Stroke - The Royal Melbourne Hospital Neuroscience Foundation


	Stroke The Stroke Care Unit at the RMH The RMH Comprehensive Stroke Centre is the most active in Australia and treats approximately 800 acute stroke patients each year at the RMH. The Stroke Clinic, headed by Dr Peter Hand, has been a great success and it provides a high-quality outpatient service to follow up acute stroke patients. A major research program underpins the clinical service and involves a team of neurologists, neuroradiologists, MRI physicists, statisticians and research nurses and is supported by an NHMRC program grant and the Royal Melbourne Hospital Neuroscience Foundation. Patients participating in research trials participate in world leading programs in primary stroke care and secondary prevention. “Code Stroke” was introduced to optimise collaboration between Stroke Care Unit and Emergency Department to deliver acute therapies of tPA to patients who have been diagnosed with stroke and are within the therapeutic window for this treatment. Yes, I want to fight against stroke and make a donation. For more information please contact us on 9342 8447 or email neuro.foundation@mh.org.au
	Research Themes in Stroke EPITHET (Stroke) The EPITHET trial, supported by an NHMRC grant, involved 101 patients from 14 participating centres, in Australia, New Zealand and Belgium. This trial tested the hypothesis that imaging of the ischaemic penumbra using MRI could allow selection of patients for thrombolysis with tPA beyond the accepted three hour clinical window. While other studies have suggested that tPA can be administered to patients with a penumbra beyond three hours, EPITHET is the only randomised controlled trial that has formally tested this hypothesis in a prospective design. Based on the EPITHET dataset, a large number of substudies are being performed to address basic questions about recanalisation and reperfusion in ischemic stroke. We are conducting research into the causes of expansion of hematoma after intracerebral hemorrhage, using novel imaging techniques.
	Another study is aimed at better prediction of factors that lead to recurrent brain ischemic events after TIAs and minor strokes. High blood sugar (hyperglycemia) is known to be a major predictor of poor stroke outcomes and a theme of our research in recent years has been to better understand the precise mechanisms of this deleterious effect. We have shown that hyperglycemia in stroke is particularly prominent when the insular cortex is involved. We have explored the interactions between hyperglycemia and various markers of the prothrombotic state after stroke. The ischaemic penumbra is a region of brain where there is critical reduction of blood flow, but potential viability can be restored with early treatment. It is widely considered that rapid identification of the penumbra could allow selection of patients for thrombolytic therapy at much later time points than those established in the clinical trials. The EPITHET trial results were presented in Feb 2008 in New Orleans and published concurrently in Lancet Neurology. We showed that there was increased reperfusion and strong trends to limitation of infarct growth and improved clinical outcomes, confirming our hypotheses and supporting the role for thrombolysis beyond 3 hours. The RMH conducts many other trials. Professor Davis is a member of the Steering Committees of the Novo 7 program in intracerebral hemorrhage and the recently concluded SAINT program of NXY-059 in acute ischemic stroke. Both of these programs have produced positive trial results in the last 18 months, with two publications in the New England Journal of Medicine.
	Imaging Predictors of Stroke Research funding supported by the RMH Neuroscience Foundation has been of enormous benefit in our stroke research program over previous years. The overall theme of the current proposed program is the better prediction of outcome after stroke, which has the real possibility of leading to better therapies for stroke patients. In Australia, stroke is the 3rd most common cause of death, the most common cause of disability and an enormous burden to patients, carers and the community. ‘PREDICT’ Prediction in ischemic cerebral transient events – The use of MRI to predict recurrent vascular events in transient ischemic attack (TIA) and minor stroke. Many patients with stroke have warning attacks, or mini-strokes, called transient ischemic attacks (TIA). The goal of Project 1 is to identify those patients who are at high risk of a subsequent devastating stroke, so that therapies can be optimised for these patients. Our research suggests that early subtle changes on brain MRI scans can predict these high risk patients. Another aspect of this project is to use new blood tests (called biomarkers) which identify chemical factors in the blood that may also help in prediction of high risk patients. This project is supported by the Human Research & Ethics Committee at the RMH and the results should be of great importance to the international stroke community.
	‘ENHANCE’ Enhancement of Hematoma in the Analysis of Clot Evolution: CT angiography in the prediction of hematoma growth in primary Intracerebral hemorrhage (ICH) ‘EXPANDS’ CT predictors of hematoma growth in primary intracerebral hemorrhage: density heterogeneity and shape These two projects concern brain hemorrhage, the cause of stroke in about 15% of patients. Patients with brain hemorrhage (where blood vessels rupture) have much worse outcomes than those with ischemic stroke (where blood vessels are blocked by blood clots), with a higher mortality rate. Unfortunately many survivors are destined for nursing home care. In recent years, a major advance in this field has been the identification that a high proportion of patients within the first few hours after onset of cerebral hemorrhage exhibit further growth of these bleeds within the brain. In fact, our research at the Royal Melbourne Hospital has shown that over 70% of patients show growth of their initial hemorrhage and that this further growth independently predicts a worse outcome and increased risk of death. Our research program is analysing two important predictors of hemorrhage growth. ENHANCE is based on a new sign recently described called the “spot sign”, where an intravenous injection of contrast during a CT scan can actually show leakage of blood out of the blood vessels in the brain and hence indicate ongoing bleeding. We are trying to determine whether the presence of this spot sign at later times over 24 hours predicts further growth. Again, this project is being supported by our Human Research & Ethics Committee at the RMH and has the potential to help identify these patients at high risk of hemorrhage growth and further clinical worsening. EXPANDS involves an analysis of the shape of the initial hemorrhage (regular versus irregular shapes) and variations in the density of the blood clots in the brain. We predict that more irregular hemorrhages, larger hemorrhages and those imaged early will show a greater tendency to further expansion. The aim again is to identify these high-risk patients, who are potentially going to exhibit substantial growth and clinical worsening, so that we can use new treatments that make the blood stickier and prevent this further bleeding. Therefore, this research program has great potential to impact on future treatments. This project has also been approved by the Human Research & Ethics Committee at the RMH. In summary, the research program in both the patients with transient ischemic attacks and cerebral hemorrhage, should help in identifying high risk patients for further worsening and allow more focused, aggressive therapy to improve outcomes.