Lacunar stroke may arise from damage in the brain’s small blood vessels rather than fatty plaque in larger arteries, pointing researchers toward new treatment strategies.
Scientists have found new evidence that calls into question a long-standing explanation for a common form of stroke, and it may help clarify why standard prevention treatments often fall short.
The study suggests that fatty deposits in arteries are unlikely to be the cause of lacunar ischemic stroke, a type that makes up about one quarter of all ischemic strokes, which are strokes caused by blocked blood vessels, in the UK each year.
Instead, the investigators found a strong connection between lacunar stroke and a separate blood vessel change: arteries in the brain that become enlarged and widened.
The findings may explain why aspirin and other antiplatelet medicines, which are widely used to prevent strokes, are less effective against lacunar ischemic stroke.
The results are already shaping new treatment strategies, including the LACunar Intervention Trial 3 (LACI-3), which is evaluating medicines designed to act directly on the brain’s small blood vessels.
Small vessels hold the clue
Lacunar stroke results from injury to the brain’s tiniest blood vessels, a condition known as small vessel disease. It is a major cause of disability, cognitive decline, dementia, and additional strokes. Yet scientists have not fully understood what drives it, making it difficult to develop better treatments.
To study the problem, investigators from the University of Edinburgh, the UK Dementia Research Institute, and collaborating institutions examined 229 people who had experienced either lacunar stroke or mild non-lacunar stroke.
The participants completed clinical and cognitive evaluations and had brain MRI scans when their stroke occurred and again one year later. Those scans helped the investigators identify the type of stroke, measure signs of small vessel disease, and detect new areas of brain injury.
They then compared two vascular features: fatty narrowing in large arteries and widening with elongation of arteries inside the brain.
Widened arteries changed the picture
The study found no link between narrowing in large arteries and lacunar stroke or small vessel disease. That narrowing appeared more often in other stroke types and did not predict new brain injury on later scans.
By contrast, widened arteries were closely associated with lacunar disease. People with this feature were more than four times as likely to have had a lacunar stroke.
Arterial widening was also tied to more severe small vessel disease, faster progression of brain damage, and a higher chance of developing new ‘silent’ strokes, which are small areas of brain tissue injury caused by disrupted blood flow that may occur without clear symptoms.
More than a quarter of the participants developed silent strokes during the study, even though they were receiving standard treatments intended to prevent additional strokes.
Treatment targets are shifting
The findings suggest that future therapies should focus on the small vessel damage underlying lacunar stroke. Trials such as LACI-3 are now examining whether existing medicines, including cilostazol and isosorbide mononitrate, can protect the brain, lower the risk of further strokes, and help prevent memory problems, mobility difficulties, and dementia after lacunar stroke.
Joanna Wardlaw, Professor of Applied Neuroimaging at the University of Edinburgh’s Institute for Neuroscience and Cardiovascular Disease and Group Leader at the UK Dementia Research Institute, said: “This study provides strong evidence that lacunar stroke is not caused by fatty blockage of larger arteries, but by disease of the small vessels within the brain itself. Recognizing this distinction is crucial, because it explains why conventional treatments like antiplatelet drugs are not as effective for this type of stroke and highlights the urgent need to develop new therapies that target the underlying microvascular damage.”
Reference: “Implications of Cranial Arterial Stenosis and Dolichoectasia for Cerebral Small-Vessel Disease Etiopathogenesis: Findings From a Prospective Mild Stroke Cohort” by Fei Han, Una Clancy, Carmen Arteaga-Reyes, Michael J. Thrippleton, Maria del C. Valdés Hernández, Daniela Jaime Garcia, Michael S. Stringer, Ellen Backhouse, Francesca M. Chappell, Yajun Cheng, Dillys Xiaodi Liu, Junfang Zhang, Angela C.C. Jochems, Eleni Sakka, Charlotte Jardine, Gayle Barclay, Donna McIntyre, Iona Hamilton, Rosalind Brown, Yi-Cheng Zhu, Fergus N. Doubal and Joanna M. Wardlaw, 6 May 2026, Circulation.
DOI:10.1161/CIRCULATIONAHA.126.079493
Funded by the UK Dementia Research Institute (funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK), the Leducq Foundation, the Stroke Association, British Heart Foundation, Scottish Government’s Chief Scientist Office, Row Fogo Charitable Trust, Wellcome Trust and other national agencies.
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