Stroke treatment now focusing on fast restoration of blood flow to brain
Treatment of stroke has moved forward hugely, and there is potential to improve outcomes further, says Prof Keith Muir
Strokes cause 4,300 deaths in Scotland each year and over 25,000 hospital visits are attributed to it. While medical research has improved treatments, a lot more needs to be done.
The British Heart Foundation is the biggest independent funder of research into heart disease and stroke in Scotland, currently committing £63 million in universities and institutions across the country.
Thanks to nearly £1m of funding, including a £750,000 BHF grant, my team is running a major clinical study into new clot-busting drugs.
The majority of strokes happen because a blood clot, usually originating from the heart or the major blood vessels, travels to the brain and blocks the circulation. When this occurs, brain tissue is starved of oxygen and nutrients. The brain does not tolerate this for very long: if tissue has very severely reduced blood flow, then it becomes irreversibly damaged very quickly, potentially within minutes. Usually some tissue can survive for a period of time if some blood supply is maintained via alternative blood vessels, but this amount of flow is insufficient for survival and tissue can last no more than a few hours before becoming permanently damaged.
A great deal of stroke research over recent years has concentrated on ways of restoring the blood supply to the brain tissue that is still potentially viable. “Clot busting” drug treatment is one way of achieving this, and, if given within the first few hours after onset of a stroke, significantly increases the chances of restoring blood supply, saving brain tissue, and improving the chances of recovery.
Our existing clot-busting drug treatment isn’t ideal, however. It needs to be given as soon as possible after onset of symptoms to have the best chance of benefit – the clot becomes harder to break down as time passes, and more brain tissue becomes damaged. There is a risk of causing bleeding, particularly bleeding in the brain, which can be serious or even fatal. And for the most severe strokes, where a large blood clot has blocked a major artery, drug treatment is not very effective because it cannot break down enough clot fast enough to avoid major damage. Our best current treatment is therefore least effective for the patients with the worst strokes.
Much of the research work that the stroke research team in Glasgow have undertaken has aimed at improving our options for restoring blood flow to the brain.
One issue is that treatment is currently not possible when the time of onset of stroke symptoms isn’t known – this often happens when a stroke happens during sleep, but also when people don’t recognise that they have symptoms, or are unable to communicate because of the stroke affecting their speech and language functions. One major trial, called WAKE-UP (funded by the European Union and led from Germany), is testing whether MRI scanning can be used to identify people whose stroke occurred within the time period suitable for clot-busting drug treatment, by using the fact that two different types of MRI scan change at different rates (one very quickly, and one rather slowly).
Another of our main trials is looking at the possible role for some of the newer types of scanning in identifying whether or not viable tissue is present in an individual. We can look both at blood vessels, and also at the state of blood flow in the brain using CT scanning, and there are some suggestions that this might allow treatment to be targeted to those who are likely to benefit and also avoid treatment in people who are potentially at risk of bleeding. In the PRACTISE trial we are testing whether the extra scans are helpful by randomly assigning people to have extra scans or standard ones. This is taking place in around ten sites around the UK.
Last year we completed the PISTE trial, which addressed the problem of the poor response of large clots to drug treatment, and established that devices that can be fed through the blood vessels to remove these clots improves the chances of recovery very significantly, above and beyond the use of clot-busting drugs alone Introducing this treatment is a challenge for all hospitals since it needs highly specialised services and skilled teams.
My team’s major clinical trial, that is just starting across multiple UK hospitals, is testing a different clotbusting drug treatment that has shown some promising results in
small studies done previously. The ATTEST-2 trial, funded by the BHF and the Stroke Association, will compare the two different drugs to see whether one is better and/or safer than the other, by allocating people randomly to one or other clotbusting treatment.
Treatment of stroke has moved forward enormously over the past 20 years, and, as a result of research, our focus has moved increasingly to restoring blood flow as quickly as possible. There is great potential to improve outcomes further, and our ongoing trials will test new treatment approaches, and new scanning methods that will hopefully make more effective treatment available to more of our patients.
(WAKE-UP is funded by the EU; PRACTISE by the National Institute of Health Research; PISTE by the Stroke Association and NIHR; and ATTEST-2 by the Stroke Association and British Heart Foundation) l Professor Keith W Muir, SINAPSE Professor of Clinical Imaging & Consultant Neurologist, University of Glasgow