Ischaemic stroke currently affects more than 50,000 Australians each year. This figure is expected to climb over the coming decades, due to the nation’s aging population. Prompt treatment of stroke is crucial to minimise brain damage and post-stroke symptoms that can profoundly impact the lives of the survivors, and their families. Timely treatment is, however, complicated by reliance on specialist assessment and medical imaging to diagnose stroke, which significantly disadvantages patients outside metropolitan areas.
A James Cook University (JCU) research team has discovered a pattern of genes, found in the blood of ischaemic stroke patients, that show strong potential to diagnose the condition. Unlike heart attacks, there is currently no blood test available to confirm stroke, which requires rapid treatment to minimise brain damage.
In their pioneering study, the team identified the stroke blood markers through a comparison of genes expressed in blood samples taken from hospital patients with stroke – and those with conditions that mimic stroke. It revealed a novel combination of 11 genes which appeared in markedly different concentration levels in the stroke patients.
Ischaemic stroke, which accounts for 80 per cent of all strokes, occurs when a blockage in blood supply to the brain (often caused by a clot) begins to starve the organ of oxygen and glucose. Prompt diagnosis is essential, as front-line thrombolytics – drugs designed to dissolve clots – must be delivered within four and a half hours of stroke onset.
However conclusive identification of stroke currently relies on specialist neurological assessment and brain imaging, both of which may not be accessible within the window of opportunity for drug treatment.
Patients living in rural and remote areas, including North Queensland, are particularly disadvantaged, as the necessary diagnostic infrastructure is only available in larger tertiary hospitals – possibly many hours travel away, according to research project leader, JCU Senior Research Fellow and Associate Dean, Research, Dr Joe Moxon.
“Data from the Stroke Foundation – the Acute Services Report – demonstrates that rural patients are doing significantly worse than the metropolitan equivalent, largely just because of lack of access to this infrastructure,” he said.
Accurate diagnosis is complicated by the existence of numerous other conditions, including migraine and epilepsy, which mimic non-specific neurological symptoms of stroke. This can result in the administration of thrombolytics to patients who don’t need them – with potentially perilous side effects.
“Because these drugs break down clots in the body, they have a risk of causing bleeding, if given to the wrong patient,” said Dr Moxon.
While many previous studies have tried to identify blood markers for stroke by comparing blood samples taken from confirmed stroke patients with those of a healthy control group, JCU researchers have opted to simulate real clinical situations, as closely as possible.
“This is closer to a ‘real world’ challenge,” said Dr Moxon. “We are working to identify blood markers within a frontline, hospital-based setting, which is where they would ultimately be used to facilitate rapid decisions about patient treatment.”
In collaboration with the Townsville University Hospital Departments of Neurology and Vascular Surgery, JCU has been recruiting research participants who arrive at Townville Hospital with suspected stroke, obtaining their blood samples, then retrospectively confirming whether the patients were definitively diagnosed with ischaemic stroke – or a stroke mimic condition (the study control group).
Using a technology called RNA sequencing, JCU Associate Professor in Bioinformatics, Matt Field, assisted the team to profile the expression of more than 50,000 genes in the provided blood samples, and perform a bioinformatic analysis to identify any that differed significantly between patients with ischaemic stroke and those with stroke mimics.
Previous studies had highlighted enormous differences in gene expression between stroke patients and healthy volunteers, but the JCU study revealed relatively few differences between patients with ischaemic stroke and stroke mimics.
Undeterred, the team then employed machine learning approaches to identify combinations of genes which could distinguish stroke patients from those with stroke mimics.
Those results proved exciting. They revealed the 11-gene pattern.
“It’s early days. We are in the process now of trying to confirm those findings, potentially using additional blood samples from our patients, as well as collaborating with research institutes across the world to use their gene expression datasets,” said Dr Moxon.
Until recently, the research project has been funded by an Advance Queensland Mid-Career Fellowship awarded to Dr Moxon in 2017, and the philanthropic Donald and Joan Wilson Foundation.
However, JCU and the Townsville Hospital have now received a grant of almost $100,000 from the Emergency Medicine Foundation to investigate whether there is also a specific gene pattern associated with large arterial strokes, which are more severe and require specialist surgery.
Dr Moxon said it was particularly rewarding to undertake such a research initiative in North Queensland, where a breakthrough could help to redress the current imbalance in stroke outcomes between underserved rural patients and those in living in large regional centres.
