Nitrous oxide exposure does not seem to be associated with increased mortality, stroke, and myocardial infarction: a non-randomized subgroup analysis of the General Anaesthesia compared with Local Anaesthesia for carotid surgery (GALA) trial.

BACKGROUND: Nitrous oxide has been associated with increased vascular risk in the perioperative period. Here, we conducted a secondary analysis of the GALA trial to ascertain the impact of nitrous oxide on outcomes after carotid surgery under general anaesthesia (GA). METHODS: One thousand seven hundred and seventy-three patients underwent GA, but 158 patients were excluded from this analysis as nitrous oxide use was unknown. The decision to use nitrous oxide was at the discretion of the anaesthetist and was not randomized. Six hundred and seventy-one patients received nitrous oxide and 944 patients did not. Logistic regression was used to analyse the same primary outcome as the original trial (risk of death, stroke, or myocardial infarction within 30 days of the operation). RESULTS: Patients who received nitrous oxide were more likely to have had coronary artery disease, peripheral vascular disease, and atrial fibrillation (all P<0.05). Overall, there were 35 (5.2%) primary outcome events in patients receiving nitrous oxide compared with 44 (4.7%) in those who did not [relative risk 1.12, 95% confidence interval (CI: 0.73, 1.73); P=0.63]. The adjustment for the imbalanced baseline variables using logistic regression reduced the point estimate of harm for nitrous oxide [adjusted odds ratio 1.09, 95% CI (0.68, 1.74); P=0.73]. CONCLUSIONS: Given the greater prevalence of vascular risk factors in the nitrous oxide group and the lack of any definite effect on the primary outcome measure, these data do not support a clinically meaningful adverse effect of nitrous oxide on our composite outcome in patients undergoing carotid surgery.

Disability, distress and unemployment in neurology outpatients with symptoms 'unexplained by organic disease'.

OBJECTIVES: To determine the disability, distress and employment status of new neurology outpatients with physical symptoms unexplained by organic disease and to compare them with patients with symptoms explained by organic disease. METHODS: As part of a cohort study (the Scottish Neurological Symptoms Study) neurologists rated the extent to which each new patient's symptoms were explained by organic disease. Patients whose symptoms were rated as 'not at all' or only 'somewhat' explained by disease were considered cases, and those whose symptoms were 'largely' or 'completely' explained by disease were considered controls. All patients completed self-ratings of disability, health status (Medical Outcomes Study Short Form 12-Item Scale (SF-12)) and emotional distress (Hospital Anxiety and Depression Scale) and also reported their employment and state financial benefit status. RESULTS: 3781 patients were recruited: 1144 (30%) cases and 2637 (70%) controls. Cases had worse physical health status (SF-12 score 42 vs 44; difference in means 1.7 (95% CI -2.5 to 0.9)) and worse mental health status (SF-12 score 43 vs 47; difference in means -3.5 (95% CI -4.3 to to 2.7)). Unemployment was similar in cases and controls (50% vs 50%) but cases were more likely not to be working for health reasons (54% vs 37% of the 50% not working; OR 2.0 (95% CI 1.6 to 2.4)) and also more likely to be receiving disability-related state financial benefits (27% vs 22%; (OR 1.3, 95% CI 1.1 to 1.6)). CONCLUSIONS: New neurology patients with symptoms unexplained by organic disease have more disability-, distress- and disability-related state financial benefits than patients with symptoms explained by disease.

Cost-effectiveness analysis of general anaesthesia versus local anaesthesia for carotid surgery (GALA Trial).

BACKGROUND: Health outcomes and costs are both important when deciding whether general (GA) or local (LA) anaesthesia should be used during carotid endarterectomy. The aim of this study was to assess the cost-effectiveness of carotid endarterectomy under LA or GA in patients with symptomatic or asymptomatic carotid stenosis for whom surgery was advised. METHODS: Using patient-level data from a large, multinational, randomized controlled trial (GALA Trial) time free from stroke, myocardial infarction or death, and costs incurred were evaluated. The cost-effectiveness outcome was incremental cost per day free from an event, within a time horizon of 30 days. RESULTS: A patient undergoing carotid endarterectomy under LA incurred fewer costs (mean difference pound178) and had a slightly longer event-free survival (difference 0.16 days, but the 95 per cent confidence limits around this estimate were wide) compared with a patient who had GA. Existing uncertainty did not have a significant impact on the decision to adopt LA, over a wide range of willingness-to-pay values. CONCLUSION: If cost-effectiveness was considered in the decision to adopt GA or LA for carotid endarterectomy, given the evidence provided by this study, LA is likely to be the favoured treatment for patients for whom either anaesthetic approach is clinically appropriate.

Neurology out-patients with symptoms unexplained by disease: illness beliefs and financial benefits predict 1-year outcome.

BACKGROUND: Patients whose symptoms are 'unexplained by disease' often have a poor symptomatic outcome after specialist consultation, but we know little about which patient factors predict this. We therefore aimed to determine predictors of poor subjective outcome for new neurology out-patients with symptoms unexplained by disease 1 year after the initial consultation. METHOD: The Scottish Neurological Symptom Study was a 1-year prospective cohort study of patients referred to secondary care National Health Service neurology clinics in Scotland (UK). Patients were included if the neurologist rated their symptoms as 'not at all' or only 'somewhat explained' by organic disease. Patient-rated change in health was rated on a five-point Clinical Global Improvement (CGI) scale ('much better' to 'much worse') 1 year later. RESULTS: The 12-month outcome data were available on 716 of 1144 patients (63%). Poor outcome on the CGI ('unchanged', 'worse' or 'much worse') was reported by 482 (67%) out of 716 patients. The only strong independent baseline predictors were patients' beliefs [expectation of non-recovery (odds ratio [OR] 2.04, 95% confidence interval [CI] 1.40-2.96), non-attribution of symptoms to psychological factors (OR 2.22, 95% CI 1.51-3.26)] and the receipt of illness-related financial benefits (OR 2.30, 95% CI 1.37-3.86). Together, these factors predicted 13% of the variance in outcome. CONCLUSIONS: Of the patients, two-thirds had a poor outcome at 1 year. Illness beliefs and financial benefits are more useful in predicting poor outcome than the number of symptoms, disability and distress.

Symptoms 'unexplained by organic disease' in 1144 new neurology out-patients: how often does the diagnosis change at follow-up?

It has been previously reported that a substantial proportion of newly referred neurology out-patients have symptoms that are considered by the assessing neurologist as unexplained by 'organic disease'. There has however been much controversy about how often such patients subsequently develop a disease diagnosis that, with hindsight, would have explained the symptoms. We aimed to determine in a large sample of new neurology out-patients: (i) what proportion are assessed as having symptoms unexplained by disease and the diagnoses given to them; and (ii) how often a neurological disorder emerged which, with hindsight, explained the original symptoms. We carried out a prospective cohort study of patients referred from primary care to National Health Service neurology clinics in Scotland, UK. Measures were: (i) the proportion of patients with symptoms rated by the assessing neurologist as 'not at all' or only 'somewhat explained' by 'organic disease' and the neurological diagnoses recorded at initial assessment; and (ii) the frequency of unexpected new diagnoses made over the following 18 months (according to the primary-care physician). One thousand four hundred and forty-four patients (30% of all new patients) were rated as having symptoms 'not at all' or only 'somewhat explained' by 'organic disease'. The most common categories of diagnosis were: (i) organic neurological disease but with symptoms unexplained by it (26%); (ii) headache disorders (26%); and (iii) conversion symptoms (motor, sensory or non-epileptic attacks) (18%). At follow-up only 4 out of 1030 patients (0.4%) had acquired an organic disease diagnosis that was unexpected at initial assessment and plausibly the cause of the patients' original symptoms. Eight patients had died at follow-up; five of whom had initial diagnoses of non-epileptic attacks. Seven other types of diagnostic change with very different implications to a 'missed diagnosis' were found and a new classification of diagnostic revision is presented. One-third of new neurology out-patients are assessed as having symptoms 'unexplained by organic disease'. A new diagnosis, which with hindsight explained the original symptoms, rarely became apparent to the patient's primary care doctor in the 18 months following the initial hospital consultation.

General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial.

BACKGROUND: The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. METHODS: We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. FINDINGS: A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. INTERPRETATION: We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. FUNDING: The Health Foundation (UK) and European Society of Vascular Surgery.

Differences between intracranial vascular malformation types in the characteristics of their presenting haemorrhages: prospective, population-based study.

OBJECTIVE: To determine the imaging and demographic characteristics of intracranial haemorrhages, which are subsequently found to be due to an underlying intracranial vascular malformation (IVM). METHODS: We compared the demographic and brain imaging characteristics of adults presenting with intracranial haemorrhage, subsequently found to be due to a brain arteriovenous malformation (BAVM), dural arteriovenous fistula (DAVF) or cavernous malformation (CM) in a prospective, population-based cohort of adults diagnosed for the first time with an IVM (The Scottish IVM Study (SIVMS)). RESULTS: Of the 141 adults in SIVMS who presented with intracranial haemorrhage, those with CMs presented at a younger age and were less handicapped. A total of 115 (82%) had intracerebral haemorrhage (ICH) with or without subarachnoid, intraventricular or subdural extension. ICH without extension into other compartments accounted for all CM bleeds, but only 50% of BAVM and DAVF bleeds. Median haematoma volumes differed (Kruskal-Wallis, p<0.0001): ICH due to BAVM (16.0 cm3, inter-quartile range (IQR) 4.7 to 42.0) and DAVF (14.1 cm3, IQR 4.9 to 21.5) were similar, but CM haematoma volumes were smaller (median 1.8 cm3, IQR 1.3 to 4.3). These findings were robust in sensitivity analyses. Small haematoma volumes occurred among all IVM types; the largest haematoma volume due to CM was 12 cm3, and volumes of >34 cm3 were only due to BAVM. CONCLUSIONS: Intracranial haemorrhages found to be due to IVMs differ in adults' age of presentation and clinical severity, as well as the volume and distribution of the haematoma within the brain compartments.

Carotid endarterectomy in the UK: acceptable risks but unacceptable delays.

Carotid endarterectomy (CEA) is of benefit for stroke prevention in the presence of severe carotid stenosis, provided surgical morbidity and mortality are acceptably low. To assess the current performance of CEA in the UK, an interim analysis of 30-day postoperative outcome data, blinded to anaesthetic allocation, from the first 1,001 UK patients randomised in the GALA Trial (multicentre randomised trial of general versus local anaesthesia for CEA) took place and the time from last symptomatic event to surgery was recorded. The 30-day risk of stroke was 5.3%, myocardial infarction (MI) 0.4%, death 1.7%, and stroke, MI or death 6.4%. Median delay between symptoms and surgery was 82 days. These risks are similar to those reported in the large randomised trials of CEA, but current delays to surgery are excessive and must have substantially reduced the benefit of endarterectomy.

Effect of timing and method of enteral tube feeding for dysphagic stroke patients (FOOD): a multicentre randomised controlled trial.

BACKGROUND: Undernutrition is common in patients admitted with stroke. We aimed to establish whether the timing and route of enteral tube feeding after stroke affected patients' outcomes at 6 months. METHODS: The FOOD trials consist of three pragmatic multicentre randomised controlled trials, two of which included dysphagic stroke patients. In one trial, patients enrolled within 7 days of admission were randomly allocated to early enteral tube feeding or no tube feeding for more than 7 days (early versus avoid). In the other, patients were allocated percutaneous endoscopic gastrostomy (PEG) or nasogastric feeding. The primary outcome was death or poor outcome at 6 months. Analysis was by intention to treat. FINDINGS: Between Nov 1, 1996, and July 31, 2003, 859 patients were enrolled by 83 hospitals in 15 countries into the early versus avoid trial. Early tube feeding was associated with an absolute reduction in risk of death of 5.8% (95% CI -0.8 to 12.5, p=0.09) and a reduction in death or poor outcome of 1.2% (-4.2 to 6.6, p=0.7). In the PEG versus nasogastric tube trial, 321 patients were enrolled by 47 hospitals in 11 countries. PEG feeding was associated with an absolute increase in risk of death of 1.0% (-10.0 to 11.9, p=0.9) and an increased risk of death or poor outcome of 7.8% (0.0 to 15.5, p=0.05). INTERPRETATION: Early tube feeding might reduce case fatality, but at the expense of increasing the proportion surviving with poor outcome. Our data do not support a policy of early initiation of PEG feeding in dysphagic stroke patients.

Routine oral nutritional supplementation for stroke patients in hospital (FOOD): a multicentre randomised controlled trial.

BACKGROUND: Undernutrition is common in hospital patients with stroke, can develop or worsen in hospital, and is associated with poor outcomes. We aimed to establish whether routine oral nutritional supplements improve outcome after stroke. METHODS: The FOOD trials are a family of three pragmatic, multicentre, randomised controlled trials. We measured the outcomes of stroke patients who could swallow and who were randomly allocated normal hospital diet or normal hospital diet plus oral nutritional supplements until hospital discharge. The primary outcome was death or poor outcome (modified Rankin scale [MRS] grade 3-5), 6 months after enrollment, measured unaware of treatment allocation. Analysis was by intention to treat. FINDINGS: Between Nov 1, 1996, and July 31, 2003, 4023 patients were enrolled by 125 hospitals in 15 countries. Only 314 (8%) patients were judged to be undernourished at baseline. Vital status and MRS at the end of the trial were known for 4012 and 4004 patients, respectively. Supplemented diet was associated with an absolute reduction in risk of death of 0.7% (95% CI -1.4 to 2.7) and an increased risk of death or poor outcome of 0.7% (-2.3 to 3.8). INTERPRETATION: We could not confirm the anticipated 4% absolute benefit for death or poor outcome from routine oral nutritional supplements for mainly well nourished stroke patients in hospital. Our results would be compatible with a 1% or 2% absolute benefit or harm from oral supplements. These results do not support a policy of routine oral supplementation after stroke.

A simple score (ABCD) to identify individuals at high early risk of stroke after transient ischaemic attack.

BACKGROUND: Effective early management of patients with transient ischaemic attacks (TIA) is undermined by an inability to predict who is at highest early risk of stroke. METHODS: We derived a score for 7-day risk of stroke in a population-based cohort of patients (n=209) with a probable or definite TIA (Oxfordshire Community Stroke Project; OCSP), and validated the score in a similar population-based cohort (Oxford Vascular Study; OXVASC, n=190). We assessed likely clinical usefulness to front-line health services by using the score to stratify all patients with suspected TIA referred to OXVASC (n=378, outcome: 7-day risk of stroke) and to a hospital-based weekly TIA clinic (n=210; outcome: risk of stroke before appointment). RESULTS: A six-point score derived in the OCSP (age [> or =60 years=1], blood pressure [systolic >140 mm Hg and/or diastolic > or =90 mm Hg=1], clinical features [unilateral weakness=2, speech disturbance without weakness=1, other=0], and duration of symptoms in min [> or =60=2, 10-59=1, <10=0]; ABCD) was highly predictive of 7-day risk of stroke in OXVASC patients with probable or definite TIA (p<0.0001), in the OXVASC population-based cohort of all referrals with suspected TIA (p<0.0001), and in the hospital-based weekly TIA clinic-referred cohort (p=0.006). In the OXVASC suspected TIA cohort, 19 of 20 (95%) strokes occurred in 101 (27%) patients with a score of 5 or greater: 7-day risk was 0.4% (95% CI 0-1.1) in 274 (73%) patients with a score less than 5, 12.1% (4.2-20.0) in 66 (18%) with a score of 5, and 31.4% (16.0-46.8) in 35 (9%) with a score of 6. In the hospital-referred clinic cohort, 14 (7.5%) patients had a stroke before their scheduled appointment, all with a score of 4 or greater. CONCLUSIONS: Risk of stroke during the 7 days after TIA seems to be highly predictable. Although further validations and refinements are needed, the ABCD score can be used in routine clinical practice to identify high-risk individuals who need emergency investigation and treatment.

Interventions for treating brain arteriovenous malformations in adults.

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.

Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery.

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.

Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study).

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.

Promoting awareness and practice of testicular self-examination.

AIM: To evaluate the efficacy of a health promotion initiative on men's knowledge of testicular cancer and self-examination rates. METHOD: A quasi-experimental, pre- and post-test questionnaire study of men at 14 workplace and leisure sites across two primary care trusts was undertaken: ten experimental sites received the intervention and four acted as a control. Men at all 14 sites were given a pre- and post-test questionnaire. RESULTS: Of the 835 pre-test and 835 post-test questionnaires distributed, 518 (62.0 per cent) and 356 (42.6 per cent) were respectively returned for evaluation. In the intervention group, the median total knowledge score increased from three points (interquartile range: 2,4) at baseline to four points (interquartile range: 2,4) at post-test. However, no statistically significant change was observed in the control group. Post-intervention, the percentage of test participants examining their testicles regularly increased from 58.4 per cent to 68.3 per cent, while levels among control peers did not significantly alter. CONCLUSION: This evaluation highlights the potential of using a low-cost initiative which targets innovative venues to improve men's knowledge of testicular cancer and rates of self-examination. Longer-term follow-up may be required to determine whether such increases are sustained.

N-acetylaspartate distribution in proton spectroscopic images of ischemic stroke: relationship to infarct appearance on T2-weighted magnetic resonance imaging.

BACKGROUND AND PURPOSE: It is generally considered that tissue that appears abnormal on T2 MRI is already infarcted and that any penumbra lies outside the T2-visible lesion. We investigated the distribution of infarcted tissue using proton spectroscopic MRI. METHODS: In patients with symptoms of acute hemispheric ischemic stroke, imaged within a maximum of 3 days of stroke, we explored the distribution of N:-acetylaspartate (NAA), a marker of intact neurons, within and around the abnormal (hyperintense) areas on T2-weighted MR images, using proton spectroscopic MRI. RESULTS: In 11 patients, imaged 24 to 72 hours after stroke onset, there was little evidence of damaged neurons (reduced NAA) beyond the margins of hyperintensity on the T2 image. However, within the abnormal T2 area, there were statistically significant differences in the amount of NAA (ie, the proportion of intact neurons) between areas that were obviously abnormal on T2 (very hyperintense) and those that were only slightly abnormal (slightly hyperintense). CONCLUSIONS: The extent and degree of hyperintensity of the T2-visible lesion directly reflect the amount of neuronal damage; lack of a T2-visible lesion would suggest predominantly intact neurons at the time of imaging. We hypothesize that once tissue damage has reached a critical (probably irreversible) level, the T2 image quickly becomes abnormal without any significant time lag between the pathological staging of the infarct and its visualization on T2. Further testing in a larger study with information on blood flow levels would be required to confirm this.

Performance of a statistical model to predict stroke outcome in the context of a large, simple, randomized, controlled trial of feeding.

BACKGROUND AND PURPOSE: Statistical models to predict the outcome of stroke patients have several uses. Their utility depends on their predictive accuracy in patients other than those on whom they were developed (ie, external validity). We sought to test the external validity of some recently described models in patients enrolled in the FOOD (Feed Or Ordinary Diet) trial: a large randomized trial evaluating feeding policies in patients with stroke. METHODS: The predictive variables were collected during a telephone call to randomize the patient a median of 5 days after stroke onset. Patients were followed up 6 months later to establish their survival, functional status, and residence. Charts were plotted to demonstrate the discrimination and calibration of the models. RESULTS: The models performed well in the first 2955 patients enrolled and followed up in the FOOD trial. The area under the receiver operating characteristic curves varied between 0.78 and 0.81 (with 0.5 indicating no discrimination and 1.0 indicating perfect discrimination). The discrimination was marginally better for patients enrolled within the first day of stroke than later. The models tended to provide rather pessimistic predictions in all groups except those predicted to have a high likelihood of surviving free of dependency. CONCLUSIONS: As one might predict, the discriminatory power in the selected cohort of trial patients was marginally less good than in previously studied unselected cohorts used to test their external validity. These models provide a well-tested tool for stratification in trials, comparing outcomes in different cohorts and examining the additional predictive power of novel factors.

Reanalysis of the final results of the European Carotid Surgery Trial.

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.

Prevalence of stroke survivors in rural South Africa: results from the Southern Africa Stroke Prevention Initiative (SASPI) Agincourt field site.

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.

Sex difference in the effect of time from symptoms to surgery on benefit from carotid endarterectomy for transient ischemic attack and nondisabling stroke.

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.