Showing papers by "Peter M. Rothwell published in 2007"

Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials

Abstract: Summary Background Malignant infarction of the middle cerebral artery (MCA) is associated with an 80% mortality rate. Non-randomised studies have suggested that decompressive surgery reduces this mortality without increasing the number of severely disabled survivors. To obtain sufficient data as soon as possible to reliably estimate the effects of decompressive surgery, results from three European randomised controlled trials (DECIMAL, DESTINY, HAMLET) were pooled. The trials were ongoing when the pooled analysis was planned. Methods Individual data for patients aged between 18 years and 60 years, with space-occupying MCA infarction, included in one of the three trials, and treated within 48 h after stroke onset were pooled for analysis. The protocol was designed prospectively when the trials were still recruiting patients and outcomes were defined without knowledge of the results of the individual trials. The primary outcome measure was the score on the modified Rankin scale (mRS) at 1 year dichotomised between favourable (0–4) and unfavourable (5 and death) outcome. Secondary outcome measures included case fatality rate at 1 year and a dichotomisation of the mRS between 0–3 and 4 to death. Data analysis was done by an independent data monitoring committee. Findings 93 patients were included in the pooled analysis. More patients in the decompressive-surgery group than in the control group had an mRS≤4 (75% vs 24%; pooled absolute risk reduction 51% [95% CI 34–69]), an mRS≤3 (43% vs 21%; 23% [5–41]), and survived (78% vs 29%; 50% [33–67]), indicating numbers needed to treat of two for survival with mRS≤4, four for survival with mRS≤3, and two for survival irrespective of functional outcome. The effect of surgery was highly consistent across the three trials. Interpretation In patients with malignant MCA infarction, decompressive surgery undertaken within 48 h of stroke onset reduces mortality and increases the number of patients with a favourable functional outcome. The decision to perform decompressive surgery should, however, be made on an individual basis in every patient.

Risk of stroke early after transient ischaemic attack: a systematic review and meta-analysis.

Abstract: Summary Background Stroke is often preceded by transient ischaemic attack (TIA), but studies of stroke risk after TIA are logistically difficult and have yielded conflicting results. However, reliable estimation of this risk is necessary for planning effective service provision, clinical trials, and public education. We therefore did a systematic review of all studies of stroke risk early after TIA. Methods All studies of stroke risk within 7 days of TIA were identified by use of electronic databases and by hand searches of reference lists, relevant journals, and conference abstracts. Stroke risks at 2 days and 7 days after TIA were calculated overall and analyses for heterogeneity were done, if possible, after categorisation by study method, setting, population, and treatment. Findings 18 independent cohorts were included, which reported stroke risk in 10 126 TIA patients. The pooled stroke risk was 5·2% (95% CI 3·9–6·5) at 7 days, but there was substantial heterogeneity between studies (p vs 8–90 days, r =0·89, p Interpretation The reported early risks of stroke after TIA were highly heterogeneous, but this could be largely accounted for by differences in study method, setting, and treatment, with lowest risks in studies of emergency treatment in specialist stroke services.

Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study

Abstract: Summary Background UK stroke mortality data suggest that the incidence of haemorrhagic stroke has fallen in the past 20 years, but these data do not include deaths of individuals aged 75 years or over. Trends in the older population might differ, since cause varies with age. Our aim was to investigate changes in the population-based incidence of intracerebral haemorrhage according to age and likely aetiology. Methods We used data from the Oxford Community Stroke Project (OCSP; 1981–86) and the Oxford Vascular Study (OXVASC; 2002–06) to investigate changes in the incidence of intracerebral haemorrhage with time, above and below age 75 years, together with associated risk factors and premorbid medications. Incidences were standardised to the 2001 census population of England and Wales. Findings In the population aged under 75 years the incidence of intracerebral haemorrhage decreased substantially (rate ratio 0·53, 95% CI 0·29–0·95; p=0·03), but the number of cases of intracerebral haemorrhage at all ages were similar in OXVASC and OCSP (52 vs 55 cases) as the proportion of cases occurring at 75 years and over tended to increase (2·0, 0·8–4·6; p=0·09). The incidence of intracerebral haemorrhage associated with premorbid hypertension (blood pressure ≥160/100 mm Hg) fell overall (0·37, 0·20–0·69; p=0·002), but the incidence of intracerebral haemorrhage associated with antithrombotic use was increased (7·4, 1·7–32; p=0·007). Above age 75 years the proportion of cases who were non-hypertensive with lobar bleeds and presumed to have had mainly amyloid-related haemorrhages, also increased (4·0, 1·1–17; p=0·003). Interpretation There has been a substantial fall in hypertension-associated intracerebral haemorrhage over the past 25 years, but not in the overall number of cases of intracerebral haemorrhage in older age-groups, in part due to a rise in intracerebral haemorrhage associated with antithrombotic use. These trends, along with the expected increase in prevalence of amyloid angiopathy with the ageing population, suggest that, in contrast to projections based on mortality data below age 75 years, absolute number of cases of intracerebral haemorrhage might increase in future.

Bleeding Risk Analysis in Stroke Imaging Before ThromboLysis (BRASIL) Pooled Analysis of T2*-Weighted Magnetic Resonance Imaging Data From 570 Patients

Abstract: Background and Purpose— There has been speculation that the risk of secondary symptomatic intracranial hemorrhage (SICH) may be increased after thrombolytic therapy in ischemic stroke patients who have cerebral microbleeds (CMBs) on T2*-weighted magnetic resonance imaging. Because of this concern, some centers withhold potentially beneficial thrombolytic therapy from these patients. Methods— We analyzed magnetic resonance imaging data acquired within 6 hours after symptom onset from 570 ischemic stroke patients treated with intravenous tissue plasminogen activator in 13 centers in Europe, North America, and Asia. Baseline T2*-weighted magnetic resonance images were evaluated for the presence of CMBs. The primary end point was SICH, defined as clinical deterioration with an increase in the National Institutes of Health Stroke Scale score by ≥4 points, temporally related to a parenchymal hematoma on follow-up-imaging. Results— A total of 242 CMBs were detected in 86 of 570 patients (15.1%). The number of CM...

Systematic Review of Associations Between the Presence of Acute Ischemic Lesions on Diffusion-Weighted Imaging and Clinical Predictors of Early Stroke Risk After Transient Ischemic Attack

Abstract: Background and Purpose— Early risk of stroke after a transient ischemic attack can be reliably predicted with risk scores based on clinical features of the patient and of the ischemic event, but it is unclear how these features correlate with findings on brain imaging. Methods— We performed a systematic review of the literature and identified all previous studies which reported patient characteristics and the nature of transient ischemic attack symptoms in relation to appearances on diffusion-weighted imaging (DWI). We then performed a meta-analysis of the associations between the components of the risk scores and positive DWI. Authors were contacted for additional unpublished data. Results— Nineteen studies were identified by the systematic review, and additional unpublished data were obtained from 11 of these studies. On meta-analysis, several components of the risk scores were associated with positive DWI, including symptom duration ≥60 minutes (13 studies, odds ratio [OR], 1.50; 95% CI, 1.16 to 1.96; ...

Substantial underestimation of the need for outpatient services for TIA and minor stroke

Abstract: OBJECTIVES: To measure the number of all transient ischaemic attack (TIAs) and minor strokes managed as outpatients, and hence, the need for 'TIA clinics' in comparison to current estimates of 20,000 TIAs annually in England, based on previous rates of incident-definite events. SUBJECTS: All individuals with confirmed or suspected TIA or stroke between 2002 and 2005 in a population-based study of 91,105 individuals in Oxfordshire, UK. OUTCOME MEASURES: Numbers, rates, and risks of recurrent stroke for incident-definite TIA, any probable or definite TIA, stroke, and all referrals of suspected TIA and stroke, stratified according to inpatient versus outpatient management. RESULTS: Of 1,174 confirmed or suspected events ascertained, 729 (62.1%) were managed as outpatients and 445 (37.9%) as inpatients. Among 757 probable or definite events, 432 (57%) were managed as outpatients. Incident-definite TIAs accounted for only 18% of all referrals to outpatient services. Annual rates per 1,000 population were 2.98 (2.77-3.2) for all referrals to outpatient services and 1.88 (1.71-2.06) for inpatient admissions. Of 73 recurrent strokes within 90 days of initial TIA or stroke, 48 (65.8%) occurred in the outpatient population. Applying these rates to the population of England yields approximately 150,000 new referrals annually to TIA clinics with about 10,000 early recurrent strokes. CONCLUSION: More patients with TIA or stroke are managed as outpatients than inpatients in the UK, and this group has the majority of possibly preventable early recurrent strokes. Current projections of need for TIA clinics in England substantially underestimate the overall requirement for outpatient services.

Performance of the ABCD and ABCD2 Scores in TIA Patients with Carotid Stenosis and Atrial Fibrillation

Abstract: Background: It has been suggested that scores for risk stratification of TIA patients might not identify patients with carotid stenosis or atrial fibrillation (AF) and that this mig

Heritability of ischaemic stroke in women compared with men: a genetic epidemiological study

Abstract: Summary Background Ischaemic stroke is partly heritable. However, although the genetic and non-genetic factors responsible could be sex-specific, interactions between the sex of the parent affected and the sex of the proband or affected siblings are unknown. We sought to assess the relation between the sex and phenotype of affected probands and the sex of affected first-degree relatives. Methods We determined the prevalence of history of stroke in the mother, father, and other first-degree relatives in female and male probands with ischaemic stroke or transient ischaemic attack in the population-based Oxford Vascular Study (OXVASC). We validated our findings using unpublished individual patient data from two independent Oxford studies. Findings In OXVASC, detailed family history was available in 806 (93%) probands. Female probands were more likely than males to have at least one affected first-degree relative (146/423 vs 104/383; OR 1·4, 95% CI 1·1–2·0, p=0·02) due entirely to an excess of affected female relatives in female probands (female relative vs male relative OR=1·7, 1·3–2·4, p=0·0004; female only vs male only OR=2·1, 1·4–3·1, p=0·0001). Maternal stroke was more common than paternal stroke in female probands (OR=1·8, 1·2–2·7, p=0·001) but not in males (OR=1·1, 0·7–1·7, p=0·38), and female probands were more likely than males to have an affected sister (OR=3·1, 1·5–6·7, p=0·004) but not an affected brother (OR=1·1, 0·6–2·1, p=0·80). Ages at first stroke were also correlated within families among affected females ( r =0·36, p=0·004) but not among affected males, such that the excess of affected female relatives of female probands was greatest when the difference in age at first stroke was less than 5 years (OR=3·7, 1·6–8·6, p=0·0007) and fell as the age difference increased (p for trend=0·004). These findings were independent of traditional risk factors and stroke subtype. Data from the other Oxford studies confirmed the excess maternal history of stroke in female probands (OR=2·3, 1·5–3·8, p Interpretation Heritability of ischaemic stroke is greater in women than in men, with an excess of affected mothers and affected sisters in female probands independent of traditional vascular risk factors, which could be explained by sex-specific genetic, epigenetic, or non-genetic mechanisms.

Association between cortical metabolite levels and clinical manifestations of migrainous aura: an MR-spectroscopy study.

Abstract: Previous studies suggest an abnormal cerebral cortical energy metabolism in migraineurs. If causally related to the pathophysiology of migraine, these abnormalities might show a dose–response relationship with the duration and severity of aura symptoms. While such a trend has been suggested in phosphorus spectroscopy (31P-MRS) studies, it has not been considered in proton spectroscopy (1H-MRS) studies and it has not been studied in cerebral white matter. We aimed to determine whether for any of the metabolites measured by 31P-MRS or 1H-MRS there was a dose-response relationship with aura duration and severity, and whether such an association was also present in cerebral white matter. We studied patients with migraine with aura and healthy controls with 31P-MRS and with 1H-MRS. We measured metabolite ratios in grey and in white matter and in the patients, we related metabolite levels to the clinical characteristics and duration of the aura. In patients, the phosphocreatine/phosphate (PCr/Pi) ratio decreased significantly with increasing aura duration and was significantly lower in patients with hemiplegic migraine than in patients with non-motor aura. Overall the metabolite ratios did not differ significantly between patients and controls, but compared with controls the PCr/Pi ratio in patients with hemiplegic migraine and in patients with persistent aura >7 days was significantly lower. These changes were only present in grey matter. Results for 1H-MRS did not differ significantly between patients and controls, and they showed no association with duration or severity of symptoms. In this study, metabolite ratios differed significantly between patients with different aura phenotypes and with increasing aura duration. In addition, only in some patient subgroups were metabolite ratios significantly different from controls. These findings support the concept that migraine with aura is a heterogeneous disorder with distinct pathophysiological subtypes. They further suggest that rather than determining the susceptibility to developing a migraine attack, changes in cortical energy metabolism may determine the clinical manifestations of the migrainous aura once an attack has started.

Presence of Acute Ischaemic Lesions on Diffusion-Weighted Imaging Is Associated with Clinical Predictors of Early Risk of Stroke after Transient Ischaemic Attack

Abstract: Background: Early risk of stroke after a transient ischaemic attack (TIA) can be reliably predicted with risk scores based on clinical features of the patient and the event, but it

Asymptomatic carotid stenosis: what to do.

Abstract: Purpose of reviewPatients with asymptomatic carotid stenosis are at increased vascular risk but optimal treatment is controversial. We reviewed the current evidence for medical and surgical intervention in these patients.Recent findingsOptimal medical treatment is the most important aspect of manage

Atherothrombosis and ischaemic stroke.

Abstract: Thrombosis due to “unstable” atherosclerotic plaque is the main mechanism underlying acute coronary syndromes, and vascular research has focused mostly on this model. Plaque also causes a substantial proportion of ischaemic stroke, although multiple mechanisms are involved and “stable” plaque is sometimes responsible. For example, in the basilar and proximal middle cerebral arteries, stroke can result from occlusion of a small branch vessel by slow growth of otherwise “stable” plaque in the parent vessel. Slowly growing but stable plaque can also cause cerebral ischaemia due to stenosis and hypoperfusion without thromboembolism. Recent evidence, however, suggests that the predominant mechanism of stroke, at least in patients with carotid stenosis, is similar to the coronary model and involves mainly unstable plaque.1,2,3 This observation has implications for the way we manage and prevent strokes. Carotid plaques are typically slow growing or quiescent for long periods but may suddenly develop ruptures, fissures, or endothelial erosions, triggering platelet aggregation and formation of thrombus, which leads to local occlusion or embolisation to more distal vessels. Recent studies have correlated histology of the plaque with time since last symptoms in patients with symptomatic stenosis undergoing endarterectomy.2,3 Spagnoli and colleagues studied 187 symptomatic plaques and reported that the frequency of thrombotically active plaque was greater after stroke than after transient ischaemic attack, and that it fell with time from first ischaemic symptoms to surgery.2 A similar study of 565 symptomatic carotid plaques found a high frequency of features that mark unstable plaque (for example, rupture of cap in 56.7%, a large lipid core in 59.6%, marked inflammatory infiltrate in 66.9%) and found that many of these features, particularly inflammation, were most frequent in patients with recent cerebral ischaemic events, especially after stroke.3 Interestingly, cap thickness in ruptured carotid plaques is much greater than that reported in ruptured coronary plaques,3 which has implications for identifying at risk plaques by imaging. However, rupture is still associated with a relatively thin cap and with pronounced macrophage infiltration.3 The finding that coronary-type “unstable” plaque is responsible for a high proportion of transient ischaemic attacks and strokes in patients with carotid stenosis has important implications for prevention. Firstly, it highlights the need for urgency in investigation and treatment. The risk of major stroke distal to symptomatic carotid stenosis is up to 30% during the first month after the presenting event,4 but this risk falls rapidly with time, as does benefit from endarterectomy.5 In relevant trials, for patients with 50% or higher stenosis, the number needed to undergo surgery (number needed to treat) to prevent one ipsilateral stroke in five years was five for patients randomised within two weeks after their last ischaemic event versus 125 for patients randomised after 12 weeks.5 Unfortunately, the current average delay before endarterectomy in the United Kingdom is about 12 weeks,4 and many patients have a major stroke before investigation or surgery. The rapid fall in risk of stroke with time since presenting event could be due to the development of collateral circulation or the loss of a small subgroup of patients who are particularly susceptible to stroke for some other reason, but this fall is most likely to be due to healing of unstable plaque. Secondly, the role of unstable plaque in the aetiology of ischaemic stroke indicates that sheer induced platelet aggregation could be involved in thrombus formation and that antiplatelet agents may have potential in the prevention of ischaemic stroke. This is consistent with recent data on the potential benefit of a short course of combinations of antiplatelet agents in patients with acutely symptomatic carotid stenosis,6 and the lack of efficacy of warfarin in patients with intracranial stenosis.7 There are also important implications for research. Firstly, unstable carotid plaque can be imaged in vivo, so imaging might have a role in risk stratification. Ulceration of the surface of the plaque on conventional arterial angiography, which is strongly associated with unstable plaque on histology,1 is a strong independent predictor of stroke,5 and has been included in risk models for patients with symptomatic carotid stenosis.8 Carotid ultrasound can identify lipid-rich echolucent plaques, and magnetic resonance imaging can detect both lipid core and intraplaque haemorrhage, although more research is needed to determine whether these assessments predict stroke. Novel imaging techniques using magnetic resonance imaging, positron emission tomography, and molecular radiolabelling also allow quantification of macrophage infiltration, neovascularisation, metabolic activity, and even protease activity and apoptosis.9 Secondly, carotid plaques also provide an indirect window on the coronary circulation. Non-invasive measurements of carotid stenosis can predict severe coronary artery disease in patients with suspected ischaemic heart disease and future acute coronary events in patients with coronary artery disease. Importantly, ruptured carotid plaques are more likely than smooth plaques to be associated with future coronary events,10 which suggests that plaque instability is a systemic phenomenon and that non-invasive assessment of carotid plaque instability might also be a useful index of coronary risk. Thirdly, the importance of instability of stenosing carotid plaques as a cause of transient ischaemic attack and stroke raises the possibility that, as in the coronary circulation, many acute carotid ischaemic events might be caused by instability in non-stenosing plaque. Although the average risk of stroke in patients without appreciable carotid stenosis is insufficient to merit endarterectomy, recent developments in imaging techniques allow the subgroup of patients with unstable plaques to be better identified9 and will necessitate further research to determine optimal treatment. Finally, most of what we know about atherosclerotic plaque and stroke relates to disease at the carotid bifurcation—the only arterial segment routinely imaged after a stroke or transient ischaemic attack in most centres. However, many other points of branching, tortuosity, or confluence of the arterial supply to the brain are also prone to disease. Common sites of extracranial atheroma include the aortic arch, where large plaques are an important risk factor for ischaemic stroke11; the proximal subclavian and common carotid arteries; and the origins of the vertebral arteries.12 The intracranial arteries are prone to atherosclerosis at the carotid siphon, the proximal middle cerebral artery, the intracranial vertebral arteries, and the basilar artery origin.13,14 Although intracranial disease does appear to be associated with a high risk of recurrent stroke on medical treatment,7 the proportion of all strokes caused by plaque at sites other than the carotid bifurcation is unknown and will differ between populations. Carotid and other extracranial atherosclerosis is most common in white men, whereas intracranial disease is most common in black, Hispanic, and oriental populations, in patients with type 1 diabetes, and in younger women.13,14 More research is required into imaging and treatment of disease at sites other than the carotid bifurcation, particularly in patients with ischaemic events in the posterior circulation, in whom the early risk of recurrent stroke is probably as high as in patients with carotid stenosis.15

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

Abstract: 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.

Reporting of observational studies

Abstract: In this week's BMJ, von Elm and colleagues report the STROBE (strengthening the reporting of observational studies in epidemiology) statement, which recommends what should be included in an accurate and complete report of an analytical observational study.1 Observational epidemiology has made an immense contribution to our understanding of the causes and treatment of disease. Numerous causal associations between risks factors and disease have been identified (see box in version on bmj.com). Most of these observations have led to substantial improvements in public health by causing changes in policy or by leading to the development of effective treatments. A few examples of important causal associations between risk factors and disease that have been identified by clinical epidemiological studies Smoking and cancerw1 Radiation exposure and cancerw2 Lipids and coronary diseasew3 Blood pressure and strokew4 Sleeping position and sudden infant deathw5 Folate and risk of neural tube defectsw6 Hormone replacement therapy and breast cancerw7 Male circumcision and HIV infectionw8 Aspirin use and colorectal cancerw9 Observational studies are also essential for effective clinical practice. Cohort studies allow us to improve the reliability of diagnosis; to understand prognosis; to develop and validate risk scores to target treatment appropriately; to monitor the safety of treatments in routine practice; to identify treatment effects (adverse or beneficial) that are not reliably detected in trials (perhaps because they are too rare, have too long a latency, or are confined to people excluded from trials); and to estimate the effects of interventions in circumstances in which randomised trials are not feasible. To make the most of the enormous potential of observational epidemiology to transform clinical practice and improve public health, studies must be designed and reported as rigorously as possible. However, as with other areas of research, including laboratory sciences2 3 and randomised controlled clinical trials,4 the design and reporting of epidemiological studies can be poor, with consequences for the reliability of results.5 6 Quality control is unlikely to improve in the near future, given the ever increasing number of medical journals, and the consequently reduced influence of peer review on the likelihood that poor quality research will be published. The STROBE guidelines on the reporting of epidemiological studies are therefore welcome.1 The summary paper published in this week's journal will be backed up by a more detailed document, which will explain the background and justification for each guideline. Such guidelines inevitably have limitations, and there is always a risk that poorly designed studies will be made more difficult to spot by superficial improvements in the way they are reported. However, experience with similar guidelines for reporting randomised trials and systematic reviews has generally been positive. Are there any matters that are not covered by the STROBE guidelines or that deserve particular emphasis? Firstly, the definition and prespecification of outcomes is crucial, particularly in cohort studies, where composite outcomes are often used to increase statistical power. For example, outcomes such as “coronary events” and “cardiovascular events” are often used in studies of potential new risk factors for cardiovascular disease. However, these composites have no widely accepted standard definitions. In our systematic review of published studies of seven new vascular risk factors,7 of 266 eligible studies (167 case-control studies and 99 cohort studies), 56 (21%) reported a risk association based on a composite outcome. The 23 studies reporting composites of different coronary events used 11 different terms and 21 different composites. The 33 studies reporting composites of cardiac and extracardiac events (usually termed cardiovascular events) used 25 different composites, and seven studies gave no information on what events were included in their composite outcome. Only one composite was used by two different studies, and these had the same authors. Such variation between studies undermines the potential to compare studies and perform meta-analysis. It also raises the possibility of post hoc choices of composites that are dependent on data—by far the most effective way to increase the “statistical power” of a study. Secondly, the importance of reporting data on the precision of measurement of the exposure(s) under study also deserves particular emphasis, whether it is a physiological parameter or a behavioural risk factor. For example, in a recent systematic review of case-control studies of the use of aspirin and risk of colorectal cancer, only studies that collected and reported detailed exposure data stratified by dose, frequency, and duration of aspirin use identified the same strong protective effect of aspirin that was found by long term follow-up of randomised trials.8 Interestingly, smaller studies tended to have the most discriminating measures of exposure, resulting in a highly asymmetrical funnel plot, which could be misinterpreted as evidence of publication bias. The potential advantages of smaller more rigorous epidemiological studies over larger simpler studies have been outlined previously.5 Finally, the design of studies and the interpretation of results must have expert clinical input. Just as clinical studies can suffer from a lack of statistical and epidemiological expertise, epidemiological studies can suffer from a lack of clinical expertise. A statement about the extent of any input from people with relevant clinical expertise might be an additional future STROBE recommendation. Overall, however, the STROBE guidelines are an important and timely initiative, which researchers and journals should support and put into practice.

Making the Most of Secondary Prevention

Abstract: See related article, pages 1881–1885. Recurrent strokes are more likely to be fatal than first strokes, and survivors are more likely to be left with major disability. In this issue of Stroke , Hackman and Spence’s report1 of their interesting modeling study of the potential effectiveness of combining multiple medications/interventions in the secondary prevention of stroke is therefore to be welcomed. They suggest that at least 80% of recurrent cerebrovascular events might be prevented by a comprehensive, multifactorial approach. Indeed, relative reductions in risk of 90% are estimated for more intensive treatment and nearly 95% if carotid endarterectomy is included in the …

National Stroke Association Guidelines for the Management of Transient Ischemic Attacks

Abstract: 目的：短暂性脑缺血发作（TIA）是常见和重要的卒中先兆。其处理方法多样，大多数发表的指南在近年来均未被更新。我们试图制定一个全面的、无偏倚的、循证的TIA处理指南。方法：根据一种客观标准（可以预测在该研究领域中执业医师对专家提名的文献测量学方法）挑选出15名专家组成员。通过系统回顾检索到过去发表的指南，由专家对其中的推荐意见的质量进行独立评价。选择出质量最高的推荐意见，然后让专家组采用改良Delphi法通过多次问卷调查的方式进行修订，从而对新的修改达成共识。给专家们提供近期临床研究的系统评价，要求专家根据新的证据判断措辞修改的合理性并且根据证据等级和质量对最终的推荐意见进行评定。不允许专家在预期有可能存在任何利益冲突的专题方面提出推荐意见。结果：通过系统回顾检索到257个指南，其中有13篇文献包括的137条推荐意见符合所有纳入标准。需要6次重复的问卷调查对53条最终推荐意见的措辞达成共识。最终的推荐意见涉及TIA的初步处理、评价、内科治疗、外科治疗和危险因素控制。结论：对TIA患者医疗诊治的最终推荐意见强调了紧急评价和治疗的重要性。这种用于制定本指南的新方法是可行的，考虑到了快速更新并能减少偏倚。

Evolution of the diffusion-weighted signal and the apparent diffusion coefficient in the late phase after minor stroke: a follow-up study.

Abstract: Diffusion-weighted imaging (DWI) is mainly used in acute stroke, and signal evolution in the acute phase has been studied extensively. However, patients with a minor stroke frequently present late. Recent studies suggest that DWI may be helpful at this stage, but only very few published data exist on the evolution of the DW-signal in the weeks and months after a stroke. We performed a follow-up study of DWI in the late stages after a minor stroke. 28 patients who presented 48 hours to 14 days after a minor stroke underwent serial MRI at baseline, 4 weeks, 8 weeks, 12 weeks, 6 months and ≥9 months after their event. Signal intensity within the lesion was determined on T2-weighted images, DW-images and the Apparent Diffusion Coefficient (ADC) map at each time-point, and ratios were calculated with contralateral normal values (T2r, DWIr, ADCr). T2r was increased in all patients from the beginning, and showed no clear temporal evolution. ADCr normalized within 8 weeks in 83% of patients, but still continued to increase for up to 6 months after the event. The DW-signal decreased over time, but was still elevated in 6 patients after ≥6 months. The evolution of ADCr and DWIr showed statistically highly significant inter-individual variation (p < 0.0001), which was not accounted for by age, sex, infarct size or infarct location. The ADC and the DW-signal may continue to evolve for several months after a minor ischaemic stroke. Signal evolution is highly variable between individuals. Further studies are required to determine which factors influence the evolution of the ADC and the DW-signal.

Current Status of Carotid Endarterectomy and Stenting for Symptomatic Carotid Stenosis

Abstract: There is still considerable uncertainty about the place of carotid stenting in patients with recently symptomatic carotid bifurcation stenosis. Most reviews of carotid endarterectomy versus carotid st

Primary Prevention and Health Services Delivery

Abstract: Stroke remains the third leading cause of death in the US and other Western countries,1 and at least 1 population-based study found that the incidence of stroke was greater than that of acute coronary syndromes.2 Although there have been substantial falls in stroke incidence in some countries over the last 2 decades,3 a large US study found that the advances in stroke prevention during the 1990s were not associated with decreases in the rate of stroke hospitalizations or in case-fatality rates between 1993 and 1999.4 Moreover, based solely on demographic changes in the population of selected countries within the European Union, the World Health Organization predicts a 27% increase in stroke events between the years 2000 and 2025.5 The proportion of deaths attributed to stroke is even higher in Asian countries.6 Although much of stroke risk may be related to socioeconomic factors, more effective prevention strategies are critical. Several studies have contributed to the body of knowledge related to primary stroke prevention over the last year. Numerous studies support an association between elevated homocysteine levels and atherosclerotic disease.7 The B vitamins (folic acid, B12, and B6) reduce homocysteine serum levels raising the hope that treatment would be associated with reduced risk. That hope was diminished with publication of results of the Vitamin Intervention for Stroke Prevention (VISP) trial in 2004.8 Although a secondary rather than a primary stroke prevention trial, VISP had compared high- and low-dose B-vitamin supplementation and found no treatment effect on the risk of recurrent stroke (risk ratio [RR] 1.0; 95% CI, 0.8 to 1.3), or in the combined risk of any stroke, coronary heart event, or death (RR, 1.0; 95% CI, 0.8 to 1.1). The difference in homocysteine levels between treatment groups, however, was small …

Transient ischaemic attacks: time to wake up

Abstract: “The risk of stroke in the week after a transient ischaemic attack or minor stroke is high and relatively predictable. Emergency investigation and treatment are justified.”

Commentary: Aspirin and colorectal cancer—an epidemiological success story

Abstract: primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 2007;146:365–75. 19 U.S. Preventive Services Task Force. Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2007;146:361–64. 20 Baron JA, Cole BF, Sandler RS et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348:891–99. 21 Sandler RS, Halabi S, Baron JA et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003;348:883–90. 22 Logan RFA, Grainge MJ, Shepherd VC, Armitage NC, Muir KR. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 2007. (in press).