Scientists have discovered evidence that could change the way doctors think about stroke in general and why standard preventive treatments often fail.
A new study suggests that lacunar ischemic stroke is not primarily caused by fatty plaques that build up within the arteries, as many assume. Rather, it appears to be most closely associated with changes in the brain’s blood vessels themselves, particularly dilation and dilation of the arteries.
The findings may help explain why commonly prescribed stroke prevention drugs, such as aspirin and other antiplatelet drugs, have limited effectiveness in preventing this type of stroke.
Researchers say the results are already helping guide new treatment strategies, such as the LACunar Intervention Trial 3 (LACI-3), which is evaluating drugs designed to protect and support the brain’s smallest blood vessels.
Cerebral small vessel disease and stroke risk
Lacunar strokes occur when the smallest blood vessels in the brain are damaged by a condition known as small vessel disease. This form of stroke is a leading cause of disability and is associated with cognitive decline, dementia, and increased risk of future stroke. Despite its importance, scientists have struggled to pinpoint the cause of the disease, making it difficult to develop effective treatments.
For the study, researchers from the University of Edinburgh, the British Dementia Research Institute, and international collaborators tested 229 people who had suffered a lacunar stroke or a mild non-lacunar stroke.
Participants underwent clinical and cognitive assessments and underwent brain MRI scans immediately after the stroke and again one year later. Imaging allowed scientists to assess the type of stroke, monitor for signs of small vessel disease, and identify new areas of brain damage that developed over time.
The research team compared two different blood vessel changes: fatty narrowing of large arteries and dilation and elongation of arteries in the brain.
Dilated arteries emerge as a key clue
Analysis showed that aortic stenosis was not associated with lacunar stroke or small vessel disease. Arterial narrowing is more common in other forms of stroke, but follow-up scans did not predict new brain damage.
In contrast, arterial dilatation showed a strong association with lacunar stroke. Patients with dilated arteries were more than four times more likely to experience a lacunar stroke.
Researchers also found that dilated arteries were associated with more severe small vessel disease, faster progression of brain damage, and a higher likelihood of developing new “silent” strokes (small areas of brain tissue damage caused by disruption of blood supply that can occur without obvious symptoms).
More than one in four participants developed such a silent stroke during the study, despite receiving standard treatment aimed at preventing further strokes.
New treatment approaches are being tested
The findings suggest that future treatments should focus on the underlying damage affecting the brain’s small blood vessels, rather than fatty plaques in large arteries.
Studies such as LACI-3 are currently investigating whether existing drugs such as cilostazol and isosorbide mononitrate can protect the brain, reduce the risk of further strokes, and reduce long-term problems such as memory, motor skills, and dementia after lacunar stroke.
Joanna Wardlow, Professor of Applied Neuroimaging at the Institute of Neuroscience and Cardiovascular Diseases at the University of Edinburgh and Group Leader at the UK Dementia Research Institute, said: “This study provides strong evidence that lacunar strokes are not caused by fatty blockages in large arteries, but rather by disease in small vessels within the brain itself. It is important to recognize this distinction as it explains why traditional treatments such as antiplatelet drugs are less effective against this type of stroke.” and highlights the urgent need to develop new treatments that target the underlying microvascular damage. ”
The study was published in the journal circulation. Funding was provided by Dementia UK (funded by Medical Research Council UK, Alzheimer’s Society, Alzheimer’s Research UK), Leduc Foundation, Stroke Association, British Heart Foundation, Scottish Government Office of the Chief Scientist, Lowe Fogo Charitable Trust, Wellcome Trust, and other national funding agencies. The research team also included scientists from China and Mexico.
