Microembolic signals in patients with systemic lupus erythematosus.

INTRODUCTION: Central nervous system (CNS) involvement is a common and less understood aspect of systemic lupus erythematosus (SLE). Microembolic signals (MES) have been reported in SLE. We conducted a prospective study to evaluate the frequency of MES among patients with CNS involvement and those without. The main aim of the study is to clarify the pathophysiology of the CNS involvement in SLE. METHODS AND MATERIALS: Sixty eight patients with a diagnosis of SLE (60 females, 8 males) participated in the study. Both middle cerebral arteries were monitored using transcranial Doppler for 60 min to detect MES. All cases underwent neurology and psychiatry assessments. RESULTS: MES were detected in 7/68 patients (10.3%) with the mean number of 3.5 per hour. MES were significantly higher in patients with CNS involvement (6/24, 25%) than those without (1/44, 2.2%) (P=0.006). SLE disease activity index, duration of disease, plaque formation, intima-media thickness, and antiphospholipid antibodies were not associated with MES. MES were more frequent in patients receiving Aspirin and/or Warfarin (p=0.02). CONCLUSIONS: MES may be a predictor for CNS involvement in SLE patients at risk for neuropsychiatric syndromes. Cerebral embolism may be implicated in the pathophysiology of neuropsychiatric SLE.

Paracentral strip infarcts of the middle cerebral artery: borderzone ischaemia or cortical artery occlusion?

BACKGROUND AND PURPOSE: We have noted the presence of small strip-like infarcts involving the cortex within the interdivisional territory of the middle cerebral artery (MCA) and sometimes extending to the periventricular region. The incidence in a stroke unit population, mechanisms, clinical expression and prognosis of patients with these cortical infarcts are unknown. To clarify these issues we retrospectively and prospectively identified these patients in our own stroke unit population. METHODS: Patients were identified retrospectively and prospectively from the Austin Hospital Stroke Unit from March 2001 to May 2007. All were selected on the basis of the recent onset of an acute neurological deficit with imaging showing strip infarction within the MCA territory. Clinical features were recorded and the mechanism of infarction was classified based on the TOAST criteria from standard investigations. RESULTS: From 4,274 acute stroke admissions, there were 24 patients (0.6%), 12 males and 12 females (mean age 75 years; range 44-92 years) with CT or MRI showing characteristic linear infarction in the middle cerebral territory. In most cases, infarction was adjacent to the central sulcus. Common clinical features included mild-to-moderate hemiparesis with cortical signs. The most common TOAST criterion mechanism categories were artery-to-artery or cardiac embolism. It is postulated that this resulted in either isolated small cortical artery branch occlusion or borderzone infarction between superior and inferior divisions of the MCA due to more proximal large-artery vessel occlusion. Prognosis was good. CONCLUSIONS: We describe the phenotypic expression, postulated mechanisms and prognosis of strip-like infarcts between the superior and inferior MCA divisions. The likely artery-artery or cardio-embolic mechanisms should prompt clinicians to search for an embolic source. While the prognosis of the syndrome is generally good, its recognition may allow specific therapies to be developed to improve clinical outcomes further.

Microembolic signals in subarachnoid hemorrhage.

Microembolic signals (MES) detected by transcranial Doppler (TCD) have been reported in subarachnoid hemorrhage (SAH), although their origin and contribution to brain ischemia remain uncertain. We conducted a prospective study to evaluate the frequency of MES among patients with SAH and to determine their origin. Twenty-seven patients with SAH, comprising 15 aneurysmal and 12 non-aneurysmal patients, participated in the study. TCD evaluation was performed using a 2 MHz probe. Patients were studied three times per week during their in-patient stay to detect vasospasm, and then each middle cerebral artery (MCA) was monitored for 30 min using the Monolateral Multigate mode to detect MES. Using this method, MES were detected in 7 out of 15 patients (47%) with aneurysmal SAH and were not seen in non-aneurysmal patients (p=0.007). Vasospasm occurred in 52% (14/27) of cases. However, clinical signs and symptoms of vasospasm were identified in only 18.5% (5/27). There was no significant relationship between MES and vasospasm (p=0.224). Also, no relationship was found between MES and the location of the aneurysm (p=0.685). Thus, in this study MES were only detected in aneurysmal SAH. However, we did not find a relationship between the location of the aneurysm and MES, or the presence of vasospasm and MES. Therefore, MES in patients with SAH may also originate from vascular pathology other than the aneurysm sac or vascular spasm.

Doppler ultrasound detection of side-vessel occlusion: an in vitro study.

BACKGROUND AND PURPOSE: Small-vessel knock is a recently reported Doppler ultrasound finding that has been identified in patients with cerebral ischemia. It has been hypothesized that knock-type signals are linked to the presence of either small-vessel occlusion or wall motion. The aim of this study was to investigate the origins of "knock-type" signals by reproducing occlusion of a peripheral artery model in vitro. METHODS: Synthetic bifurcations were fabricated from glass and latex and placed in a flow-rig mimicking physiological blood-flow conditions. The glass model permitted study of fluid flow in the absence of wall motion, whereas the latex model also produced wall motion effects. Vessels were artificially obstructed to examine Doppler signal characteristics associated with blood flow and wall motion. RESULTS: Complete obstruction of the peripheral branch of the glass model revealed discrete (<100 ms) knock-type signals caused by local fluid flow in the occluded branch. Imaging of the obstructed vessel using color Doppler revealed forward and reflected flow. The walls produced periodic bidirectional knock-type signals, which occurred during systole and were not related to the presence of an obstruction. CONCLUSIONS: In our laboratory model, transcranial Doppler ultrasound was found to be capable of detecting knock signals produced by circulating fluid within an occluded branch. However, because similar signals are also generated by nonpathological wall motion, these results cannot be directly translated to a clinical setting. Clinicians should be careful to avoid casual overinterpretation of transcranial Doppler ultrasound data.

Asymptomatic carotid artery stenosis.

Severe asymptomatic carotid stenosis is associated with a stroke risk of approximately 2% per annum. Aggressive management of risk factors is recommended, including cessation of smoking, and treatment of hypertension, diabetes, and hypercholesterolemia. Patients should be treated with antiplatelet agents. Carotid endarterectomy (CEA) in patients with greater than or equal to 60% stenosis reduces the risk of stroke by approximately 1% per annum overall. The benefit is greatest for men and younger patients. There may be no benefit for women or for older patients. Carotid angioplasty and stenting is not recommended as an alternative to CEA until there is clinical trial evidence of efficacy in asymptomatic stenosis, except in some patients with technical contraindications to CEA. There is no evidence that patients with asymptomatic severe carotid stenosis should undergo carotid revascularization prior to other surgical procedures, including coronary bypass surgery.

What should we do with asymptomatic carotid stenosis?

The benefit of prophylactic carotid endarterectomy (CEA) for patients with asymptomatic severe carotid stenosis in the major randomised surgical studies was small, expensive and may now be absorbed by improvements in best practice medical intervention. Strategies to identify patients with high stroke risk are needed. If surgical intervention is to be considered the complication rates of individual surgeons should be available. Clinicians will differ in their interpretation of the same published data. Maintaining professional relationships with clinicians from different disciplines often involves compromise. As such, the management of a patient will, in part, depend on what kind of specialist the patient is referred to. The clinician's discussion with patients about this complex issue must be flexible to accommodate differing patient expectations. Ideally, patients prepared to undergo surgical procedures should be monitored in a trial setting or as part of an audited review process to increase our understanding of current practice outcomes.

Embolic signals and prediction of ipsilateral stroke or transient ischemic attack in asymptomatic carotid stenosis: a multicenter prospective cohort study.

BACKGROUND AND PURPOSE: We tested the hypothesis that transcranial Doppler embolic signal (ES) detection identifies an increased risk of ipsilateral carotid stroke or transient ischemic attack (TIA) in subjects with asymptomatic severe carotid stenosis. METHODS: Subjects with duplex-determined 60% to 99% carotid stenosis, without other apparent cerebroembolic sources, underwent 6-monthly neurological assessment and 60-minute ES monitoring. ES positivity was defined as > or =1 ES detected in > or =1 study, ES negativity as no ES in any study, and consistent ES negativity as no ES in any study where > or =6 studies were performed. Rates of ipsilateral carotid stroke/TIA were calculated using Kaplan-Meier analysis and correlated with ES status using odds ratios (ORs) and Cox proportional hazards regression analysis. RESULTS: A total of 202 subjects (138 male; mean age 74 years; mean follow-up 34 months) were recruited. The average annual rate of ipsilateral carotid stroke/TIA was 3.1%. A total of 231 arteries were monitored at least once (mean 4.3 studies/artery). Six of 60 (10.0%) ES-positive arteries had an ipsilateral carotid stroke/TIA compared with 12 of 171 (7.0%) ES-negative arteries (OR, 1.47; 95% CI, 0.43, 4.48; P=0.624) and 2 of 41 (4.9%) consistently ES-negative arteries (OR, 2.17; 95% CI, 0.36, 22.90; P=0.59). Differences in survival free of ipsilateral carotid stroke/TIA according to ES status were not statistically significant. CONCLUSIONS: Although there were more ipsilateral carotid cerebrovascular events among ES-positive arteries, this was not statistically significant. Less labor-intensive techniques are required to make further study and clinical application practical.

Warfarin for atrial fibrillation: the end of an era?

BACKGROUND: Warfarin has been in routine clinical use for more than 50 years; however, it was not proven to be of benefit in both primary and secondary prevention of stroke for patients with non-valvular atrial fibrillation (AF) until about a decade ago. Despite its efficacy in reducing the risk of stroke in patients with AF by about 60%, with an absolute reduction of about 3% per year, there have always been barriers to its use. These barriers have included the need for monitoring the degree of anticoagulation with blood tests to measure the international normalised ratio, frequent dose adjustments to maintain this ratio within quite a narrow therapeutic range, and the risk of bleeding should the upper limits of this range be exceeded. Aspirin has also been used but is less effective. RECENT DEVELOPMENTS: New oral drugs are being tested; these may be as effective at reducing stroke risk as warfarin in patients with AF. Direct thrombin inhibitors such as ximelagatran are not inferior to warfarin and, based on results from the SPORTIF III and V trials, are perhaps safer, with no need for long-term monitoring and dose adjustment. However, the side-effect of raised amounts of the liver enzyme alanine amino-transferase in 6% of patients needs to be resolved. In the ACTIVE trial, the efficacy of a combination of antiplatelet drugs (aspirin plus clopidogrel) is being tested against dose-adjusted warfarin; and in AMADEUS, the factor-Xa inhibitor and pentasaccharide idraparinux is being assessed in a similar way. Several surgical procedures and devices are also being developed to control AF rhythm and prevent stroke. WHERE NEXT?: The place of these new drugs in the management of AF needs to be established. In the short term, it seems that ximelagatran will replace warfarin in patients for whom there is evidence of a favourable risk-to-benefit ratio. The SPORTIF population consists of patients with AF plus at least one risk factor. More information about the effect of raised liver enzymes will probably not be available until phase IV studies are completed. Combination antiplatelet drugs need to be tested further--perhaps even triple therapy with aspirin, clopidogrel, and dipyridamole--if the results of ACTIVE are encouraging. The place of surgical procedures and devices to control rhythm and prevent stroke is unclear. Whatever happens, there is a high probability that the days of warfarin are numbered.

Trial application of a Model of Resource Utilization, Costs, and Outcomes for Stroke (MORUCOS) to assist priority setting in stroke.

BACKGROUND AND PURPOSE: Cost-effectiveness data for stroke interventions are limited, and comparisons between studies are confounded by methodological inconsistencies. The aim of this study was to trial the use of the intervention module of the economic model, a Model of Resource Utilization, Costs, and Outcomes for Stroke (MORUCOS) to facilitate evaluation and ranking of the options. METHODS: The approach involves using an economic model together with added secondary considerations. A consistent approach was taken using standard economic evaluation methods. Data from the North East Melbourne Stroke Incidence Study (NEMESIS) were used to model "current practice" (base case), against which 2 interventions were compared. A 2-stage process was used to measure benefit: health gains (expressed in disability-adjusted life years [DALYs]) and filter analysis. Incremental cost-effectiveness ratios (ICERs) were calculated, and probabilistic uncertainty analysis was undertaken. RESULTS: Aspirin, a low-cost intervention applicable to a large number of stroke patients (9153 first-ever cases), resulted in modest health benefits (946 DALYs saved) and a mean ICER (based on incidence costs) of US 1421 dollars per DALY saved. Although the health gains from recombinant tissue-type plasminogen activator (rtPA) were less (155 DALYs saved), these results were impressive given the small number of persons (256) eligible for treatment. rtPA dominates current practice because it is more effective and cost-saving. CONCLUSIONS: If used to assess interventions across the stroke care continuum, MORUCOS offers enormous capacity to support decision-making in the prioritising of stroke services.

High intensity transient signals in patients with carotid stenosis may persist after carotid endarterectomy.

BACKGROUND: This study was undertaken to elucidate the natural history of high intensity transient signals (HITS) after carotid endarterectomy (CEA) and to determine whether this differs between patients with and without HITS detected preoperatively. METHODS: A 30-min transcranial Doppler (TCD) recording was performed to detect HITS in 141 patients at 0-1 h, 2-3 h, 4-6 h and 24-36 h following CEA. 104 of these patients also had 30-min TCD monitoring within 48 h prior to CEA. RESULTS: In the preoperative HITS-negative group, the proportion with postoperative HITS fell from 53% at 0-1 h to 17% at 24-36 h. In the preoperative HITS-positive group, the proportion with postoperative HITS remained steady (43% at 0-1 h, 52% at 24-36 h). During the 24-36 h postoperative epoch, 11 of 21 (52%) of the preoperative HITS-positive group had at least one HITS compared to 11 of 66 (17%) of the preoperative HITS-negative group (p = 0.001). In a multiple logistic regression analysis, preoperative HITS was the only factor associated with persistent postoperative HITS. CONCLUSION: The proportion of cases with postoperative HITS diminished in the 24-36 h after CEA except for preoperative HITS-positive patients. About half of our patients undergoing CEA with preoperative HITS might have another embolic source.

Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome.

BACKGROUND AND PURPOSE: Hyperglycemia at the time of ischemic stroke is associated with increased mortality and morbidity. Animal studies suggest that infarct expansion may be responsible. The influence of persisting hyperglycemia after stroke has not previously been examined. We measured the blood glucose profile after acute ischemic stroke and correlated it with infarct volume changes using T2- and diffusion-weighted MRI. METHODS: We recruited 25 subjects within 24 hours of ischemic stroke symptoms. Continuous glucose monitoring was performed with a glucose monitoring device (CGMS), and 4-hour capillary glucose levels (BGL) were measured for 72 hours after admission. MRI and clinical assessments were performed at acute (median, 15 hours), subacute (median, 5 days), and outcome (median, 85 days) time points. RESULTS: Mean CGMS glucose and mean BGL glucose correlated with infarct volume change between acute and subacute diffusion-weighted MRI (r>or=0.60, P<0.01), acute and outcome MRI (r=0.56, P=0.01), outcome National Institutes of Health Stroke Scale (NIHSS; r>or=0.53, P<0.02), and outcome modified Rankin Scale (mRS; r>or=0.53, P=0.02). Acute and final infarct volume change and outcome NIHSS and mRS were significantly higher in patients with mean CGMS or mean BGL glucose >or=7 mmol/L. Multiple regression analysis indicated that both mean CGMS and BGL glucose levels >or=7 mmol/L were independently associated with increased final infarct volume change. CONCLUSIONS: Persistent hyperglycemia on serial glucose monitoring is an independent determinant of infarct expansion and is associated with worse functional outcome. There is an urgent need to study normalization of blood glucose after stroke.

Source of microembolic signals in patients with high-grade carotid stenosis.

BACKGROUND AND PURPOSE: In patients with both symptomatic and asymptomatic carotid artery stenoses, the relationship between carotid plaque characteristics and transcranial Doppler (TCD)-detected microembolic signals (MES) is unclear. The purpose of this study was to examine the relationship between macroscopically described plaque characteristics and MES in patients undergoing carotid endarterectomy. METHODS: Sequential patients scheduled for carotid endarterectomy underwent preoperative 30-minute TCD monitoring of the ipsilateral middle cerebral artery to detect MES. TCD signal analysis, by researchers who were blinded to patient information, was performed offline. Clinical variables of patients and macroscopic carotid plaque features seen at surgery were documented prospectively. RESULTS: Of the 109 patients (74 male, 35 female; mean age, 68.8+/-8.7 years) enrolled, 71 had ipsilateral carotid territory symptoms. MES were detected in 27 of all patients (25%). Twenty-two of 71 symptomatic patients (31%) compared with 5 of 38 asymptomatic patients (13%) had MES (P=0.046). Also, symptomatic patients had more emboli (total MES counts) than asymptomatic patients (P=0.010). The presence or absence of MES was not associated with plaque characteristics. CONCLUSIONS: Our data do not confirm previous reports of an association between MES and macroscopic plaque characteristics. We hypothesize that smaller platelet aggregates and fibrin clots, which are not detected macroscopically, are the most likely sources of TCD-detected MES.

Possible determinants of early microembolism after carotid endarterectomy.

BACKGROUND AND PURPOSE: High numbers of microembolic signals (MES) have been associated with increased risk of postoperative stroke after carotid endarterectomy (CEA). We sought to identify factors predictive of postoperative MES. METHODS: Transcranial Doppler monitoring of the ipsilateral middle cerebral artery for MES was performed for 30 minutes during the first postoperative hour in sequential patients undergoing CEA. Stepwise binomial logistic regression analysis was performed to identify preoperative and intraoperative variables that predicted the occurrence of postoperative MES. RESULTS: We studied 141 patients (mean age, 69 years); 102 (72%) were male, and 69 (49%) had at least 1 MES (range, 1 to 118) detected in the first postoperative hour. The risk of postoperative MES was greater in women (P=0.027), patients not receiving antiplatelet therapy (P=0.033), and patients undergoing left-sided CEA (P=0.049). Other variables such as residual stenosis seen on completion angiography and operative technique were not associated with postoperative MES. CONCLUSIONS: Postoperative MES were most likely in women, patients not receiving preoperative antiplatelet therapy, and patients who had a left CEA. Microembolism might explain why these same factors are associated with higher rates of perioperative stroke.

The influence of diabetes mellitus and hyperglycaemia on stroke incidence and outcome.

Diabetes mellitus is a complex metabolic syndrome with significant effects on the systemic and cerebral vasculature. The incidence and severity of ischaemic stroke are increased by the presence of diabetes, and outcome from stroke is poorer. More than one third of patients admitted with acute stroke are hyperglycaemic at presentation. Reasons for the altered prognosis in diabetes associated stroke are multifactorial. A direct influence of hyperglycaemia at the time of ischaemia is likely to be important. The use of novel methods to delineate stroke topography and pathophysiology such as MR spectroscopy, diffusion and perfusion weighted MRI appear helpful in delineating the effects of hyperglycaemia on stroke pathophysiology. Randomised clinical trials to determine optimal management for patients with hyperglycaemia following stroke are ongoing. Such trials will determine if aggressive control of acute hyperglycaemia following stroke has similar benefits to that observed following acute myocardial infarction. Clinicians responsible for stroke patients should be aware of the importance of adequate glycaemic control in both primary and secondary prevention of stroke.