Intracranial atherosclerotic disease associated with moyamoya collateral formation: histopathological findings.

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

Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage

Statins may promote vasodilation following subarachnoid hemorrhage (SAH) and improve the response to blood pressure elevation. We sought to determine whether simvastatin increases cerebral blood flow (CBF) and alters the response to induced hypertension after SAH

The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (v(r)*) (v(r)* 5 0 indicating excellent agreement and v(r)* = 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (v(r)*) for both cohorts was 0.026 (95% CI 0.019-0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.Peer reviewe

Multidisciplinary Consensus on Assessment of Unruptured Intracranial Aneurysms Proposal of an International Research Group

Peer reviewe

Cerebellum as the Normal Reference for the Detection of Increased Cerebral Oxygen Extraction

Hemispheric ratios of oxygen extraction fraction (OEF), a proven methodology for the detection of severe hemodynamic impairment and stroke risk, are not sensitive for detecting bilateral hemispheric increases in OEF. The aim of this study was to investigate the use of cerebellum as the reference normal. We analyzed positron emission tomographic (PET) measurements of count-based OEF and clinical data from 57 patients with unilateral atherosclerotic carotid occlusion and 13 controls enrolled in a prospective study of stroke risk. The ipsilateral, contralateral, and total cerebellum were each evaluated as possible reference regions, and the ratios of the middle cerebral artery (MCA) hemispheric OEF counts against those in each reference region were determined. A statistically significant correlation (P<0.0001) was observed with all three MCA-to-cerebellar ratios when compared with the gold standard of ipsilateral-to-contralateral MCA hemispheric ratio. Kaplan–Meier analyses showed all MCA-to-cerebellar ratios to be predictive of stroke. By using the total cerebellum method, 7 strokes were found to have occurred in 20 patients with increased OEF (P=0.0007), compared with 7 strokes out of 16 patients with elevated OEF using the ipsilateral or contralateral cerebellum methods (P<0.0001). These methods may be useful for categorizing the hemodynamic status of patients with bilateral cerebral occlusive diseases, including atherosclerosis and moyamoya, to determine the association with the risk of subsequent stroke

Recruitment in Acute Stroke Trials: Challenges and Potential Solutions

Randomized clinical trials of acute stroke have led to major advances in acute stroke therapy over the past decade. Despite these successes, recruitment in acute trials is often difficult. We outline challenges in recruitment for acute stroke trials and present potential solutions, which can increase the speed and decrease the cost of identifying new treatments for acute stroke. One of the largest opportunities to increase the speed of enrollment and make trials more generalizable is expansion of inclusion criteria whose impact on expected recruitment can be assessed by epidemiologic and registry databases. Another barrier to recruitment besides the number of eligible patients is availability of study investigators limited to business hours, which may be helped by financial support for after-hours call. The wider use of telemedicine has accelerated quicker stroke treatment at many hospitals and has the potential to accelerate research enrollment but requires training of clinical investigators who are often inexperienced with this approach. Other potential solutions to enhance recruitment include rapid prehospital notification of clinical investigators of potential patients, use of mobile stroke units, advances in the process of emergency informed consent, storage of study medication in the emergency department, simplification of study treatments and data collection, education of physicians to improve equipoise and enthusiasm for randomization of patients within a trial, and clear recruitment plans, and even potentially coenrollment, when there are competing trials at sites. Without successful recruitment, scientific advances and clinical benefit for acute stroke patients will lag

Natural History of Hemodynamics in Vertebrobasilar Disease: Temporal Changes in the VERiTAS Study Cohort.

BACKGROUND AND PURPOSE: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort. METHODS: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status. RESULTS: Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2-48.7]). CONCLUSIONS: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00590980