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Biomedical subjects

Alastair M Buchan

Publications and source records attributed to Alastair M Buchan.

At least 19 recordsLinked to original sources
PubMed2006

Asymptomatic hemorrhage after thrombolysis may not be benign: prognosis by hemorrhage type in the Canadian alteplase for stroke effectiveness study registry.

BACKGROUND AND PURPOSE: There is ongoing controversy about the impact of hemorrhagic transformation after thrombolysis on long-term functional outcome. We sought to study the relation between the type of hemorrhagic transformation on CT scans and functional outcome. METHODS: Data were obtained from the Canadian Alteplase for Stroke Effectiveness Study. This study was established as a registry to prospectively collect data for acute stroke patients receiving intravenous alteplase within 3 hours from stroke onset between February 1999 and June 2001. Follow-up was completed at 90 days, and good functional outcome was defined as a modified Rankin Scale score of 0 or 1. Copies of head CT scans obtained at 24 to 48 hours after starting treatment were read in consensus by a central reading panel consisting of 1 neuroradiologist and 1 stroke neurologist. According to European Cooperative Acute Stroke Study criteria, hemorrhagic transformation was classified as none, hemorrhagic infarction (HI-1 and HI-2), or parenchymal hematoma (PH-1 and PH-2). We compared outcome across groups and performed a multivariable analysis including previously determined important predictors of good outcome in acute ischemic stroke. RESULTS: From 1135 patients enrolled at 60 centers across Canada, 954 follow-up CT scans were assessable. We observed some hemorrhagic transformation in 259 of 954 (27.1%) patients (110 HI-1, 57 HI-2, 48 PH-1, and 44 PH-2). Proportions of patients with good outcome were 41% with no hemorrhagic transformation, 30% with HI-1, 17% with HI-2, 15% with PH-1, and 7% with PH-2 (P<0.0001, chi(2) test). After adjustment for age, baseline serum glucose, baseline Alberta Stroke Program Early CT score, and baseline National Institutes of Health Stroke Scale score, HI-1 was not a predictor of outcome. However, HI-2 (odds ratio=0.38, 95% CI=0.17 to 0.83), PH-1 (odds ratio=0.32, 95% CI=0.12 to 0.80), and PH-2 (odds ratio=0.14, 95% CI=0.04 to 0.48) were all negative predictors of outcome. CONCLUSIONS: The likelihood of a poor outcome after thrombolysis was proportional to the extent of hemorrhage on CT scans. HI grades of hemorrhagic transformation may not be benign.

Adult↗
PubMed2006

Improved regional cerebral blood flow is important for the protection seen in a mouse model of late phase ischemic preconditioning.

INTRODUCTION: Ischemic preconditioning (IPC) induces protection to cerebral ischemia. However, it was previously unclear whether this protection resulted from altered susceptibility to ischemia. The current study examines the effects of late phase ischemic preconditioning in a mouse model of middle cerebral artery occlusion (MCAO). Specific examination of the regional cerebral blood flow (rCBF) was conducted. EXPERIMENTAL PROCEDURE: Intra-abdominal radiofrequency probes were implanted in animals and core temperature was regulated. Mice were subjected to MCAO: (1) brief 15 min duration (preconditioning ischemia) and (2) 45 min MCAO (injurious ischemia). Naive (i.e. not preconditioned) animals were compared with preconditioned animals (preconditioning ischemia plus injurious ischemia at 72 h reperfusion). rCBF was measured using laser Doppler flowmetry (LDF) and magnetic resonance cerebral perfusion (MRP) arterial spin labeling. Percentage of brain infarcted was compared between groups. RESULTS: rCBF was significantly improved in the preconditioned cohorts of mice. Naive animals showed flow reductions to 16+/-3.59% (MCAO_45; injurious, unpreconditioned) and 17.1+/-8.6% (MCAO_15; preconditioning ischemia alone) of baseline, while preconditioned animals had flows 33.9+/-13.2% (IPC_45; preconditioned animals with injurious ischemia at 72 h reperfusion) of baseline (p=0.001). Percentage of brain infarcted was 17.2+/-6.2% in naive animals, while it was 5.1+/-4.6% in the preconditioned animals (p=0.003). MRP of the perfusion to the ischemic hemisphere, in a striatal coronal slice of the brain was 26.7+/-5.8% of the contralateral hemisphere in naive animals while preconditioned mice had flows of 38.7+/-6.8% of contralateral (p=0.04). CONCLUSIONS: Improved rCBF is an important factor in the protection of IPC, during injurious MCAO in the mouse. Stringent monitoring of rCBF is required in future studies of IPC.

Animals↗
PubMed2006

How well does ASPECTS predict the outcome of acute stroke treated with IV tPA?

The authors measured the association of early ischemic change on CT scan, measured using the Alberta Stroke Programme Early CT score (ASPECTS), and functional outcome in 825 patients with anterior circulation stroke treated with IV thrombolysis within 3 hours of onset. ASPECTS predicted outcome in a graded fashion (linearly for ASPECTS 6 through 10; pattern ill-defined for ASPECTS 0 through 5) but discriminated individual outcomes weakly. Except perhaps when early ischemic change is extensive, clinicians should not estimate prognosis using ASPECTS alone.

Acute Disease↗
PubMed2006

Sex-based differences in the effect of intra-arterial treatment of stroke: analysis of the PROACT-2 study.

BACKGROUND AND PURPOSE: Sex influences outcome after intravenous thrombolysis. In a combined analysis of the tissue plasminogen activator clinical trials, a sex-by-treatment interaction was observed. We sought to confirm that observation in an independent data set. METHODS: Data were from the Pro-Urokinase for Acute Cerebral Thromboembolism-2 (PROACT-2) trial. Baseline factors were compared by sex. The primary outcome was an assessment of a sex-by-treatment interaction term within a logistic regression model, using a modified Rankin Scale score <or=2 at 90 days as the binary outcome. We also assessed whether there were differences in CT-scan appearance and recanalization at 2 hours post-treatment. RESULTS: In the PROACT-2 study of intra-arterial stroke thrombolysis, in both women and men, prourokinase resulted in better outcomes than control. A sex by prourokinase treatment interaction was observed, with women showing a larger treatment effect (20% absolute benefit) compared with men (10% absolute benefit). The reason for this interaction is that thrombolytic treatment nullifies the worse outcome for untreated women compared with men. The reasons for effect modification do not include improved recanalization at 2 hours among women. CONCLUSIONS: Women with middle cerebral artery ischemic stroke benefit more from intra-arterial therapy. Further study of how sex affects stroke outcome is needed.

Aged↗
PubMed2006

Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study.

BACKGROUND: The benefit of intravenous tissue plasminogen activator (tPA) given within 3 h of acute ischaemic stroke to patients over 80 years of age is uncertain. AIM: To examine the clinical characteristics and complications and the predictors of outcome after intravenous tPA treatment in patients aged > or = 80 years. METHODS: Data (n = 1135) prospectively collected from the Canadian Alteplase for Stroke Effectiveness Study were reviewed and patients aged > or = 80 years (n = 270) treated with intravenous tPA for acute ischaemic stroke were compared with those aged <80 years (n = 865). RESULTS: The risk of symptomatic intracerebral haemorrhage did not differ between patients aged > or = 80 years and <80 years (4.4% (95% CI 2.3 to 7.6) v 4.6% (95% CI 3.3 to 6.2), p = 1.0). Favourable outcome, defined as a modified Rankin Score of 0-1 at 90 days, was seen in 26% of patients aged > or = 80 years and in 40% of those <80 (p<0.001). The following baseline characteristics were found to be more common in those aged > or = 80 years than in those aged <80 years: atrial fibrillation (37% v 18%; p<0.001); congestive heart failure (11% v 6%; p = 0.004); hypertension (59% v 48%; p = 0.002); and severity of stroke with a median National Institutes of Health Stroke Scale (NIHSS) score of 16 v 14 (p = 0.004). In the multivariable logistic regression analysis, age > or = 80 years, stroke severity, baseline Alberta Stroke Program Early CT Score and glucose level were found to be the major independent predictors of outcome. CONCLUSION: In carefully selected elderly patients, the use of intravenous tPA was not found to be associated with an increased risk of symptomatic intracerebral haemorrhage. Age-related differences were seen in the clinical characteristics and outcome in the elderly population.

Acute Disease↗
PubMed2006

Prior deafferentation confers long term protection to CA1 against transient forebrain ischemia and sustains GluR2 expression.

Hippocampal CA1 pyramidal neurons undergo delayed neurodegeneration after transient forebrain ischemia, and the phenomenon is dependent upon hyperactivation of l-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subtype of glutamate receptors, resulting in aberrant intracellular calcium influx. The GluR2 subunit of AMPA receptors is critical in limiting the influx of calcium. The CA1 pyramidal neurons are very sensitive to ischemic damage and attempts to achieve neuroprotection, mediated by drugs, have been unsuccessful. Moreover, receptor antagonism strategies in the past have failed to provide long-term protection against ischemic injury. Long-term protection against severe forebrain ischemia can be conferred by fimbria-fornix (FF) deafferentation, which interrupts the afferent input to CA1. Our study evaluated the long-term protective effect of FF deafferentation, 12 days prior to induction of ischemia, on vulnerable CA1 neurons. Our results indicate that at 7 and 28 days post-ischemia, prior FF deafferentation protected 60% of neurons against ischemic cell death. Furthermore, we sought to evaluate whether FF deafferentation also sustained GluR2 levels in these neurons. GluR2 protein and mRNA expression were sustained by deafferentation at 70% of control following ischemia. Correlation studies revealed a positive correlation between GluR2 protein and mRNA level. These results demonstrate that protection conferred by FF deafferentation was long-term and related to sustained GluR2 expression.

Afferent Pathways↗
PubMed2006

MR angiography compared to conventional selective angiography in acute stroke.

BACKGROUND AND PURPOSE: Accuracy of intracranial magnetic resonance angiography (MRA) and reliability of interpretation are not well established compared to conventional selective catheter angiography. The purpose of this study was to determine the accuracy of MRA in evaluation of intracranial vessels in acute stroke and transient ischemic attack (TIA) patients METHODS: Twenty-nine patients (seven females, 22 males; median age 53) with acute stroke or TIA were enrolled into the study. All patients underwent both MRA using a 3 T clinical magnet and conventional angiography within 48 hours. Median time between MRA and angiography was 263 minutes. Conventional angiography preceded MRA in 15 cases. Fourteen patients received thrombolysis during MRA or angiography. National Institutes of Health Stroke Scale scores were obtained prior to the MR exam. One neuroradiologist rated all conventional angiograms, which were used as gold standard. Five observers, blinded to conventional angiography results and all clinical information except symptom side, rated the MR angiograms. Kappa statistics were used to assess reliability; contingency tables were used to assess accuracy of non-enhanced and enhanced MRA. RESULTS: Two hundred and fifty two intracranial vessels were assessed. Agreement between raters was good for both non-enhanced (kappa = 0.50) and gadolinium-enhanced (kappa = 0.46) images. There were a total of 26 vessels occluded by DSA. Overall, the non-enhanced MRA showed sensitivity of 84.2% (95% CI 60.4-96.6) and specificity of 84.6% (95% CI 78.6-89.4). The enhanced MRA showed sensitivity of 69.2 (95% CI 38.6-90.9) and specificity of 73.6 (95% CI 65.5-80.7). CONCLUSIONS: Magnetic resonance angiography is a good non-invasive screening tool for assessing intracranial vessel status in acute ischemic stroke. Angiography remains the gold standard for definitive assessment of the intracranial circulation.

Adolescent↗
PubMed2005

Statins are associated with better outcomes after carotid endarterectomy in symptomatic patients.

BACKGROUND AND PURPOSE: Statins have been associated with a reduction in mortality from noncardiac surgery. This study aimed to determine whether statin use on admission to hospital for carotid endarterectomy was associated with a reduction of in-hospital adverse outcomes. METHODS: Data describing patient characteristics, surgical indication, statin treatment, and in-hospital outcomes of death, ischemic stroke or death and cardiac outcomes were collected from a chart review of all patients (3360) undergoing carotid endarterectomy in Western Canada from January 2000 to December 2001. Outcomes of patients on statins versus those not on statins were compared using logistic regression to account for differences in patient characteristics, and propensity score methods to account for factors influencing patient allocation to statins. RESULTS: Eight hundred and fifteen of 2031 symptomatic patients and 665 of 1252 asymptomatic patients were on a statin at the time of hospital admission. Statin use by symptomatic patients was associated with reduced in-hospital mortality and in-hospital ischemic stroke or death, but not in-hospital cardiac outcomes (adjusted odds ratio 0.25 [CI, 0.07 to 0.90], 0.55 [CI, 0.32 to 0.95], 0.87 [CI, 0.49 to 1.54], respectively). The improvement in outcomes was robust when tested using propensity score matching. This association was not seen in asymptomatic patients on statins (adjusted odds ratio, in-hospital mortality 0.54 [CI, 0.13 to 2.24]; in-hospital ischemic stroke or death 1.34 [CI, 0.61 to 2.93]; in-hospital cardiac outcomes 1.37 [CI, 0.73 to 2.58]). CONCLUSIONS: These findings are suggestive of a protective effect of statin therapy in symptomatic patients pre-treated at the time of carotid endarterectomy, though this needs confirmation in a randomized controlled trial.

Aged↗
PubMed2005

Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study.

BACKGROUND: Thrombolysis for acute ischemic stroke has remained controversial. The Canadian Alteplase for Stroke Effectiveness Study, a national prospective cohort study, was conducted to assess the effectiveness of alteplase therapy for ischemic stroke in actual practice. METHODS: The study was mandated by the federal government as a condition of licensure of alteplase for the treatment of stroke in Canada. A registry was established to collect data over 2.5 years for stroke patients receiving such treatment from Feb. 17, 1999, through June 30, 2001. All centres capable of administering thrombolysis therapy according to Canadian guidelines were eligible to submit patient data to the registry. Data collection was prospective, and follow-up was completed at 90 days after stroke. Copies of head CT scans obtained at baseline and at 24-48 hours after the start of treatment were submitted to a central panel for review. RESULTS: A total of 1135 patients were enrolled at 60 centres in all major hospitals across Canada. The registry collected data for an estimated 84% of all treated ischemic stroke patients in the country. An excellent clinical outcome was observed in 37% of the patients. Symptomatic intracranial hemorrhage occurred in only 4.6% of the patients (95% confidence interval [CI] 3.4%-6.0%); however, 75% of these patients died in hospital. An additional 1.3% (95% CI 0.7%-2.2%) of patients had hemiorolingual angioedema. CONCLUSIONS: The outcomes of stroke patients undergoing thrombolysis in Canada are commensurate with the results of clinical trials. The rate of symptomatic intracranial hemorrhage was low. Stroke thrombolysis is a safe and effective therapy in actual practice.

Aged↗
PubMed2005

Triaging transient ischemic attack and minor stroke patients using acute magnetic resonance imaging.

We examined whether the presence of diffusion-weighted imaging (DWI) lesions and vessel occlusion on acute brain magnetic resonance images of minor stroke and transient ischemic attack patients predicted the occurrence of subsequent stroke and functional outcome. 120 transient ischemic attack or minor stroke (National Institutes of Health Stroke Scale < or = 3) patients were prospectively enrolled. All were examined within 12 hours and had a magnetic resonance scan within 24 hours. Overall, the 90-day risk for recurrent stroke was 11.7%. Patients with a DWI lesion were at greater risk for having a subsequent stroke than patients without and risk was greatest in the presence of vessel occlusion and a DWI lesion. The 90-day risk rates, adjusted for baseline characteristics, were 4.3% (no DWI lesion), 10.8% (DWI lesion but no vessel occlusion), and 32.6% (DWI lesion and vessel occlusion) (p = 0.02). The percentages of patients who were functionally dependent at 90 days in the three groups were 1.9%, 6.2%, and 21.0%, respectively (p = 0.04). The presence of a DWI lesion and a vessel occlusion on a magnetic resonance image among patients presenting acutely with a transient ischemic attack or minor stroke is predictive of an increased risk for future stroke and functional dependence.

Acute Disease↗
PubMed2005

A novel method to derive separate gray and white matter cerebral blood flow measures from MR imaging of acute ischemic stroke patients.

Perfusion-weighted imaging (PWI) measures can predict tissue outcome in acute ischemic stroke. Accuracy might be improved if differential tissue susceptibility to ischemia is considered. We present a novel voxel-by-voxel analysis to characterize cerebral blood flow (CBF) separately in gray (GM) and white matter (WM). Ten patients were scanned with inversion-recovery spin-echo EPI (IRSEPI), diffusion-weighted imaging (DWI), PWI<6 h from onset and fluid attenuated inversion-recovery (FLAIR) at 30 days. Image processing included coregistration to PWI, automatic segmentation of IRSEPI into GM, WM and CSF and semiautomatic segmentation of DWI/FLAIR to derive the acute and 30-day lesions. Five tissue compartments were defined: (1) 'Core' (abnormal acutely and at 30 days), (2) 'Growth' (or 'infarcted penumbra', abnormal only at 30 days), (3) 'Reversed' (abnormal acutely but normal at 30 days), (4) 'MTT-Delayed ' (tissue with delayed mean transit time but not part of the acute or 30-day lesion), and (5) 'Normal' brain. Cerebral blood flow in GM and WM of each compartment was obtained from quantitative maps. Gray matter and WM mean CBF in the growth region differed by 5.5 mL/100 g min (P=0.015). Mean CBF also differed significantly within normal and MTT-Delayed compartments. The difference in the reversed region approached statistical significance. In core, GM and WM CBF did not differ. The results suggest separate ischemic thresholds for GM and WM in stroke penumbra.

Aged↗
PubMed2005

Stroke prevention. MATCHing therapy to the patient with TIA.

The short-term risk of stroke after transient ischemic attack (TIA) is about 10% to 20% in the first 3 months, with much of the risk front-loaded in the first week. Unfortunately, little is known about the best therapies for hyperacute stroke prevention after TIA. A recent trial referred to by the acronym MATCH (for Management of Atherothrombosis With Clopidogrel in High-risk Patients With Recent Transient Ischemic Attack or Ischemic Stroke) provides hypothesis-generating data to suggest that double antiplatelet therapy in the short term may be appropriate. Here, the authors discuss treatment considerations, outlining the current knowledge and stressing the need for formal randomized trials to definitively establish the effectiveness of preventive therapies after minor stroke or TIA.

Aspirin↗