Summary Intracranial saccular or berry aneurysms are common, occurring in about 1–2% of the population. Unruptured intracranial aneurysms are increasingly being detected as cross-sectional imaging ...techniques are used more frequently in clinical practice. Once an unruptured intracranial aneurysm is detected, decisions regarding optimum management are made on the basis of careful comparison of the short-term and long-term risks of aneurysmal rupture with the risk associated with the intervention, whether that be surgical clipping or endovascular management. Several factors need to be carefully considered, including aneurysm size and location, the patient's family history and medical history, and the availability of an interventional option that has an acceptable risk. The patient's knowledge that they have an unruptured intracranial aneurysm can lead to substantial stress and anxiety, and their perspective regarding treatment, after hearing an unbiased appraisal of the rupture risks and the risk of interventional treatment, is of the utmost importance. Controversy remains regarding optimum management, and thorough assessments of the risks and benefits of contemporary management options, specific to aneurysm size, location, and many other aneurysm and patient factors, are needed.
Summary Background The IMS III trial did not show a clinical benefit of endovascular treatment compared with intravenous alteplase (recombinant tissue plasminogen activator) alone for moderate or ...severe ischaemic strokes. Late reperfusion of tissue that was no longer salvageable could be one explanation, as suggested by previous exploratory studies that showed an association between time to reperfusion and good clinical outcome. We sought to validate this association in a preplanned analysis of data from the IMS III trial. Methods We used data for patients with complete proximal arterial occlusions in the anterior circulation who received endovascular treatment and achieved angiographic reperfusion (score on Thrombolysis in Cerebral Infarction scale of grade 2–3) during the endovascular procedure (within 7 h of symptom onset). We used logistic regression to model good clinical outcome (defined as a modified Rankin Scale score of 0–2 at 3 months) as a function of the time to reperfusion. We prespecified variables to be considered for adjustment, including age, baseline National Institutes of Health Stroke Scale score, sex, and baseline blood glucose concentration. Findings Of 240 patients who were otherwise eligible for inclusion in our analysis, 182 (76%) achieved angiographic reperfusion. Mean time from symptom onset to reperfusion (ie, procedure end) was 325 min (SD 52). Increased time to reperfusion was associated with a decreased likelihood of good clinical outcome (unadjusted relative risk for every 30-min delay 0·85 95% CI 0·77–0·94; adjusted relative risk 0·88 0·80–0·98). Interpretation Delays in time to angiographic reperfusion lead to a decreased likelihood of good clinical outcome in patients after moderate to severe stroke. Rapid reperfusion could be crucial for the success of future acute endovascular trials. Funding US National Institutes of Health and National Institute of Neurological Disorders and Stroke.
In this trial in patients with stroke who had a mismatch between sizes of early infarction and a hypoperfused brain region, endovascular thrombectomy at 6 to 16 hours after stroke onset was ...associated with a favorable shift in the distribution of disability scores at 90 days.
Intracerebral hemorrhage (ICH) is a major public-health problem worldwide. No proven treatments are available for this condition, which is associated with high rates of morbidity and mortality. Only ...20% of individuals who survive ICH are independent at 6 months. Hypertension, cerebral amyloid angiopathy (CAA) and anticoagulation are known to be associated with such hemorrhages. No effective preventive therapies exist specifically for CAA-related ICH. The incidence of hypertension-related ICH might be decreasing in some populations with improvements in the treatment of hypertension; however, the incidence of anticoagulant-related ICH is increasing, as the use of anticoagulants rises. Many questions remain unanswered regarding the clinical management of ICH, although in the past 10 years completed medical and surgical clinical trials-examining hemostatic therapy, blood pressure control and/or hematoma evacuation-have refined our understanding of the goals of such management. Ongoing clinical trials, which have built on the lessons of past studies, hold promise for the development of effective, scientifically proven treatments for ICH. In this Review, we discuss clinical trials for ICH that have been completed in the past 10 years, the contributions of these studies to the clinical management of ICH, and the ongoing trials that might further improve clinical care.
Population-based studies have estimated that about 15% of ischemic strokes are caused by large-vessel cerebrovascular disease. We determined the types of large-vessel atherosclerosis responsible for ...ischemic strokes in a population-based stroke study.
Patients with first-ever or recurrent ischemic stroke in the Greater Cincinnati area were identified during 2005 at all local hospitals. Study physicians assigned ischemic stroke subtypes. Overall event rates and incidence rates for first-ever events were calculated, and age-, race- and sex-adjusted to the 2000 US population.
There were 2,204 ischemic strokes, including 365 strokes of large-vessel subtype (16.6% of all ischemic strokes). Extracranial internal carotid artery (ICA) stenosis was associated with 8.0% of all ischemic strokes, while extracranial ICA occlusion and intracranial atherosclerosis were each associated with 3.5% of strokes. The annual rate of first-ever and recurrent stroke attributed to extracranial ICA was 13.4 (11.4-15.4) per 100,000 persons. We conservatively estimate that about 41,000 strokes may be attributed to extracranial ICA stenosis annually in the United States.
Large-vessel atherosclerosis is an important cause of stroke, with extracranial ICA stenosis being significantly more common than extracranial ICA occlusion or intracranial atherosclerotic disease.
BACKGROUND AND PURPOSE—We derived and validated the Cincinnati Prehospital Stroke Severity Scale (CPSSS) to identify patients with severe strokes and large vessel occlusion (LVO).
METHODS—CPSSS was ...developed with regression tree analysis, objectivity, anticipated ease in administration by emergency medical services personnel and the presence of cortical signs. We derived and validated the tool using the 2 National Institute of Neurological Disorders and Stroke (NINDS) tissue-type plasminogen activator Stroke Study trials and Interventional Management of Stroke III (IMS III) Trial cohorts, respectively, to predict severe stroke (National Institutes of Health Stroke Scale NIHSS ≥15) and LVO. Standard test characteristics were determined and receiver operator curves were generated and summarized by the area under the curve.
RESULTS—CPSSS score ranges from 0 to 4; composed and scored by individual NIHSS items2 points for presence of conjugate gaze (NIHSS ≥1); 1 point for presence of arm weakness (NIHSS ≥2); and 1 point for presence abnormal level of consciousness commands and questions (NIHSS level of consciousness ≥1 each). In the derivation set, CPSSS had an area under the curve of 0.89; score ≥2 was 89% sensitive and 73% specific in identifying NIHSS ≥15. Validation results were similar with an area under the curve of 0.83; score ≥2 was 92% sensitive, 51% specific, a positive likelihood ratio of 3.3, and a negative likelihood ratio of 0.15 in predicting severe stroke. For 222 of 303 IMS III subjects with LVO, CPSSS had an area under the curve of 0.67; a score ≥2 was 83% sensitive, 40% specific, positive likelihood ratio of 1.4, and negative likelihood ratio of 0.4 in predicting LVO.
CONCLUSIONS—CPSSS can identify stroke patients with NIHSS ≥15 and LVO. Prospective prehospital validation is warranted.
Rationale
Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic ...strokes.
Aims
The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy.
Sample size estimate
1100 participants.
Methods and design
Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet.
Population studied
Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force >5000 µV × ms in ECG lead V1, serum NT-proBNP > 250 pg/mL, and left atrial diameter index ≥ 3 cm/m2 on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation.
Study outcomes
The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage.
Discussion
ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.
This randomized comparison of low-dose and standard-dose alteplase in acute ischemic stroke did not establish noninferiority of low-dose alteplase for the primary outcome of death or disability at 90 ...days. Fewer patients had intracerebral hemorrhages in the low-dose group.
Thrombolytic therapy with intravenous alteplase (recombinant tissue-type plasminogen activator) at a dose of 0.9 mg per kilogram of body weight is an effective treatment for acute ischemic stroke, despite increasing the risk of intracerebral hemorrhage.
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However, the Japanese drug safety authority has approved the use of alteplase at a dose of 0.6 mg per kilogram after an uncontrolled, open-label study showed that this dose resulted in equivalent clinical outcomes and a lower risk of intracerebral hemorrhage than that reported in published studies in which the 0.9-mg-per-kilogram dose was used.
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Other registry studies in Asia
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have shown inconsistent results, . . .
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