M. Suri

Intra-Arterial Recanalization Techniques for Patients 80 Years or Older with Acute Ischemic Stroke: Pooled Analysis from 4 Prospective Studies

BACKGROUND AND PURPOSE: Previous studies have demonstrated limited benefit with endovascular procedures such as stent placement in octogenarians. We evaluated the safety and effectiveness of intra-arterial recanalization techniques to treat ischemic stroke in patients 80 years or older presenting within 6 hours of symptom onset. MATERIALS AND METHODS: We pooled the data from 4 prospective studies by evaluating intra-arterial recanalization techniques for treatment of ischemic stroke. Clinical and radiologic evaluations were performed before treatment and at 24 hours, 7 to 10 days, and 1 to 3 months after treatment. We performed multivariate analyses to evaluate the effect of ages 80 years and older on angiographic recanalization, favorable outcome (modified Rankin scale of 0–2), and mortality rate at 1 to 3 months. RESULTS: A total of 101 patients were treated in the 4 protocols. Of these, 24 were 80 years or older. There was no significant difference between the 2 age groups in sex, initial stroke severity, time to treatment, site of vascular occlusion, and rate of symptomatic and asymptomatic intracranial hemorrhage (ICH). In logistic regression analysis, age 80 years or older was associated with a lower likelihood of a favorable outcome (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.13–1.2; P = .11) and recanalization (OR, 0.36; 95% CI, 0.12–1.1; P = .07) and with higher mortality rate (OR, 3.17; 95% CI, 1.05–9.55; P = .04) after adjusting for study protocol. After adjusting for recanalization in addition to study protocol, the older age group still had a lower likelihood of favorable outcomes (OR, 0.34; 95% CI, 0.1–1.1; P = .07) and higher mortality rates (OR, 3.62; 95% CI, 1.15–11.36; P = .027). CONCLUSIONS: Our study demonstrates that patients 80 years and older are at higher risk for poor outcome at 1 to 3 months following intra-arterial recanalization techniques. This relationship is independent of recanalization rate and symptomatic ICH supporting the role of other mechanisms.

Microcatheter to Recanalization (Procedure Time) Predicts Outcomes in Endovascular Treatment in Patients with Acute Ischemic Stroke: When Do We Stop?

This study addresses the relationship among procedure time, recanalization, and clinical outcomes in patients with acute ischemic stroke undergoing endovascular treatment. Demographics, NIHSS scores before and 1 day after the procedure, and modified Rankin Scale scores were assessed in 209 patients. Patients with procedure times ≤30 minutes had lower rates of unfavorable outcome at discharge compared with patients with procedure times ≥30 minutes. Rates of favorable outcomes in endovascularly treated patients after 60 minutes were lower than rates observed with placebo treatment. Unfavorable outcome was positively associated with age, admission NIHSS strata, and longer procedure times. BACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke consists of various mechanical and pharmacologic modalities used for recanalization of arterial occlusions. We performed this study to determine the relationship among procedure time, recanalization, and clinical outcomes in patients with acute ischemic stroke undergoing endovascular treatment. MATERIALS AND METHODS: We analyzed data from consecutive patients with acute ischemic stroke who underwent endovascular treatment during a 6-year period. Demographic characteristics, NIHSS score before and 24 hours after the procedure, and discharge mRS score were ascertained. Procedure time was defined by the time interval between microcatheter placement and recanalization or completion of the procedure. We estimated the procedure time after which favorable clinical outcome was unlikely, even after adjustment for age, time from symptom onset, and admission NIHSS scores. RESULTS: We analyzed 209 patients undergoing endovascular treatment (mean age, 65 ± 16 years; 109 [52%] men; mean admission/preprocedural NIHSS score, 15.3 ± 6.8). Complete or partial recanalization was observed in 176 (84.2%) patients, while unfavorable outcome (mRS 3–6) was observed in 138 (66%) patients at discharge. In univariate analysis, patients with procedure time ≤30 minutes had lower rates of unfavorable outcome at discharge compared with patients with procedure time ≥30 minutes (52.3% versus 72.2%, P = .0049). In our analysis, the rates of favorable outcomes in endovascularly treated patients after 60 minutes were lower than rates observed with placebo treatment in the Prourokinase for Acute Ischemic Stroke Trial. In logistic regression analysis, unfavorable outcome was positively associated with age (P = .0012), admission NIHSS strata (P = .0017), and longer procedure times (P = .0379). CONCLUSIONS: Procedure time in patients with acute ischemic stroke appears to be a critical determinant of outcomes following endovascular treatment. This highlights the need for procedure time guidelines for patients being considered for endovascular treatment in acute ischemic stroke.

Intracranial-derived atherosclerosis assessment: an in vitro comparison between virtual histology by intravascular ultrasonography, 7T MRI, and histopathologic findings.

BACKGROUND AND PURPOSE: Atherosclerotic plaque composition and structure contribute to the risk of plaque rupture and embolization. Virtual histology by intravascular ultrasonography and high-resolution MR imaging are new imaging modalities that have been used to characterize plaque morphology and composition in peripheral arteries. MATERIALS AND METHODS: The objectives of this study were 1) to determine the correlation between virtual histology–intravascular ultrasonography and histopathologic analysis (reference standard) and 2) to explore the comparative results of 7T MR imaging (versus histopathologic analysis), both to be performed in vitro by use of intracranial arterial segments with atherosclerotic plaques. Thirty sets of postmortem samples of intracranial circulation were prepared for the study. These samples included the middle cerebral artery (n = 20), basilar artery (n = 8), and anterior cerebral artery (n = 2). Virtual histology–intravascular ultrasonography and 7T MR imaging were performed in 34 and 10 points of interest, respectively. The formalin-fixed arteries underwent tissue processing and hematoxylin-eosin staining. The plaques were independently categorized according to revised Stary classification after review of plaque morphology and characteristics obtained from 3 modalities. The proportion of fibrous, fibrofatty, attenuated calcium, and necrotic components in the plaques were determined in histology slides and compared with virtual histology–intravascular ultrasonography and MR imaging. RESULTS: Of 34 points of interest in the vessels, 32 had atherosclerotic plaques under direct visualization. Plaques were visualized in gray-scale intravascular ultrasonography as increased wall thickness, outer wall irregularity, and protrusion. The positive predictive value of virtual histology–intravascular ultrasonography for identifying fibroatheroma was 80%. Overall, virtual histology–intravascular ultrasonography accurately diagnosed the type of the plaque in 25 of 34 samples, and κ agreement was 0.58 (moderate agreement). The sensitivity and specificity of virtual histology–intravascular ultrasonography readings for fibroatheroma were 78.9% and 73.3%, respectively. The overall sensitivity and specificity for virtual histology–intravascular ultrasonography were 73.5% and 96.6%, respectively. Plaques were identified in 7T MR imaging as increased wall thickness, luminal stenosis, or outer wall protrusion. The positive predictive value of 7T MR imaging for detecting fibrous and attenuated calcium deposits was 88% and 93%, respectively. CONCLUSIONS: This in vitro study demonstrated that virtual histology–intravascular ultrasonography and high-resolution MR imaging are reliable imaging tools to detect atherosclerotic plaques within the intracranial arterial wall, though both imaging modalities have some limitations in accurate characterization of the plaque components. Further clinical studies are needed to determine the clinical utility of plaque morphology and composition assessment by noninvasive tests.

Prevalence of Intracranial Atherosclerotic Stenosis Using High-Resolution Magnetic Resonance Angiography in the General Population The Atherosclerosis Risk in Communities Study

Background and Purpose— Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke, but little is known about its epidemiology. We studied the prevalence of ICAS and its association with vascular risk factors using high-resolution magnetic resonance angiography in a US cardiovascular cohort. Methods— The Atherosclerosis Risk in Communities (ARIC) study recruited participants from 4 US communities from 1987 to 1989. Using stratified sampling, we selected 1980 participants from visit 5 (2011–2013) for high-resolution 3T-magnetic resonance angiography. All images were analyzed in a centralized laboratory, and ICAS was graded as: no stenosis, <50% stenosis, 50% to 69% stenosis, 70% to 99% stenosis, and complete occlusion. We calculated per-vessel and per-person prevalence of ICAS (weighted for n=6538 visit 5 participants) and also estimated the US prevalence. We used multivariable logistic regression to identify variables independently associated with ICAS. Results— Subjects who had an adequate magnetic resonance angiography (n=1765) were aged 67 to 90 years, 41% were men, 70% were white, and 29% were black. ICAS was prevalent in 31% of participants and 9% had ICAS ≥50%. Estimated US prevalence of ICAS ≥50% for 65 to 90 years old was 8% for whites and 12% for blacks. Older age, black race, higher systolic blood pressure, and higher low-density lipoprotein cholesterol levels were associated with increased odds of ICAS, whereas higher levels of high-density lipoprotein cholesterol and use of cholesterol-lowering medications were associated with decreased odds of ICAS. Body mass index and smoking were not associated with ICAS. Conclusions— The prevalence of ICAS in older adults is high, and it could be a target for primary prevention of stroke and dementia in this population.

Incident Cancer in a Cohort of 3,247 Cancer Diagnosis Free Ischemic Stroke Patients

Background: Subclinical cancer can manifest as a thromboembolic event and may be detected at a later interval in ischemic stroke survivors. We determined the rate of incident cancer and effect on cardiovascular endpoints in a large cohort of ischemic stroke survivors. Methods: An analysis of 3,680 adults with nondisabling cerebral infarction who were followed for two years within the randomized, double-blinded VISP trial was performed. The primary intervention was best medical/surgical management plus a daily supplementation of vitamin B6, vitamin B12, and folic acid. We calculated age-adjusted rates of incidence of cancer among ischemic stroke survivors and standardized incidence ratios (SIR) with 95% confidence intervals (CI) based on comparison with age-adjusted rates in the general population. The significant variables from univariate analysis were entered in a Cox Proportional Hazards analysis to identify the association between various baseline factors and incident cancer after adjusting age, gender, and race/ethnicity. A logistic regression analysis evaluated the association between incident cancer and various endpoints including stroke, coronary heart disease, myocardial infarction, and death after adjusting age, gender, and race/ethnicity. Results: A total of 3,247 patients (mean age ± SD of 66 ± 11; 2,013 were men) were cancer free at the time of enrollment. The incidence of new cancer was 0.15, 0.80, 1.2, and 2.0 per 100 patients at 1 month, 6 months, 1 year, and 2 years, respectively. The age-adjusted annual rate of cancer in patients with ischemic stroke was higher than in persons in the general population at 1 year (581.8/100,000 persons vs. 486.5/100,000 persons, SIR 1.2, 95% CI 1.16-1.24) and 2 years (1,301.7/100,000 vs. 911.5/100,000, SIR 1.4, 95% CI 1.2-1.6) after recruitment. There was a higher risk for death (odds ratio (OR) 3.1, 95% CI 1.8-5.4), and composite endpoint of stroke, coronary heart disease, and/or death (OR 1.4, 95% CI 1.0-2.2) among participants who developed incident cancer compared with those who were cancer free after adjusting for potential confounders. Conclusions: The annual rate of age-adjusted cancer incidence was higher among ischemic stroke patients compared with those in the general population. The odds of mortality were three folds higher among stroke survivors who developed incident cancer.

Drug evaluation of clopidogrel in patients with ischemic stroke

Clopidogrel is an effective antiplatelet medication used for the secondary prevention of ischemic events in patients with various cardiovascular, cerebrovascular and peripheral vascular disease conditions. The objective of this paper is to discuss the role of clopidogrel in ischemic stroke patients and to review the existing data from randomized trials supplemented by pilot and mechanistic studies that supports these indications for its use. An analysis of the mechanism of action and pharmacology of clopidogrel is provided. After Phase III trials, such as the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events) and MATCH (Management of Atherothrombosis with Clopidogrel in High-risk patients) trials, the role of clopidogrel in secondary prevention is well defined. The role of clopidogrel in acute ischemic stroke and neurointerventional procedures is evolving based on new pilot trials. At present, there is insufficient data to recommend the use of clopidogrel in acute ischemic stroke. Clopidogrel may be a valuable alternative to aspirin. However, more studies are required to assess the role of clopidogrel in selected patient groups with respect to acute ischemic stroke.

Short- and Intermediate-Term Angiographic and Clinical Outcomes of Patients with Various Grades of Coil Protrusions Following Embolization of Intracranial Aneurysms

After embolization, not uncommonly one sees coils protruding outside of the aneurysm into the lumen of the parent artery. What does this mean? The authors identified 256 patients with this finding from 3 different medical centers and set out to assess their short- and intermediate-term outcomes. They graded coil protrusions from a single loop projecting into less than half of the parent artery (grade 1) to those protruding into more than half (grade 3). Most protrusions in the series were grade 1. All patients were placed on aspirin and complications were not directly related to coil protrusions. The authors concluded that antiplatelet therapy is efficacious in preventing vessel thrombosis in this situation. BACKGROUND AND PURPOSE: An infrequent occurrence during endovascular treatment is protusion of detachable coils into the parent lumen with a subsequent thrombosis within in the parent vessel or embolic events. We report the short- and intermediate-term angiographic and clinical outcomes of patients who experience coil or loop protrusions and are managed with medical or additional endovascular treatments. MATERIALS AND METHODS: The coil protrusions were identified by retrospective review of 256 consecutive patients treated at 3 centers with endovascular embolizations for intracranial aneurysms and subsequently categorized as grade I when a single loop or coil protruded into the parent vessel lumen less than half the parent artery diameter; grades II and III were assigned when a single coil or loop protruded more than half the parent artery diameter, respectively. RESULTS: There were 19 patients with grade I (n = 9), grade II (n = 4), or grade III (n = 6) coil protrusions. Patients with active hemodynamic compromise (n = 6) had intracranial stents placed in addition to aspirin (indefinitely) and clopidogrel (range, 1–12 months; mean, 4.5 months) treatment. The remaining patients were placed on aspirin indefinitely. Complete aneurysm obliteration was achieved in all patients except in 3 in whom near-complete obliteration was achieved. Two patients had intraprocedural aneurysm ruptures, both of whom survived hospitalization. There were 4 deaths (4–21 days), all due to major strokes in different vascular distributions related to vasospasm (unrelated to the coil protrusion). CONCLUSIONS: Management of coil protrusions with antiplatelet therapy and placement of stents (in selected patients) appears efficacious in preventing vessel thrombosis.

Population-based estimates of neuroendovascular procedures: results of a state-wide study.

Background: The Brain Attack Coalition identified the availability of neuroendovascular procedures as an essential component of a comprehensive stroke center. Objective: To provide population-based estimates of neuroendovascular procedures. Methods: State-wide estimates of cervicocerebral angiograms, endovascular ischemic stroke treatments, carotid angioplasty and stent placements, intracranial angioplasty and stent placements, endovascular treatment of intracranial aneurysms, and endovascular treatment of intracranial arteriovenous malformations (AVMs) were obtained. We calculated the annual incidence rates of various neuroendovascular and neurosurgical procedures (per 100,000 persons). For the denominator, total persons in each year were categorized in 10-year age intervals. Results: The incidence of carotid endarterectomy (387.6 per 100,000 persons) and carotid stent placement (34.7 per 100,000 persons) peaked at 75–84 years. The incidence of aneurysm embolization also peaked in that population bracket (67.9 per 100,000 persons), yet there was a dramatic reduction in the incidence of surgical aneurysm treatment (3.6 per 100,000 persons) in those aged 75–84 years. There was a prominent reduction in the incidence of all procedures in the population aged ≥85 years, except for intravenous/intra-arterial thrombolytic use in ischemic stroke. The incidence of ischemic stroke increased almost by 50% in the population aged ≥85 years compared to those aged 75–84 years. However, the incidence of endovascular procedures for acute ischemic stroke decreased from 22.8 per 100,000 persons in the population aged 75–84 years to 13.2 per 100,000 persons in the population aged ≥85 years. Conclusions: A marked disproportion of neuroendovascular procedures performed and disease prevalence was noted in persons aged ≥85 years, an increasing segment of the population according to recent Census.

Intracranial atherosclerosis and dementia: The Atherosclerosis Risk in Communities (ARIC) Study

Objective: To explore the association of intracranial atherosclerotic disease (ICAD) with mild cognitive impairment (MCI) and dementia. Methods: From 2011 to 2013, 1,744 participants completed high-resolution vessel wall MRI from the population-based Atherosclerosis Risk in Communities Study by a sampling strategy that allowed weighting back to the cohort. We defined ICAD by plaque features (presence, territory, stenosis, number). Trained clinicians used an algorithm incorporating information from interviews and neuropsychological and neurologic examinations to adjudicate for MCI and dementia. We determined the relative prevalence ratio (RPR) of MCI or dementia after adjusting for risk factors at midlife using multinomial logistic regression. Results: A total of 601 (34.5%) participants had MCI (mean age ± SD, 76.6 ± 5.2 years), 83 (4.8%) had dementia (79.1 ± 5.3 years), and 857 (49.1%) were current or former smokers. Anterior cerebral artery (ACA) plaque (adjusted RPR 3.81, 95% confidence interval [CI] 1.57–9.23), >2 territories with plaque (adjusted RPR 2.12, 95% CI 1.00–4.49), and presence of stenosis >50% (adjusted RPR 1.92, 95% CI 1.01–3.65) were associated with increased prevalence of dementia in separate models. Posterior cerebral artery plaque was associated with MCI but did not reach statistical significance for dementia (adjusted RPR MCI 1.43, 95% CI 1.04–1.98; adjusted RPR dementia 1.58, 95% CI 0.79–2.85). There were no associations with middle cerebral artery atherosclerotic lesions or cognitive impairment. Many participants had plaque in >1 territory (n = 291, 46%) and participants with ACA plaques (n = 69) had the greatest number of plaques in other territories (mean 6.0, SD 4.4). Conclusions: This study demonstrates associations between ICAD and clinical MCI and dementia.

A trivariate meta-analysis of diagnostic studies accounting for prevalence and non-evaluable subjects: re-evaluation of the meta-analysis of coronary CT angiography studies.

BackgroundA recent paper proposed an intent-to-diagnose approach to handle non-evaluable index test results and discussed several alternative approaches, with an application to the meta-analysis of coronary CT angiography diagnostic accuracy studies. However, no simulation studies have been conducted to test the performance of the methods.MethodsWe propose an extended trivariate generalized linear mixed model (TGLMM) to handle non-evaluable index test results. The performance of the intent-to-diagnose approach, the alternative approaches and the extended TGLMM approach is examined by extensive simulation studies. The meta-analysis of coronary CT angiography diagnostic accuracy studies is re-evaluated by the extended TGLMM.ResultsSimulation studies showed that the intent-to-diagnose approach under-estimate sensitivity and specificity. Under the missing at random (MAR) assumption, the TGLMM gives nearly unbiased estimates of test accuracy indices and disease prevalence. After applying the TGLMM approach to re-evaluate the coronary CT angiography meta-analysis, overall median sensitivity is 0.98 (0.967, 0.993), specificity is 0.875 (0.827, 0.923) and disease prevalence is 0.478 (0.379, 0.577).ConclusionsUnder MAR assumption, the intent-to-diagnose approach under-estimate both sensitivity and specificity, while the extended TGLMM gives nearly unbiased estimates of sensitivity, specificity and prevalence. We recommend the extended TGLMM to handle non-evaluable index test subjects.