Citations

INTRODUCTION: Cognitive changes can occur following procedural interventions and subarachnoid hemorrhage in unruptured intracranial aneurysms (UIA). The International Study of Unruptured Intracranial Aneurysms conducted cognitive assessment using the Mini-Mental State Exam at baseline and the Telephone Interview Cognitive Status Exam (TICS) at follow-up. Hypothesis: The purpose of this analysis was to compare the 1 year and 5 year outcome in the treatment cohorts (surgery and endovascular) with those of the untreated subgroup. Methods: Patients were subdivided into the initial treatment and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort and 2388 in the treated cohort. The cohorts were followed annually with measures of neurological status, Rankin Scale and cognition (TICS). Outcomes were determined prospectively. Comparison of outcomes was done using continuous data and by categories. Covariate adjustment was done using general linear models. Stratified analysis was done by Rankin Score at the time of follow-up. Results: The mean TICS score at 1 year in the cohort was 33.4 with a median of 34 (maximum is 40). In the treated patients the mean was 33.5 and in the untreated patients it was 33.3 (P=0.644). However, Rankin Score at 1 year was significant with a higher percentage of 3-5 scores in the treated group (P=0.003) Categorical analysis of the TICS Score when stratified by Rankin Score at 1 year showed small but significant differences, P=0.03 for Rankin 0-2, and P=0.07 for Rankin 3-5. However after adjustment for baseline variables treatment TICS Score was no longer significant.. The 5 year results showed that the untreated patients did worse than the treated group in TICS. However after adjustment no differences were apparent. Conclusions: Cognitive changes associated with treatment may be minor source of disability post-treatment compared to observation and patient outcomes may be worse in the observation group over time. Differences in outcome also were better explained through the Rankin Score at follow-up than by cognitive deficits.

Introduction: There is ongoing debate regarding the rupture risk of an unruptured intracranial aneurysm (UIA), and the predictors of rupture. Hypothesis: There are aneurysm morphology characteristics which predict rupture in patients with an UIA. The purpose of this analysis was to assess for such characteristics utilizing the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort. Methods: Patients were entered prospectively at 61 centers. Patients must have had at least one UIA, which may or may not have been symptomatic. Patients were followed for a median of 9 years and all potential hemorrhages were carefully adjudicated. A case-control design was used. The cases were 57 patients with aneurysmal rupture during followup for whom detailed radiology data were available from arteriography. Controls were 198 size- (+/- 2 mm maximum diameter) and location- (parent artery) matched patients without rupture during followup. Numerous aneurysm morphology characteristics were assessed on arteriogram review. Multivariable condition logistic regression modeling was performed. Results: A total of 57 cases and 198 controls were included. Most (76%) of the 255 cases were women, and 20% had a prior history of SAH from some other aneurysm. There were no differences between cases and controls in aneurysm maximum diameter, aneurysm location, patient age, gender, reason for presentation, or prior medical history. Multivariate analysis identified that only perpendicular height of the aneurysm--the measurement of the aneurysm height at a perpendicular to the center of the aneurysm neck to the aneurysm dome-was an independent predictor of aneurysm rupture. Aspect ratio, size ratio, parent vessel diameter, presence of daughter sac, and aneurysm angle were not independent predictors of rupture. Conclusions: After controlling for aneurysm size and location, the aneurysm perpendicular height remained a predictor of UIA rupture during long-term followup. The assessment of perpendicular height may be helpful in clinical practice, in addition to the other key predictors of UIA rupture, aneurysm maximum diameter and location. Further investigation into the use of perpendicular height as a predictor of rupture in patients with UIA is indicated.

Background and Purpose: Ultrasound is the most commonly used imaging modality for assessment of carotid artery stenosis. A number of studies have demonstrated that surface irregularities, heterogeneous echotexture and hypoechoic plaques are risk factors for acute ischemic stroke. We performed a systematic review and meta-analysis of the literature to better define the risk of stroke based off of the sonographic characteristics of carotid plaques. Materials and Methods: We performed a comprehensive literature search evaluating the association of carotid plaque characteristics on ultrasound with ischemic outcomes. We included both case-control and cohort studies examining the relationship between complex plaque and acute ischemic stroke. Complex plaque was defined as plaque that had any of the following characteristics: heterogeneous plaque echogenicity, hypoechoic plaque, plaque neovascularization, plaque surface irregularity, plaque ulceration, and intraplaque motion. Meta-analyses using the random-effects model were performed for complex plaque and each of the individual complex plaque characteristics. Results: A total of 1013 articles were screened and 30 studies with 11528 patients (3054 symptomatic and 8474 asymptomatic) were included. The odds ratios for the association between complex plaque and ischemic symptoms was 5.18 (95%CI=4.63-5.79). Heterogeneous echotexture (OR=11.72, 95%CI=9.82-13.98), intraplaque motion (OR=1.57, 95%CI=1.02-2.41), plaque echolucency (OR=3.23, 95%CI=2.72-3.84), plaque neovascularity (OR=5.66, 95%CI=3.15-10.16) and plaque ulceration (OR=2.65, 95%CI=1.89-3.73) were all associated with ischemic symptoms. Surface irregularity without frank ulceration was not associated with ischemic symptoms (OR=1.35, 95%CI=0.98-1.86). Conclusions: Complex plaque, heterogeneous plaque echogenicity, hypoechoic plaque, plaque neovascularization, plaque ulceration and intraplaque motion are associated with ischemic symptoms. Assessment of carotid plaque on ultrasound provides stroke risk information beyond measurement of luminal stenosis.

Introduction: Giant intracranial aneurysms are uncommon, have a high risk for rupture and are difficult to treat. The International Study of Unruptured Intracranial Aneurysms (ISUIA) prospective cohort included 187 patients with maximal diameter of 25 mm or greater. This analysis was to determine the long-term prognosis of these aneurysms both treated and untreated. Methods: Patients were enrolled into ISUIA at 61 centers from 1991-1998. A prospective cohort included the managed with observation, surgery or endovascular treatment. Patients were followed for a median of 9.2 years. Aneurysms were measured using a central reading of bi-planar cerebral angiography. Outcomes were determined prospectively and with central review. Results: 187 patients with a maximum diameter of 25 mm were followed. The mean size was 30.3 mm, ranging from 25 to 63 mm. 39% of the aneurysms were surgically treated at baseline, 27% were endovascularly treated, and 32% were managed conservatively;3% had subsequent endovascular treatment and 5% surgical treatment. Patients with giant aneurysms were predominantly women (83%), had a baseline Rankin Score of in 93%, were located predominantly in the anterior circulation (internal carotid 44%, cavernous ICA 28%, middle cerebral 12%). 80% of the patients were symptomatic with cranial nerve deficit in 47% (III and VI nerves), mass effect in 16%, headaches in 44%, orbital pain in 21%, and vision loss in 25%. Smoking history was present in 67%, hypertension in 44%, vascular headaches in 29% and family history in 10%. 70 patients (39%) died during follow-up however 59% were still Rankin 1 or 2. Both surgical and endovascular treated patients had 60-64% good outcome and 34-36% mortality. Untreated patients had a 57% mortality. Subarachnoid hemorrhage occurred in 11 untreated patients and 12 treated patients with most occurring in the first year. Conclusions: Giant intracranial aneurysms are typically symptomatic, and have a high risk of rupture early after diagnosis. Outcome was similar with surgical and endovascular treatment but post-procedure hemorrhage did occur.

Purpose: The safety of revascularization for asymptomatic carotid stenosis, and the efficacy of medical therapy for stroke prevention have improved. Therefore, results of prior randomized trials may not apply to current treatment decisions. The NINDS-funded CREST-2 will compare carotid endarterectomy and intensive medical therapy (IMT) versus IMT alone (n=1240), and carotid stenting and IMT versus IMT alone (n=1240) in asymptomatic patients with≥70% stenosis. Materials & Methods: CREST-2 consists of two parallel randomized clinical trials to be conducted at a target of ≈120 centers, including within NINDS StrokeNet. The composite primary outcome is stroke or death during the peri-procedural period or ipsilateral ischemic stroke thereafter up to 4 years. Blinded assessment of cognition will be done periodically. Centrally directed IMT includes tight control of blood pressure (systolic target <140 mm Hg) and cholesterol (LDL target <70 mg/dl) as well as lifestyle coaching. Results: As of June 12, 2015, 94 centers have been approved by the Site Selection Committee. Credentialing is ongoing, with 198 approved surgeons and 64 approved interventionists; 124 additional conditionally approved interventionists will be able to submit additional cases for review under the CREST-2 Registry. The Centers for Medicare and Medicaid will offer CAS reimbursement for Registry enrollees. As of June 12, 2015, there are 39 actively enrolling centers, and 37 patients have been randomized. Conclusion: CREST-2 is designed to identify the best approach for asymptomatic carotid stenosis. The first patient was randomized in December, 2014. An update will be provided regarding the numbers of patients randomized, centers certified, as well as surgeons and interventionists fully approved. Registration: ClinicalTrials.gov Identifier: NCT02089217

Background: Although vulnerable plaques are considered the pathological substrate for acute cardiovascular events, the pursuit of imaging surrogate markers for systemic atherothrombotic risk is currently focused on plaque burden. The prognostic value of vulnerable plaque characteristics as novel markers for systemic cardiovascular outcomes remains elusive. Advances in magnetic resonance imaging (MRI) have enabled characterization of the vulnerable carotid plaque. In a prospective study, we tested whether MRI-detected carotid plaque characteristics predict subsequent cardiovascular events. Methods: As part of an event-driven clinical trial, subjects with clinically established atherosclerotic disease were recruited. A multi-sequence protocol was used to measure the volumes of calcification and necrotic core (NC), and to identify the presence of intraplaque hemorrhage (IPH) and thin/ruptured fibrous cap (FC) using published criteria. The primary endpoint included fatal and non-fatal myocardial infarction or ischemic stroke, hospitalization for acute coronary syndrome, and symptom-driven revascularization. Cox regression analysis was used to present results as hazard ratio (HR) with 95% confidence interval (CI). Results: Of 232 subjects recruited, 214 (92.2%) with diagnostic image quality constituted the study population (mean age: 61±9 years; male: 82%; statin use: 94%). Calcification, NC, IPH, and thin/ruptured FC were detected in 48%, 52%, 8% and 14% of subjects, respectively. During a median follow-up of 35.1 months, 18 (8.4%) subjects reached the primary endpoint. MRI-detected plaque characteristics associated with the primary endpoint included larger NC (HR per 1 standard deviation increase in volume [1-SD]: 1.43 [1.16, 1.75], p<0.001), thin/ruptured FC (HR: 4.31 [1.67, 11.12], p=0.003), and marginally IPH (HR: 3.00 [0.99, 9.13], p=0.053). Although calcium deposition is traditionally pursued as a marker for atherosclerosis, subjects with larger calcification (HR per 1-SD: 0.60 [0.26, 1.41], p=0.20) did not show increased risk. Conclusions: Vulnerable plaque characteristics are prevalent in carotid arteries of patients with established atherosclerosis and are predictive of systemic cardiovascular outcomes.

BackgroundA low‐cryogen, compact 3T (C3T) MRI scanner with high‐performance gradients capable of simultaneously achieving 80 mT/m gradient amplitude and 700 T/m/second slew rate has been in use to study research patients since March 2016 but has not been implemented in the clinical practice.PurposeTo compare head MRI examinations obtained with the C3T system and a conventional whole‐body 3T (WB3T) scanner in seven parameters across five commonly used brain imaging sequences.Study TypeProspective.SubjectsThirty patients with a clinically indicated head MRI.Sequence 3T; T1 FLAIR, T1 MP‐RAGE, 3D T2 FLAIR, T2 FSE, and DWI.AssessmentAll patients tolerated the scans well. Three board‐certified neuroradiologists scored the comparative quality of C3T and WB3T images in blinded fashion using a five‐point Likert scale in terms of: signal‐to‐noise ratio, lesion conspicuity, motion artifact, gray/white matter contrast, cerebellar folia, susceptibility artifact, and overall quality.Statistical TestLeft‐sided, right‐sided, and two‐sided Wilcoxon signed rank test; Fisher's method. A P value <0.05 was considered statistically significant.ResultsThe C3T system performed better than the WB3T in virtually all comparisons, except for motion artifacts for the T1 FLAIR and T1 MP‐RAGE sequences, where the WB3T system was deemed better. When combining all sequences together, the C3T system outperformed the WB3T system in all image quality parameters evaluated, except for motion artifact (P = 0.13).Data ConclusionThe C3T scanner provided better overall image quality for all sequences, and performed better in all individual categories, except for motion artifact on the T1 FLAIR and T1 MP‐RAGE.Level of Evidence2Technical Efficacy Stage1

Background: Perfusion weighted imaging on MRI (MRP) and computerized tomography perfusion (CTP) are increasingly required to manage large vessel disease. Computerized algorithms can quantify perfusion data, but the programs are expensive and not widely used outside acute stroke evaluation. We aimed to determine how well human observers can identify asymmetries in cerebral perfusion images compared with an automated computer algorithm. Methods: Ten clinicians experienced in treating carotid artery disease (4 vascular neurologists, 3 neuroradiologists, 1 vascular surgeon, 1 neurosurgeon, 1 interventional radiologist) were given 28 post-processed, color-coded, axial-slice MRP scans from patients in the Carotid Revascularization Endovascular versus Stenting Trial - Hemodynamics (CREST-H) study. All patients had >70%, unilateral, asymptomatic carotid artery stenosis and had varying degrees of time-to-peak (TTP) delay on the side of stenosis, ranging from 0 to 2 secs, quantified by a semi-automated system that computes quantitative perfusion maps, using deconvolution of tissue and arterial signals (Olea, Cambridge, MA). A minimum volume of 10cc was required for a given TTP delay. Clinicians were asked to determine asymmetry (y/n) and side of occlusion for each case. Number of correct responses that matched the computer output were tallied. Results: We averaged correct responses by the 10 clinicians for cases at each increment of TTP delay; (Figure). At TTP delays ≥1.5 seconds, accuracy was ≥80%. At 1.25 sec accuracy fell to 60%, and at ≤ 1 sec, accuracy was ≤50%. For TTP=0 (no asymmetry), accuracy was 71%. Conclusions: Visual impression of hemodynamic asymmetry among experienced clinicians was reasonably accurate for TTP delays ≥1.5 seconds, but declined with more subtle asymmetries. Depending on the clinical impact of TTP delays (for CREST-H: correlation with cognitive decline), experienced clinicians may perform as well as an automated algorithm.

Background: Presence of atherosclerotic disease in more than one vascular bed (polyvascular disease) is associated with an increased risk of long-term vascular events. In the setting of asymptomatic carotid stenosis, the predictors of disease in other vascular beds is not well delineated. Objective: To identify the frequency and predictors of disease in other vascular beds the CREST 2 randomized trial population with hemodynamically significant stenosis. Methods: Recorded baseline characteristics among CREST 2 participants included: demographics, past medical history, lifestyle factors, and laboratory studies. Each variable was tested against three potential definitions of disease in other beds (cardiac, peripheral arterial disease (PAD) or disease in cardiac + PAD). Statistical analysis was done with Chi square and t tests as appropriate. Results: Data from 1447 patients were available for analysis. In these subjects with carotid disease, 51% also had cardiac disease, 24% also had PAD, and 16% had disease in in both cardiac and PAD. There was no relationship between age or race and presence of disease in other beds. Those with cardiac disease were more likely to be male. Diabetes, hypertension, hypercholesterolemia, and former history of smoking were all more common in those with either cardiac and PAD (TABLE). Elevated triglyceride and low HDL levels were also associated with all three definitions of disease in other beds. Those with either PAD or cardiac + PAD were more likely to be current smokers. Conclusions: Among CREST 2 participants, several medical conditions and lifestyle factors were associated with an increased frequency of disease in other vascular beds. Smoking, in particular, appears to be more common in those with PAD. Future analyses will address whether those with disease in other beds have higher rates of stroke or death.

Baseline Differences in Risk Factor Control and Medication Use Between 2 Trials Employing Intensive Medical Management (SAMMPRIS & CREST2) Background: The CREST2 trial Intensive Medical Management (IMM) protocol was adapted from the SAMMPRIS trial. However, since the 2011 publication of initial results of SAMMPRIS, there has been a greater appreciation for the importance of risk factor control in patients at risk of stroke associated with atherosclerosis. Therefore, we sought to determine differences in baseline risk factor control and medication use between SAMMPRIS and CREST2. Methods: Baseline risk factor and medication use data from 451 patients enrolled in SAMMPRIS (2008-2011) with severe symptomatic intracranial atherosclerosis and 1473 patients enrolled in CREST2 (2014-2019) with severe asymptomatic carotid stenosis were compared using the Chi-square test and t-test. Results: The Table shows baseline risk factor values and medications. SAMMPRIS patients were younger but had significantly worse risk factor control than CREST2 patients for all measures. There was no significant difference in statin use at baseline, but the mean SAMMPRIS subjects’ LDL was 16.1 mg/dL higher than in CREST2. CREST2 patients had higher rates of use of angiotensin receptor blockers (ARB), calcium channel blockers (CCB), and thiazides, but lower rates of use of angiotensin converting enzyme (ACE) inhibitors. Conclusions: Despite being older, CREST2 patients have significantly better baseline risk factor profiles than SAMMPRIS patients. This could be due to greater appreciation of the importance of risk factor control and healthy lifestyle habits for stroke prevention or more aggressive treatment targets in guideline recommendations. Although risk factor control appears to be improving since SAMMPRIS, many CREST2 patients are still not meeting recommended risk factor goals at baseline and may benefit from IMM protocols.