The REACT study: design of a randomized phase 3 trial to assess the efficacy and safety of clazosentan for preventing deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND: For patients presenting with an aneurysmal subarachnoid hemorrhage (aSAH), delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality. The REACT study is designed to assess the safety and efficacy of clazosentan in preventing clinical deterioration due to DCI in patients with aSAH. METHODS: REACT is a prospective, multicenter, randomized phase 3 study that is planned to enroll 400 patients with documented aSAH from a ruptured cerebral aneurysm, randomized 1:1 to 15 mg/hour intravenous clazosentan vs. placebo, in approximately 100 sites and 15 countries. Eligible patients are required to present at hospital admission with CT evidence of significant subarachnoid blood, defined as a thick and diffuse clot that is more than 4 mm in thickness and involves 3 or more basal cisterns. The primary efficacy endpoint is the occurrence of clinical deterioration due to DCI up to 14 days post-study drug initiation. The main secondary endpoint is the occurrence of clinically relevant cerebral infarction at Day 16 post-study drug initiation. Other secondary endpoints include the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) score at Week 12 post-aSAH, dichotomized into poor and good outcome. Radiological results and clinical endpoints are centrally evaluated by independent committees, blinded to treatment allocation. Exploratory efficacy endpoints comprise the assessment of cognition status at 12 weeks and quality of life at 12 and 24 weeks post aSAH. DISCUSSION: In the REACT study, clazosentan is evaluated on top of standard of care to determine if it reduces the risk of clinical deterioration due to DCI after aSAH. The selection of patients with thick and diffuse clots is intended to assess the benefit/risk profile of clazosentan in a population at high risk of vasospasm-related ischemic complications post-aSAH. TRIAL REGISTRATION (ADDITIONAL FILE 1): ClinicalTrials.gov (NCT03585270). EU Clinical Trial Register (EudraCT Number: 2018-000241-39).

Combined Use of X-ray Angiography and Intraprocedural MRI Enables Tissue-based Decision Making Regarding Revascularization during Acute Ischemic Stroke Intervention.

Background For patients with acute ischemic stroke undergoing endovascular mechanical thrombectomy with x-ray angiography, the use of adjuncts to maintain vessel patency, such as stents or antiplatelet medications, can increase risk of periprocedural complications. Criteria for using these adjuncts are not well defined. Purpose To evaluate use of MRI to guide critical decision making by using a combined biplane x-ray neuroangiography 3.0-T MRI suite during acute ischemic stroke intervention. Materials and Methods This retrospective observational study evaluated consecutive patients undergoing endovascular intervention for acute ischemic stroke between July 2019 and May 2020 who underwent either angiography with MRI or angiography alone. Cerebral tissue viability was assessed by using MRI as the reference standard. For statistical analysis, Fisher exact test and Student t test were used to compare groups. Results Of 47 patients undergoing acute stroke intervention, 12 patients (median age, 69 years; interquartile range, 60-77 years; nine men) underwent x-ray angiography with MRI whereas the remaining 35 patients (median age, 80 years; interquartile range, 68-86 years; 22 men) underwent angiography alone. MRI results influenced clinical decision making in one of three ways: whether or not to perform initial or additional mechanical thrombectomy, whether or not to place an intracranial stent, and administration of antithrombotic or blood pressure medications. In this initial experience, decision making during endovascular acute stroke intervention in the combined angiography-MRI suite was better informed at MRI, such that therapy was guided in real time by the viability of the at-risk cerebral tissue. Conclusion Integrating intraprocedural 3.0-T MRI into acute ischemic stroke treatment was feasible and guided decisions of whether or not to continue thrombectomy, to place stents, or to administer antithrombotic medication or provide blood pressure medications. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lev and Leslie-Mazwi in this issue.

Brain Arteriovenous Malformation Recurrence After Apparent Microsurgical Cure: Increased Risk in Children Who Present With Arteriovenous Malformation Rupture.

BACKGROUND AND PURPOSE: Do children have an increased risk for brain arteriovenous malformation (AVM) recurrence compared with adults and does this risk vary depending on initial presentation with AVM rupture? METHODS: We retrospectively studied 115 patients initially presenting with brain AVM under age 25 years who underwent complete surgical resection of the AVM as documented by digital subtraction angiography (DSA) and had delayed follow-up DSA to evaluate for AVM recurrence after apparent initial cure. RESULTS: The mean time from baseline DSA to follow-up DSA was 2.3 years, ranging from 0 to 15 years. Twelve patients (10.4% of the 115 patient cohort and 16.7% of 72 patients with hemorrhage at initial presentation) demonstrated AVM recurrence on follow-up DSA. All patients with recurrence initially presented with intracranial hemorrhage, and intracranial hemorrhage was a significant predictor of recurrence (log rank P=0.037). Among patients with initial hemorrhage, the 5-year recurrence rate was 17.8% (95% CI, 8.3%-35.7%). All recurrences occurred in patients who were children at the time of their initial presentation; the oldest was 15 years of age at the time of initial AVM surgery. The 5-year recurrence rate for children (0-18 years of age) with an initial presentation of hemorrhage was 21.4% (95% CI, 10.1%-41.9%). Using Cox regression, we found the risk of AVM recurrence decreased by 14% per each year increase in age at the time of initial surgical resection (hazard ratio=0.86 [95% CI, 0.75-0.99]; P=0.031). CONCLUSIONS: There is a high rate of recurrence of apparently cured brain AVMs in children who initially present with AVM rupture. Imaging follow-up is warranted to prevent re-rupture.

Indications for the Performance of Intracranial Endovascular Neurointerventional Procedures: A Scientific Statement From the American Heart Association.

Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice.

Thick and Diffuse Subarachnoid Blood as a Treatment Effect Modifier of Clazosentan After Subarachnoid Hemorrhage.

Background and Purpose- Clazosentan, an endothelin receptor antagonist, has been shown to reduce angiographic vasospasm and vasospasm-related morbidity after aneurysmal subarachnoid hemorrhage (SAH), although no effect on long-term functional outcome has been demonstrated. Thick clot on initial computed tomography is associated with an increased risk of vasospasm and delayed cerebral ischemia. In this post hoc analysis, we hypothesized that use of clazosentan in this subpopulation would provide stronger benefit. Methods- We analyzed SAH patients enrolled in the CONSCIOUS-2 and CONSCIOUS-3 studies (Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage) and compared the effects of clazosentan 5 mg/h, 15 mg/h, and placebo starting the day after aneurysm repair. The analysis was performed separately based on the presence or absence of thick (≥4 mm) and diffuse (≥3 cisterns) SAH on admission computed tomography. The primary composite end point was all-cause mortality and vasospasm-related morbidity at 6 weeks, and the main secondary end point was the extended Glasgow Outcome Scale at 3 months, adjusted for admission clinical grade. Results- Of 1718 randomized patients, 919 (53%) had thick and diffuse SAH. The primary composite end point in this group occurred in 36% of placebo-treated patients (n=294), 30% patients treated with clazosentan 5 mg/h (n=514; relative risk, 0.82; 95% CI, 0.67-0.99), and 19% patients treated with clazosentan 15 mg/h (n=111; relative risk, 0.54; 95% CI, 0.36-0.80). Despite this, death or poor functional outcome (Glasgow Outcome Scale ≤4) occurred in 33% of placebo-treated patients, 34% of patients treated with clazosentan 5 mg/h (relative risk 1.02; 95% CI, 0.84-1.23), and 35% of patients treated with clazosentan 15 mg/h (relative risk 1.14; 95% CI, 0.88-1.48). Conclusions- In an enriched population with thick and diffuse SAH, clazosentan at a dose of 5 and 15 mg/h was able to significantly reduce vasospasm-related morbidity in a dose-dependent manner. The absence of an effect on long-term functional status likely reflects the complexity and multiplicity of factors that contribute to poor outcome after SAH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00558311; NCT00940095.

Prevention of Stroke in Patients With Silent Cerebrovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to prevent stroke, the Stroke Council of the American Heart Association convened a writing committee to evaluate existing evidence, to discuss clinical considerations, and to offer suggestions for future research on stroke prevention in patients with 3 cardinal manifestations of silent cerebrovascular disease: silent brain infarcts, magnetic resonance imaging white matter hyperintensities of presumed vascular origin, and cerebral microbleeds. The writing committee found strong evidence that silent cerebrovascular disease is a common problem of aging and that silent brain infarcts and white matter hyperintensities are associated with future symptomatic stroke risk independently of other vascular risk factors. In patients with cerebral microbleeds, there was evidence of a modestly increased risk of symptomatic intracranial hemorrhage in patients treated with thrombolysis for acute ischemic stroke but little prospective evidence on the risk of symptomatic hemorrhage in patients on anticoagulation. There were no randomized controlled trials targeted specifically to participants with silent cerebrovascular disease to prevent stroke. Primary stroke prevention is indicated in patients with silent brain infarcts, white matter hyperintensities, or microbleeds. Adoption of standard terms and definitions for silent cerebrovascular disease, as provided by prior American Heart Association/American Stroke Association statements and by a consensus group, may facilitate diagnosis and communication of findings from radiologists to clinicians.

Reversible cerebral vasoconstriction syndrome is a rare cause of stroke after carotid endarterectomy.

Neurologic events after carotid endarterectomy (CEA) require prompt diagnosis and management to avoid potentially catastrophic sequelae. This report describes a 69-year-old gentleman who underwent a left CEA for a high-grade asymptomatic carotid stenosis with concomitant contralateral carotid occlusion. He had transient and crescendo neurologic events in the first 3 postoperative weeks that culminated in right hand weakness and paresthesia, despite dual antiplatelet therapy, maximal anticoagulation, and undergoing stenting of the endarterectomy site. Neurologic events recurred despite these measures and subsequent angiography showed reversible cerebral vasoconstriction syndrome that was successfully managed without further events. Reversible cerebral vasoconstriction syndrome is an unusual but important cause of neurologic events after CEA that requires aggressive and directed medical therapy.

Monitoring cerebral tissue oxygen saturation at frontal and parietal regions during carotid artery stenting.

Cerebral oximetry is normally placed on the upper forehead to monitor the frontal lobe cerebral tissue oxygen saturation (SctO2). We present a case in which the SctO2 was simultaneously monitored at both frontal and parietal regions during internal carotid artery (ICA) stenting. Our case involves a 79-year-old man who presented after a sudden fall and was later diagnosed with a watershed ischemic stroke in the distal fields perfused by the left middle cerebral artery. He had diffuse atherosclerotic occlusive lesions in the carotid and cerebral arterial systems including an 85 % stenotic lesion in the left distal cervical ICA. The brain territory perfused by the left ICA was devoid of collateral flow from anterior and posterior communicating arteries due to an abnormal circle of Willis. During stenting, the SctO2 monitored at both frontal and parietal regions tracked the procedure-induced acute flow change. However, the baseline SctO2 values of frontal and parietal regions differed. The SctO2-MAP correlation was more consistent on the stroked hemisphere than the non-stroked hemisphere. This case showed that SctO2 can be reliably monitored at the parietal region, which is primarily perfused by the ICA. SctO2 of the stroked brain is more pressure dependent than the non-stroked brain.

Risk adjustment of ischemic stroke outcomes for comparing hospital performance: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

BACKGROUND AND PURPOSE: Stroke is the fourth-leading cause of death and a leading cause of long-term major disability in the United States. Measuring outcomes after stroke has important policy implications. The primary goals of this consensus statement are to (1) review statistical considerations when evaluating models that define hospital performance in providing stroke care; (2) discuss the benefits, limitations, and potential unintended consequences of using various outcome measures when evaluating the quality of ischemic stroke care at the hospital level; (3) summarize the evidence on the role of specific clinical and administrative variables, including patient preferences, in risk-adjusted models of ischemic stroke outcomes; (4) provide recommendations on the minimum list of variables that should be included in risk adjustment of ischemic stroke outcomes for comparisons of quality at the hospital level; and (5) provide recommendations for further research. METHODS AND RESULTS: This statement gives an overview of statistical considerations for the evaluation of hospital-level outcomes after stroke and provides a systematic review of the literature for the following outcome measures for ischemic stroke at 30 days: functional outcomes, mortality, and readmissions. Data on outcomes after stroke have primarily involved studies conducted at an individual patient level rather than a hospital level. On the basis of the available information, the following factors should be included in all hospital-level risk-adjustment models: age, sex, stroke severity, comorbid conditions, and vascular risk factors. Because stroke severity is the most important prognostic factor for individual patients and appears to be a significant predictor of hospital-level performance for 30-day mortality, inclusion of a stroke severity measure in risk-adjustment models for 30-day outcome measures is recommended. Risk-adjustment models that do not include stroke severity or other recommended variables must provide comparable classification of hospital performance as models that include these variables. Stroke severity and other variables that are included in risk-adjustment models should be standardized across sites, so that their reliability and accuracy are equivalent. There is a pressing need for research in multiple areas to better identify methods and metrics to evaluate outcomes of stroke care. CONCLUSIONS: There are a number of important methodological challenges in undertaking risk-adjusted outcome comparisons to assess the quality of stroke care in different hospitals. It is important for stakeholders to recognize these challenges and for there to be a concerted approach to improving the methods for quality assessment and improvement.

Density of thrombus on admission CT predicts revascularization efficacy in large vessel occlusion acute ischemic stroke.

BACKGROUND AND PURPOSE: Can lysability of large vessel thrombi in acute ischemic stroke be predicted by measuring clot density on admission nonenhanced CT (NECT), postcontrast enhanced CT, or CT angiogram (CTA)? METHODS: We retrospectively studied 90 patients with acute large vessel ischemic strokes treated with intravenous (IV) tPA, intra-arterial (IA) tPA, and/or mechanical thrombectomy devices. Clot density [in Hounsfield unit (HU)] was measured on NECT, postcontrast enhanced CT, and CTA. Recanalization was assessed by the Thrombolysis in Cerebral Infarction grading system (TICI) on digital subtraction angiography. RESULTS: Thrombus density on preintervention NECT correlated with postintervention TICI grade regardless of pharmacological (IV tPA r=0.69, IA tPA r=0.72, P<0.0001) or mechanical treatment (r=0.73, P<0.0001). Patients with TICI≥2 demonstrated higher HU on NECT (mean corrected HU IV tPA=1.58, IA tPA=1.66, mechanical treatment=1.7) compared with patients with TICI<2 (IV tPA=1.39, IA tPA=1.4, mechanical treatment=1.3) (P=0.01, 0.006, <0.0001 respectively). There was no association between recanalization and age, sex, baseline National Institute of Health Stroke Scale, treatment method, time to treatment, or clot volume. CONCLUSIONS: Thrombi with lower HU on NECT appear to be more resistant to pharmacological lysis and mechanical thrombectomy. Measuring thrombus density on admission NECT provides a rapid method to analyze clot composition, a potentially useful discriminator in selecting the most appropriate reperfusion strategy for an individual patient.

Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association.

BACKGROUND AND PURPOSE: Stroke is a leading cause of disability, cognitive impairment, and death in the United States and accounts for 1.7% of national health expenditures. Because the population is aging and the risk of stroke more than doubles for each successive decade after the age of 55 years, these costs are anticipated to rise dramatically. The objective of this report was to project future annual costs of care for stroke from 2012 to 2030 and discuss potential cost reduction strategies. METHODS AND RESULTS: The American Heart Association/American Stroke Association developed methodology to project the future costs of stroke-related care. Estimates excluded costs associated with other cardiovascular diseases (hypertension, coronary heart disease, and congestive heart failure). By 2030, 3.88% of the US population>18 years of age is projected to have had a stroke. Between 2012 and 2030, real (2010$) total direct annual stroke-related medical costs are expected to increase from $71.55 billion to $183.13 billion. Real indirect annual costs (attributable to lost productivity) are projected to rise from $33.65 billion to $56.54 billion over the same period. Overall, total annual costs of stroke are projected to increase to $240.67 billion by 2030, an increase of 129%. CONCLUSIONS: These projections suggest that the annual costs of stroke will increase substantially over the next 2 decades. Greater emphasis on implementing effective preventive, acute care, and rehabilitative services will have both medical and societal benefits.

An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term "stroke" is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.

Randomised trial of clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping (CONSCIOUS-2).

We report here results of a randomized, double-blind, placebo-controlled study ( http://www.ClinicalTrials.gov , NCT00558311) that investigated the effect of clazosentan (5 mg/h, n = 768) or placebo (n = 389) administered for up to 14 days in patients with aneurysmal subarachnoid hemorrhage (SAH) repaired by surgical clipping. The primary endpoint was a composite of all-cause mortality, new cerebral infarction or delayed ischemic neurological deficit due to vasospasm, and rescue therapy for vasospasm. The main secondary endpoint was the Glasgow Outcome Scale Extended (GOSE), which was dichotomized. Twenty-one percent of clazosentan- compared to 25% of placebo-treated patients met the primary endpoint (relative risk reduction [RRR] [95% CI]: 17% [-4% to 33%]; p = 0.10). Poor outcome (GOSE score ≤ 4) occurred in 29% of clazosentan- and 25% of placebo-treated patients (RRR: -18% [-45% to 4%]; p = 0.10). In prespecified subgroups, mortality/vasospasm-related morbidity was reduced in clazosentan-treated patients by 33% (8-51%) in poor WFNS (World Federation of Neurological Surgeons) grade (≥III) and 25% (5-41%) in patients with diffuse, thick SAH. Lung complications, anemia and hypotension occurred more frequently with clazosentan. Mortality (week 12) was 6% in both groups. The results showed that clazosentan nonsignificantly decreased mortality/vasospasm-related morbidity and nonsignificantly increased poor functional outcome in patients with aneurysmal SAH undergoing surgical clipping.

Transvenous coil embolization of a Cognard V transverse-sigmoid sinus dural arteriovenous fistula.

Dural arteriovenous fistulas with drainage into the spinal veins, classified as Cognard type 5, can be challenging to diagnose and treat. Brainstem and cervical spinal cord signal abnormalities on magnetic resonance imaging result from venous congestion, and can mimic tumor, infection, or inflammation.1-3 Transarterial and transvenous embolization techniques can be used to treat dural arteriovenous fistulas endovascularly. Efficacious transvenous treatment relies on the ability to safely catheterize the draining vein at the dural arteriovenous fistula site. Transvenous access options may seem limited in the setting of occluded venous sinuses. This case highlights the technical aspects of the transvenous approach to embolization of a transverse-sigmoid sinus dural arteriovenous fistula within an isolated sinus,4,5 demonstrating traversal of the occluded venous sinus from a contralateral approach.6,7[Media: see text].

Evolving indications for pediatric neurointerventional radiology: A single institutional 25-year experience in infants less than one year of age and a brief historical review.

BACKGROUND AND PURPOSE: Pediatric neurointerventional radiology is an evolving subspecialty with growing indications and technological advancement such as miniaturization of devices and decreased radiation dose. The ability to perform these procedures is continuously balanced with necessity given the inherently higher risks of radiation and cerebrovascular injury in infants. The purpose of this study is to review our institution's neurointerventional experience in infants less than one year of age to elucidate trends in this patient population. METHODS: We retrospectively identified 132 patients from a neurointerventional database spanning 25 years (1997-2022) who underwent 226 procedures. Treatment type, indication, and location as well as patient demographics were extracted from the medical record. RESULTS: Neurointerventional procedures were performed as early as day of life 0 in a patient with an arteriovenous shunting malformation. Average age of intervention in the first year of life is 5.9 months. Thirty-eight of 226 procedures were completed in neonates. Intra-arterial chemotherapy (IAC) for the treatment of retinoblastoma comprised 36% of neurointerventional procedures completed in infants less than one year of age followed by low flow vascular malformations (21.2%), vein of Galen malformations (11.5%), and dural arteriovenous fistulas (AVF) (9.3%). Less frequent indications include non-Galenic pial AVF (4.4%) and tumor embolization (3.0%). The total number of interventions has increased secondary to the onset of retinoblastoma treatment in 2010 at our institution. CONCLUSION: The introduction of IAC for the treatment of retinoblastoma in the last decade is the primary driver for the increased trend in neurointerventional procedures completed in infants from 1997 to 2022.

Percutaneous sclerotherapy for head and neck lymphatic malformations in neonates and infants ≤12 months of age.

BACKGROUND: Percutaneous sclerotherapy is an effective treatment for lymphatic malformations (LM) of the head and neck in adults. The purpose of this study was to examine the indications and efficacy of sclerotherapy for head/neck LM in the neonate and infant population. METHODS: We retrospectively reviewed patients treated with percutaneous sclerotherapy for LM of the head/neck at age ≤12 months at a single vascular anomalies clinic. The clinical, anatomic, and technical aspects of each treatment, complications, and post-treatment clinical and imaging outcomes were analyzed. RESULTS: 22 patients underwent 36 treatments during the first year of life. Median age at first treatment was 6.2 months (range 2-320 days). Severe airway compromise was the most frequent indication for treatment (31.8%). Sclerosants included doxycycline (80.5%), sodium tetradecyl sulfate (55.5%), bleomycin (11.1%) and ethanol (2.8%). There were no immediate procedure-related complications; sclerosant-related laboratory complications included transient metabolic acidosis (8.3%) and hemolytic anemia (5.5%). Median follow-up was 3.7 years (IQR 0.6-4.8). 47.6% of patients showed >75% lesion size reduction and 19.0% showed minimal response (<25% improvement). At last follow-up, 71.4% of children were developmentally normal and asymptomatic, 23.8% had recurring symptoms, and 4.8% required permanent tracheostomy. Patients with ongoing symptoms or limited response to percutaneous sclerotherapy (33.3%) were treated with long-term sirolimus. CONCLUSIONS: Percutaneous sclerotherapy is a safe and effective treatment for symptomatic LM of the head and neck in neonates and infants. Treatment strategy and management of recurrent symptoms requires consensus from an experienced, multidisciplinary team.

Clarifying the clinical landscape of pediatric spinal arteriovenous shunts: an institutional experience and individual patient-data meta-analysis.

BACKGROUND: Pediatric spinal arteriovenous shunts (SAVS) are rare lesions with heterogeneous pathogenesis and clinical manifestations. OBJECTIVE: To evaluate the clinical characteristics, angioarchitecture, and technical/clinical outcomes in SAVS through a large single-center cohort analysis and meta-analysis of individual patient data. METHODS: A retrospective institutional database identified children (aged 0-21 years) who underwent digital subtraction spinal angiography (DSA) for SAVS between January 1996 and July 2021. Clinical data were recorded to evaluate angioarchitecture, generate modified Aminoff-Logue gait disturbance scores (AL) and McCormick grades (MC), and assess outcomes. We then performed a systematic literature review following PRISMA-IPD (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for individual patient data) guidelines, extracting similar data on individual patients for meta-analysis. RESULTS: The cohort consisted of 28 children (M:F=11:17) with 32 SAVS lesions, with a mean age of 12.8±1.1 years at diagnosis. At presentation, SAVS were most highly concentrated in the cervical region (40.6%). Children had a median AL=2 and MC=2, with thoracolumbar AVS carrying the greatest disability. Among treated cases, complete obliteration was achieved in 48% of cases and median AL scores and MC grades both improved by one point. Systematic literature review identified 161 children (M:F=96:65) with 166 SAVS lesions with a mean age of 8.7±0.4 years. Among studies describing symptom chronicity, 37/51 (72.5%) of children presented acutely. At presentation, children had a median AL=4 and MC=3, with thoracolumbar AVS carrying the highest MC grades. After intervention, median AL and MC both improved by one point. CONCLUSIONS: This study provides epidemiologic information on the location, onset, and presentation of the full spectrum of pediatric SAVS, highlighting the role of targeted treatment of high-risk features.

Current status of endovascular stroke treatment.

The management of acute ischemic stroke is rapidly developing.Although acute ischemic stroke is a major cause of adult disability and death, the number of patients requiring emergency endovascular intervention remains unknown, but is a fraction of the overall stroke population. Public health initiatives endeavor to raise public awareness about acute stroke to improve triage for emergency treatment, and the medical community is working to develop stroke services at community and academic medical centers throughout the United States. There is an Accreditation Council for Graduate Medical Education­approved pathway for training in endovascular surgical neuroradiology, the specialty designed to train physicians specifically to treat cerebrovascular diseases. Primary and comprehensive stroke center designations have been defined, yet questions remain about the best delivery model. Telemedicine is available to help community medical centers cope with the complexity of stroke triage and treatment. Should comprehensive care be provided at every community center, or should patients with complex medical needs be triaged to major stroke centers with high-level surgical,intensive care, and endovascular capabilities? Although the answers to these and other questions about stroke care delivery remain unanswered owing to the paucity of empirical data, we are convinced that stroke care regionalization is crucial for delivery of high-quality comprehensive ischemic stroke treatment. A stroke team available 24 hours per day, 7 days per week requires specialty skills in stroke neurology, endovascular surgical neuroradiology, neurosurgery, neurointensive care, anesthesiology, nursing, and technical support for optimal success. Several physician groups with divergent training backgrounds (i.e., interventional neuroradiology, neurosurgery,neurology, peripheral interventional radiology, and cardiology) lay claim to the treatment of stroke patients,particularly the endovascular or interventional methods. Few would challenge neurologists over the responsibility for emergency evaluation and triage of stroke victims for intra intravenous fibrinolysis, even though emergency physicians are most commonly the first to evaluate these patients. There are many unanswered questions about the role of imaging in defining best treatment. Perfusion imaging with CT or MRI appears to have relevance even though its role remains undefined and is the subject of ongoing research. Meanwhile, investigators are exploring new, and perhaps more specific,imaging methods with cerebral metabolic rate of oxygen and cellular acid-base imbalance. There are currently 6 ongoing trials of stroke intervention, many with proprietary technologies and private funding, competing for the same patient population as multicenter trials funded by the NIH. At the same time, much of the interventional stroke treatment currently occurs outside of trials in the community and academic settings without the collection of much-needed data. Market forces will certainly shape future stroke therapy, but it is unclear whether the current combination of private and public funding for these endeavors is the best method of development.

Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling.

BACKGROUND AND PURPOSE: Clazosentan, an endothelin receptor antagonist, has been shown to reduce vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). CONSCIOUS-3 assessed whether clazosentan reduced vasospasm-related morbidity and all-cause mortality postaSAH secured by endovascular coiling. METHODS: This double-blind, placebo-controlled, phase III trial randomized patients with aSAH secured by endovascular coiling to ≤ 14 days intravenous clazosentan (5 or 15 mg/h) or placebo. The primary composite end point (all-cause mortality; vasospasm-related new cerebral infarcts or delayed ischemic neurological deficits; rescue therapy for vasospasm) was evaluated 6 weeks postaSAH. The main secondary end point was dichotomized extended Glasgow Outcome Scale (week 12). RESULTS: CONSCIOUS-3 was halted prematurely following completion of CONSCIOUS-2; 577/1500 of planned patients (38%) were enrolled and 571 were treated (placebo, n=189; clazosentan 5 mg/h, n=194; clazosentan 15 mg/h, n=188). The primary end point occurred in 50/189 of placebo-treated patients (27%), compared with 47/194 patients (24%) treated with clazosentan 5 mg/h (odds ratio [OR], 0.786; 95% CI, 0.479-1.289; P=0.340), and 28/188 patients (15%) treated with clazosentan 15 mg/h (OR, 0.474; 95% CI, 0.275-0.818; P=0.007). Poor outcome (extended Glasgow Outcome Scale score ≤ 4) occurred in 24% of patients with placebo, 25% of patients with clazosentan 5 mg/h (OR, 0.918; 95% CI, 0.546-1.544; P=0.748), and 28% of patients with clazosentan 15 mg/h (OR, 1.337; 95% CI, 0.802-2.227; P=0.266). Pulmonary complications, anemia, and hypotension were more common in patients who received clazosentan than in those who received placebo. At week 12, mortality was 6%, 4%, and 6% with placebo, clazosentan 5 mg/h, and clazosentan 15 mg/h, respectively. CONCLUSIONS: Clazosentan 15 mg/h significantly reduced postaSAH vasospasm-related morbidity/all-cause mortality; however, neither dose improved outcome (extended Glasgow Outcome Scale).

Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association.

PURPOSE: The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A formal literature search of MEDLINE (November 1, 2006, through May 1, 2010) was performed. Data were synthesized with the use of evidence tables. Writing group members met by teleconference to discuss data-derived recommendations. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation. The guideline draft was reviewed by 7 expert peer reviewers and by the members of the Stroke Council Leadership and Manuscript Oversight Committees. It is intended that this guideline be fully updated every 3 years. RESULTS: Evidence-based guidelines are presented for the care of patients presenting with aSAH. The focus of the guideline was subdivided into incidence, risk factors, prevention, natural history and outcome, diagnosis, prevention of rebleeding, surgical and endovascular repair of ruptured aneurysms, systems of care, anesthetic management during repair, management of vasospasm and delayed cerebral ischemia, management of hydrocephalus, management of seizures, and management of medical complications. CONCLUSIONS: aSAH is a serious medical condition in which outcome can be dramatically impacted by early, aggressive, expert care. The guidelines offer a framework for goal-directed treatment of the patient with aSAH.