Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study.

BACKGROUND AND OBJECTIVE: We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS-International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies. METHODS: We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014-2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST. RESULTS: Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44-47), 46.0% (42-50), 38% (35-41) and 37% (35-41), respectively; death was 19.2% (19-21), 15.3% (12.7-18.4), 29.2% (27-32) and 28.6% (27-31); and SICH was 3.6% (3-4), 4.4% (3.0-6.4), 5.8% (4.7-7.1) and not available. CONCLUSION: Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.

Cerebral small vessel disease, medial temporal lobe atrophy and cognitive status in patients with ischaemic stroke and transient ischaemic attack.

BACKGROUND AND PURPOSE: Small vessel disease (SVD) and Alzheimer's disease (AD) are two common causes of cognitive impairment and dementia, traditionally considered as distinct processes. The relationship between radiological features suggestive of AD and SVD was explored, and the association of each of these features with cognitive status at 1 year was investigated in patients with stroke or transient ischaemic attack. METHODS: Anonymized data were accessed from the Virtual International Stroke Trials Archive (VISTA). Medial temporal lobe atrophy (MTA; a marker of AD) and markers of SVD were rated using validated ordinal visual scales. Cognitive status was evaluated with the Mini Mental State Examination (MMSE) 1 year after the index stroke. Logistic regression models were used to investigate independent associations between (i) baseline SVD features and MTA and (ii) all baseline neuroimaging features and cognitive status 1 year post-stroke. RESULTS: In all, 234 patients were included, mean (±SD) age 65.7 ± 13.1 years, 145 (62%) male. Moderate to severe MTA was present in 104 (44%) patients. SVD features were independently associated with MTA (P < 0.001). After adjusting for age, sex, disability after stroke, hypertension and diabetes mellitus, MTA was the only radiological feature independently associated with cognitive impairment, defined using thresholds of MMSE ≤ 26 (odds ratio 1.94; 95% confidence interval 1.28-2.94) and MMSE ≤ 23 (odds ratio 2.31; 95% confidence interval 1.48-3.62). CONCLUSION: In patients with ischaemic cerebrovascular disease, SVD features are associated with MTA, which is a common finding in stroke survivors. SVD and AD type neurodegeneration coexist, but the AD marker MTA, rather than SVD markers, is associated with post-stroke cognitive impairment.

Determinants of post-stroke cognitive impairment: analysis from VISTA.

BACKGROUND: Post-stroke cognitive impairment (PSCI) occurs commonly and is linked with development of dementia. We investigated the relationship between demographic, clinical and stroke symptoms at stroke onset and the presence of PSCI at 1 and 3 years after stroke. METHODS: We accessed anonymized data from the Virtual International Stroke Trial Archive (VISTA), including demographic and clinical variables. Post-stroke cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score of ≤26. We assessed univariate relationships between baseline stroke symptoms and PSCI at 1 and 3 years following stroke, retaining the significant and relevant clinical factors as covariates in a final adjusted logistic regression model. RESULTS: We analysed data on 5435 patients with recent (median 33 days) stroke or transient ischaemic attack (TIA). Mean (±SD) age was 62.6 (±12.6) years; 3476 (65%) patients were male. Follow-up data were available for 2270 and 1294 patients at 1 and 3 years, respectively. At 1 year, 781 (34%) patients had MMSE≤26; at 3 years, 391 (30%) had MMSE≤26. After adjusting for age, stroke severity, hypertension, diabetes and type of qualifying event, initial stroke impairment (leg paralysis) was associated with increased rate of PSCI at 1 year (OR=1.62; 95% CI=1.20-2.20) and at 3 years (OR=1.95; 95% CI=1.23-3.09). Associations were consistent on subgroup analysis restricted to ischaemic stroke and transient ischaemic attack (N=4992). CONCLUSIONS: Besides well-known determinants of PSCI such as age, stroke severity and the presence of vascular risk factors, also leg paralysis is associated with subsequent of PSCI up to 3 years after stroke.

Small vessel disease and clinical outcomes after IV rt-PA treatment.

INTRODUCTION: Cerebral small vessel disease (SVD) contributes to dementia and disability in the elderly, and may negatively affect stroke outcomes. We aimed to evaluate to what extent single features and global burden of SVD detected with magnetic resonance (MR) are associated with worse outcomes in patients with ischaemic stroke treated with intravenous thrombolysis. METHODS: We accessed anonymized data and MR images from the Stroke Imaging Repository (STIR) and the Virtual International Stroke Trials Archive (VISTA) Imaging. We described SVD features using validated scales and quantified the global burden of SVD with a combined score. Our mainoutcome was the modified Rankin Scale (mRS) at 90 days after stroke. We used logistic regression and ordinal regression models (adjusted for age, sex, stroke severity, onset to treatment time) to examine the associations between each SVD feature, SVD global burden and clinical outcomes. RESULTS: A total of 259 patients had MR scans available at baseline (mean age±SD=68.7±15.5 years; 131 [49%] males). After adjustment for confounders, severe white matter changes were associated with disability (OR=5.14; 95%CI=2.30-11.48), functional dependency (OR=4.38; 95%CI=2.10-9.13) and worse outcomes in ordinal analysis (OR=2.71; 95%CI=1.25-5.85). SVD score was associated with disability (OR=1.66; 95%CI=1.03-2.66) and functional dependency (OR=1.47; 95%CI=1.00-2.45). Lacunes, enlarged perivascular spaces and brain atrophy showed no association with clinical outcomes. CONCLUSION: Our results suggest that SVD negatively affects stroke outcomes after intravenous thrombolysis. Although white matter changes seem to be the major driver in relation to worse outcomes, global estimation of SVD is feasible and may provide helpful information.

Impact of heart rate on admission on mortality and morbidity in acute ischaemic stroke patients - results from VISTA.

BACKGROUND AND PURPOSE: Elevated heart rate (HR) is associated with worse outcomes in patients with cardiovascular disease. Its predictive value in acute stroke patients is less well established. We investigated the effects of HR on admission in acute ischaemic stroke patients. METHODS: Using the Virtual International Stroke Trials Archive (VISTA) database, the association between HR in acute stroke patients without atrial fibrillation and the pre-defined composite end-point of (recurrent) ischaemic stroke, transient ischaemic attack (TIA), myocardial infarction (MI) and vascular death within 90 days was analysed. Pre-defined secondary outcomes were the composite end-point components and any death, decompensated heart failure and degree of functional dependence according to the modified Rankin Scale after 90 days. HR was analysed as a categorical variable (quartiles). RESULTS: In all, 5606 patients were available for analysis (mean National Institutes of Health Stroke Scale 13; mean age 67 years; mean HR 77 bpm; 44% female) amongst whom the composite end-point occurred in 620 patients (11.1%). Higher HR was not associated with the composite end-point. The frequencies of secondary outcomes were 3.2% recurrent stroke (n = 179), 0.6% TIA (n = 35), 1.8% MI (n = 100), 6.8% vascular death (n = 384), 15.0% any death (n = 841) and 2.2% decompensated heart failure (n = 124). Patients in the highest quartile (HR> 86 bpm) were at increased risk for any death [adjusted hazard ratio (95% confidence interval) 1.40 (1.11-1.75)], decompensated heart failure [adjusted hazard ratio 2.20 (1.11-4.37)] and worse modified Rankin Scale [adjusted odds ratio 1.29 (1.14-1.52)]. CONCLUSIONS: In acute stroke patients, higher HR (>86 bpm) is linked to mortality, heart failure and higher degree of dependence after 90 days but not to recurrent stroke, TIA or MI.

Associations of chronic heart failure with outcome in acute ischaemic stroke patients who received systemic thrombolysis: analysis from VISTA.

BACKGROUND AND PURPOSE: There are concerns that systemic thrombolysis might not achieve clinically important outcome amongst chronic heart failure (CHF) patients with acute ischaemic stroke. Our aim was to investigate the relevance of CHF on the outcome of acute stroke patients who received thrombolysis. METHODS: A non-randomized cohort analysis was conducted using data obtained from the Virtual International Stroke Trials Archive. The association of outcome amongst CHF patients with thrombolysis treatment was described using the modified Rankin scale (mRS) distribution at day 90, stratified by the presence of atrial fibrillation. Dichotomized outcomes were considered as a secondary end-point. RESULTS: 5677 patients were identified, of whom 2366 (41.7%) received thombolysis. Five hundred and three (8.9%) patients had CHF, of whom 209 (41.6%) received thrombolysis. The presence of CHF was associated with a negative impact on overall stroke outcome [odds ratio (OR) 0.73 (95% confidence interval (CI) 0.62-0.87), P < 0.001]. However, thrombolysis treatment was associated with favourable functional outcome using ordinal mRS, irrespective of CHF status, after adjustment for age and baseline National Institutes of Health Stroke Scale [OR 1.44 (95% CI 1.04-2.01, P = 0.029) for CHF patients versus OR 1.50 (95% CI 1.36-1.66, P < 0.001) for non-CHF patients]. CHF patients had higher mortality at day 90 than non-CHF patients. There was no significant difference for recurrent stroke or symptomatic intracerebral haemorrhage within 7 days of the initial stroke between CHF and thrombolysis groups. CONCLUSIONS: Chronic heart failure was associated with a worse outcome with or without thrombolysis. However, acute stroke patients who received thrombolysis had more favourable outcome regardless of CHF status, compared with their untreated peers. Our findings should reassure clinicians considering systemic thrombolysis treatment in hyperacute ischaemic stroke patients with CHF.

Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy: analysis from VISTA.

BACKGROUND AND PURPOSE: Ischaemic stroke patients with atrial fibrillation (AF) are at risk of early recurrent stroke (RS). However, antithrombotics commenced at the acute stage may exacerbate haemorrhagic transformation, provoking symptomatic intracerebral haemorrhage (SICH). The relevance of antithrombotics on the patterns and outcome of the cohort was investigated. METHODS: A non-randomized cohort analysis was conducted using data obtained from VISTA (Virtual International Stroke Trials Archive). The associations of antithrombotics with the modified Rankin Scale (mRS) outcome and the occurrence of RS and SICH (each as a combined end-point of fatal and non-fatal events) at 90 days for post-stroke patients with AF were described. Dichotomized outcomes were also considered as a secondary end-point (i.e. mortality and good outcome measure at 90 days). RESULTS: In all, 1644 patients were identified; 1462 (89%) received antithrombotics, 157 (10%) had RS and 50 (3%) sustained SICH by day 90. Combined antithrombotic therapy (i.e. anticoagulants and antiplatelets), 782 (48%), was associated with favourable outcome on ordinal mRS and a significantly lower risk of RS, SICH and mortality by day 90, compared with the no antithrombotics group. The relative risk of RS and SICH appeared highest in the first 2 days post-stroke before attenuating to become constant over time. CONCLUSIONS: The risks and benefits of antithrombotics in recent stroke patients with AF appear to track together. Early introduction of anticoagulants (2-3 days post-stroke), and to a lesser extent antiplatelet agents, was associated with substantially fewer RS events over the following weeks but with no excess risk of SICH. More evidence is required to guide clinicians on this issue.

Use of paracetamol in ischaemic stroke patients: evidence from VISTA.

OBJECTIVES: Paracetamol is frequently prescribed for pain and fever control in acute stroke patients, but its effect on stroke outcome is unclear. The aim was to investigate the safety and benefit of paracetamol administration in the acute phase of ischaemic stroke. METHODS: We analysed the impact of paracetamol exposure on functional outcome at 90 days among ischaemic stroke patients registered in a clinical trials archive. We used an adjusted Cochran-Mantel-Haenszel test to test for significance (P) followed by proportional odds logistic regression analysis to estimate the odds ratios (OR) for more favourable modified Rankin Scale score. RESULTS: Data were available for 6015 patients, of whom 2435 had received paracetamol. No association of paracetamol-use with overall stroke outcome could be detected among those patients who experienced pain and/or fever (OR 1.03, 95% CI 0.86-1.20, P = 0.931). In patients without recorded pain and/or fever events and a baseline temperature below 37°C, in whom paracetamol was started within 3 days of stroke, paracetamol was associated with worse outcome (OR 0.58, 95% CI 0.47-0.72, P = <0.001). CONCLUSION: This retrospective analysis is discouraging for prophylactic use of paracetamol in acute stroke patients, but underlines the need for a sufficiently powered randomized controlled trial.

Preoperative risk factors in 10 418 patients with prior myocardial infarction and 5241 patients with prior unstable angina undergoing elective coronary artery bypass graft surgery.

BACKGROUND: The EuroSCORE associates coronary artery bypass graft (CABG) surgery with higher perioperative risk in the first 3 months after a myocardial infarction (MI). The optimal scheduling of CABG surgery after unstable angina (UA) is unknown. We investigated the preoperative predictors of adverse outcomes in patients undergoing CABG with prior MI or UA and investigated the importance of time interval between the cardiac event and CABG. METHODS: The Hospital Episode Statistics database (April 2006-March 2010) was analysed for elective admissions for CABG. Independent preoperative patient factors influencing length of stay, readmission rates, and mortality, were identified by logistic regression and presented as adjusted odds ratios (ORs). RESULTS: A total of 10 418 patients with prior MI (mortality 1.8%) and 5241 patients with prior UA (mortality 2.2%) were included in the respective cohorts. Multiple risk factors were identified in each population including liver disease and renal failure. The time interval from cardiac event (MI or UA) to elective CABG surgery did not influence perioperative outcomes when analysed as a continuous measure or using the arbitrary 3-month threshold [MI, OR 1.1 (0.78-1.57) and UA, OR 0.65 (0.39-1.09)]. CONCLUSIONS: Our hypothesis generating data suggest that the increased risk currently allocated in the EuroSCORE for an interval of 3 months between MI and CABG should be critically re-evaluated. Furthermore, prior MI should not be discounted as a risk factor if it is more than 3 months old.

A survey of principal researchers who lead research into Adults with Incapacity in Scotland.

BACKGROUND: Scotland's 'A' Research Ethics Committee (SAREC, previously MREC A) has exclusive authority to consider research involving Adults with Incapacity in Scotland. No appeal facility exists although resubmissions are accepted. Legislation covering research in England and Wales has created anomalies. RECs 'recognised' by the UK Ethics Committee (3 in Scotland, several in England) can approve drug studies involving Adults with Incapacity in Scotland. Several English RECs can approve studies led from outside Scotland. METHODS: We conducted an anonymous online survey of researchers experienced in studies involving Adults with Incapacity to establish their opinions on the role of SAREC. The survey had 5 multiple-choice questions. Two questions invited a free-text comment. RESULTS: Seventy-seven researchers (45% response) completed the survey. The majority (61/76, 80%) received a favourable opinion from SAREC immediately/after minor revision. The consensus was a single, experienced committee is advantageous to researchers (69/77 (90%)) and research participants (65/75 (87%)). There was no association between application outcome and opinion on whether a single committee is advantageous for researchers (p = 0.39 (Fisher's exact test)) or research participants (p = 0.49). Most (42/76, 55%) favoured the current system for reviewing decisions. CONCLUSIONS: The research establishment favours retaining expertise in one committee. Most are content not having an external appeal facility.

Management of acute poststroke blood pressure and detection of atrial fibrillation: a postal questionnaire of UK stroke physicians' current clinical practice.

The aim of this study was to determine the current clinical practice of UK stroke physicians with regard to the early management of blood pressure (BP) and arrhythmia detection following acute stroke. Postal service evaluation questionnaires were sent to the lead physicians for stroke in UK hospitals. Hospitals were identified by their inclusion in the 2008 Scottish Stroke Care Audit and the 2006 Royal College of Physicians Sentinel Stroke Audit. A total of 259 questionnaires were sent with a 33% response rate. Current practice regarding acute post-stroke BP management varied considerably. Approximately one-third of respondents lowered systolic BP within the first 72 hours of stroke, but the majority (65%) delayed intervening for at least seven days. Most would not intervene until systolic BP exceeded 180 mmHg. Of those who intervene, the most commonly quoted target systolic BP was 160 ± 5 mmHg. Post-stroke arrhythmia investigation was similarly varied; 12-lead electrocardiogram recording was frequent, with further investigation being more individualized. Of all respondents, 87% expressed interest in participating in future trials of complex interventions for stroke. Current practice of UK stroke physicians regarding acute BP intervention is diverse, reflecting conflicting evidence. There is interest in the stroke community for further research aiming to answer these important clinical questions.

Natural history of complications after intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Numerous trials of haemostatic and neuroprotective agents for intracerebral haemorrhage (ICH) have failed. We characterized the risk of complications after ICH in a trial-eligible patient population, to inform safety in future trials. METHODS: We used the Virtual International Stroke Trials Archive database to identify placebo-treated patients with spontaneous ICH, who were not comatose at admission, where randomization took place within 4 h of symptom onset, and where serious complication and outcome data were available. We described the complications encountered and assessed whether the absence of common complications influenced attainment of good functional outcome (mRS < or =4) at 90 days using logistic regression. RESULTS: Of 201 patients examined, 70.2% experienced at least one serious complication. Neurological complications occurred in 21%, infections amongst 11%, and thromboembolic complications in 2%. Extension of the haemorrhage occurred most frequently: its absence was a significant predictor of good functional outcome (P < 0.0001, adjusted OR for good functional outcome = 21.9, 95% CI: [5.5, 88.3]). Neither infection, nor cardiac, nor thromboembolic complications influenced functional outcome at 90 days. CONCLUSIONS: Three month outcome in ICH patients depends on initial stroke severity and on enlargement of the haemorrhage. Our results should inform safety in future clinical trials of putative ICH therapies.

Hyperglycaemia in acute stroke--to treat or not to treat.

Diabetes is common amongst patients with stroke and is associated with poorer outcome. Post-stroke hyperglycaemia is also recognised in up to half of the patients, and is independently associated with adverse sequelae: both increased mortality and poorer functional outcomes. Neither the aetiology nor the pathophysiology of such hyperglycaemia is fully understood. Both direct neurological toxicity and systemic consequences are postulated to occur. A distinction between occult diabetes and non-diabetic hyperglycaemia seems important as prognosis and effect of intervention differ in these two groups. The optimal management of the milder forms of hyperglycaemia associated with acute stroke is unknown. Randomised trial data remain limited but presently offer no strong support for aggressive intervention in stroke, though in other critical illness settings tight control of blood sugar appears beneficial. Studies based in coronary care and high dependency units have shown a possible beneficial effect of insulin, but evidence for intervention in acute stroke is at best limited. However, if glucose management is to be undertaken, this should be instituted while there is still salvageable tissue and the glucose reduction must be substantial. Intravenous insulin may be more effective than glucose-potassium-insulin infusion. Both interventions carry a risk of hypoglycaemia and any proposed intervention must balance safety, convenience and glycaemic control. Until further trial data are available, consensus guidelines may be followed, which are generally conservative for blood glucose levels below 10 mM (180 mg/dl).

The association of post-stroke neurological improvement with risk of subsequent deterioration due to stroke events.

We sought to simultaneously confirm that substantial recovery at day 1 and day 7 after acute ischaemic stroke onset is associated with subsequent neurological deterioration in patients of the Acute Stroke Therapy by Inhibition of Neutrophils randomized clinical trial. Substantial recovery was assessed by improvement in the National Institutes of Health Stroke Score (NIHSS). Neurological deterioration was defined as any stroke event or NIHSS worsening from recovery assessment to day 90. After adjusting for age, t-PA and day 1 NIHSS, there was a non-significant tendency of substantial (pre-specified as 75%) recovery at day 1 to be associated with later deterioration [odds ratio (OR) 2.47; 95% CI, 0.95-6.50]. The corresponding OR for substantial (pre-defined as 65%) recovery at day 7 was 1.84 (0.85-3.96). Other thresholds for recovery were significantly associated with later deterioration: >50%, 80%, 90% and 100% for day 1 and >50%, 60%, 70%, 90% and 100% for day 7. The effect of recovery at day 1 was more important than that of later recovery. This study confirms the association between recovery and subsequent neurological deterioration and is the first to indicate the greater importance of acute recovery at day 1 in comparison with later recovery.

Epidemiological aspects of referral to TIA clinics in Glasgow.

A retrospective cohort study was carried out of new referrals to transient ischaemic attack (TIA) clinics in Glasgow. The aims of the study were to describe the profile of referrals and to assess the odds ratios for TIA, minor stroke or amaurosis fugax of both cardiovascular risk factors and clinical features. In total, data were collected for 813 new referrals in a period of six months. Thirteen point eight percent of referrals were from other Health Boards. The overall referral rate among residents of Greater Glasgow NHS Board was 165.6 per 100,000 per year. About 20% of referrals were made by clinicians in secondary care. The specialties from which referrals were most commonly made were accident and emergency, general medicine, ophthalmology and geriatric assessment. The most common risk factors in patients referred were hypertension (52.9%), smoking (31.7%), ischaemic heart disease (22.7%) and former smokers (22.4%). The most common clinical features were hemiparesis (13.3%), weakness of an upper limb (8.7%), vertigo (7.9%) and dysphasia (7.3%). In 48.7% of cases, a non-cerebrovascular diagnosis was made. Separate multivariate models were established for risk factors and clinical features. In the model for risk factors, five factors were significant for risk of TIA, stroke or amaurosis fugax. These were hyperlipidaemia, age over 64 years, hypertension, smoking and ex-smoking. In the model for clinical features, five factors were also significant. These were visual field defect, speech defact, facial weakness and hemiparesis.

Short runs of atrial arrhythmia and stroke risk: a European-wide online survey among stroke physicians and cardiologists.

A recording of = 30 seconds is required to diagnose paroxysmal atrial fibrillation when using ambulatory ECG monitoring. It is unclear if shorter runs are relevant with regards to stroke risk. Methods An online survey of cardiologists and stroke physicians was carried out to assess current management of patients with short runs of atrial arrhythmia within Europe. Results Respondents included 311 clinicians from 32 countries. To diagnose atrial fibrillation, 80% accepted a single 12-lead ECG and 36% accepted a single run of > 30 seconds on ambulatory monitoring. Stroke physicians were twice as likely to accept < 30 seconds of arrhythmia as being diagnostic of atrial fibrillation (OR 2.43, 95% CI 1.19-4.98). They were also more likely to advocate anticoagulation for hypothetical patients with lower risk; OR 1.9 (95% CI 1.0-3.5) for a patient with CHA2DS2-VASc = 2. Conclusion Short runs of atrial fibrillation create a dilemma for physicians across Europe. Stroke physicians and cardiologists differ in their diagnosis and management of these patients.

Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial.

BACKGROUND: Magnesium is neuroprotective in animal models of stroke, and findings of small clinical pilot trials suggest potential benefit in people. We aimed to test whether intravenous magnesium sulphate, given within 12 h of stroke onset, reduces death or disability at 90 days. METHODS: 2589 patients were randomised within 12h of acute stroke to receive 16 mmol MgSO4 intravenously over 15 min and then 65 mmol over 24 h, or matching placebo. Primary outcome was a global endpoint statistic expressed as the common odds ratio for death or disability at day 90. Secondary outcomes were mortality and death or disability, variously defined as Barthel score less than 95, Barthel score less than 60, and modified Rankin scale more than 1. Predefined subgroup analyses were for the primary endpoint in patients in whom treatment commenced within 6 h versus after 6 h, ischaemic versus non-ischaemic strokes, and cortical stroke syndromes versus non-cortical strokes. Intention-to-treat and efficacy analyses were done. FINDINGS: The efficacy dataset included 2386 patients. Primary outcome was not improved by magnesium (odds ratio 0.95, 95% CI 0.80-1.13, p=0.59). Mortality was slightly higher in the magnesium-treated group than in the placebo group (hazard ratio 1.18, 95% CI 0.97-1.42, p=0.098). Secondary outcomes did not show any treatment effect. Planned subgroup analyses showed benefit of magnesium in non-cortical strokes (p=0.011) whereas greater benefit had been expected in the cortical group. INTERPRETATION: Magnesium given within 12 h of acute stroke does not reduce the chances of death or disability significantly, although it may be of benefit in lacunar strokes.

The prognostic significance of visible infarction on computed tomography following lacunar stroke: results of a long-term follow-up study.

BACKGROUND AND PURPOSE: Substantial variability in functional outcome and relatively few factors predictive of death or degree of recovery have been observed in patients with lacunar stroke. Such indicators are of great use in the selection of optimal rehabilitation strategies after stroke. Although computed tomography (CT) of patients with a clinical diagnosis of lacunar stroke performed within the first 10 days shows evidence of cerebral infarction in 50% to 60%, the prognostic significance of a visible ischemic lesion on CT is unclear. METHODS: 633 patients who presented with symptoms consistent with lacunar stroke between June 1990 and February 1998 were studied. One hundred fourteen patients imaged with magnetic resonance, 41 patients with nonischemic diagnoses (hemorrhage or tumor), 57 patients imaged within 12 hours of ictus, and 17 patients with incomplete follow-up were excluded from the analysis. The remaining 404 patients were divided into 2 groups, depending on the appearance of the CT scan. Patients with a low-attenuation area on the CT scan consistent with an ischemic lesion in an appropriate region of the brain to explain the presenting symptoms were classified as "CT positive." Patients with either a normal CT scan of the brain or a scan that showed a lesion in an area inconsistent with the presenting symptoms were classified as "CT negative." A series of known or suspected prognostic factors were recorded for each patient: blood pressure, age, smoking, plasma glucose level, serum cholesterol level, and serum triglyceride level. Delay from stroke onset to scanning was also noted. The authors considered 3 outcome measures: survival time, outcome at 6 months after the stroke, and total length of hospital stay for the stroke admission. Six-month outcome was categorized as good (alive at home) or poor (alive in care or dead). RESULTS: There was no difference in survival between the 2 groups (P= .29, log-rank test). After adjusting for other significant prognostic factors (age; relative hazard per additional decade 1.67, P< .0001: plasma glucose level; relative hazard per additional mmol/l 1.08, P= .03) in a proportional hazards model, presence of visible infarction remained nonsignificant (relative hazard 0.84, P= .40). After adjustment for the other significant factor (age, P= .0001), there was no significant difference in 6-month outcome between CT positive and CT negative patients (P= .61). Median total length of hospital stay was not significantly different between the 2 groups (CT positive, 9 days; CT negative, 8 days; Mann-Whitney test, P= .29). CONCLUSION: The authors conclude that in their cohort of patients, having corrected for other prognostic variables, the presence of visible infarction on CT brain scan performed between 12 hours and 30 days of onset of lacunar symptoms is not predictive of duration of hospital stay or of longer term outcome.

Effect of perindopril on cerebral and renal perfusion in stroke patients with carotid disease.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effect of the angiotensin-converting enzyme inhibitor perindopril on mean arterial blood pressure (MABP), cerebral blood flow (CBF), and glomerular filtration rate in hypertensive stroke patients with moderate to severe internal carotid artery (ICA) disease or ICA occlusion. METHODS: Twenty-four nonacute ischemic stroke patients who had MABP readings >100 mm Hg and moderate to severe ICA stenosis or occlusion were randomized to receive perindopril 4 mg daily or placebo for 14 days. MABP, ICA flow, and both middle cerebral artery (MCA) velocity and resistance index were measured before dose, at 5 time points over the subsequent 24 hours, and finally at 2 weeks. Brain hexamethyl propylene amine oxide single photon emission computed tomography scans were performed before drug administration and at time of peak drug effect (6 to 8 hours) after the first dose. Glomerular filtration rate was measured with (51)Cr EDTA before medication and at 14 days. RESULTS: A placebo-corrected BP fall of 17/10 mm Hg was seen (P:=0.017), which was maximal at 5.5 hours. No significant change in ICA flow or MCA velocity was seen between groups. No significant change in hemispheric CBF was seen. The mean change from baseline in the treated group was -0.79 mL. 100 g(-1). min(-1) (95% confidence interval [CI], 1.65 to -3.23); mean change in the placebo group was -1.9 mL. 100 g(-1). min(-1) (95%CI, 3.02 to -6.92). Peri-infarct CBF was similarly unaffected. One of the treated patients developed transient acute renal impairment and was withdrawn from the study on day 4. CONCLUSIONS: Perindopril lowers BP without lowering CBF in hypertensive stroke patients with moderate to severe ICA stenosis or occlusion; monitoring of this patient population for the complications of renal artery stenosis should be considered.