OBJECTIVE: Carotid angioplasty with or without stent placement (CAS) has been proposed as an alternative method to carotid endarterectomy (CEA) for treatment of carotid stenosis. Small randomized trials have evaluated the comparative efficacy of both methods; however, definitive evidence is lacking. METHODS: A search was made for randomized clinical trials comparing CAS and CEA for treatment of carotid stenosis. A literature search of MEDLINE, PubMed, and Cochrane databases was supplemented by a review of bibliographies of relevant articles and personal files. A meta-analysis was performed using a random effects model because significant heterogeneity was observed. Outcomes compared included 1-month composite rates of stroke or death, all strokes, disabling strokes, myocardial infarction, cranial nerve injury, and major bleeding and 1-year rates of both minor and major ipsilateral strokes. RESULTS: We analyzed five randomized trials totaling 1154 patients (577 randomized to CEA and 577 randomized to CAS). The composite end point of 1-month stroke or death rate was not different between patients treated with CAS compared with those treated with CEA (relative risk [RR], 1.3; 95% confidence interval [CI], 0.6–2.8; P = 0.5). The 1-month stroke rate (831 patients analyzed: RR, 1.3; 95% CI, 0.4–3.6; P = 0.7) and disabling stroke rate (831 patients analyzed: RR, 0.9; 95% CI, 0.2–3.5; P = 0.9) was similar for CAS and CEA. The 1-month rates of myocardial infarction (814 patients analyzed: RR, 0.3; 95% CI, 0.1–0.9) and cranial nerve injury (918 patients analyzed: RR, 0.05; 95% CI, 0.01–0.3) were significantly lower for CAS. No significant differences were observed in 1-year rates of ipsilateral stroke (814 patients analyzed: RR, 0.8; 95% CI, 0.5–1.2; P = 0.2). CONCLUSION: The 30-day stroke and death rates associated with CAS and CEA were not significantly different. Lower rates of myocardial infarction and cranial nerve injury were observed with CAS compared with CEA.

Background and Purpose: Intra-arterial thrombolytic therapy with pro-urokinase has been shown to be effective when given within 6 hours of symptom onset in patients with acute ischemic stroke (AIS). We evaluated the clinical efficacy and safety of thrombolysis with intra-arterial tissue plasminogen activator (TPA) within first 6-hour in patients with AIS. Methods: The medical records of patients with AIS who received intra-arterial TPA at our institution between October 1999 and March 2003 were reviewed. The National Institute of Health Stroke Scale (NIHSS) and modified Rankin’s scale (MRS) scores were collected on admission, at 24-hours, and on discharge from the hospital. All the patients had computed tomography (CT) and CT angiography to determine the site of occlusion prior to treatment. Patients who had occlusion of major intra-cerebral vessels were treated with intra-arterial TPA within first 6-hour of stroke onset. Outcome was assessed as good for MRS scores of 0 to 2 at the time of discharge. Results: A total of 40 patients (Age 65 17 years; Range: 21–94; 22 were men) had received intra-arterial TPA. One patient had spontaneous recanalization during cerebral angiogram and was excluded from the analysis. Twenty-three patients (58%) had arterial occlusions in the middle cerebral artery (MCA); 11 (28%) had occlusions in the internal carotid artery (ICA), 4(10%) had occlusions in the basilar artery (BA) and one (2%) had an occlusion in the anterior cerebral artery (ACA). The mean NIHSS on admission was 19. The mean TPA dose used was 9 mg (Range 3–24). Recanalization rate was 92% with intra-arterial TPA. Outcome was good in 17 (43%) of all patients. Five (12%) patients died. Symptomatic cerebral hemorrhage occurred in 3 (7%) patients. Outcome was good in 14 (60%) patients with MCA occlusion, 3 (27%) patients with ICA occlusion, and poor in 4 patients with BA and 1 patient with ACA occlusion. Conclusion: Intra-arterial TPA was found to be beneficial in AIS patients with large vessel occlusion identified by CT angiography. Whether this strategy of pre-selecting AIS patients for aggressive intra-arterial therapy leads to an improved risk-benefit profile for acute stroke interventions needs to be evaluated prospectively in a larger group of patients.

Recent advances in endovascular interventional therapies have revolutionized the management of acute ischemic stroke. For patients who present with occluded circle of Willis vessels, timely and successful arterial recanalization is the best predictor of clinical improvement. Diagnostic neuroimaging has advanced noninvasive tools--namely, transcranial Doppler, CT angiography, and MR angiography--to screen individuals with acute neurologic syndromes rapidly for arterial occlusion, and hence to exclude from treatment those who are unlikely to benefit from or could be harmed by arterial recanalization strategies. Intra-arterial thrombolysis has been proven to be of benefit in large clinical trials. Moreover, the US Food and Drug Administration has recently approved the use of a mechanical clot retrieval device for acute embolic stroke, and a number of other similar strategies are under various stages of investigation. This article reviews the diagnostic and interventional approach to the management of large vessel embolic stroke.

In acute stroke, chemical neuroprotection is an important strategy aimed at limiting the biochemical cascade of events induced by cerebral ischemia which lead to secondary neuronal damage. Among multiple pharmaceutical interventions tried magnesium (Mg++), which is a physiological voltage-dependent N-metyl-D-aspartate (NMDA) antagonist, has demonstrated promising results. As opposed to other antiglutamate agents, Mg++ has limited adverse effects, is widely available, easy to administer, and has good penetrability in the central nervous system (CNS). Mg++ is involved in the pathogenesis of an expanding array of clinical conditions via vascular and cellular effects. Experimental stroke models and pilot clinical studies have provided encouraging data regarding the neuroprotective role of Mg++ in acute ischemic stroke. Observations from subarachnoid hemorrhage (SAH) animal models have suggested that Mg++ might have a neuroprotective effect directed against the ischemic injury which accompanies cerebral vasospasm. Large randomized, double blind clinical studies assessing Mg++ efficacy in stroke are already in progress. Magnesium sulfate is also under active investigation as a neuroprotective agent in SAH. Keywords: neuroprotection, excitotoxicity, nmda, magnesium, stroke, sah

BACKGROUND AND PURPOSEEarly reocclusion of recanalized arteries has been observed after thrombolysis for acute coronary occlusion and has been attributed to platelet activation after exposure to thrombolytic agents. We conducted a retrospective study to determine the rate of reocclusion during intra-arterial thrombolysis for acute ischemic stroke and the effect of reocclusion on functional outcome.METHODSPatients treated for acute ischemic stroke at our center between September 2000 and May 2002 received a maximum total dose of 4 U of reteplase intra-arterially in 1-U increments via superselective catheterization. Pharmacologic thrombolysis was supplemented by mechanical thrombolysis with balloon angioplasty or snare manipulation at the occlusion site. Angiography was performed after each unit of reteplase or mechanical maneuver, and the images were interpreted by a blinded reviewer. Reocclusion was defined as partial or complete initial recanalization with occlusion recurring at the same site as documented by angiography during the endovascular treatment. Reocclusions were treated by further pharmacologic and/or mechanical thrombolysis according to the discretion of the treating physician. Clinical evaluations were performed before and 24 hr, 7 to 10 days, and 1 to 3 months after treatment.RESULTSForty-six consecutive patients underwent intra-arterial thrombolysis. Reocclusion was observed in eight (17%). Among these patients, initial sites of occlusion were in the following arteries: intracranial internal carotid artery (n = 2), M1 segment of the middle cerebral artery (n = 3), M1 and M2 segments of the middle cerebral artery (n = 2), and basilar artery (n = 1). The mean initial National Institutes of Health Scale score for these eight patients was 23.3 +/- 6.2; mean time from symptom onset to treatment was 4.4 +/- 1.2 hr. The reocclusions were treated by using additional doses of reteplase alone (n = 1), reteplase with snare maneuver and/or angioplasty (n = 5), reteplase with angioplasty or snare and then stent placement (n = 1), and angioplasty with stent placement (n = 1). The reocclusions resolved in six of eight patients after further treatment. Six patients died and two survived but were severely disabled at 1 month (modified Rankin Scale scores of 4 and 5, respectively). Independent functional outcome scores (modified Rankin Scale scores of 0-2) were significantly lower among patients with angiographically shown reocclusion than in those without (0 of 8 versus 17 of 38, P =.02).CONCLUSIONReocclusion occurs relatively frequently during intra-arterial thrombolysis for ischemic stroke and seems to be associated with poor clinical outcomes.

ABSTRACT Objective. To identify the prevalence and characteristics of aortic atherosclerotic plaque disease and its association with cerebrovascular risk factors in patients with cerebral ischemic events. Background. Aortic atheroma is associated with ischemic stroke. Its characteristics, including morphology and distribution among different stroke subtypes, are not well described. Method. From July 2000 to August 2001, all patients evaluated by transesophageal echocardiography (TEE) with diagnoses of transient ischemic attacks (TIAs) and strokes were prospectively studied. Demographics, including age, gender, ethnicity, cerebrovascular risk factors, and stroke subtypes, were collected. Results. Thoracic aortic atheromas (TAAs) were present in 141 of 237 patients (59%) (mean age = 59 ± 14, 119 [50%] male). Mild plaque (<2mm) was present in 13 of 237 (5%), moderate plaque (2–4 mm) in 49 (21%), severe plaque (≥4 mm) in 79 (33%), and complex plaque in 64 (27%). Patients’ ages (odds ratio [OR] = 1.05, confidence interval [CI] 1.03–1.08, P < .001), coronary artery disease (OR = 2.2, CI 1.02–4.8, P < .042), and patent foramen ovale (PFO) (OR = 0.39, CI 0.22–0.70, P < .002) were associated with the severity and complexity of aortic plaque. In multivariate analysis, age (OR = 1.06, CI 1.03–1.08, P < .001) and the presence of PFO (OR = 0.35, CI 0.18–0.65, P < .001) continued to be significant to the severity and complexity of aortic atheroma. Gender, history of stroke, hypertension, diabetes mellitus, hyperlipidemia, and history of smoking were not associated with TAA. Conclusion. One third of TAA plaques are severe and complex in nature and more frequently present in the descending aorta and the arch of the aorta than in the ascending aorta. TEE should be considered for the early detection and treatment of TAA in patients without identified causes of stroke.

Background and Purpose— We developed a model to estimate the costs incurred by ineffective primary and secondary prevention in terms of excess cardiovascular disease (CVD) mortality in a nationally representative sample of the US population. Methods— Cox proportional hazards analyses were used to examine the effect of inadequate risk factor control on the incidence of fatal stroke and myocardial infarction (MI) during a follow-up period of 13.4±3.6 years after adjusting for differences in age, gender, and ethnicity in a national cohort of 9252 adults who participated in the Second National Health and Nutrition Examination Survey (NHANES) Mortality Follow-up Study. Inadequate risk factor modification was defined by presence of either blood pressure >140/90 mm Hg, serum cholesterol >200 mg/dL, or active cigarette smoking. Using the data from 4115 adults screened in the NHANES 1999 to 2000, population attributable risk (PAR) percent and associated cost incurred (expressed as proportion of total 1-year cost incurred for CVD mortality in year 2001) was estimated. Results— CVD mortality risk increased in a stepwise manner for persons with no previous MI or stroke and ≥2 inadequately controlled risk factors (2×); and previous history of MI and stroke and adequately controlled risk factors (2.6×), 1 inadequately controlled risk factor (4.3×), and ≥2 inadequately controlled risk factors (5.7×). The PAR was 14% (estimated cost incurred $13.2 billion) among persons with ≥2 inadequately controlled risk factors without previous MI or stroke (estimated 17% of total US population). Among persons with previous MI or stroke, the PAR was 7% (cost incurred $6.2 billion) and 8% (cost incurred $7.4 billion) for 1 inadequately controlled risk factor and ≥2 inadequately controlled risk factors, respectively. An excess of cost of $13.6 billion was spent on 4% of the total population (persons with inadequate secondary prevention). Conclusions— The model demonstrates the differential risk of mortality from inadequately controlled cardiovascular risk factors in primary and secondary prevention settings. The large financial cost incurred by inadequate primary and secondary prevention justifies intensive efforts directed toward detection and treatment of cardiovascular risk factors.

The authors report two patients with suspected brain death who required confirmatory tests other than clinical examination because of prolonged barbiturate administration for intracranial hypertension. Absence of intracranial blood flow was documented on CT angiography and confirmed by CT perfusion images. Cerebral angiography confirmed the findings consistent with brain death. CT angiography with CT perfusion may represent a rapid noninvasive method for diagnosis of brain death.