Seasonal Variation in Stroke in the Hunter Region, Australia: a 5-year Hospital-based Study, 1995-2000

Stroke; a Journal of Cerebral Circulation. May, 2003  |  Pubmed ID: 12677016

Seasonal variation in stroke has long been recognized. To date, there are minimal published data on seasonal variations in rates of stroke and subsequent case fatality in the Southern Hemisphere. The aim of this study was to examine stroke seasonality through the use of data from a hospital-based stroke register in the Hunter Region of New South Wales, Australia.

A Prospective Study of Predictors of Prolonged Hospital Stay and Disability After Stroke

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Nov, 2003  |  Pubmed ID: 14592613

This study examined predictors of prolonged hospitalisation (>30 days) and significant disability (modified Rankin Scale >2) in 257 patients with acute ischaemic stroke. These patients were assessed prospectively regarding stroke severity, comorbidities and complications in hospital. Multivariate logistic regression was used to select variables that best predicted prolonged hospital stay and significant disability on discharge. Four factors significantly predicted prolonged hospital stay: older age (>65); diabetes mellitus; in-hospital infection; and significant disability on discharge. Significant disability on discharge was in turn associated with diabetes, infection, premorbid disability, stroke in progression and atrial fibrillation. Diabetes and in-hospital infection, together with other factors, can significantly predict prolonged hospital stay and disability in stroke patients. These two potentially modifiable factors are possible targets for interventions to reduce the burden of illness and healthcare costs of stroke.

Imaging the Ischemic Penumbra with 18F-fluoromisonidazole in a Rat Model of Ischemic Stroke

Stroke; a Journal of Cerebral Circulation. Apr, 2004  |  Pubmed ID: 15017016

The ischemic penumbra is a major focus of stroke research. 18F-fluoromisonidazole (18F-FMISO), a positron emission tomography (PET) marker of hypoxic cells, has shown promise as a technique to image the penumbra in humans. Our aim was to delineate the pattern of 18F-FMISO binding in a rat middle cerebral artery transient thread-occlusion model, and correlate this with tissue outcome at 24 hours. We hypothesized that the pattern of 18F-FMISO binding would mimic that seen in humans.

Ischaemic Tolerance and Mitochondrial Uncoupling--can We Learn from the Cell?

Cerebrovascular Diseases (Basel, Switzerland). 2005  |  Pubmed ID: 15703472

Modification of the Method of Thread Manufacture Improves Stroke Induction Rate and Reduces Mortality After Thread-occlusion of the Middle Cerebral Artery in Young or Aged Rats

Journal of Neuroscience Methods. Sep, 2006  |  Pubmed ID: 16513179

Improving models of human stroke by the use of aged animals has been advocated; however the commonly used rat middle cerebral artery thread-occlusion model has produced suboptimal stroke induction and excess mortality in aged rats. We report the development of a modified method for silicone-coating the tip of occluding threads which produces a malleable silicone-coated tip which is firmly bonded and of highly consistent diameter, and overcomes problems of thread insertion through the narrowed carotid canal found in aged animals. Comparison of stroke outcomes and mortality were made between these threads and heat-treated poly-L-lysine coated threads. The rate of successful stroke induction in aged rats was significantly improved (from 14% to 86%). Similarly, mortality fell from 21-31% to 3-7% or less in both young and old rats with or without diabetes and hypertension. An occluding thread tip diameter of 0.35-0.38 mm was optimal for induction of mid-sized strokes in both young and old rats. This method of thread manufacture overcomes problems of inconsistency of diameter and bonding of the silicone-coated tip, and these threads produce significant improvements in stroke induction by MCA occlusion, particularly in aged animals and those with co-morbidities.

Characterization of Fluoromisonidazole Binding in Stroke

Stroke; a Journal of Cerebral Circulation. Jul, 2006  |  Pubmed ID: 16763190

[18F]fluoromisonidazole (FMISO) positron emission tomography has been used to image hypoxia early after human stroke. To further study the role of hypoxia in stroke and the binding characteristics of FMISO, we aimed to develop [3H]FMISO autoradiography in an animal stroke model. We hypothesized that [3H]FMISO binding is prolonged, allowing correlation with 24-hour histology, and that there is no FMISO binding after effective reperfusion.

Improving Access to Acute Stroke Therapies: a Controlled Trial of Organised Pre-hospital and Emergency Care

The Medical Journal of Australia. Oct, 2008  |  Pubmed ID: 18928434

To assess the effectiveness of the PAST (Pre-hospital Acute Stroke Triage) protocol in reducing pre-hospital and emergency department (ED) delays to patients receiving organised acute stroke care, thereby increasing access to thrombolytic therapy.

The Independent Predictive Utility of Computed Tomography Angiographic Collateral Status in Acute Ischaemic Stroke

Brain : a Journal of Neurology. Aug, 2009  |  Pubmed ID: 19509116

It is unknown whether collateral vessel status, as seen on computed tomography angiography, can predict the fate of penumbral tissue identified on perfusion computed tomography and thereby influence clinical outcome. We tested this hypothesis in consecutive patients who underwent perfusion computed tomography/computed tomography angiography within 6 h of anterior circulation stroke, who also had repeat perfusion/infarct volume imaging at 24 h, and modified Rankin Scale at 3 months. Collateral status was graded as good or reduced depending on the extent of contrast visualized distal to the occlusion on computed tomography angiography. 'Perfusion computed tomography mismatch' ratio was calculated from the ratio of the mean transit time lesion/cerebral blood volume lesion. Of 92 patients with proximal intracranial vessel occlusion, good collateral status (51/92) was significantly associated with reduced infarct expansion and more favourable functional outcomes (modified Rankin Scale 0-2). Significant univariate predictors of favourable outcome were good collateral status, major reperfusion at 24 h, presence of perfusion computed tomography mismatch (for a range of ratios: > or = 1.2, > or = 2, > or = 3, > or = 3.5) and baseline National Institutes of Health Stroke Scale score. Notably, none of the 37 patients with a perfusion computed tomography mismatch ratio < 3.0 had a favourable outcome. In patients with perfusion computed tomography mismatch, significant independent predictors of favourable outcome were good collateral status, major reperfusion and baseline National Institutes of Health Stroke Scale score. There was also a strong interaction between major reperfusion and good collateral status in the regression models. In patients with proximal vessel occlusion, perfusion computed tomography mismatch is a prerequisite for a favourable clinical response, but good collateral status appears a critical determinant of ultimate outcome, particularly if major reperfusion occurs.

Characterisation of the Timing of Binding of the Hypoxia Tracer FMISO After Stroke

Brain Research. Sep, 2009  |  Pubmed ID: 19595680

The hypoxia tracer fluorine-18 fluoromisonidazole ([18F]FMISO) and its tritiated counterpart ([(3)H]FMISO) have been used as markers of potentially salvageable brain (ischemic penumbra) after stroke. In experimental models, the dynamics and half-life of [3H]FMISO allow concurrent histology after 24 h. Our aim was to further validate these techniques, by determining the optimum tracer exposure interval to delineate ischemic penumbra, and the effects of prolonged exposure on tracer retention in permanent ischemia. Middle cerebral artery occlusion (MCAO) of varying durations was created in rats using the thread occlusion model. Autoradiography using objective thresholding to define tracer-retention volume was performed to determine the time course of tracer retention in hypoxic tissues and the duration of ongoing retention after bolus administration. An ischemic duration of < or =90 min resulted in a tracer-retention volume underestimating 'tissue at risk' (histological infarction 24 h after permanent occlusion) by >1/2. Two hour ischemia resulted in a volume equal to 'tissue at risk'. Twenty-four hour permanent ischemia resulted in tracer-retaining tissue volumes greater than final infarction. However, the use of more stringent thresholding of autoradiographic signal produced a volume of FMISO retention closely approximating infarct volume. The findings indicate that the timing of imaging is crucial, with an optimal imaging time of 2 h using the current threshold. Earlier imaging is limited by tracer dynamics with this particular agent, however autoradiography with a longer ischemic interval (permanent occlusion) is feasible with modified thresholds. These findings support a role for hypoxia tracers in providing new insight into the ischemic penumbra.

Inducing Stroke in Aged, Hypertensive, Diabetic Rats

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. Apr, 2010  |  Pubmed ID: 20068574

Animal models of ischemic stroke often neglect comorbidities common in patients. This study shows the feasibility of inducing stroke by 2 h of thread occlusion of the middle cerebral artery in aged (56 week old) spontaneously hypertensive rats (SHRs) with both acute (2 weeks) and chronic (36 weeks) diabetes. After modifying the streptozotocin dosing regimen to ensure that old SHRs survived the induction of diabetes, few died after induction of stroke. Induction of stroke is feasible in rats with multiple comorbidities. Inclusion of such comorbid animals may improve translation from the research laboratory to the clinic.

Cardiogenic Shock Complicating Subarachnoid Haemorrhage Diagnosed As Tako Tsubo Cardiomyopathy: a Cautionary Tale

Heart, Lung & Circulation. Aug, 2010  |  Pubmed ID: 20418161

Tako Tsubo or "stress" cardiomyopathy and its variants are well recognised as potential causes of acute coronary presentations, with manifestations including chest pain, cardiac failure and arrhythmia. Similarly, subarachnoid haemorrhage may be associated with cardiac abnormalities. Tako Tsubo cardiomyopathy is a diagnosis of exclusion with typical left ventricular dysfunction in the absence of epicardial coronary disease, but importantly also after exclusion of an intracerebral insult. We describe a case of unrecognised intracerebral haemorrhage with left ventricular dysfunction consistent with both variant Tako Tsubo cardiomyopathy and subarachnoid haemorrhage in a patient treated with intra-aortic balloon pump counterpulsation and associated heparinisation.

An Enriched Environment Improves Sensorimotor Function Post-ischemic Stroke

Neurorehabilitation and Neural Repair. Nov-Dec, 2010  |  Pubmed ID: 20834046

An enriched environment (EE) refers to conditions that facilitate or enhance sensory, cognitive, motor, and social stimulation relative to standard (laboratory) conditions. Despite numerous published studies investigating this concept in animal stroke models, there is still debate around its efficacy. The authors performed a systematic review and meta-analysis to determine the efficacy of an EE on neurobehavioral scores, learning, infarct size, and mortality in animal models of ischemic stroke.

Trends in Stroke Attack Rates and Case Fatality in the Hunter Region, Australia 1996-2008

Cerebrovascular Diseases (Basel, Switzerland). 2010  |  Pubmed ID: 20861621

The Hunter area in New South Wales, Australia, is a well-defined geographical area with a population of 578,486 (2006). This paper presents trends from 1996 to 2008 for prospectively registered hospital admissions of adults aged 20 years and above with acute stroke.

The Rural Prehospital Acute Stroke Triage (PAST) Trial Protocol: a Controlled Trial for Rapid Facilitated Transport of Rural Acute Stroke Patients to a Regional Stroke Centre

International Journal of Stroke : Official Journal of the International Stroke Society. Dec, 2010  |  Pubmed ID: 21050409

Access to intravenous thrombolysis for acute ischaemic stroke is limited worldwide, particularly in regional and rural areas including in Australia. We are testing the effectiveness of a new rural Prehospital Acute Stroke Triage protocol that includes prehospital assessment and rapid transport of patients from a rural catchment to the major stroke centre in Newcastle, NSW, Australia. The local district hospitals within the rural catchment do not have the capability or infrastructure to deliver acute stroke thrombolysis. The trial has relevance to stroke clinicians, health service managers and planners responsible for rural populations.

Defining the Extent of Irreversible Brain Ischemia Using Perfusion Computed Tomography

Cerebrovascular Diseases (Basel, Switzerland). 2011  |  Pubmed ID: 21178348

Perfusion computed tomography (PCT) shows promise in acute stroke assessment. However, the accuracy of CT perfusion thresholds in defining the acute infarct core remains uncertain.

Acute Stroke Thrombolysis: Time to Dispense with the Clock and Move to Tissue-based Decision Making?

Expert Review of Cardiovascular Therapy. Apr, 2011  |  Pubmed ID: 21517729

Currently, imaging is predominantly used to exclude patients for thrombolysis, rather than identify patients most likely to benefit. This means that patients are being selected for treatment without reference to tissue pathophysiology. Imaging of specific stroke pathophysiology may be the key to selecting patients most likely to benefit from thrombolysis, and could revolutionize acute stroke assessment and treatment. The technology is available to identify the acute infarct core and possibly the penumbra, via magnetic resonance diffusion-weighted imaging, and both magnetic resonance- and computed tomography-perfusion imaging techniques. However, these modalities require fine tuning before they can be reliably implemented in a routine clinical setting.

Establishing a Rodent Stroke Perfusion Computed Tomography Model

International Journal of Stroke : Official Journal of the International Stroke Society. Aug, 2011  |  Pubmed ID: 21609409

Brain computed tomography perfusion imaging in acute stroke may help guide therapy. However, the perfusion thresholds defining potentially salvageable (penumbra) and irreversibly injured (infarct core) tissue require further validation. The aim of this study was to validate infarct core and penumbra perfusion thresholds in a rodent stroke model by developing and optimising perfusion computed tomography imaging, performing serial scanning and correlating scans with final histology. Stroke was induced in male Wistar rats (n=17) using the middle cerebral artery thread-occlusion method. Perfusion computed tomography scans were obtained immediately pre- and postocclusion, and every 30 min for 2.5 h. Histological changes of infarction were assessed after 24 h. High-quality maps of cerebral blood flow and cerebral blood volume were generated at multiple coronal planes after optimisation of contrast injection and scanning parameters. The prestroke absolute cerebral blood flow and cerebral blood volume values (mean ± SD) were 158.2 ± 49.94 ml/min per 100 g and 5.6 ± 1.13 ml per 100 g, respectively. Cerebral blood flow was significantly lower in the infarct region of interest than the contralateral hemisphere region of interest at all time points, except the 0.5 h postocclusion time point. However, cerebral blood volume was only significantly lower in the infarct region of interest than the contralateral hemisphere region of interest at the 1 h and the 1.5 h time points (postocclusion). This study has demonstrated for the first time the feasibility of performing perfusion computed tomography in the most commonly used animal model of stroke. The model will allow definitive studies to determine optimal thresholds and the reliability of perfusion computed tomography measures for infarct core and penumbra.

Perfusion Computer Tomography: Imaging and Clinical Validation in Acute Ischaemic Stroke

Brain : a Journal of Neurology. Nov, 2011  |  Pubmed ID: 22075524

Computed tomography perfusion imaging in acute stroke requires further validation. We aimed to establish the optimal computed tomography perfusion parameters defining the infarct core and critically hypoperfused tissue. Sub-6-h computed tomography perfusion and 24-h magnetic resonance imaging were analysed from 314 consecutive patients with ischaemic stroke. Diffusion-weighted imaging lesion volume at 24 h was used to define the extent of critically hypoperfused tissue (in patients without reperfusion between acute and 24-h time points), and infarct core (in patients with major reperfusion at 24 h). Pixel-based analysis of co-registered computed tomography perfusion and diffusion-weighted imaging was then used to define the optimum computed tomography perfusion thresholds for critically hypoperfused at-risk tissue and infarct core. These optimized acute computed tomography perfusion threshold-based lesion volumes were then compared with 24-h diffusion-weighted imaging infarct volume, as well as 24-h and 90-day clinical outcomes for validation. Relative delay time >2 s was the most accurate computed tomography perfusion threshold in predicting the extent of critically hypoperfused tissue with both receiver operating curve analysis (area under curve 0.86), and the volumetric validation (mean difference between computed tomography perfusion and 24-h diffusion-weighted imaging lesions = 2 cm(2), 95% confidence interval 0.5-3.2 cm(2)). Cerebral blood flow <40% (of contralateral) within the relative delay time >2 s perfusion lesion was the most accurate computed tomography perfusion threshold at defining infarct core with both receiver operating characteristic analysis (area under curve = 0.85) and the volumetric validation. Using these thresholds, the extent of computed tomography perfusion mismatch tissue (the volume of 'at-risk' tissue between the critically hypoperfused and core thresholds) salvaged from infarction correlated with clinical improvement at 24 h (R(2) = 0.59, P = 0.04) and 90 days (R(2) = 0.42, P = 0.02). Patients with larger baseline computed tomography perfusion infarct core volume (>25 ml) also had poorer recovery at Day 90 (P = 0.039). Computed tomography perfusion can accurately identify critically hypoperfused tissue that progresses to infarction without early reperfusion, and the computed tomography perfusion cerebral blood flow infarct core closely predicts the final volume of infarcted tissue in patients who do reperfuse. The computed tomography perfusion infarct core and at-risk measures identified are also strong predictors of clinical outcome.

'Salvaged' Stroke Ischaemic Penumbra Shows Significant Injury: Studies with the Hypoxia Tracer FMISO

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. Mar, 2011  |  Pubmed ID: 20877386

The degree of cellular injury within the stroke ischaemic penumbra is controversial. Clinical and experimental studies using the hypoxia tracer fluoromisonidazole (FMISO) have shown retention of this tracer in the penumbra, but cellular outcome has not been well characterised. We hypothesised that macroscopically intact FMISO-retaining penumbral tissues would show evidence of microscopic injury, and that no FMISO retention would be seen in the infarct core. To determine the distribution of FMISO retention, a tritium-labelled tracer (hydrogen-3 FMISO ([(3)H]FMISO)) was administered 5 minutes after induction of 2-hour temporary middle cerebral artery occlusion. Coregistered brain histology and autoradiography at 24 hours revealed marked retention of FMISO within the infarct. However, 48% of the FMISO-retaining tissue was not infarcted. Within this noninfarcted tissue, only 27% (17 of 64) of sampled regions showed no evidence of neuronal loss, whereas 44% (28 of 64) showed injury to >50% of neurons within the sample. To determine whether FMISO retention occurred after the tissue was already committed to infarction, FMISO was administered 4 to 6 hours after the onset of permanent vessel occlusion. Intense FMISO retention was consistently seen throughout the infarct core. In conclusion, FMISO retention occurs both within the ischaemic penumbra and within the early infarct core. Most penumbral tissues show evidence of selective cellular injury.

A Randomized Trial of Tenecteplase Versus Alteplase for Acute Ischemic Stroke

The New England Journal of Medicine. Mar, 2012  |  Pubmed ID: 22435369

Intravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, is an alternative thrombolytic agent.