortcomings, to be able to efficiently use them to refine the peer-review process. This review critically analyzes indices that are currently available to evaluate the academic impact of scientists and physicians. These indices include the total citation count, the total number of papers, the impact factor, as well as the "h" index with eight of its most common variants. The analysis focuses on their use in the field of academic neurosurgery, and discusses means to implement them in current review processes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Object: The goal of this study was to examine the reasons for early readmissions within 30 days of discharge to a major academic neurosurgical service., Methods: A database of readmissions within 30 days of discharge between April 2009 and September 2010 was retrospectively reviewed. Clinical and administrative variables associated with readmission were examined, including age, sex, race, days between discharge and readmission, and insurance type. The readmissions were then assigned independently by 2 neurosurgeons into 1 of 3 categories: scheduled, adverse event, and unrelated. The adverse event readmissions were further subcategorized into patients readmitted although best practices were followed, those readmitted due to progression of their underlying disease, and those readmitted for preventable causes. These variables were compared descriptively., Results: A total of 348 patients with 407 readmissions were identified, comprising 11.5% of the total 3552 admissions. The median age of readmitted patients was 55 years (range 16-96 years) and patients older than 65 years totaled 31%. There were 216 readmissions (53% of 407) for management of an adverse event that was classified as either preventable (149 patients; 37%) or unpreventable (67 patients; 16%). There were 113 patients (28%) who met readmission criteria but who were having an electively scheduled neurosurgical procedure. Progression of disease (48 patients; 12%) and treatment unrelated to primary admission (30 patients; 7%) were additional causes for readmission. There was no significant difference in the proportion of early readmissions by payer status when comparing privately insured patients and those with public or no insurance (p = 0.09)., Conclusions: The majority of early readmissions within 30 days of discharge to the neurosurgical service were not preventable. Many of these readmissions were for adverse events that occurred even though best practices were followed, or for progression of the natural history of the neurosurgical disease requiring expected but unpredictably timed subsequent treatment. Judicious care often requires readmission to prevent further morbidity or death in neurosurgical patients, and penalties for readmission will not change these patient care obligations.

Background: The angle of the basilar artery bifurcation of (BAB angle) is thought to influence the risk of the development and rupture of aneurysms at this site. It is, however, unknown whether the BAB angle also influences the incidence of angiographically negative perimesencephalic subarachnoid hemorrhage (PMSAH)., Objective: We performed a retrospective cross-sectional study comparing the BAB angle in a series of patients who presented with subarachnoid hemorrhage from a ruptured aneurysm at the top of the basilar artery (BSAH) with the BAB angle in a series of patients who presented with PMSAH., Methods: Consecutive patients who presented to our institution with PMSAH or BSAH between January 1, 2005 and December 31, 2010 were studied. Patients with PMSAH were further subdivided into patients with classic PMSAH (CPMSAH) and those with nonclassic PMSAH (NCPMSAH) based on initial head computed tomography examinations. In each patient, the BAB angle was measured on the standard cranial anteroposterior projections after vertebral artery injections., Results: A total of 21 patients with CPMSAH, 30 patients with NCPMSAH, and 31 patients with BSAH were studied. The BAB angle was significantly smaller in patients with CPMSAH (87.7 ± 17.1 degrees) and NCPMSAH (98.4 ± 21.1 degrees) compared with patients with BSAH (135.0 ± 30.8 degrees) (P < .001)., Conclusion: The significantly lower BAB angle in PMSAH patients compared with BSAH patients suggests that bleeding in PMSAH is either nonarterial in nature or is secondary to variations in hemodynamic arterial stress at the top of the basilar artery that need to be studied further with computational models.

Atherosclerotic disease has been suspected as a cause of moyamoya disease in some patients but has not, to the authors' knowledge, been confirmed by pathological studies. The authors present the histopathological findings in a patient with moyamoya collateral formation associated with atherosclerotic occlusive disease of the distal internal carotid artery (ICA). Typical atheromatous changes were evident in the distal ICA and proximal middle cerebral artery. In addition, intimal thickening, fibrosis, and abnormal internal elastic lamina were present in these vessels. These findings are common in moyamoya but not in atherosclerotic disease. Proliferation and enlargement of the lenticulostriate arteries in the basal ganglia was also identified. Moyamoya phenomenon secondary to atherosclerotic disease has similar histopathological features to idiopathic moyamoya phenomenon, both in the affected large basal arteries and lenticulostriate collaterals. These findings support the hypothesis advanced by Peerless that moyamoya is a 2-step process involving an obliterative vasculopathy of the terminal ICA and a secondary proliferative response.

Background and Purpose: Reduced risk and severity of stroke in adult females are thought to depend on normal levels of endogenous estrogen, which is a known neuro- and vasoprotective agent in experimental cerebral ischemia. Recently, a novel G protein-coupled estrogen receptor (GPER, formerly GPR30) has been identified and may mediate the vasomotor and -protective effects of estrogen. However, the signaling mechanisms associated with GPER in the cerebral microcirculation remain unclear. We investigated the mechanism of GPER-mediated vasoreactivity and also its vasoprotective effect after hypoxia/reoxygenation (H/RO) injury., Methods: Rat cerebral penetrating arterioles from both sexes were isolated, cannulated, and pressurized. Vessel diameters were recorded by computer-aided videomicroscopy. To investigate vasomotor mechanism of the GPER agonist (G-1), several inhibitors with or without endothelial impairment were tested. Ischemia/reperfusion injury was simulated using H/RO. Vasomotor responses to adenosine triphophate after H/RO were measured with or without G-1 and compared with controls., Results: G-1 produced a vasodilatory response, which was partially dependent on endothelium-derived nitric oxide (NO) but not arachidonic acid cascades and endothelial hyperpolarization factor. Attenuation of G-1-vasodilation by the NO synthase inhibitor and endothelium-impairment were greater in vessels from female than male animals. G-1 treatment after H/RO injury fully restored arteriolar dilation to adenosine triphophate compared with controls., Conclusions: GPER agonist elicited dilation, which was partially caused by endothelial NO pathway and induced by direct relaxation of smooth muscle cells. Further, GPER agonist restored vessel function of arterioles after H/RO injury and may play an important role in the ability of estrogen to protect the cerebrovasculature against ischemia/reperfusion injury.

Object: The purpose of aneurysm surgery is complete aneurysm obliteration while sparing associated arteries. Indocyanine green (ICG) videoangiography is a new technique that allows for real-time evaluation of blood flow in the aneurysm and vessels. The authors performed a retrospective study to compare the accuracy of ICG videoangiography with intraoperative angiography (IA), and determine if ICG videoangiography can be used without follow-up IA., Methods: From June 2007 through September 2009, 155 patients underwent craniotomies for clipping of aneurysms. Operative summaries, angiograms, and operative and ICG videoangiography videos were reviewed. The number, size, and location of aneurysms, the ICG videoangiography and IA findings, and the need for clip adjustment after ICG videoangiography and IA were recorded. Discordance between ICG videoangiography and IA was defined as ICG videoangiography demonstrating aneurysm obliteration and normal vessel flow, but post-IA showing either an aneurysmal remnant and/or vessel occlusion requiring clip adjustment., Results: Thirty-two percent of patients (49 of 155) underwent both ICG videoangiography and IA. The post-ICG videoangiography clip adjustment rate was 4.1% (2 of 49). The overall rate of ICG videoangiography-IA agreement was 75.5% (37 of 49) and the ICG videoangiography-IA discordance rate requiring post-IA clip adjustment was 14.3% (7 of 49). Adjustments were due to 3 aneurysmal remnants and 4 vessel occlusions. These adjustments were attributed to obscuration of the residual aneurysm or the affected vessel from the field of view and the presence of dye in the affected vessel via collateral flow. Although not statistically significant, there was a trend for ICG videoangiography-IA discordance requiring clip adjustment to occur in cases involving the anterior communicating artery complex, with an odds ratio of 3.3 for ICG videoangiography-IA discordance in these cases., Conclusions: These results suggest that care should be taken when considering ICG videoangiography as the sole means for intraoperative evaluation of aneurysm clip application. The authors further conclude that IA should remain the gold standard for evaluation during aneurysm surgery. However, a combination of ICG videoangiography and IA may ultimately prove to be the most effective strategy for maximizing the safety and efficacy of aneurysm surgery.

Object: The aim of this study was to define the optimal treatment for patients with symptomatic intraluminal carotid artery thrombus (ICAT)., Methods: The authors performed a retrospective chart review of patients who had presented with symptomatic ICAT at their institution between 2001 and 2011., Results: Twenty-four patients (16 males and 8 females) with ICAT presented with ischemic stroke (18 patients) or transient ischemic attack ([TIA], 6 patients). All were initially treated using anticoagulation with or without antiplatelet drugs. Eight of these patients had no or only mild carotid artery stenosis on initial angiography and were treated with medical management alone. The remaining 16 patients had moderate or severe carotid stenosis on initial angiography; of these, 10 underwent delayed revascularization (8 patients, carotid endarterectomy [CEA]; 2 patients, angioplasty and stenting), 2 refused revascularization, and 4 were treated with medical therapy alone. One patient had multiple TIAs despite medical therapy and eventually underwent CEA; the remaining 23 patients had no TIAs after treatment. No patient suffered ischemic or hemorrhagic stroke while on anticoagulation therapy, either during the perioperative period or in the long-term follow-up; 1 patient died of an unrelated condition. The mean follow-up was 16.4 months., Conclusions: Results of this study suggest that initial anticoagulation for symptomatic ICAT leads to a low rate of recurrent ischemic events and that carotid revascularization, if indicated, can be safely performed in a delayed manner.

Object: The goal of this study was to determine the clinical course of Borden-Shucart Type I cranial dural arteriovenous fistulas (DAVFs) and to calculate the annual rate of conversion of these lesions to more aggressive fistulas that have cortical venous drainage (CVD)., Methods: A retrospective chart review was conducted of all patients harboring DAVFs who were seen at the authors' institution between 1997 and 2009. Twenty-three patients with Type I DAVFs who had available clinical follow-up were identified. Angiographic and clinical data from these patients were reviewed. Neurological outcome and status of presenting symptoms were assessed during long-term follow-up., Results: Of the 23 patients, 13 underwent endovascular treatment for intolerable tinnitus or ophthalmological symptoms, and 10 did not undergo treatment. Three untreated patients died of unrelated causes. In those who were treated, complete DAVF obliteration was achieved in 4 patients, and palliative reduction in DAVF flow was achieved in 9 patients. Of the 19 patients without radiographic cure, no patient developed intracranial hemorrhage or nonhemorrhagic neurological deficits (NHNDs), and no patient died of DAVF-related causes over a mean follow-up of 5.6 years. One patient experienced a spontaneous, asymptomatic obliteration of a partially treated DAVF in late follow-up, and 2 patients experienced a symptomatic conversion of their DAVF to a higher-grade fistula with CVD in late follow-up. The annual rate of conversion to a higher-grade DAVF based on Kaplan-Meier cumulative event-free survival analysis was 1.0%. The annual rate of intracranial hemorrhage, NHND, and DAVF-related death was 0.0%., Conclusions: A small number of Type I DAVFs will convert to more aggressive DAVFs with CVD over time. This conversion to a higher-grade DAVF is typically heralded by a change in patient symptoms. Follow-up vascular imaging is important, particularly in the setting of recurrent or new symptoms.

Background and Purpose: Since 2002 the Neuroform stent has expanded endovascular treatment of wide-necked intracranial aneurysms. A study was undertaken to assess the technical success rates and angiographic and clinical outcomes in stent-assisted coiling with Neuroform 1, 2, 2 Treo and 3., Methods: Patients undergoing Neuroform stent-assisted coiling were enrolled in a prospective registry that included 156 stent deployment attempts in 113 consecutive patients (mean age 53, range 25-78). Deployment success and difficulty, stent movement, procedural complications, immediate/delayed aneurysm occlusion and in-stent stenosis on angiographic follow-up were compared among Neuroform 1, 2, 2 Treo and 3 stents using a log likelihood ratio χ2 test., Results: Of 156 stent attempts, 123 (79%) were deployed (Neuroform 1: 8/9 (89%), Neuroform 2: 50/66 (76%), Neuroform 2 Treo: 9/11 (82%), Neuroform 3: 56/70 (80%)) with a symptomatic complication rate of 1.9% (3/156; 2 transient ischemic attacks, 1 stroke, no deaths). Non-target stent placement (1/8 (13%), 6/50 (12%), 2/9 (22%), 3/56 (5%)), difficult placement (2/8 (25%), 10/50 (20%), 5/9 (56%), 6/56 (11%)), stent movement (1/8 (13%), 4/50 (8%), 0/9 (0%), 4/56 (7%)), procedural complications (1/9 (11%), 7/66 (11%), 2/11 (18%), 2/70 (3%)) and immediate near complete aneurysm occlusion (6/6 (100%), 24/37 (65%), 5/7 (71%), 40/45 (89%)) trended towards improvement with each generation. Improvements in difficult stent placement and immediate aneurysm occlusion were significant (p=0.01 and 0.03, respectively)., Conclusion: Neuroform stent-assisted coiling has evolved through four generations as a safe and effective means of treating wide-necked intracranial aneurysms.

Object: The yield of CT angiography (CTA) and MR angiography (MRA) in patients with subarachnoid hemorrhage (SAH) who have a negative initial catheter angiogram is currently not well understood. This study aims to determine the yield of CTA and MRA in a prospective cohort of patients with SAH and a negative initial catheter angiogram., Methods: From January 1, 2005, until September 1, 2010, the authors instituted a prospective protocol in which patients with SAH-as documented by noncontrast CT or CSF xanthochromia and a negative initial catheter angiogram- were evaluated using CTA and MRA to assess for causative cerebral aneurysms. Two neuroradiologists independently evaluated the noncontrast CT scans to determine the SAH pattern (perimesencephalic or not) and the CT and MR angiograms to assess for causative cerebral aneurysms., Results: Seventy-seven patients were included, with a mean age of 52.8 years (median 54 years, range 19-88 years). Fifty patients were female (64.9%) and 27 male (35.1%). Forty-three patients had nonperimesencephalic SAH (55.8%), 29 patients had perimesencephalic SAH (37.7%), and 5 patients had CSF xanthochromia (6.5%). Computed tomography angiography demonstrated a causative cerebral aneurysm in 4 patients (5.2% yield), all of whom had nonperimesencephalic SAH (9.3% yield). Mean aneurysm size was 2.6 mm (range 2.1-3.3 mm). Magnetic resonance angiography demonstrated only 1 of these aneurysms. No causative cerebral aneurysms were found in patients with perimesencephalic SAH or CSF xanthochromia., Conclusions: Computed tomography angiography is a valuable adjunct in the evaluation of patients with nonperimesencephalic SAH who have a negative initial catheter angiogram, demonstrating a causative cerebral aneurysm in 9.3% of patients.

Background and Importance: To describe the novel use of the AutoLITT System (Monteris Medical, Winnipeg, Manitoba, Canada) for focused laser interstitial thermal therapy (LITT) with intraoperative magnetic resonance imaging (MRI) and stereotactic image guidance for the treatment of metastatic adenocarcinoma in the left insula., Clinical Presentation: The patient was a 61-year-old right-handed man with a history of metastatic adenocarcinoma of the colon. He had previously undergone resection of multiple lesions, Gamma Knife radiosurgery, and whole-brain radiation. Despite treatment of a left insular tumor, serial imaging revealed that the lesion continued to enlarge. Given the refractory nature of this tumor to radiation and the deep-seated location, the patient elected to undergo LITT treatment. The center of the lesion and entry point on the scalp were identified with STEALTH (Medtronic, Memphis, Tennessee) image-guided navigation. The AXiiiS Stereotactic Miniframe (Monteris Medical) for the LITT system was secured onto the skull, and a trajectory was defined to achieve access to the centroid of the tumor. After a burr hole was made, a gadolinium template probe was inserted into the AXiiiS base. The trajectory was confirmed via an intraoperative MRI, and the LITT probe driver was attached to the base and CO2-cooled, side-firing laser LITT probe. The laser was activated and thermometry images were obtained. Two trajectories, posteromedial and anterolateral, produced satisfactory tumor ablation., Conclusion: LITT with intraoperative MRI and stereotactic image guidance is a newly available, minimally invasive, and therapeutically viable technique for the treatment of deep seated brain tumors.

Background: The yield of repeat catheter angiography in patients with subarachnoid hemorrhage (SAH) who have negative initial catheter and computed tomography (CT) angiograms is not well understood., Objective: To determine the yield of repeat catheter angiography in a prospective cohort of patients with SAH and negative initial catheter and CT angiograms., Methods: From January 1, 2005, until September 1, 2010, we instituted a prospective protocol in which patients with SAH documented by noncontrast CT (NCCT) or cerebrospinal fluid (CSF) xanthochromia and negative initial catheter and CT angiograms were evaluated with repeat catheter angiography 7 days and 3 months after presentation to assess for causative vascular abnormalities., Results: Seventy-two patients were included, with a mean age of 53.1 years (median, 53.5 years; range, 19-88 years). Forty-six patients were female (63.9%) and 26 male (36.1%). Thirty-nine patients had nonperimesencephalic SAH (54.2%), 29 patients had perimesencephalic SAH (40.3%), and 4 patients had CSF xanthochromia (5.5%). The first repeat catheter angiogram performed 7 days after presentation demonstrated a causative vascular abnormality in 3 patients (yield of 4.2%), 2 of which had nonperimesencephalic SAH (yield of 5.1%), and 1 had perimesencephalic SAH (yield of 3.4%). The second repeat catheter angiogram performed in 43 patients (59.7%) did not demonstrate any causative vascular abnormalities. No causative abnormalities were found in patients with CSF xanthochromia., Conclusion: Repeat catheter angiography performed 7 days after presentation is valuable in the evaluation of patients with SAH who have negative initial catheter and CT angiograms, demonstrating a causative vascular abnormality in 4.2% of patients.