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Aneurysmal subarachnoid hemorrhage (aSAH) occurs less often than other stroke types but affects younger patients, imposing a disproportionately high burden of long-term disability. Although management advances have improved outcomes over time, relatively few aSAH treatments have been tested in randomized clinical trials (RCTs). One lesson learned from COVID-19 is that trial platforms can facilitate the efficient execution of multicenter RCTs even in complex diseases during challenging conditions. An aSAH trial platform with standardized eligibility criteria, randomization procedures, and end point definitions would enable the study of multiple targeted interventions in a perpetual manner, with treatments entering and leaving the platform based on predefined decision algorithms. An umbrella institutional review board protocol and clinical trial agreement would allow individual arms to be efficiently added as amendments rather than stand-alone protocols. Standardized case report forms using the National Institutes of Health/National Institute of Neurological Disorders and Stroke common data elements and general protocol standardization across arms would create synergies for data management and monitoring. A Bayesian analysis framework would emphasize frequent interim looks to enable early termination of trial arms for futility, common controls, borrowing of information across arms, and adaptive designs. A protocol development committee would assist investigators and encourage pragmatic designs to maximize generalizability, reduce site burden, and execute trials efficiently and cost-effectively. Despite decades of steady clinical progress in the management of aSAH, poor patient outcomes remain common, and despite the increasing availability of RCT data in other fields, it remains difficult to perform RCTs to guide more effective care for aSAH. The development of a platform for pragmatic RCTs in aSAH would help close the evidence gap between aSAH and other stroke types and improve outcomes for this important disease with its disproportionate public health burden., Competing Interests: Dr Kamel reports an ownership stake in TET Medical, compensation from American Medical Association and Javelin Medical for consultant services, compensation from Boehringer Ingelheim for end point review committee services, employment by Weill Cornell Medical College, compensation from Medtronic and Janssen Biotech for other services, and compensation from Novo Nordisk and AstraZeneca for end point review committee services. Dr Suarez reports compensation from Acasti Pharma for data and safety monitoring services and compensation from Cyban for consultant services. Dr Mack reports compensation from Viseon, Inc, for consultant services, compensation from Spartan Micro for consultant services, compensation from Cerebrotech for other services, compensation from Integra LifeSciences for consultant services, stock options in Spartan Micro, compensation from Egret for consultant services, stock options in Stream Biomedical, compensation from Viseon for other services, compensation from Endostream for other services, compensation from Vastrax for other services, stock holdings in Rebound Therapeutics, employment by the University of Southern California, compensation from Q’Apel for consultant services, compensation from Imperative Care, Inc, for consultant services, compensation from Radical Catheters for other services, compensation from Q’Apel for other services, stock options in Egret, compensation from Medtronic for other services, compensation from Stream Biomedical for consultant services, stock holdings in Truvic, compensation from Borvo for other services, and compensation from Stryker for data and safety monitoring services. Dr Chou reports compensation from Acasti for consultant services; employment by Northwestern Medicine; compensation from CSL Behring for consultant services; service as a member of the Board of Directors for the Neurocritical Care Society; grants from the Neurocritical Care Society; compensation from BioVie for consultant services; grants from the National Institute of Neurological Disorders and Stroke; and employment by Northwestern University. Dr Busl reports grants from the National Institutes of Health (NIH). Dr Derdeyn reports compensation from noNO for data and safety monitoring services, compensation from Silk Road Medical, Inc, for data and safety monitoring services, stock options in Euphrates Vascular, and compensation from Penumbra, Inc, for data and safety monitoring services. Dr Dangayach reports employment by Icahn School of Medicine at Mount Sinai, grants from Visionable, compensation from The Jacob’s Institute for consultant services, grants from Ceibahealth, grants from The Aneurysm and AVM Foundation (TAAF), grants from Neurosteer, and grants from American Academy of Neurology. Dr Elm reports compensation from CSL Behring for consultant services and grants from NIH. Dr Beall reports grants from NIH. Dr Ko reports compensation from Route 92 Medical, Inc, for data and safety monitoring services; service on the Board of Directors for TAAF; employment by the School of Medicine, University of California, San Francisco; and funding from the American Heart Association and NIH. The other authors report no conflicts.

Competing Interests: Disclosures None.

Aim: The "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage" replaces the 2012 "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage." The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage., Methods: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. Structure: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients' and their families' and caregivers' interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Background Familial cerebral cavernous alformation (CCM) is an autosomal dominant disease caused by mutations in KRIT1 , CCM2 , or PDCD10 . Cases typically present with multiple lesions, strong family history, and neurological symptoms, including seizures, headaches, or other deficits. Intracranial hemorrhage (ICH) is a severe manifestation of CCM, which can lead to death or long-term neurological deficits. Few studies have reported ICH rates and risk factors in familial CCM. We report ICH rates and assess whether CCM lesion burden, a disease severity marker, is associated with risk of symptomatic ICH during follow-up in a well-characterized cohort of familial CCM cases. Methods and Results We studied 386 patients with familial CCM with follow-up data enrolled in the Brain Vascular Malformation Consortium CCM Project. We estimated symptomatic ICH rates overall and stratified by history of ICH before enrollment. CCM lesion burden (total lesion count and large lesion size) assessed at baseline enrollment was tested for association with increased risk of subsequent ICH during follow-up using Cox regression models adjusted for history of ICH before enrollment, age, sex, and family structure and stratified on recruitment site. The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without ( P =0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P =0.006). The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without ( P =0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P =0.006). Conclusions Patients with familial CCM with prior history of an ICH event are at higher risk for rehemorrhage during follow-up. In addition, total CCM lesion burden is significantly associated with increased risk of subsequent symptomatic ICH; hence lesion burden may be an important predictor of patient outcome and aid patient risk stratification.

Background: Giant cell arteritis (GCA) is a systemic vasculitis that may cause ischemic stroke. Rarely, GCA can present with aggressive intracranial stenoses, which are refractory to medical therapy. Endovascular treatment (EVT) is a possible rescue strategy to prevent ischemic complications in intracranial GCA but the safety and efficacy of EVT in this setting are not well-described., Methods: A systematic literature review was performed to identify case reports and series with individual patient-level data describing EVT for intracranial GCA. The clinical course, therapeutic considerations, and technique of seven endovascular treatments in a single patient from the authors' experience are presented., Results: The literature review identified 9 reports of 19 treatments, including percutaneous transluminal angioplasty (PTA) with or without stenting, in 14 patients (mean age 69.6 ± 6.3 years). Out of 12 patients 8 (66.7%) with sufficient data had > 1 pre-existing cardiovascular risk factor. All patients had infarction on MRI while on glucocorticoids and 7/14 (50%) progressed despite adjuvant immunosuppressive agents. Treatment was PTA alone in 15/19 (78.9%) cases and PTA + stent in 4/19 (21.1%). Repeat treatments were performed in 4/14 (28.6%) of patients (PTA-only). Non-flow limiting dissection was reported in 2/19 (10.5%) of treatments. The indications, technical details, and results of PTA are discussed in a single illustrative case. We report the novel use of intra-arterial calcium channel blocker infusion (verapamil) as adjuvant to PTA and as monotherapy, resulting in immediate improvement in cerebral blood flow., Conclusion: Endovascular treatment, including PTA with or without stenting or calcium channel blocker infusion, may be effective therapies in medically refractory GCA with intracranial stenosis., (© 2022. The Author(s).)

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making., Competing Interests: The authors declare no conflict of interest.

Prior research suggests substantial between-center differences in functional outcome following aneurysmal subarachnoid hemorrhage (aSAH). One hypothesis is that these differences are due to practice variability. To characterize practice variability, we sent a survey to 230 centers, of which 145 (63%) responded. Survey respondents indicated that an estimated 65% of ruptured aneurysms were treated endovascularly. Sixty-five percent of aneurysms were treated within 24 h of symptom onset, 18% within 24-48 h, and eight percent within 48-72 h. Centers in the United States (US) and Europe (EU) treat aneurysms more often endovascularly (72% and 70% vs. 51%, respectively, US vs. other p < 0.001, and EU vs. other p < 0.01) and more often within 24 h (77% and 64% vs. 46%, respectively, US vs. other p < 0.001, EU vs. other p < 0.01) compared to other centers. Most centers aim for euvolemia (96%) by administrating intravenous fluids to 0 (53%) or +500 mL/day (41%) net fluid balance. Induced hypertension is more often used in US centers (100%) than in EU (87%, p < 0.05) and other centers (81%, p < 0.05), and endovascular therapies for cerebral vasospasm are used more often in US centers than in other centers (91% and 60%, respectively, p < 0.05). We observed significant practice variability in aSAH treatment worldwide. Future comparative effectiveness research studies are needed to investigate how practice variation leads to differences in functional outcome.

Background: Sporadic brain arteriovenous malformations (BAVM) are a major cause of hemorrhagic stroke in younger persons. Prior studies have reported contradictory results regarding the risk of hemorrhage during pregnancy, and there are no standard guidelines for the management of pregnant women who present with BAVM rupture. The purpose of this study is to describe maternal and fetal outcomes and treatment strategies in patients with BAVM hemorrhage during pregnancy., Methods: We performed a retrospective review of the University of California, San Francisco Brain AVM Project database for female patients who were pregnant at the time of BAVM hemorrhage between 2000 and 2017. Clinical and angiographic characteristics at presentation, BAVM treatment, and maternal outcomes using modified Rankin scale (mRS) score at presentation and 2-year follow-up were recorded. Fetal outcomes were abstracted from medical records and maternal reports., Results: Sixteen patients presented with BAVM hemorrhage during pregnancy, 81% (n = 13) of whom were in their second or third trimester. Three patients (19%) who were in their first trimester terminated or miscarried pregnancy prior to BAVM intervention. Of the remaining 13 patients, 77% (n = 10) received emergent BAVM treatment at time of hemorrhage prior to delivery, and 85% of patients achieved BAVM obliteration and good maternal outcomes (mRS 0-2) at 2-year follow-up. All patients had uncomplicated deliveries (69% cesarean and 23% vaginal) with no reports of postnatal cognitive or developmental delays in infants at 2-year follow-up., Conclusions: Our study shows good long-term maternal and fetal outcomes in ruptured BAVM patients presenting during pregnancy, the majority who received BAVM interventional treatment prior to delivery., (© 2021 S. Karger AG, Basel.)

Background: A sustained release microparticle formulation of nimodipine (EG-1962) was developed for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH)., Objective: To assess safety, tolerability, and pharmacokinetics of intracisternal EG-1962 in an open-label, randomized, phase 2 study of up to 12 subjects., Methods: Subjects were World Federation of Neurological Surgeons grades 1 to 2, modified Fisher grades 2 to 4, and underwent aneurysm clipping within 48 h of aSAH. EG-1962, containing 600 mg nimodipine, was administered into the basal cisterns. Outcome on the extended Glasgow Outcome Scale (eGOS), pharmacokinetics, delayed cerebral ischemia and infarction, rescue therapy, and safety were evaluated., Results: The study was halted when a phase 3 study of intraventricular EG-1962 stopped because that study was unlikely to meet its primary endpoint. Six subjects were randomized (5 EG-1962 and 1 oral nimodipine). After 90-d follow-up, favorable outcome on the eGOS occurred in 1 of 5 EG-1962 and in the single oral nimodipine patient. Four EG-1962 and the oral nimodipine subject had angiographic vasospasm. One EG-1962 subject had delayed cerebral ischemia, and all subjects with angiographic vasospasm received rescue therapy except 1 EG-1962 patient. One subject treated with EG-1962 developed right internal carotid and middle cerebral artery narrowing 5 mo after placement of EG-1962, leading to occlusion and cerebral infarction. Pharmacokinetics showed similar plasma concentrations of nimodipine in both groups., Conclusion: Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of EG-1962. Internal carotid artery narrowing and occlusion after placement of EG-1962 in the basal cisterns has not been reported., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.

Background: Though there are many biomarker studies of plasma and serum in patients with aneurysmal subarachnoid hemorrhage (SAH), few have examined blood cells that might contribute to vasospasm. In this study, we evaluated inflammatory and prothrombotic pathways by examining mRNA expression in whole blood of SAH patients with and without vasospasm., Methods: Adult SAH patients with vasospasm (n = 29) and without vasospasm (n = 21) were matched for sex, race/ethnicity, and aneurysm treatment method. Diagnosis of vasospasm was made by angiography. mRNA expression was measured by Affymetrix Human Exon 1.0 ST Arrays. SAH patients with vasospasm were compared to those without vasospasm by ANCOVA to identify differential gene, exon, and alternatively spliced transcript expression. Analyses were adjusted for age, batch, and time of blood draw after SAH., Results: At the gene level, there were 259 differentially expressed genes between SAH patients with vasospasm compared to patients without (false discovery rate < 0.05, |fold change| ≥ 1.2). At the exon level, 1210 exons representing 1093 genes were differentially regulated between the two groups (P < 0.005, ≥ 1.2 |fold change|). Principal components analysis segregated SAH patients with and without vasospasm. Signaling pathways for the 1093 vasospasm-related genes included adrenergic, P2Y, ET-1, NO, sildenafil, renin-angiotensin, thrombin, CCR3, CXCR4, MIF, fMLP, PKA, PKC, CRH, PPARα/RXRα, and calcium. Genes predicted to be alternatively spliced included IL23A, RSU1, PAQR6, and TRIP6., Conclusions: This is the first study to demonstrate that mRNA expression in whole blood distinguishes SAH patients with vasospasm from those without vasospasm and supports a role of coagulation and immune systems in vasospasm.

Significant improvements have been achieved in cardiac arrest resuscitation and postarrest resuscitation care, but mortality remains high. Most of the poor outcomes and deaths of cardiac arrest survivors have been attributed to widespread brain injury. This brain injury, commonly manifested as a comatose state, is a marker of poor outcome and a major basis for unfavorable neurological prognostication. Accurate prognostication is important to avoid pursuing futile treatments when poor outcome is inevitable but also to avoid an inappropriate withdrawal of life-sustaining treatment in patients who may otherwise have a chance of achieving meaningful neurological recovery. Inaccurate neurological prognostication leading to withdrawal of life-sustaining treatment and deaths may significantly bias clinical studies, leading to failure in detecting the true study outcomes. The American Heart Association Emergency Cardiovascular Care Science Subcommittee organized a writing group composed of adult and pediatric experts from neurology, cardiology, emergency medicine, intensive care medicine, and nursing to review existing neurological prognostication studies, the practice of neurological prognostication, and withdrawal of life-sustaining treatment. The writing group determined that the overall quality of existing neurological prognostication studies is low. As a consequence, the degree of confidence in the predictors and the subsequent outcomes is also low. Therefore, the writing group suggests that neurological prognostication parameters need to be approached as index tests based on relevant neurological functions that are directly related to the functional outcome and contribute to the quality of life of cardiac arrest survivors. Suggestions to improve the quality of adult and pediatric neurological prognostication studies are provided.

Background: The National Institute of Neurological Disorders and Stroke (NINDS) Common Data Elements (CDEs) have been generated to standardize and define terms used by the scientific community. The widespread use of these CDEs promotes harmonized data collection in clinical research. The aim of the NINDS Unruptured Intracranial Aneurysms (UIA) and Subarachnoid Hemorrhage (SAH), and Subject Characteristics working group (WG) was to identify, define, and classify CDEs describing the characteristics of patients diagnosed with an UIA and SAH. Thus, "Participant/Subject characteristics" is a set of factors defining a population of selected individuals and allowing comparisons with a reference population and overtime., Methods: Based on standard terms defined by the United States' Census Bureau, CDEs previously defined by several (Stroke, Epilepsy and Traumatic Brain Injury) NINDS CDE working groups literature and expert opinion of the WG, the "Participant/Subject characteristics" domain has been defined., Results: A set of 192 CDEs divided in 7 subsections: demographics (8 CDEs), social status (8 CDEs), behavioral status (22 CDEs), family and medical history (144 CDEs), pregnancy and perinatal history (8 CDEs), history data source reliability (3 CDEs), and prior functional status (3 CDEs) was defined. SAH is characterized by 6 core elements, all classified in the "Participant/Subject characteristics" domain. Four exploratory elements out of the 39 for SAH overall are in the "Participant/Subject characteristics" domain, and all remaining 182 CDEs in the "Participant/Subject characteristics" domain are classified as Supplemental-Highly Recommended elements., Conclusions: These CDEs would allow the development of best practice guidelines to standardize the assessment and reporting of observations concerning UIA and SAH.

Background: Infection with HIV predisposes patients to a myriad of neurologic disorders, including cerebrovascular disease. The pathophysiology is likely multifactorial, with proposed mechanisms including infectious vasculitis, HIV-induced endothelial dysfunction and adverse effects of combination antiretroviral therapy (cART). Epidemiologic data on clinically evident cerebral vasculopathy in HIV-infected adults is scarce, even though stroke hospitalizations are rising in this patient population., Methods: A total of 6,298 HIV-infected adults (San Francisco General Hospital, 2000-2013) were screened to generate a cohort of patients with dedicated neuroimaging of the intra- and extracranial cerebral vasculature. We extracted information regarding the extent of HIV disease (including serial viral load and CD4 counts), cardiovascular disease risk factors and exposure to cART (cross-referenced with pharmacy records) and performed multivariate logistic regression analysis to identify predictors of vasculopathy., Results: Of 144 patients, 55 patients (38.2%) had radiographic evidence of cerebral vasculopathy. Twenty (13.9%) had a vasculopathy characterized by vessel dolichoectasia and intracranial aneurysm formation. Thirty-five patients (24.3%) had intra- and or extracranial stenosis/occlusion. cART use (OR 2.27, 95% CI 1.03-5) and tobacco abuse (OR 2.35, 95% CI 1.04-5.25) were independently associated with the development of any vasculopathy, whereas cART use was also an independent risk factor for the stenosis/occlusion subtype specifically (OR 2.87, 95% CI 1.11-7.45)., Conclusions: There was a high frequency of cerebral arterial disease in this neuroimaging cohort of HIV/AIDS patients. A history of cART use and a history of tobacco abuse were independent risk factors for vasculopathy, though these findings should be confirmed with large-scale prospective studies., (© 2016 S. Karger AG, Basel.)

Background: We previously reported the presence of a cranial "bruit" in patients with cerebral vasospasm by signal processing cranial accelerometry signals time locked to the cardiac cycle. This shift to higher frequencies is likely related to the turbulence of blood flow produced by vascular narrowing. We sought to build a more quantitative model to predict cerebral vasospasm then test the accuracy of this technique to detect cerebral vasospasm in a prospective blinded study., Methods: Skull accelerometry was performed using an array of 6 highly sensitive accelerometers placed in contact with the scalp. Paired transcranial Doppler (TCD) recordings and accelerometry epochs were obtained in consecutive patients with subarachnoid hemorrhage undergoing TCD recordings for surveillance of cerebral vasospasm. The energy of rectified acceleration measurements within systolic and diastolic bands of the cardiac cycle were measured and correlated with TCD-defined spasm. This model was then tested prospectively in a blinded consecutive sample of subarachnoid hemorrhage patients to determine accuracy of the technique., Results: We developed a model predicting cerebral vasospasm from analysis of 14 unblinded subjects with varying degrees of cerebral vasospasm as detected by TCD. We then recorded from 58 subjects obtaining 125-paired recordings of accelerometry and TCD to test this model in a blinded analysis. Accelerometry detection of any spasm versus non-spasm correlated with TCD-defined vasospasm (P < 0.001). The model was 81 % sensitive for detecting any cerebral vasospasm in patients, while the negative predictive value was 61 %., Conclusion: Highly sensitive skull accelerometry can detect cerebral vasospasm with clinically meaningful accuracy. This tool holds promise in the ICU environment to detect as well as reject cerebral vasospasm as the cause of neurological deficits in subarachnoid hemorrhage.

Purpose: Spontaneous echo-contrast (SEC) appears on B-mode images as moving curls of smoke in the lumen of veins. The aims of this study were to investigate the prevalence and characteristics of internal jugular vein SEC among patients with stroke, in comparison with control subjects., Methods: We enrolled 97 Korean patients with acute ischemic stroke and 50 controls. Both internal jugular veins were examined for the presence and severity of SEC and measurement of flow velocity. Venous samples were obtained for laboratory evaluation of hematologic factors., Results: In 294 internal jugular veins, the prevalence of SEC was 81% in stroke patients and 68% in controls (odds ratio, 2.0; 95% confidence interval, 1.1-3.6; p = 0.013). Stroke patients were more likely to have SEC on the left (p = 0.025) than on the right (p = 0.184) internal jugular vein. Overall, the association between stroke and SEC remained significant after adjustment for other variables (odds ratio, 4.3; 95% confidence interval, 1.7-10.8; p = 0.002)., Conclusions: Internal jugular vein SEC was found more frequently in stroke patients than in controls. However, local as well as systemic factors must be considered in the interpretation of this finding., (© 2014 Wiley Periodicals, Inc.)

Object: Although the development and prevalence of cerebral vasospasm (CV) has been extensively investigated in adults, little data exist on the development of CV in children. The authors hypothesized that even though children have highly vasoreactive arteries, because of a robust cerebral collateral blood flow, they rarely develop symptomatic CV., Methods: The authors retrospectively reviewed their university hospital's neurointerventional database for children (that is, patients ≤ 18 years) who were examined or treated for aneurysmal or traumatic subarachnoid hemorrhage (SAH) during the period 1990-2013. Images from digital subtraction angiography (DSA) were analyzed for the extent of CV and collateralization of the cerebral circulation. Results from transcranial Doppler (TCD) ultrasonography were correlated with those from DSA. Cerebral vasospasm on TCD ultrasonography was defined according to criteria developed for adults. Clinical outcomes of CV were assessed with the pediatric modified Rankin Scale (mRS)., Results: Among 37 children (21 boys and 16 girls ranging in age from 8 months to 18 years) showing symptoms of an aneurysmal SAH (comprising 32 aneurysms and 5 traumatic pseudoaneurysms), 17 (46%) had CV confirmed by DSA; CV was mild in 21% of these children, moderate in 50%, and severe in 29%. Only 3 children exhibited symptomatic CV, all of whom had poor collateralization of cerebral vessels. Among the 14 asymptomatic children, 10 (71%) showed some degree of vessel collateralization. Among 16 children for whom TCD data were available that could be correlated with the DSA findings, 13 (81%) had CV according to TCD criteria. The sensitivity and specificity of TCD ultrasonography for diagnosing CV were 95% and 59%, respectively. The time to CV onset detected by TCD ultrasonography was 5 ± 3 days (range 2-10 days). Twenty-five (68%) of the children had good long-term outcomes (that is, had mRS scores of 0-2)., Conclusions: Children have a relatively high incidence of angiographically detectable, moderate-to-severe CV. Children rarely develop symptomatic CV and have good long-term outcomes, perhaps due to robust cerebral collateral blood flow. Criteria developed for detecting CV with TCD ultrasonography in adults overestimate the prevalence of CV in children. Larger studies are needed to define TCD ultrasonography-based CV criteria for children.

Brain arteriovenous malformations (AVMs) are abnormal connections of arteries and veins, resulting in arteriovenous shunting of blood. Primary medical therapy is lacking; treatment options include surgery, radiosurgery, and embolization, often in combination. Judicious selection of AVM patients for treatment requires balancing risk of treatment complications against the risk of hemorrhage in the natural history course. This review focuses on the epidemiology, hemorrhage risk, and factors influencing risk of hemorrhage in the untreated natural course associated with sporadic brain AVM.

Vascular abnormalities of the spinal cord are an important cause of myelopathy. Clinicians need to be aware of these disorders as they can present with a variety of neurologic symptoms ranging from acute spinal neurologic emergencies, relapsing/remitting spells to gradually progressive dysfunction. The unique topography and vascular anatomy of the spinal cord lends to the variety of clinical presentations. Both ischemic and hemorrhagic insults can occur. Increased clinical suspicion, better detection with newer imaging modalities and early treatment can often impact outcomes. The authors review clinical diagnoses, novel imaging, and advanced treatment modalities for the most common causes of vascular myelopathy.

Brain arteriovenous malformations (BAVMs) are an important cause of intracranial hemorrhage (ICH) in young adults. Gene expression profiling of blood has led to the identification of stroke biomarkers, and may help identify BAVM biomarkers and illuminate BAVM pathogenesis. It is unknown whether blood gene expression profiles differ between 1) BAVM patients and healthy controls, or 2) unruptured and ruptured BAVM patients at presentation. We characterized blood transcriptional profiles in 60 subjects (20 unruptured BAVM, 20 ruptured BAVM, and 20 healthy controls) using Affymetrix whole genome expression arrays. Expression differences between groups were tested by ANOVA, adjusting for potential confounders. Genes with absolute fold change ≥ 1.2 (false discovery rate corrected p ≤ 0.1) were selected as differentially expressed and evaluated for over-representation in KEGG biological pathways (p ≤ 0.05). Twenty-nine genes were differentially expressed between unruptured BAVM patients and controls, including 13 which may be predictive of BAVM. Patients with ruptured BAVM compared to unruptured BAVM differed in expression of 1490 genes, with over-representation of genes in 8 pathways including MAPK, VEGF, Wnt signaling and several inflammatory pathways. These results suggest clues to the pathogenesis of BAVM and/or BAVM rupture and point to potential biomarkers or new treatment targets.

Background: Elevated levels of B-type natriuretic peptide (BNP) have been associated with cardiac dysfunction and adverse neurological outcomes after subarachnoid hemorrhage (SAH). We sought to determine whether elevated levels of BNP are independently associated with radiographic cerebral infarction after SAH., Methods: Plasma BNP levels were measured after admission, a mean of 5.5 ± 3.0 days after SAH onset. Cerebral infarction was determined by retrospective review of computerized tomography (CT) scans. Cerebral vasospasm was confirmed by the presence of vascular narrowing on cerebral angiogram. The association between BNP and cerebral infarction was quantified using multivariable logistic regression and reverse stepwise elimination of clinical covariates. A stratified analysis was performed to quantify the association between BNP levels and infarction in patients with and without angiographic vasospasm., Results: BNP levels were measured from 119 subjects. The median BNP level was 105 pg/ml (interquartile range 37-275 pg/ml). In our multivariable model, the top quartile of BNP levels (≥ 276 pg/ml) were associated with an increased odds of cerebral infarction (OR 4.2, P = 0.009). The stratified analysis showed that the association between BNP and infarction was strongest in patients without angiographic vasospasm (OR 7.8, P = 0.006)., Conclusions: Elevated levels of BNP are strongly and independently associated with cerebral infarction, and the association is most pronounced in patients without angiographic vasospasm. These results provide further evidence that other mechanisms can contribute to infarction, and BNP may be a useful biomarker in detecting patients at risk for adverse outcomes without large vessel vasospasm.

Objectives: Randomized trials have suggested that hypertonic saline solutions may be superior to mannitol for the treatment of elevated intracranial pressure, but their impact on clinical practice has been limited, partly by their small size. We therefore combined their findings in a meta-analysis., Data Sources: We searched for relevant studies in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and ISI Web of Knowledge., Study Selection: Randomized trials were included if they directly compared equiosmolar doses of hypertonic sodium solutions to mannitol for the treatment of elevated intracranial pressure in human subjects undergoing quantitative intracranial pressure measurement., Data Extraction: Two investigators independently reviewed potentially eligible trials and extracted data using a preformed data collection sheet. Disagreements were resolved by consensus or by a third investigator if needed. We collected data on patient demographics, type of intracranial pathology, baseline intracranial pressure, osms per treatment dose, quantitative change in intracranial pressure, and prespecified adverse events. Our primary outcome was the proportion of successfully treated episodes of elevated intracranial pressure., Data Synthesis: Five trials comprising 112 patients with 184 episodes of elevated intracranial pressure met our inclusion criteria. In random-effects models, the relative risk of intracranial pressure control was 1.16 (95% confidence interval, 1.00-1.33), and the difference in mean intracranial pressure reduction was 2.0 mm Hg (95% confidence interval, -1.6 to 5.7), with both favoring hypertonic saline over mannitol. A mild degree of heterogeneity was present among the included trials. There were no significant adverse events reported., Conclusions: We found that hypertonic saline is more effective than mannitol for the treatment of elevated intracranial pressure. Our meta-analysis is limited by the small number and size of eligible trials, but our findings suggest that hypertonic saline may be superior to the current standard of care and argue for a large, multicenter, randomized trial to definitively establish the first-line medical therapy for intracranial hypertension.

Background and Purpose: CV following aneurysmal SAH is a significant cause of morbidity and mortality. We review our experiences using PTA and IA verapamil infusion for treating medically refractory cases., Materials and Methods: We performed a retrospective review of patients with SAH admitted from July 2003 to January 2008., Results: Of 546 patients admitted within 72 hours of symptom onset, 231 patients (42%) developed symptomatic CV and 189 patients (35%) required endovascular therapy. A total of 346 endovascular sessions were performed consisting of 1 single angioplasty, 286 IA verapamil infusions, and 59 combined treatments. PTA was performed on 151 vessel segments, and IA verapamil was infused in 720 vessel segments. IA verapamil doses ranged from 2.0 to 30.0 mg per vessel segment and from 3.0 to 55.0 mg per treatment session. Repeat treatments were necessary in 102 patients (54%) for persistent, recurrent, or worsening CV. There were 6 treatment-related complications, of which 2 resulted in clinical worsening. No deaths were attributable to endovascular therapy. At follow-up, 115 patients (61%) had a good outcome and 55 patients (29%) had a poor outcome. Sixteen patients died from causes related to SAH, while 3 died from other medical complications., Conclusions: Endovascular treatments are an integral part of managing patients with medically refractory CV. In our experience, PTA and IA verapamil are safe, with a low complication rate, but further studies are required to determine appropriate patient selection and treatment efficacy.

Object: Neurointensivists are specialists trained to manage all aspects of the intensive care unit (ICU) stay of neurologically ill patients. No study to date has examined the role of neurointensivists specifically in subarachnoid hemorrhage (SAH) management. This study examined the use of a team-based neurointensivist co-management approach., Methods: The authors reviewed all cases involving patients with SAH admitted to the neurosurgical service during a period of more than 4 years. A comparison was made between those patients admitted before and those admitted after the initiation of a mandatory neurointensivist co-management strategy. The primary outcome examined was length of ICU stay. Secondary outcomes included in-hospital mortality, ventriculoperitoneal shunt placement, and other complications such as fever, antibiotic use, pressor utilization, and ventilator-associated pneumonia., Results: A total of 512 patients were included, 216 prior to and 296 after the initiation of neurointensivist comanagement. Length of ICU stay was significantly decreased after the initiation of neurointensivist co-management (mean 12.4 vs 10.9 days, p = 0.02), even after adjusting for demographic characteristics and admission Hunt and Hess grade. The percentage of patients requiring a ventriculoperitoneal shunt significantly decreased after initiation of the co-management approach (23.0 vs 11.5%, p = 0.001), but in-house mortality was unaffected., Conclusions: Initiation of a strategy of routine involvement of a neurointensivist, charged with managing all aspects of the patients' care, resulted in a significantly reduced length of ICU stay for neurosurgical SAH patients. This team-based approach, using neurointensivists to manage neurosurgical SAH patients, merits further study as a successful model of care.

Background: Polymorphisms in the proinflammatory cytokine interleukin (IL)-1beta gene have been associated with systemic atherogenesis, thrombosis and rupture. The aim of this study was to investigate associations between single nucleotide polymorphisms (SNPs) in IL-1beta and intracranial hemorrhage (ICH) in the natural course of brain arteriovenous malformation (BAVM) patients., Method: Two IL-1beta promoter SNPs (-511C-->T, -31T-->C) and 1 synonymous coding SNP in exon 5 at +3953C-->T (Phe) were genotyped in 410 BAVM patients. We performed a survival analysis of time to subsequent ICH, censoring cases at first treatment, death or last follow-up. A Cox regression analysis was performed to obtain hazard ratios (HRs) for genotypes adjusted for age, sex, Caucasian race/ethnicity and hemorrhagic presentation., Results: Subjects with the -31 CC genotype (HR = 2.7; 95% CI 1.1-6.6; p = 0.029) or the -511 TT genotype (HR = 2.6; 95% CI 1.1-6.5; p = 0.039) had a greater risk of subsequent ICH compared with reference genotypes, adjusting for covariates. The +3953C-->T SNP was not significantly associated with an increased ICH risk (p = 0.22). The IL-1beta promoter polymorphisms were also associated with BAVM susceptibility among a subset of 235 BAVM cases and 255 healthy controls of Caucasian race/ethnicity (p < 0.001)., Conclusion: IL-1beta promoter polymorphisms were associated with an increased risk of ICH in BAVM clinical course and with BAVM susceptibility. These results suggest that inflammatory pathways, including the IL-1beta cytokine, may play an important role in ICH., (Copyright (c) 2008 S. Karger AG, Basel.)

Background: The purpose of this study was to compare simple visual grading of perfusion CT (PCT) maps to a more quantitative, threshold-based interpretation of PCT parameters in the characterization of presence and severity of vasospasm., Methods: Thirty-three patients with acute subarachnoid hemorrhage were enrolled in a prospective study and underwent a total of 40 paired PCT and digital subtraction angiography (DSA) examinations. A neuroradiologist and a neurologist reviewed the PCT mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume maps independently; they evaluated five anatomical regions (frontal, temporal, parietal, occipital/thalami, and basal ganglia/insula) and graded them for abnormality (0 if normal, 1 if abnormal in <50% of the region, and 2 if abnormal in >or=50% of the region). A third neuroradiologist blinded to the PCT results reviewed the DSA examinations and assessed 19 segments for the presence or absence of vasospasm. Correlation between PCT and DSA scores was assessed, as well as the sensitivity and specificity of PCT compared to DSA used as a gold standard., Results: MTT (R(2) = 0.939) and CBF (R(2) = 0.907) scores correlated best with DSA scores (p < 0.001). MTT scoring had a sensitivity of 92% and a specificity of 86% compared to DSA; CBF scoring had a sensitivity of 75% and a specificity of 95%. The interobserver agreement between neuroradiologist and neurologist was found to have kappa = 0.789 for MTT and 0.658 for CBF., Conclusion: We propose a user-friendly visual grading system for PCT maps in patients with suspected vasospasm. This visual approach compares favorably to the results of DSA. Sensitive MTT maps should be used for screening, and specific CBF maps for confirmation of vasospasm., ((c) 2008 S. Karger AG, Basel.)

Objective: We previously reported specific genotypes of polymorphisms in two genes, tumor necrosis factor-alpha (TNF-alpha-238G > A) and Apolipoprotein E (ApoE e2), as independent predictors of new intracranial hemorrhage (ICH) in the natural course of untreated brain arteriovenous malformations. We hypothesized that the risk of posttreatment ICH would also be greater in patients with brain arteriovenous malformations with these genotypes., Methods: Two hundred fifteen patients undergoing brain arteriovenous malformation treatment (embolization, arteriovenous malformation resection, radiosurgery, or any combination of these) were genotyped and followed longitudinally. Association of genotype with new symptomatic ICH after initiation of treatment was assessed using Cox proportional hazards adjusted for treatment type, demographics, and established ICH risk factors censored at the time of the last follow-up evaluation or death., Results: The cohort was 48% male and 55% Caucasian, and 52% had an ICH before the initiation of treatment; the mean age +/- standard deviation was 36.6 +/- 17.2 years. Posttreatment ICH occurred in 34 (16%) patients with a median follow-up period of 1.9 years (interquartile range, 1.6 yr). After adjustment, the risk of posttreatment ICH was greater for TNF-alpha-238 AG genotype (hazard ratio [HR], 3.5; 95% confidence interval [CI], 1.3-9.8; P = 0.016) and ApoE e2 (HR, 3.2; 95% CI, 1.0-9.7; P = 0.042). Similar trends for the TNF-alpha-238 AG genotype were seen in surgery (HR, 4.2; 95% CI, 0.6-28.8; P = 0.14) and radiosurgery subsets (HR, 3.8; 95% CI, 0.7-19.4; P = 0.11). An effect of ApoE e2 was seen in radiosurgery subsets (HR, 10.9; 95% CI, 1.3-93.7; P = 0.030), but not in surgery subsets (HR, 1.4; 95% CI, 0.3-7.4; P = 0.67)., Conclusion: Despite a variety of different mechanisms for posttreatment hemorrhage, these data suggest that the TNF-alpha and ApoE genotypes may contribute common phenotypes of enhanced vascular instability that increase the risk of hemorrhagic outcome.

Purpose: Intracranial aneurysm (IA) growth is associated with increased morbidity. We sought to establish a quantitative computational method based on contrast-enhanced MR angiography (CE-MRA) for estimating aneurysmal volume changes over time., Materials and Methods: Computational volume calculations were tested against a distensible phantom. Untreated patients with IA were followed longitudinally with annual MRI. Maximal linear dimensions along the longitudinal axis and two transverse axes were determined by visual review of maximum intensity projection (MIP) data, and aneurysm volume was approximated as (length x width x height)/2. Averages of the visual approximations were compared to the lumenal volume as determined with a computational algorithm using the MRI data., Results: MRI-based measurements accurately represented volume changes in the phantom (R2 = 0.97, Y = 1.06x + 271 CM3). In the clinical study there were a total of 11 intervals of one-year follow-up in six patients (mean +/- SD, age = 53 +/- 20 years). The raw one-year growth using the computational volume was 9% +/- 17%. The corresponding value for the averaged measurement of the reviewers was 8% +/- 14%. Neither the mean values nor the SDs were different (P = .51)., Conclusion: MRI-based measurement of aneurysm volume appears feasible for longitudinal studies of aneurysm natural history., (Copyright 2007 Wiley-Liss, Inc.)

Objective: Patients with brain arteriovenous malformation (AVM) are at life-threatening risk of intracranial hemorrhage (ICH). Identification of genetic variants associated with increased new ICH risk would facilitate risk stratification and guide therapeutic intervention., Methods: Brain AVM patients evaluated at University of California, San Francisco or Kaiser Permanente Northern California were followed longitudinally. Primary outcome was new ICH after diagnosis; censoring events were any AVM treatment or last follow-up examination. The association of ApoE epsilon2 and epsilon4 genotype with new ICH was evaluated by Kaplan-Meier survival analysis and further characterized via a Cox proportional hazards model., Results: We genotyped 284 brain AVM patients (50% women; 57% Caucasian; median follow-up time, 0.3 yr) including 18 patients with a history of new ICH). ApoE epsilon2, but not ApoE epsilon4 genotype, was associated with new ICH (P = 0.0052). ApoE epsilon2 carriers had fivefold increased risk of new ICH (hazard ratio, 5.09; 95% confidence interval, 1.46-17.7; P = 0.010; Cox proportional hazards model adjusting for race/ethnicity and clinical presentation). Subset analysis in the largest homogenous ethnic subcohort (Caucasians) confirmed the increased risk of new ICH in ApoE epsilon2 carriers (hazard ratio, 8.71; 95% confidence interval, 1.4-53.9; P = 0.020; multivariate model adjusting for clinical presentation)., Conclusion: ApoE genotype may influence the risk of ICH in the natural course of brain AVM. The identification of genetic predictors of ICH risk may facilitate estimation of AVM natural history risk and individualize clinical decision-making and therapeutic recommendations.

Purpose: To evaluate the utility of perfusion CT (PCT) combined with CT angiography (CTA) for the diagnosis and management of vasospasm, by using conventional digital subtraction angiography (DSA) as the gold standard., Methods: We retrospectively identified 27 patients with acute subarachnoid hemorrhage who had undergone CTA/PCT, DSA, and transcranial Doppler (TCD) ultrasonography within a time interval of 12 hours of one another. The patients' charts were reviewed for treatment of vasospasm. CTA, PCT, TCD, and DSA examinations were independently reviewed and quantified for vasospasm. PCT thresholds, CTA findings, noncontrast CT (NCT) hypodensities, and TCD thresholds were evaluated for accuracy, sensitivity, and specificity, as well as for negative (NPV) and positive predictive values (PPV) in the prediction of angiographic vasospasm and endovascular treatment, considering DSA as the gold standard., Results: Thirty-five CTA/PCT, TCD, and DSA examinations were performed on these 27 patients. A total of 123 arterial territories in 11 patients demonstrated angiographic vasospasm. Six patients underwent endovascular therapy. CTA qualitative assessment and PCT-derived mean transit time (MTT) with a threshold at 6.4 seconds represented the most accurate (93%) combination for the diagnosis of vasospasm, whereas MTT considered alone represented the most sensitive parameter (NPV, 98.7%). A cortical regional cerebral blood flow value

Eighteen patients underwent stenting for symptomatic basilar artery stenosis. There were three major periprocedural complications (16.7%) without fatality. At a mean 26.7 +/- 12.1-month follow-up, 15 patients (83.3%) had an excellent long-term outcome. Only one patient (5.6%) had moderate disability from recurrent stroke, and two patients died of medical illness at 30 and 36 months after stenting. In this uncontrolled study, stenting appeared to be effective in reducing stroke risk and death and worthy of further scrupulous trial.

Background and Purpose: To compare magnetic resonance (MR) perfusion to gold-standard cerebral blood flow (CBF) determined by intra-arterial (133)Xe washout method., Methods: Eight patients with high-grade carotid stenoses underwent bolus-tracking MR perfusion and intra-arterial (133)Xe washout before and after carotid stenting. MR perfusion was compared with 133Xe-CBF values using Pearson linear correlation analysis., Results: We observed a mean 37+/-38% increase in 133Xe-CBF and a mean 19+/-27% increase in relative CBF (rCBF) by MR perfusion immediately after stent placement. Relative (percent) changes in MR-rCBF showed a close and linear correlation to those seen in 133Xe-CBF (r=0.91; R2=0.84; P=0.002). There was a trend for MR perfusion to underestimate change in CBF at higher relative changes in flow., Conclusions: Bolus-tracking MR perfusion correlates with 133Xe-CBF in estimating postprocedural increases in blood flow but may underestimate the magnitude of the change with higher relative changes.

Background and Purpose: Symptomatic cerebral hyperperfusion has an incidence of 5% after endovascular stent placement. We hypothesized that increases in cerebral blood flow (CBF) after endovascular stent placement are positively correlated with the severity of stenosis., Methods: We studied patients with carotid (n=20) or vertebrobasilar (n=3) stenosis who were undergoing endovascular stent placement. Hemispheric CBF was measured by using intra-arterial xenon-133 technique (initial slope)., Results: CBF increased from 29 +/- 10 to 35 +/- 12 mL/100 g/min (P=.0003) at 39 +/- 12 minutes (range 13-60 minutes) after endovascular stent placement. Baseline characteristics or type of anesthesia did not affect the findings. Physiologic parameters remained constant between measurements: PaCO2 was 43 +/- 6 mmHg and arterial pressure was 89 +/- 16 mmHg. The degree of vascular stenosis (70% +/- 13%, range, 40-99%) was not correlated with change in CBF (r2=0.007, P=.70) or baseline CBF (r2=0.005, P=.31)., Conclusion: CBF increased by 21% +/- 10% after treatment in the absence of clinical symptoms and without intracranial hemorrhage. Modest increases in CBF were common after endovascular revascularization. However, the increased CBF appeared to be unrelated to the degree of vascular stenosis, suggesting a relationship to availability of collateral flow pathways or a neurogenic influence.

Background and Purpose: Dynamic perfusion CT (PCT) with deconvolution produces maps of time-to-peak (TTP), mean transit time (MTT), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV), with a computerized automated map of the infarct and penumbra. We determined the accuracy of these maps in patients with suspected acute hemispheric stroke., Methods: Forty-six patients underwent nonenhanced CT and dynamic PCT, with follow-up CT or MR imaging. Two observers reviewed the nonenhanced studies for signs of stroke and read the PCT maps for TTP, MTT, rCBF, and rCBV abnormalities. Sensitivity, specificity, accuracy, and interobserver agreement were compared (Wilcoxon tests). Nonenhanced CT and PCT data were reviewed for stroke extent according to previously reported methods. Sensitivity, specificity, and accuracy of the computerized maps in detecting ischemia and its extent were determined., Results: Compared with nonenhanced CT, PCT maps were significantly more accurate in detecting stroke (75.7-86.0% vs. 66.2%; P <.01), MTT maps were significantly more sensitive (77.6% vs. 69.2%; P <.01), and rCBF and rCBV maps were significantly more specific (90.9% and 92.7%, respectively, vs. 65.0%; P <.01). Regarding stroke extent, PCT maps were significantly more sensitive than nonenhanced CT (up to 94.4% vs. 42.9%; P <.01) and had higher interobserver agreement (up to 0.763). For the computerized map, sensitivity, specificity, and accuracy, respectively, were 68.2%, 92.3%, and 88.1% in detecting ischemia and 72.2%, 91.8%, and 87.9% in showing the extent., Conclusion: Dynamic PCT maps are more accurate than nonenhanced CT in detecting hemispheric strokes. Despite limited spatial coverage, PCT is highly reliable to assess the stroke extent.

Background and Purpose: Papaverine is used to vasodilate cerebral arteries undergoing vasospasm from subarachnoid hemorrhage. However, papaverine inhibits cellular respiration in vitro and could cause neurotoxicity in humans., Methods: We studied 5 consecutive patients with cerebral vasospasm who were treated with intra-arterial papaverine preserved with chlorobutanol and imaged with MRI fluid-attenuated inversion recovery and diffusion-weighted imaging after treatment. One patient had histological analysis of the brain at autopsy., Results: All 5 patients exhibited marked neurological decline immediately after treatment, and this was sustained through hospital discharge. In all cases, MRI images showed selective gray matter-only signal changes within the vascular territory treated with papaverine. Histological analysis of 1 case brought to autopsy showed selective injury to islands of neurons with relative sparing of white matter., Conclusions: Intra-arterial delivery of papaverine preserved with chlorobutanol into vasospastic anterior cerebral arteries may result in marked neurological deterioration with selective gray matter changes on MRI imaging. This effect is consistent with a permanent toxic effect to human brain. It is unclear whether this toxicity is caused by papaverine or chlorobutanol, and its use in the treatment of cerebral vasospasm should be reserved for cases without alternatives.

Background and Purpose: Numerous parameters are involved in dynamic perfusion CT (PCT). We assessed the influence of the temporal sampling rate and the volume of contrast material., Methods: Sixty patients with ischemic hemispheric stroke lasting > or = 12 hours underwent PCT. Groups of 15 patients each received 30, 40, 50, or 60 mL of contrast agent. Regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), mean transit time (MTT), and time-to-peak (TTP) maps were calculated for temporal sampling intervals of 0.5, 1, 2, 3, 4, 5, and 6 seconds. Results were statistically compared. Signal-to-noise ratios (SNRs), duration of arterial entrance to venous exit, and radiation dose were also assessed., Results: Increasing temporal sampling intervals lead to significant overestimation of rCBV, rCBF, and TTP and significant underestimation of MTT compared with values for an interval of 1 second. Maximal allowable intervals to avoid these effects were 2, 3, 3, and 4 seconds for 30, 40, 50, and 60-mL boluses, respectively. Venous exit of contrast material occurred in 97.5% of patients after 36, 42, 42, and 48 seconds, respectively, for the four volumes. SNRs did not differ with volume. The effective radiation dose varied between 0.852 and 1.867 mSv, depending on the protocol. The cine mode with two 40-mL boluses and the toggling-table technique with one 60-mL bolus had the lowest doses., Conclusion: Temporal sampling intervals greater than 1 second can be used without altering the quantitative accuracy of PCT. Increased sampling intervals reduce the radiation dose and may allow for increased spatial coverage.

Background: There is a shortage of data addressing the clinical characteristics of patients with arteriovenous malformations (AVMs) who present with intracerebral hemorrhages (ICH)., Methods: A retrospective cohort study of members of a large, pre-paid health care program was conducted to identify factors that distinguish ICH secondary to cerebral AVMs from all other causes. Univariate and multivariate analysis was performed using Student's t test, Wilcoxon rank-sum test, and logistic regression., Results: Patients with an underlying AVM were younger and more likely to be female, non-smokers with lower blood pressures, lower cholesterol, and lower white blood cell counts on presentation., Conclusions: These clinical characteristics may be useful in defining potential risk factors in future prospective studies as well as targeting candidates for additional imaging studies after ICH with no apparent etiology., (Copyright 2003 S. Karger AG, Basel)

A 51-year-old man had a 4-month history of progressive headache and gradual onset of somnolence. MRI suggested spontaneous intracranial hypotension (SIH) with diencephalic compression, but he did not improve after three epidural blood patches. He became alert following intrathecal saline infusion that normalized his CSF pressure. A CSF leak was noted on spinal MRI and confirmed with CT contrast myelography. Surgical ligation of a torn dural root sleeve isolating a ruptured Tarlov's cyst resulted in permanent cure.