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Biomedical subjects

J M Wardlaw

Publications and source records attributed to J M Wardlaw.

At least 19 recordsLinked to original sources
PubMed2000

Thrombolysis for acute ischaemic stroke.

BACKGROUND: The majority of strokes are due to blockage of an artery in the brain by a blood clot. Clot dissolving (or thrombolytic) drugs may reduce brain damage from the stroke, but may also cause serious bleeding in the brain. Thrombolytic therapy has now been evaluated in several randomised trials in acute ischaemic stroke. OBJECTIVES: The objective of this review was to assess the safety and efficacy of thrombolytic agents in patients with acute ischaemic stroke. SEARCH STRATEGY: Cochrane Stroke Review Group search strategy plus ongoing contact with researchers and pharmaceutical companies. Last search conducted March 1999. SELECTION CRITERIA: Randomised trials of any thrombolytic agent compared with control in patients with definite ischaemic stroke. DATA COLLECTION AND ANALYSIS: One reviewer applied the inclusion criteria and extracted the data. Trial quality was assessed. The extracted data were verified by the principal investigators of all major trials. MAIN RESULTS: Seventeen trials including 5216 patients were included. Fifteen trials were double-blind. The trials tested urokinase, streptokinase, recombinant tissue plasminogen activator or recombinant pro-urokinase. Two trials used intra-arterial administration but the rest used the intravenous route. About 50% of the data come from trials testing intravenous tissue Plasminogen Activator. Thrombolytic therapy significantly increased the odds of death within the first ten days (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.48 to 2.32). The main cause of the increase in deaths was fatal intracranial haemorrhage following thrombolysis (OR 4.15, 95% CI 2.96 to 5.84). Symptomatic intracranial haemorrhage is also increased following thrombolysis (OR 3.53, 95% CI 2.79 to 4.45). Thrombolytic therapy also increased the odds of death at the end of follow-up (OR 1.31, 95% CI 1.13 to 1. 52). Despite this, thrombolytic therapy, administered up to six hours after ischaemic stroke, significantly reduced the proportion of patients who were dead or dependent (modified Rankin 3 to 6) at the end of follow-up (OR 0.83, 95% CI 0.73 to 0.94). For patients treated within three hours of stroke, thrombolytic therapy appeared more effective in reducing death or dependency (OR 0.58, 95% CI 0.46 to 0.74) with less adverse effect on death (OR 1.11, 95% CI 0.84 to 1.47). There was heterogeneity between the trials that could have been due to : thrombolytic drug used, variation in the concomitant use of aspirin and heparin, severity of the stroke, and time to treatment. Trials testing intravenous recombinant tissue Plasminogen Activator suggest that it may be associated with slightly less hazard and more benefit when given up to six hours after stroke - death within the first ten days OR 1.24, 95% CI 0.85 to 1.81, death at the end of follow-up OR 1.16, 95% CI 0.94 to 1.44, dead or dependent at the end of follow-up OR 0.79, 95% CI 0.68 to 0.92. One trial that tested thrombolysis plus aspirin showed an increase in deaths of patients given both drugs in combination compared with thrombolysis alone. REVIEWER'S CONCLUSIONS: Thrombolytic therapy increases deaths within the first seven to ten days, and deaths at final follow-up. Thrombolytic therapy also significantly increases symptomatic and fatal intracranial haemorrhage. These risks are offset by a reduction in disability in survivors, so that there is, overall, a significant net reduction in the proportion of patients dead or dependent in activities of daily living. The data from trials using intravenous recombinant tissue Plasminogen Activator, from which there is the most evidence on thrombolytic therapy so far, suggest that it may be associated with less hazard and more benefit. There was heterogeneity between the trials and the optimum criteria to identify the patients most likely to benefit and least likely to be harmed, the agent, dose, and route of administration, are not clear. (ABSTRACT TRUNCATED)

Brain Ischemia↗
PubMed2000

How often is haemosiderin not visible on routine MRI following traumatic intracerebral haemorrhage?

Intracerebral haemorrhage may be visible indefinitely on MRI, due to persistence of haemosiderin in macrophages around the lesion, but it is not clear whether all haemorrhages produce haemosiderin or, if not, what proportion cannot be identified as former haemorrhages on routine MRI. We performed routine MRI (spin-echo T2- and proton-density weighted images) in 116 survivors of moderate to severe head injury, 1-5 years after injury. We reviewed the images blindly and correlated them with CT in the acute stage, to determine how many haemorrhages from the acute stage were identifiable by virtue of haemosiderin deposition on late MRI. Of 106 haemorrhages in 78 patients on CT at the time of injury, 96 (90 %) were visible as haemosiderin on late MRI. Of the old haemorrhages without haemosiderin, seven of ten were in patients where another haemorrhage with haemosiderin was still visible elsewhere in the brain. No patient or haemorrhage features explained the formation or absence of haemosiderin. Thus about 10 % of definite haematomas show no trace of haemosiderin on routine spin-echo MRI. Radiologists should be alerted to supplement routine spin-echo with gradient-echo sequences if there is a reason to suspect, or specifically exclude, prior haemorrhage.

Adolescent↗
PubMed2000

The detection and management of unruptured intracranial aneurysms.

The incidence of subarachnoid haemorrhage (SAH) is 6-8 per 100 000 person years, peaking in the sixth decade. SAH, mostly due to rupture of an intracranial aneurysm, accounts for a quarter of cerebrovascular deaths. Aneurysms increase in frequency with age beyond the third decade, are 1.6 times more common in women and are associated with a number of genetic conditions. Prospective autopsy and angiographic studies indicate that between 3.6 and 6% of the population harbour an intracranial aneurysm. Studies have found an increased rate of SAH in first degree relatives of SAH patients (relative risk 3.7-6.6). In affected families, the most frequent relationship between sufferers is sibling to sibling. The rupture rate of asymptomatic aneurysms was thought to be 1-2% per annum, but the recent International Study of Unruptured Intracranial Aneurysms found that the rupture rate of small aneurysms was only 0.05% per annum in patients with no prior SAH, and 0.5% per annum for large (>10 mm diameter) aneurysms and for all aneurysms in patients with previous SAH. Non-invasive tests such as magnetic resonance angiography (MRA), computed tomographic angiography (CTA) and transcranial Doppler (TCD) have been advocated as alternatives to intra-arterial digital subtraction angiography to screen for aneurysms. Although all are promising techniques, the quality of data testing their accuracy is limited. Overall reported sensitivity for CTA and MRA (TCD is poorer) was 76-98% and specificity was 85-100%, but many subjects had an aneurysm or recent SAH, which could overestimate accuracy. CTA and MRA are much poorer methods for the detection of aneurysms <5 mm diameter, which account for up to one-third of unruptured aneurysms. Elective surgical clipping of asymptomatic aneurysms has a morbidity of 10.9% and mortality of 3. 8%. Treatment of aneurysms by Guglielmi coils, for which there is less long-term follow-up available, has a 4% morbidity and 1% mortality, but only achieves complete aneurysm occlusion in 52-78% of cases. There has been interest in screening for aneurysms, but the indication for, and cost effectiveness of screening are unclear because aneurysm prevalence varies, rupture rate is low, non-invasive imaging tests are not yet accurate enough to exclude small aneurysms and the morbidity and mortality for elective surgical treatment of unruptured aneurysms is high. There may be a limited role for investigation of high risk subgroups. Ideally, screening in such subgroups should be tested in a randomized trial. The avoidance of risk factors for aneurysms such as smoking, hypertension and hypercholesterolaemia should be part of the management of at-risk subjects.

Adult↗
PubMed2000

How well does the Oxfordshire community stroke project classification predict the site and size of the infarct on brain imaging?

OBJECTIVES: The Oxfordshire Community Stroke Project (OCSP) classification is a simple clinical scheme for subdividing first ever acute stroke. Several small studies have shown that when an infarct is visible on CT or MRI, the classification predicts its site in about three quarters of patients. The aim was to further investigate this relation in a much larger cohort of patients in hospital with ischaemic stroke. METHODS: Between 1994 and 1997, inpatients and outpatients with ischaemic stroke were assessed by one of several stroke physicians who noted the OCSP classification. A neuroradiologist classified the site and extent of recent infarction on CT or MRI. RESULTS: Of 1012 patients with ischaemic stroke, 655 (65%) had recent visible infarcts. These radiological lesions were appropriate to the clinical classification in 69/87 (79%) patients with a total anterior circulation syndrome, 213/298 (71%) with a partial anterior circulation syndrome, 105/144 (73%) with a lacunar syndrome, and 105/126 (83%) with a posterior circulation syndrome. Overall, 75% of patients with visible infarcts were correctly classified clinically. If patients without a visible infarct did have an appropriate lesion in the brain (best case), the classification would have correctly predicted its site and size in 849/1012 (84%) patients, compared with only 492/1012 (49%) in the worst case scenario. CONCLUSION: The OCSP classification predicted the site of infarct in three quarters of patients. When an infarct is visible on brain imaging, the site of the infarct should guide the use of further investigations, but if an infarct is not seen, the OCSP classification could be used to predict its likely size and site.

Aged↗
PubMed2000

Relationship between pattern of intracranial artery abnormalities on transcranial doppler and Oxfordshire Community Stroke Project clinical classification of ischemic stroke.

BACKGROUND AND PURPOSE: The Oxfordshire Community Stroke Project (OCSP) devised a simple classification for acute stroke based on clinical features only, which is of value in predicting prognosis. We investigated whether the pattern of intracranial vascular abnormalities is related to the clinical syndrome. METHODS: Patients with acute ischemic stroke were classified by a stroke physician as having total or partial anterior circulation infarct (TACI or PACI, respectively), lacunar infarct (LACI), or posterior circulation infarct (POCI). Color-coded power transcranial Doppler was done whenever possible. Intracranial arterial velocities were compared in the 4 subtypes of ischemic stroke after adjustment for age and time to transcranial Doppler. RESULTS: Middle cerebral artery velocity was abnormal (hyperemia, reduced velocity, occlusion, or focal stenosis) in 38 of 69 TACIs (55%), 50 of 171 PACIs (29%), and 20 of 236 LACIs or POCIs (8%) (P<0.001). Velocity in the A1 segment of the anterior cerebral artery was reversed in 12 of 69 TACIs (17%), 20 of 171 PACIs (12%), and 8 of 236 LACIs or POCIs (3%) (P<0.001). Basilar artery velocity was abnormal in 8 of 121 POCIs (7%) compared with 5 of 355 (1%) of the other subtypes (P=0.005). Vertebral artery velocity was abnormal (reduced velocity, occlusion, stenosis) in 20 of 121 POCIs (17%) compared with 20 of 355 others (6%) (P=0.01). CONCLUSIONS: Intracranial arterial abnormalities were related to OCSP clinical subtype. Therefore, it is possible to stratify patients according to OCSP classification in trials of new treatments in which treatment effectiveness may depend on the underlying pattern of arterial pathology and before any arterial imaging is available.

Aged↗
PubMed2000

Trials of thrombolysis in acute ischemic stroke: does the choice of primary outcome measure really matter?

BACKGROUND AND PURPOSE: Controversy regarding the risks and benefits of thrombolysis has not been helped by the perception that some trials were "positive" and others "negative" on their primary outcome measure of either "good" or "poor" functional outcome. We wondered whether the definition of good or poor functional outcome might have contributed to this perception, and what effect altering the definition might have on the individual trials and on the systematic review of all the trials combined. METHODS: We analyzed data on functional outcome, extracted from the randomized trials of thrombolysis in acute ischemic stroke, according to good (modified Rankin scale scores of 0 to 1 versus 2 to 6) and poor (modified Rankin 0 to 2 versus 3 to 6) functional outcome, to determine the effects of thrombolysis. RESULTS: Twelve trials (4342 patients, treated up to 6 hours after stroke) contributed to this analysis. Overall, there was no difference in the estimate of treatment effect between the 2 definitions (modified Rankin 0 to 2 versus 3 to 6, and 0 to 1 versus 2 to 6 [ORs 0.83 and 0.79, respectively]). However, the apparent "success" of several individual trials did alter. CONCLUSIONS: We should not place undue emphasis on the results of individual trials, when a change of a single point on the Rankin scale can make the difference between "success" and "failure." Overall, by either analysis, there was a significant benefit in patients treated with thrombolysis up to 6 hours after stroke.

Acute Disease↗
PubMed1999

The use of diffusion tensor imaging in quantifying the effect of dexamethasone on brain tumours.

The role of dexamethasone in the treatment of patients with brain tumours remains poorly understood. In this study the self-diffusion parameters of extracellular water within primary intracranial tumours and peritumoural tissue, and their response to dexamethasone, have been measured using MR diffusion tensor imaging. Maps of the mean diffusivity and two measures of diffusion anisotropy were obtained from six patients before, and typically 48-72h after, commencing dexamethasone treatment. A significant decrease in of either tumour (p < 0.02) or oedematous brain (p < 0.04) was observed in three patients. No significant changes were noted in either of the two calculated diffusion anisotropy indices before and after steroid treatment in any of the six patients.

Adult↗
PubMed1999

1H spectroscopic imaging of acute head injury--evidence of diffuse axonal injury.

Using single slice two-dimensional spectroscopic imaging (SI), nine acute head injury patients and six controls have been successfully scanned. The problems presented by the need for ITU monitoring of these patients during MR scanning was overcome using MR compatible monitoring equipment. In previous studies of head injury which used proton spectroscopy, single voxel localisation procedures have meant that the spatial extent of the spectral data has been limited. With spectral data from a whole axial slice, we have been able to identify NAA abnormalities in regions remote to any T2 visible lesions. This suggests that SI (of NAA in particular) will be useful for the diagnosis of diffuse axonal injury.

Adult↗
PubMed1999

The influence of baseline prognostic variables on outcome after thrombolysis. MAST-Italy Collaborative Group.

Thrombolysis increases case fatality but reduces the proportion of disabled survivors in recent trials in acute ischaemic stroke, although some trials show much higher mortality rates than others. One possible explanation for the different outcomes between trials is that the treatment effect with thrombolysis varies with baseline prognostic factors such as stroke severity. We examined the interaction between baseline risk and thrombolysis on outcome using individual patient data from the Multicentre Acute Stroke Trial-Italy (MAST-I). A multiple logistic regression of the MAST-I data was performed to identify which factors, identifiable at randomisation, most strongly predict a poor functional outcome. We then stratified the patients into those with severe strokes and those with mild strokes and examined the effect of thrombolysis on (a) case fatality and (b) dependency at 6 months after the stroke in the 157 patients who received streptokinase alone and the 156 controls. Streptokinase was found to cause an absolute increase of about 3% in case fatality in both "severe" and "mild" strokes; however, there was a 12% reduction in the number of dead or dependent "mild" strokes but a 6% increase in "severe" strokes. The number of patients was small, and therefore neither finding was statistically significant. In this exploratory analysis, the hazard with streptokinase appears similar in "severe" and "mild" strokes, but the benefit may be greater in "mild" strokes. Thrombolysis may be more effective in patients with "mild" strokes, but more information is required to confirm this hypothesis.

Aged↗
PubMed1999

Intracerebral haemorrhage and cerebral amyloid angiopathy: CT features with pathological correlation.

AIMS: To review the computed tomography (CT) features of intracerebral haemorrhage pathologically proven to be associated with cerebral amyloid angiopathy in order to facilitate recognition of the presence of cerebral amyloid angiopathy in life. METHODS: We prospectively collected the clinical and brain imaging records of patients dying following an intracerebral haemorrhage who underwent a post-mortem examination and were found to have cerebral amyloid angiopathy. We reviewed the brain imaging to highlight features of the haemorrhage and of the rest of the brain common to these cases. RESULTS: Seven patients aged 60-86 years were examined over a 30-month period. On CT, the notable features were that the haemorrhages appeared large, lobar, often extended through the cortex to the subarachnoid space or into the ventricles, and were multiple and recurrent in patients who survived the initial bleed. The high density (blood) within the haematoma tended to sediment posteriorly. CONCLUSIONS: There are features on CT of cerebral amyloid angiopathy associated with spontaneous intracerebral haemorrhage which should raise the possibility of this underlying diagnosis. We suspect this condition is under-recognized in life, and should perhaps be considered more widely.

Aged↗
PubMed1999

The influence of randomized trials on the use of anticoagulants for atrial fibrillation.

INTRODUCTION: Anticoagulants and anti-platelet drugs have been shown in randomized trials to reduce the risk of stroke in patients with atrial fibrillation (AF). We therefore investigated their use in patients known to be in AF before a stroke, transient ischaemic attack (either cerebral or ocular) or retinal artery occlusion to assess the influence of trials on clinical practice. METHODS: Inpatients and outpatients with acute stroke, transient ischaemic attack or retinal artery occlusion were prospectively identified by a stroke physician from 1990 to 1997. The presence or absence of AF before the vascular event, and prior use of anticoagulant and anti-platelet drugs were recorded at the time of the assessment and verified using information from general practitioner and hospital case notes. RESULTS: Of 1934 patients with stroke or retinal artery occlusion, 191 (10%) were in AF before their ischaemic event. Anticoagulants had been used in 40 (21%) of these, but only in 32 (2%) of the 1743 patients in sinus rhythm [odds ratio (OR) 14.2, 95% confidence interval (CI) 8.6-23.2]. Anti-platelet drugs had been used in 62 (32%) of those with AF compared with 500 (30%) of those in sinus rhythm (OR 1.2, 95% CI 0.9-1.64). Of the 161 patients in AF without contraindications to anticoagulants, only 36 (22%) were taking them. Although there was a statistically significant increase in anticoagulant use from 8% in 1990 to 23% in 1996, this could be explained solely by a fall in the age of the patients referred to our hospital. CONCLUSION: Anticoagulation is probably under-used in AF. We found no conclusive evidence that anticoagulation trials have influenced clinical practice. This raises issues about the dissemination and implementation of trial results.

Aged↗
PubMed1999

Accuracy of a miniature intracranial pressure monitor, its function during magnetic resonance scanning, and assessment of image artifact generation.

OBJECTIVE: We examined the accuracy and repeatability of an intracranial pressure (ICP) monitor (Codman MicroSensor; Johnson & Johnson Professional, Inc., Raynham, MA) in a nonmagnetic environment and during magnetic resonance imaging (MRI). The resulting image artifact generation was calculated. ICP monitoring is essential in management of severe head injury, but few ICP monitoring devices are compatible with use in an MRI scanner. The use of MRI to assess head injury is increasing, and developing safe methods of continuously monitoring ICP may improve patient care. METHODS: A water manometer was used as the standard for comparison. We assessed pressure readings from the ICP monitor in a nonmagnetic environment using a standard and a long connector cable between the pressure transducer and display unit. This long cable permitted testing during MRI sequences because the display unit could be distanced from the magnet. Accuracy was determined during T2-weighted imaging, proton spectroscopy, and diffusion-weighted imaging, and artifact generation was assessed. RESULTS: We found a high degree of accuracy for repeated measurements over a clinical pressure range using both standard and long connector cables outside the MRI room. During MRI scanning, the ICP monitor was accurate during T2 and proton spectroscopy sequences. Accuracy during diffusion-weighted imaging, however, was clinically unacceptable. This ICP monitor creates a reduction in signal-to-noise ratio in the received signal during T2-weighted imaging and proton spectroscopic imaging, with the obtained images still radiologically interpretable. CONCLUSION: The Codman ICP monitor is sufficiently accurate and free of artifact generation to be used during most clinical MRI applications. This could enhance patient monitoring and safety.

Artifacts↗
PubMed1999

Can simple clinical features be used to identify patients with severe carotid stenosis on Doppler ultrasound?

OBJECTIVES: Carotid endarterectomy reduces the risk of stroke in symptomatic patients with severe ipsilateral carotid stenosis. Symptomatic patients should therefore undergo carotid Doppler imaging, but in some centres access to imaging is limited. It was therefore investigated whether simple clinical features alone or in combination could be used to identify patients with severe carotid stenosis, so that they could be referred preferentially for carotid imaging. METHODS: 1041 patients with acute stroke, cerebral or retinal transient ischaemic attacks, and retinal strokes admitted to Western General Hospital or seen in neurovascular clinics were assessed by a stroke physician. Their carotid arteries were investigated using colour Doppler imaging by a consultant neuroradiologist. Patients with primary intracerebral haemorrhage, total anterior circulation strokes, posterior circulation strokes, or posterior circulation transient ischaemic attacks were excluded because carotid surgery would be inappropriate. RESULTS: 726 patients were used in the analysis. Stepwise logistic regression showed that there were significant positive associations between severe carotid stenosis and an ipsilateral bruit, diabetes mellitus, and previous transient ischaemic attacks; and a negative association with lacunar events. The strategy with the highest specificity (97%) was "any three of these four features" but sensitivity was only 17%. The strategy with the highest sensitivity (99%) was to use one or more of the four features, but specificity was only 22%. CONCLUSION: None of the strategies identified all patients with severe carotid stenosis with a reasonable specificity. When access to carotid imaging is severely limited, simple clinical features are of some use in prioritising patients for imaging, but access to carotid imaging should be improved.

Aged↗
PubMed1999

Predicting survival using simple clinical variables: a case study in traumatic brain injury.

OBJECTIVES: Prediction of patient outcome can be useful as an aid to clinical decision making, to explore possible biological mechanisms, and as part of the clinical audit process. Many studies have constructed predictive models for survival after traumatic brain injury, but these have often used expensive, time consuming, or highly specialised measurements. The aim of this study was to develop a simple easy to use model involving only variables which are rapidly and easily clinically achievable in routine practice. METHODS: All consecutive patients admitted to a regional trauma centre with moderate or severe head injury were enrolled in the study. Basic demographic, injury, and CT characteristics were recorded. Patient survival at 1 year was used to construct a simple predictive model which was then validated on a very similar patient group. RESULTS: 372 patients were included in the study, of whom 365 (98%) were followed up for survival at 1 year. Multiple logistic regression resulted in a model containing age (p<0.001), Glasgow coma scale score (p<0.001), injury severity score (p<0.001), pupil reactivity (p=0.004), and presence of haematoma on CT (p=0.004) as independently significant predictors of survival. The model was validated on an independent set of 520 patients, showing good discrimination and adequate calibration, but with a tendency to be pessimistic about very severely injured patients. It is presented as an easy to use nomogram. CONCLUSIONS: All five variables have previously been shown to be related to survival. All variables in the model are clinically simple and easy to measure rapidly in a centre with access to 24 hour CT, resulting in a model that is both well validated and clinically useful.

Adolescent↗
PubMed1999

Adding insult to injury: the prognostic value of early secondary insults for survival after traumatic brain injury.

OBJECTIVES: To assess the prognostic value of summary measures of secondary physiological insult in addition to baseline clinical variables for patients with traumatic brain injury. METHODS: A series of 110 patients with traumatic brain injury had data on intracranial pressure (ICP), arterial blood pressure (ABP), cerebral perfusion pressure (CPP), arterial O2 saturation (SaO2), temperature in degrees C (Temp), and heart rate in beats/min (HRT) monitored and recorded every minute. Secondary insults were defined according to the Edinburgh University secondary insult grading system. The prognostic value of summary measures of these secondary insults was assessed by adding them to a prognostic model for survival at 1 year after controlling for baseline clinical variables using a previously validated model. RESULTS: Of the eight secondary insults measured, only ICP added significantly to the prediction of survival in the first 72 hours after injury. The particular type of summary measure did not seem to influence the results. After the addition of ICP to the model, none of the other secondary insult measures could improve the predictive power of the model significantly. CONCLUSIONS: Early intracranial hypertension is confirmed as a sign of poor prognosis in patients with traumatic brain injury, even after controlling for baseline clinical variables. The value or otherwise of treating such secondary insults, however, can only be definitively established in the context of prospective randomised controlled trials. The specific pathophysiological evolution of secondary insults is still the subject of much research, and a clear understanding will be necessary before the development of specific treatments is feasible.

Adult↗