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Biomedical subjects

Christopher R Levi

Publications and source records attributed to Christopher R Levi.

17 recordsLinked to original sources

Quantitative measurement of cerebral haemodynamics in early vascular dementia and Alzheimer's disease.

Alzheimer's disease (AD) and vascular dementia (VaD) both share significant vascular risk factors. The present study measures the haemodynamics of these diseases in absolute rather than relative terms. Twenty-four patients were classified as either early AD or VaD and were compared with 12 non-cognitively impaired subjects. Magnetic resonance imaging flow quantification was used to measure arterial inflow and arterial pulse volume. Mean vascular resistance and compliance were calculated. In AD, the arterial inflow was lower by 18%, resistance was higher by 23% and compliance of the arterial tree was lower by 20% compared with normal (p=0.01, 0.02 and 0.05, respectively). In VaD, the arterial pulse volume was higher by 24% and compliance was higher by 35% compared with normal (p=0.05 for both). Early VaD is characterized by normal blood flow, but increased pulsation. Reduced blood flow and an incompliant arterial tree characterize early AD.

Aged↗

CT perfusion source images improve identification of early ischaemic change in hyperacute stroke.

CT perfusion scanning produces dynamic contrast-enhanced brain images, but to generate and interpret the colour maps of cerebral perfusion from these source images requires specialist neuroimaging knowledge. We hypothesized that physicians without such training might still utilise the CT perfusion source images (CTPSI) to diagnose early ischaemic change. Fifteen patients had cerebral non-contrast CT (NCCT) and perfusion CT within 6 hours of hemispheric stroke onset. We tested 15 non-stroke clinicians and radiology trainees, plus three experts, in assessing the presence and extent of early ischaemic change on NCCT versus CTPSI. Day 5-7 CT or MRI was used as the gold standard. Agreement with follow-up imaging was poor for both detection, and extent of early ischaemic change on NCCT (kappa = 0.01-0.11). There was a marked improvement in agreement for both the presence and extent of early ischaemic change on CTPSI (kappa = 0.67-0.83). CTPSI were much more accurate than NCCT in identifying acute ischaemic change. 'Less expert' users accurately identified major early ischaemic change on acute CTPSI. These findings suggest that such physicians might utilise CTPSI to screen potential thrombolysis candidates.

Acute Disease↗

The pathophysiology of the aqueduct stroke volume in normal pressure hydrocephalus: can co-morbidity with other forms of dementia be excluded?

Variable results are obtained from the treatment of normal pressure hydrocephalus (NPH) by shunt insertion. There is a high correlation between NPH and the pathology of Alzheimer's disease (AD) on brain biopsy. There is an overlap between AD and vascular dementia (VaD), suggesting that a correlation exists between NPH and other forms of dementia. This study seeks to (1) understand the physiological factors behind, and (2) define the ability of, the aqueduct stroke volume to exclude dementia co-morbidity. Twenty-four patients from a dementia clinic were classified as having either early AD or VaD on the basis of clinical features, Hachinski score and neuropsychological testing. They were compared with 16 subjects with classical clinical findings of NPH and 12 aged-matched non-cognitively impaired subjects. MRI flow quantification was used to measure aqueduct stroke volume and arterial pulse volume. An arterio-cerebral compliance ratio was calculated from the two volumes in each patient. The aqueduct stroke volume was elevated in all three forms of dementia, with no significant difference noted between the groups. The arterial pulse volume was elevated by 24% in VaD and reduced by 35% in NPH, compared to normal (P = 0.05 and P = 0.002, respectively), and was normal in AD. There was a spectrum of relative compliance with normal compliance in VaD and reduced compliance in AD and NPH. The aqueduct stroke volume depends on the arterial pulse volume and the relative compliance between the arterial tree and brain. The aqueduct stroke volume cannot exclude significant co-morbidity in NPH.

Aged↗

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.

Aged↗

Perfusion computed tomography: prediction of final infarct extent and stroke outcome.

The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) has not been previously applied to perfusion CT (CTP). Five raters assigned ASPECTS to baseline noncontrast CT (NCCT), CT angiography source images (CTA-SI), CTP source images (CTP-SI), and CTP maps of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) from 37 consecutive patients with less than 6-hour anterior circulation ischemic stroke. Major reperfusion was identified on follow-up imaging. Mean baseline ASPECTS was compared with follow-up imaging ASPECTS. Rates of favorable outcome were compared for dichotomized baseline ASPECTS. In patients with major reperfusion, mean CBV and CTP-SI ASPECTS closely predicted final infarct ASPECTS. In patients without major reperfusion, mean CBF and MTT ASPECTS best predicted final infarct ASPECTS. There were significant increases in rates of favorable outcome for CTP-SI and CBV ASPECTS of greater than 6, versus less than or equal to 6, but not for other baseline CT modalities. ASPECTS applied to CTP is more accurate at identifying the extent of reversible and irreversible ischemia and at predicting final clinical outcome than NCCTor CTA-SI.

Aged↗

Tissue plasminogen activator (tPA) in acute ischaemic stroke: time for collegiate communication and consensus.

Systematic reviews of randomised trials of tPA in acute ischaemic stroke indicate a clear benefit of treating selected patients within 3 hours of stroke onset. Moreover, a net benefit remained after adjustment for chance baseline imbalances between subgroups in stroke severity within one of these trials (National Institute of Neurological Disorders and Stroke [NINDS]). Rates of favourable outcomes and intracranial haemorrhage comparable with those in randomised trials can be achieved in routine clinical practice; however, translation of net benefit from tPA therapy requires organised and coordinated stroke management across the continuum of care. Prerequisites for well organised and coordinated acute stroke care are: consensus among care providers on the use of tPA; stroke-care teams spanning the gaps between pre-hospital care, emergency departments and stroke units; and collegiate relations and effective communication networks between care providers.

Acute Disease↗

Towards a Safer Culture: clinical pathways in acute coronary syndromes and stroke.

Towards a Safer Culture (TASC) aims to provide a safer culture in hospital departments by introducing clinical pathways for the management of patients with acute coronary syndromes or stroke. Specific clinical pathways have been implemented for patients with different levels of risk to guide the most appropriate evidence-based medical care for each patient. Pathways facilitate continuity of care across different clinical departments by identifying gaps in care, and clarifying tasks and responsibilities. A multidisciplinary and interdepartmental approach to managing patients is seen as an effective way of effecting change. A system for "point-of-care" data acquisition, a centralised database and web-based reporting enable benchmarking for participating hospitals. A comprehensive range of educational/training strategies is used to facilitate multidisciplinary teamwork and promote clinical leadership. Phase 1 of TASC was successfully piloted at four hospitals in New South Wales, Victoria and Queensland. TASC is currently being rolled out to 29 hospitals in NSW and three hospitals in Western Australia.

Acute Disease↗

Imaging the ischemic penumbra with 18F-fluoromisonidazole in a rat model of ischemic stroke.

BACKGROUND AND PURPOSE: The ischemic penumbra is a major focus of stroke research. 18F-fluoromisonidazole (18F-FMISO), a positron emission tomography (PET) marker of hypoxic cells, has shown promise as a technique to image the penumbra in humans. Our aim was to delineate the pattern of 18F-FMISO binding in a rat middle cerebral artery transient thread-occlusion model, and correlate this with tissue outcome at 24 hours. We hypothesized that the pattern of 18F-FMISO binding would mimic that seen in humans. METHODS: Thirty-eight rats underwent 2 hours transient middle cerebral artery (MCA) occlusion, and then received 18F-FMISO at time points from 0.5 to 22 hours post-MCA occlusion and were killed 2 hours later. Autoradiographic assessment of 18F-FMISO binding and assessment (triphenyltetrazolium chloride) of the area of infarction were performed on tissue slices. RESULTS: Until 1 hour after MCA occlusion, 18F-FMISO binding was increased in the entire MCA territory, with little or no infarction visible. Over the next 5 hours, the pattern of binding evolved to a small rim of intensely binding tissue surrounding the infarct core, which itself showed reduced binding compared with the contralateral hemisphere. By 24 hours, there was minimal accumulation of 18F-FMISO binding and a large area of infarction. CONCLUSIONS: The pattern of 18F-FMISO binding rats reproduced the pattern seen in humans, consistent with this tracer being a marker of the ischemic penumbra in both species. This technique may have application in studying the ischemic penumbra in animal models, and correlating this with similar studies in humans.

Animals↗

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.

Aged↗

Seasonal variation in stroke in the Hunter Region, Australia: a 5-year hospital-based study, 1995-2000.

BACKGROUND AND PURPOSE: Seasonal variation in stroke has long been recognized. To date, there are minimal published data on seasonal variations in rates of stroke and subsequent case fatality in the Southern Hemisphere. The aim of this study was to examine stroke seasonality through the use of data from a hospital-based stroke register in the Hunter Region of New South Wales, Australia. METHODS: From July 1, 1995, to June 30, 2000, 3803 stroke events were registered in residents of the Hunter Region, New South Wales, Australia. We analyzed the trend of seasonal and monthly stroke attack rates and case-fatality rates using Poisson regressions with age and sex as covariates. RESULTS: Stroke attack rates were highest in the winter and lowest in the summer. From February (summer) to July (winter), there was a significant trend in increasing stroke attack rates (rate ratio, 1.07; 95% confidence interval, 1.05 to 1.10; P<0.001). This increase was seen mainly in those >or=65 years of age. Case-fatality rates showed similar trends with a 1- to 2-month lag compared with attack rates. CONCLUSIONS: There is an increase in stroke attack rates and case-fatality rate from summer to winter in the Hunter Region, Australia. These trends are similar to those found in the Northern Hemisphere.

Adult↗

A prediction model of 1-year mortality for acute ischemic stroke patients.

OBJECTIVE: To develop a prediction model for 1-year mortality in patients with acute ischemic stroke, with the model to be at least as useful and accurate as other previously developed prediction models. DESIGN: Retrospective cohort study. SETTING: Neurology department at an Australian tertiary teaching hospital. PARTICIPANTS: Four hundred forty consecutive patients diagnosed with acute ischemic stroke between July 1, 1995, and June 30, 1997. INTERVENTIONS: Two hundred twenty-three (51%) patients were randomly assigned to the derivation sample to develop a prediction model using the Cox proportional hazards model. The model was then validated in a validation sample of 217 (49%) patients. MAIN OUTCOME MEASURE: One-year mortality. RESULTS: Eight clinical predictors were included in the final model: unconsciousness (3 points), dysphagia (7 points), urinary incontinence (9 points), both sides affected (4 points), hyperthermia (4 points), ischemic heart disease (3 points), peripheral vascular disease (3 points), and diabetes mellitus (2 points). Patients with scores of 10 or higher were allocated to the high-risk group, which had a 1-year mortality rate of 76%, compared with a 1-year mortality rate of 8% in the low-risk group. There was no statistically significant difference in terms of sensitivity, specificity, and positive predictive value in the validation sample. CONCLUSION: We developed a predictive model for 1-year mortality in acute ischemic stroke patients. The model is easy to use and is comparable in its accuracy with other predictive models.

Aged↗

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.

Adult↗

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.

Adult↗