Study challenges long-held assumptions about causes of lacunar stroke

Scientists have uncovered new evidence that challenges long-held assumptions about the causes of a common type of stroke, offering clues as to why widely used treatments may not work.

The study found that the build-up of fatty deposits in arteries does not appear to cause lacunar ischaemic stroke, which accounts for around a quarter of all ischaemic strokes – strokes caused by a blocked blood vessel – in the UK each year.

Instead, researchers identified a different vascular abnormality – enlargement and widening of arteries in the brain – as being strongly linked to lacunar stroke.

Experts say the findings help explain why aspirin and other antiplatelet drugs, commonly used to prevent stroke, are not so effective in preventing lacunar ischaemic stroke.

The results are now helping to inform new treatment approaches, including the LACunar Intervention Trial 3 (LACI-3), which is testing drugs that directly target the brain's small blood vessels.

Lacunar stroke is caused by damage to the brain's smallest blood vessels – called small vessel disease – and is a major contributor to disability, cognitive decline, dementia, and more strokes. However, its underlying causes have remained unclear, limiting progress in developing effective treatments.

To investigate this, researchers from the University of Edinburgh, the UK Dementia Research Institute, and collaborators studied 229 patients who had experienced either lacunar or mild non-lacunar stroke.

Participants underwent clinical and cognitive assessments, along with brain MRI scans at the time of their stroke and again one year later. These scans allowed researchers to track stroke type, signs of small vessel disease, and new areas of brain damage.

They compared fatty narrowing of large arteries with widening and elongation of arteries in the brain.

The study found that narrowing of large arteries was not linked to lacunar stroke or to small vessel disease. It was more commonly seen in other types of stroke and did not predict new areas of brain injury on follow-up scans.

In contrast, widening of arteries showed strong links to lacunar disease. Patients with this feature were more than four times as likely to have lacunar stroke.

Arterial widening was also associated with a greater burden of small vessel disease, faster worsening of brain damage, and a higher risk of developing new 'silent' strokes – small areas of brain tissue damage caused by interrupted blood supply that can occur without obvious symptoms.

More than one in four participants developed these silent strokes during the study, despite receiving standard treatments to prevent further strokes.

Researchers say future treatments should instead target the underlying small vessel damage. Trials such as LACI-3 are now testing whether existing drugs, including cilostazol and isosorbide mononitrate, can protect the brain, reduce further strokes, and help prevent problems with memory, mobility and dementia after lacunar stroke.

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. Recognising 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."

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