Biomedical subjects
Publications and source records attributed to C P Warlow.
We prospectively recorded CSF opening pressure in 242 adults who had a lumbar puncture with concomitant measurement of weight and height. The 95% reference interval for lumbar CSF opening pressure was 10 to 25 cm CSF. Body mass index had a small but clinically insignificant influence on CSF opening pressure.
BACKGROUND: Brain arteriovenous malformations (AVMs) are the single most common cause of intracerebral haemorrhage in young adults. Brain AVMs also cause seizure(s) and focal neurological deficits (in the absence of haemorrhage, migraine or an epileptic seizure); approximately one fifth are incidental discoveries. Various interventions are used in an attempt to eradicate brain AVMs: neurosurgical excision, stereotactic radiotherapy/'radiosurgery' (using gamma knife, linear accelerator or proton beam), endovascular embolisation (using glues, particles, fibres, coils, or balloons), and staged combinations of these interventions. OBJECTIVES: To assess the clinical effects of interventions to treat brain AVMs in adults (with the aim of either partial obliteration or total eradication), using data published in randomised controlled trials. SEARCH STRATEGY: We searched: (1) the Cochrane Stroke Group Register (last searched December 2004); (2) medical literature databases (MEDLINE 1966 to 31 December 2004 and EMBASE 1980 to 31 December 2004); (3) on-line and paper journal surveillance; (4) the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005); (5) international registers of clinical trials; (6) bibliographies of relevant articles identified by (1) to (5); and (7) we sought unpublished data from manufacturers of interventional treatments for brain AVMs. SELECTION CRITERIA: We sought randomised trials of any or all of the interventions for brain AVMs, compared against each other or against usual medical therapy, with relevant clinical outcome measures. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria and reviewed the relevant studies. MAIN RESULTS: We did not find any randomised trials meeting our selection criteria. We found two randomised trials which tested the equivalence of two embolic agents for the pre-operative embolisation of brain AVMs (one published, one unpublished), but none of the primary or secondary outcome measures in these trials met our desired criteria; although important clinical outcomes were reported, meaningful comparison of the two treatment arms was impossible. We also excluded a third RCT which studied three different blood pressure lowering treatments to induce deliberate hypotension during surgical resection of brain AVMs, because the intervention was not the focus of this review. AUTHORS' CONCLUSIONS: There is no evidence from randomised trials with clear clinical outcomes, comparing different interventional treatments for brain AVMs against each other or against usual medical therapy, to guide the interventional treatment of brain AVMs in adults. One such trial (ARUBA), comparing interventional versus conservative management for unruptured brain AVMs, is being planned.
We developed a model identifying patients with previous cerebral ischaemia at increased risk of intracerebral haemorrhage (ICH). Based on data from eight cohorts, 107 ICHs were found to have occurred among 12 648 patients. Multivariate Cox regression analysis identified the following predictors: age (> or = 60 years, hazard ratio (HR) 2.07), blood glucose level (> or = 7 mmol/l, HR 0.33), systolic blood pressure (> or = 140 mm Hg, HR 2.17), and antihypertensive drugs (HR 1.53). The highest risk quartile was associated with five times more ICHs than the lowest quartile.
BACKGROUND AND PURPOSE: Early studies showed that carotid endarterectomy (CEA) carried a high risk if performed within days after a large ischemic stroke. Therefore, many surgeons delay CEA for 4 to 6 weeks after any stroke. To determine the effect of delay to CEA on operative risk and benefit, we pooled data from the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial. METHODS: Risk of ipsilateral ischemic stroke in the medical group, operative risk of stroke and death, and overall benefit from surgery were determined in relation to the time from the last symptomatic event to randomization. Operative risk of stroke and death was also determined in relation to the time to surgery. Analyses were stratified by sex and type of presenting event. RESULTS: The 30-day perioperative risk of stroke and death was unrelated to the time since the last symptomatic event and was not increased in patients operated <2 weeks after nondisabling stroke. In contrast, the risk of ipsilateral ischemic stroke in the medical group fell rapidly with time since event (P<0.001), as did the absolute benefit from surgery (P=0.001). This decline in benefit with time was unrelated to the type of presenting event but was more pronounced in women than men (difference P<0.001). Benefit in women was confined to those randomized <2 weeks after their last event, irrespective of severity of stenosis. CONCLUSIONS: CEA can be performed safely within 2 weeks of nondisabling ischemic stroke. Benefit from endarterectomy declines rapidly with increasing delay, particularly in women.
BACKGROUND: The incidence of stroke is predicted to rise because of the rapidly ageing population. However, over the past two decades, findings of randomised trials have identified several interventions that are effective in prevention of stroke. Reliable data on time-trends in stroke incidence, major risk factors, and use of preventive treatments in an ageing population are required to ascertain whether implementation of preventive strategies can offset the predicted rise in stroke incidence. We aimed to obtain these data. METHODS: We ascertained changes in incidence of transient ischaemic attack and stroke, risk factors, and premorbid use of preventive treatments from 1981-84 (Oxford Community Stroke Project; OCSP) to 2002-04 (Oxford Vascular Study; OXVASC). FINDINGS: Of 476 patients with transient ischaemic attacks or strokes in OXVASC, 262 strokes and 93 transient ischaemic attacks were incident events. Despite more complete case-ascertainment than in OCSP, age-adjusted and sex-adjusted incidence of first-ever stroke fell by 29% (relative incidence 0.71, 95% CI 0.61-0.83, p=0.0002). Incidence declined by more than 50% for primary intracerebral haemorrhage (0.47, 0.27-0.83, p=0.01) but was unchanged for subarachnoid haemorrhage (0.83, 0.44-1.57, p=0.57). Thus, although 28% more incident strokes (366 vs 286) were expected in OXVASC due to demographic change alone (33% increase in those aged 75 or older), the observed number fell (262 vs 286). Major reductions were recorded in mortality rates for incident stroke (0.63, 0.44-0.90, p=0.02) and in incidence of disabling or fatal stroke (0.60, 0.50-0.73, p<0.0001), but no change was seen in case-fatality due to incident stroke (17.2% vs 17.8%; age and sex adjusted relative risk 0.85, 95% CI 0.57-1.28, p=0.45). Comparison of premorbid risk factors revealed substantial reductions in the proportion of smokers, mean total cholesterol, and mean systolic and diastolic blood pressures and major increases in premorbid treatment with antiplatelet, lipid-lowering, and blood pressure lowering drugs (all p<0.0001). INTERPRETATION: The age-specific incidence of major stroke in Oxfordshire has fallen by 40% over the past 20 years in association with increased use of preventive treatments and major reductions in premorbid risk factors.
BACKGROUND: Carotid endarterectomy reduces the risk of stroke in patients with recently symptomatic stenosis. Benefit depends on the degree of stenosis, and we aimed to see whether it might also depend on other clinical and angiographic characteristics, and on the timing of surgery. METHODS: We analysed pooled data from the European Carotid Surgery Trial and North American Symptomatic Carotid Endarterectomy Trial. The risk of ipsilateral ischaemic stroke for patients on medical treatment, the perioperative risk of stroke and death, and the overall benefit from surgery were determined in relation to seven predefined and seven post hoc subgroups. RESULTS: 5893 patients with 33000 patient-years of follow-up were analysed. Sex (p=0.003), age (p=0.03), and time from the last symptomatic event to randomisation (p=0.009) modified the effectiveness of surgery. Benefit from surgery was greatest in men, patients aged 75 years or older, and those randomised within 2 weeks after their last ischaemic event, and fell rapidly with increasing delay. For patients with 50% or higher stenosis, the number of patients needed to undergo surgery (ie, number needed to treat) to prevent one ipsilateral stroke in 5 years was nine for men versus 36 for women, five for age 75 years or older versus 18 for younger than 65 years, and five for those randomised within 2 weeks after their last ischaemic event, versus 125 for patients randomised after more than 12 weeks. These results were consistent across the individual trials. INTERPRETATION: Benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other clinical characteristics such as delay to surgery after the presenting event. Ideally, the procedure should be done within 2 weeks of the patient's last symptoms.
BACKGROUND AND PURPOSE: The importance of stroke in low-income regions such as sub-Saharan Africa has recently been emphasized. However, little is known about the burden of stroke in sub-Saharan Africa. We investigated the prevalence of stroke survivors in the Agincourt Health and Population Unit, a demographic surveillance site in the rural northeast of South Africa. METHODS: Census workers asked household informants 2 screening questions for stroke during the annual census. If either question was answered positively, a clinician visited individuals aged > or =15 years to confirm the likely diagnosis of stroke. We performed a detailed assessment and defined stroke according to the World Health Organization criteria. RESULTS: A total of 42 378 individuals were aged > or =15 years. There were 982 positive responses to the questionnaire, and we examined 724 individuals (74%). We identified 103 strokes (crude prevalence, 243/100 000). After adjustment for those we did not examine, the prevalence was 300/100 000 (95% CI, 250 to 357). Sixty-six percent of stroke survivors needed help with at least 1 activity of daily living (Segi age-standardized prevalence, 200/100 000). CONCLUSIONS: Stroke prevalence in rural South Africa is higher than previously documented in Africa but lower than in high-income countries. However, the prevalence of stroke survivors requiring help with at least 1 activity of daily living is already at high-income country levels. South Africa suffers from a huge burden of HIV/AIDS and diseases of poverty and violence and now faces the challenge of adapting its health systems to face the coming epidemic of vascular disease.
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Many studies have found that women have a higher risk of perioperative stroke or death from carotid endarterectomy. Other vascular surgical procedures have demonstrated that body size and morphology impact on operative risk. We correlated the 30 day operative risk of stroke and death in the European Carotid Surgery Trial (ECST) with height, weight, body surface area (BSA), and body mass index using single variable analyses and multivariable logistic regression. Women were at significantly higher risk of perioperative stroke and death in the ECST. Both height and BSA confounded the effect of sex, implying that the generally smaller size of women may contribute to their increased risk. This finding should be validated in other large datasets.
BACKGROUND AND PURPOSE: The commonly quoted early risks of stroke after a first transient ischemic attack (TIA)-1% to 2% at 7 days and 2% to 4% at 1 month-are likely to be underestimates because of the delay before inclusion into previous studies and the exclusion of patients who had a stroke during this time. Therefore, it is uncertain how urgently TIA patients should be assessed. We used data from the Oxford Community Stroke Project (OCSP) to estimate the very early stroke risk after a TIA and investigated the potential effects of the delays before specialist assessment. METHODS: All OCSP patients who had a first-ever definite TIA during the study period (n=209) were included. Three analyses were used to estimate the early stroke risk after a first TIA starting from 3 different dates: assessment by a neurologist, referral to the TIA service, and onset of first TIA. RESULTS: The stroke risk from assessment by a neurologist was 1.9% [95% confidence interval (CI), 0.1 to 3.8] at 7 days and 4.4% (95% CI, 1.6 to 7.2) at 30 days. The 7- and 30-day stroke risks from referral were 2.4% (95% CI, 0.3 to 4.5) and 4.9% (95% CI, 1.9 to 7.8), respectively, and from onset of first-ever TIA were 8.6% (95% CI, 4.8 to 12.4) and 12.0% (95% CI, 7.6 to 16.4), respectively. CONCLUSIONS: The early risk of stroke from date of first-ever TIA is likely to be higher than commonly quoted. Public education about the symptoms of TIA is needed so that medical attention is sought more urgently and stroke prevention strategies are implemented sooner.
BACKGROUND: Endarterectomy reduces risk of stroke in certain patients with recently symptomatic internal carotid stenosis. However, investigators have made different recommendations about the degree of stenosis above which surgery is effective, partly because of differences between trials in the methods of measurement of stenosis. To accurately assess the overall effect of surgery, and to increase power for secondary analyses, we pooled trial data and reassessed carotid angiograms. METHODS: We pooled data from the European Carotid Surgery Trial (ECST), North American Symptomatic Carotid Endarterectomy Trial, and Veterans Affairs trial 309 from the original electronic data files. Outcome events were re-defined, if necessary, to achieve comparability. Pre-randomisation carotid angiograms from ECST were re-measured by the method used in the other two trials. RESULTS: Risks of main outcomes in both treatment groups and effects of surgery did not differ between trials. Data for 6092 patients, with 35000 patient-years of follow-up, were therefore pooled. Surgery increased the 5-year risk of ipsilateral ischaemic stroke in patients with less than 30% stenosis (n=1746, absolute risk reduction -2.2%, p=0.05), had no effect in patients with 30-49% stenosis (1429, 3.2%, p=0.6), was of marginal benefit in those with 50-69% stenosis (1549, 4.6%, p=0.04), and was highly beneficial in those with 70% stenosis or greater without near-occlusion (1095, 16.0%, p<0.001). There was a trend towards benefit from surgery in patients with near-occlusion at 2 years' follow-up (262, 5.6%, p=0.19), but no benefit at 5 years (-1.7%, p=0.9). INTERPRETATION: Re-analysis of the trials with the same measurements and definitions yielded highly consistent results. Surgery is of some benefit for patients with 50-69% symptomatic stenosis, and highly beneficial for those with 70% symptomatic stenosis or greater but without near-occlusion. Benefit in patients with carotid near-occlusion is marginal in the short-term and uncertain in the long-term.
BACKGROUND: Although the symptoms of unilateral "medically unexplained" or "functional" weakness and sensory disturbance present commonly to neurologists, little is known about their long term prognosis. OBJECTIVE: To determine the long term outcome of functional weakness and sensory disturbance. PATIENTS: A previously assembled cohort of 60 patients seen as inpatients by consultant neurologists in Edinburgh between 1985 and 1992 and diagnosed as having unilateral functional weakness or sensory disturbance. METHODS: Current symptoms, disability, and distress were assessed by postal questionnaire to the patients and their family doctors. RESULTS: Follow up data relating to mortality were obtained in 56 patients (93%) and to current diagnosis in 48 patients (80%). Patient questionnaire data were obtained in 42 patients (70%). The median duration of follow up was 12.5 years (range 9 to 16). Thirty five of the 42 patients (83%) still reported weakness or sensory symptoms, and the majority reported limitation of physical function, distress, and multiple other somatic symptoms. Twenty nine per cent had taken medical retirement. An examination of baseline predictors indicated that patients who had sensory symptoms had better functioning at follow up than those who had weakness. Only one patient had developed a neurological disorder which, in hindsight, explained the original presentation. Another patient had died of unrelated causes. CONCLUSIONS: Many patients assessed by neurologists with unilateral functional weakness and sensory symptoms as inpatients remain symptomatic, distressed, and disabled as long as 12 years after the original diagnosis. These symptoms are only rarely explained by the subsequent development of a recognisable neurological disorder in the long term.
BACKGROUND AND PURPOSE: The European Carotid Surgery Trial (ECST) and North American Symptomatic Carotid Endarterectomy Trial (NASCET) have shown that endarterectomy reduces the risk of stroke in certain patients with recently symptomatic carotid stenosis. However, they differed in the degree of stenosis above which surgery was reported to be effective. This disparity has led to inconsistent clinical recommendations but may have been due to differences between the trials in the methods of measurement of carotid stenosis and definitions of outcome events. METHODS: To allow direct comparison of analyses from ECST and NASCET, we remeasured the prerandomization ECST carotid angiograms and redefined the outcome events the same way as in NASCET. RESULTS: We randomized 3018 patients and followed them up for a mean of 73 months. Surgery reduced the 5-year risk of any stroke or surgical death by 5.7% (95% CI, 0 to 11.6) in patients with 50% to 69% stenosis (n=646, P=0.05) and by 21.2% (95% CI, 12.9 to 29.4) in patients with 70% to 99% stenosis without "near occlusion" (n=429, P<0.0001). These benefits were maintained at the 10-year follow-up. However, surgery was of no benefit in patients (n=125) with near occlusion. The effect of surgery in this group was highly significantly different from that in patients with 70% to 99% stenosis without near occlusion (P=0.002). Surgery was harmful in patients with <30% stenosis (n=1321, P=0.007) and of no benefit in patients with 30% to 49% stenosis (n=478, P=0.6). CONCLUSIONS: Results of the ECST and NASCET were consistent when analyzed in the same way. In ECST, surgery was highly beneficial for 70% to 99% stenosis and moderately beneficial for 50% to 69% stenosis. However, contrary to clinical recommendations and current practice, surgery was of little benefit in patients with carotid near occlusion.
OBJECTIVES: Lacunar infarcts are thought to be mostly due to intracranial small vessel disease. Therefore, when a stroke patient with a relevant lacunar infarct does have severe ipsilateral internal carotid artery (ICA) or middle cerebral artery (MCA) disease, it is unclear whether the arterial disease is causative or coincidental. If causative, we would expect ICA/MCA disease to be more severe on the symptomatic side than on the asymptomatic side. Therefore, our aim was to compare the severity of ipsilateral with contralateral ICA and MCA disease in patients with lacunar ischaemic stroke. METHODS: We studied 259 inpatients and outpatients with a recent lacunar ischaemic stroke and no other prior stroke. We used carotid Duplex ultrasound and transcranial Doppler (TCD) ultrasound to identify ICA and MCA disease, and compared our results with previously published data. RESULTS: In our study, there was no difference between the severity of ipsilateral and contralateral ICA stenosis within individuals (median difference 0%, Wilcoxon paired data p=0.24, comparing severity of ipsilateral and contralateral stenosis). The overall prevalence of severe ipsilateral stenosis was 5%, and the prevalence of severe contralateral stenosis was 4% (OR 1.6, 95% CI 0.6, 4.8). There was no difference in the prevalence of ipsilateral and contralateral MCA disease. A systematic review of the other available studies strengthened this conclusion. CONCLUSION: Carotid stenosis in patients with a lacunar ischaemic stroke may be coincidental. Further studies are required to elucidate the causes of lacunar stroke, and to evaluate the role of carotid endarterectomy.
OBJECTIVES: carotid endarterectomy is associated with significant morbidity and mortality. A better understanding of the relationships between baseline characteristics and outcome may help to reduce the risks of surgery. In order to make accurate and unbiased estimates of surgical risk it is important to study cohorts of patients that were established prospectively, where independent physicians assessed outcome, and where the decision to analyse and report the results was not data-dependent. The surgical arm of the European Carotid Surgery Trial (ECST) is such a cohort. METHODS: the 30-day outcome of carotid endarterectomy was analysed in ECST surgery patients in relation to their baseline clinical and angiographic characteristics. The severity of operative strokes was compared with that of strokes that occurred in the medical group. RESULTS: 1729 patients underwent trial surgery. There were 17 deaths (1.0%, 95% CI=0.6-1.6) and 105 non-fatal major strokes (6.1%, 95% CI=5.0-7.3) within 30 days of surgery. The risk of major stroke or death was 7.1% (95% CI=5.9-8.4). The risk of disabling or fatal stroke was 3.0% (95% CI=2.1-3.8). The ratio of disabling to non-disabling operative strokes was similar to that in the medical group. Several baseline characteristics predicted the operative risk of stroke and death in univariate analyses, but only four were independent risk factors in a multiple regression analysis: presentation with cerebral TIA vs ocular ischaemic events only (HR=2.99, 95% CI=1.33-6.69, p=0.008); female sex (HR=2.04, 95% CI=1.37--3.06, p=0.001); systolic hypertension (HR=1.01 per 10 mmHg, 95% CI=1.00-1.02, p=0.03) and peripheral vascular disease (HR=2.17, 95% CI=1.17-2.89, p=0.001). CONCLUSIONS: the operative risk of stroke and death in the ECST was comparable with other prospective studies and trials in which patients were assessed postoperatively by both a physician and a surgeon. Case fatality and disability after operative stroke are similar to strokes that occur on medical treatment only. Several baseline patient characteristics predict surgical risk and it may be possible to use these characteristics to aid patient selection and surgical audit.
OBJECTIVES: several ancillary surgical techniques, such as shunting and patching, are used in association with carotid endarterectomy. However, the balance of risks and benefits of these techniques is uncertain because of the lack of large randomised controlled trials (RCTs). To assess the potential for further trials, we studied the variation in use of these techniques by surgeon and by country in the European Carotid Surgery Trial (ECST). METHODS: use of each ancillary technique was assessed by surgeon and by country. For each technique, the relationships between the use of the technique and baseline patient characteristics, use of other techniques, and the 30-day operative risk of stroke and death were determined. RESULTS: there was considerable variation between surgeons in the use of ancillary operative techniques both within (p<0.001 for shunting and patching), and between countries (p<0.001 for shunting and patching). Some surgeons used techniques selectively, and so the characteristics of patients differed depending on which techniques were used. Use of each technique was also significantly associated with the use of other techniques. Multiple regression analysis, taking into account all these factors, found no statistically significant associations between operative risk and the use of shunting, patching, intra-operative EEG monitoring, or type of anaesthetic. The only surgical technique significantly associated with an increased operative risk was not using intra-operative anticoagulation (hazard ratio=2.33, 95% CI=1.4-4.2). Other factors associated with an increased risk were an operation time of less than 1 h, or greater than 1.5 h, and the surgeons' subjective assessment that the operation was difficult. CONCLUSIONS: in the ECST, operative risk was more closely related to patient characteristics, length of surgery, and the surgeons' perception of the difficulty of the operation, than to the use of particular ancillary operative techniques. The considerable variation between surgeons, and between countries, in the use of ancillary techniques is in keeping with the lack of convincing data from RCTs, and suggests that there should be sufficient uncertainty to make large pragmatic trials possible.
OBJECTIVE: To conduct a population based study of brain arteriovenous malformation (AVM) prevalence. METHODS: Multiple, overlapping sources of case ascertainment were used to establish the point prevalence of brain AVMs in the adult population of the Lothian health board of Scotland. Patients were sought retrospectively from all local general (family) practitioners, neurologists, neurosurgeons, stroke physicians, the specialist AVM clinic at the regional neuroscience centre, and routine coding of hospital discharge data. Case notes, brain imaging, and pathology reports were reviewed to validate each patient's diagnosis and to ensure that each was alive, over the age of 16 years, and resident in the geographical area of the study on the prevalence date of 30 June 1998. RESULTS: Of 148 potentially eligible people, 93 adults met the inclusion criteria. There were 40 women and 53 men. Men were significantly younger than women on the prevalence date (median age 39 years v 51 years, p = 0.003). Of those included, 25 (27%) had radiological evidence of prior therapeutic obliteration of their brain AVM and 9 (10%) had coexisting aneurysms. The minimum crude brain AVM prevalence was 15 per 100 000 adults and capture-recapture analysis gave an ascertainment adjusted prevalence of 18 (95% confidence interval 16 to 24) per 100 000 adults. CONCLUSIONS: The minimum estimate of brain AVM prevalence helps to assess its burden and comparative epidemiology and stresses the importance of brain AVMs as a cause of long term disability in adults.
OBJECTIVES: To test the hypothesis that unilateral motor and sensory symptoms unexplained by identifiable disease are more common on the left side of the body than the right. METHODS: Systematic review of the literature published since 1965. RESULTS: 121 eligible studies, involving 1139 patients, were analysed. The pooled proportion of functional left sided weakness and sensory symptoms in adults was 58% (95% confidence interval (CI) 55 to 61%). A much higher proportion of left sided symptoms (66%, 95% CI 61 to 71%) was found in studies where laterality featured in the title of the paper. However, when laterality was not mentioned in the title, no significant difference between left and right was observed (53% on the left, 95% CI 48 to 57%). This difference could not be explained on the basis of sex differences between the groups or the date of the study. Functional or "psychogenic" movement disorder was right sided in 68% (95% CI 61 to 75%). Handedness did not influence symptom lateralisation. CONCLUSIONS: The findings of this systematic review question whether functional weakness and sensory symptoms do in fact occur more commonly on the left side of the body. A type of outcome variable reporting bias in combination with non-blinding of investigators may be responsible for this long held but erroneous belief.