A study has shed new light on what might cause one of the most common forms of stroke, which could have major implications for how doctors treat and prevent it.
The type of stroke under investigation was lacunar stroke, a form of ischemic stroke. Lacunar strokes are smaller in size than other strokes and occur deep within the subcortical areas of the brain.
Lacunar strokes can happen when small blood vessels in these areas become damaged, a process that is also known as cerebral small vessel disease (cSVD). It has been unclear what underlying mechanisms cause this damage in the first place, however.
“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,” said study author Joanna Wardlaw, CBE, FRCP, FRSE FMedSci, FRCR, Professor of Applied Neuroimaging at the University of Edinburgh in the United Kingdom in a press release.
“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,” Wardlaw explained.
Ischemic strokes occur due to blood vessels becoming blocked, reducing blood flow to the brain. Around 87% of all strokes are ischemic strokes. Roughly a quarter of these are lacunar strokes.
Doctors tend to treat lacunar stroke in the same way as other forms of ischemic stroke, and the typical methods for preventing ischemic stroke aim to stop arteries narrowing and becoming blocked by buildups of fat.
However, the use of medications like aspirin has appeared to be less effective at preventing lacunar stroke than other forms of the disease.
For the study, published in Circulation, the researchers examined data from a total of 229 stroke patients. Of these, 131 had experienced lacunar stroke with the rest having experienced a mild non-lacunar stroke.
These patients were recruits of the Mild Stroke Study 3, a group consisting of people who had recently experienced strokes in Edinburgh, U.K., between 2018 and 2021.
Each participant underwent a range of clinical assessments and MRI brain scanning at the time of their recruitment to the study. Clinicians then repeated these assessments a year later.
The researchers wanted to investigate how changes to the arteries related to the different types of stroke as well as the cardiovascular health of the participants over time.
They were particularly interested in the narrowing of large arteries, which clinicians have traditionally seen as a major risk factor for all ischemic strokes, as well as the widening and lengthening of smaller arteries within the brain itself.
The researchers found that the narrowing of large arteries was not associated with lacunar stroke or any markers of cSVD.
However, widening and elongation of the small arteries within the brain did have an association with lacunar stroke. In fact, the patients whose scans showed these changes were four times more likely to have had a lacunar stroke.
These changes in the small arteries within the brain were also strongly associated with nearly all the markers for cSVD that the researchers measured for, as well as a higher risk of having a new silent stroke in the year after the initial assessments.
A silent stroke is a small amount of brain tissue damage that can occur due to restricted blood supply to the area. The word “silent” comes from the fact that they often appear to be symptomless.
More than a quarter of the patients experienced these silent strokes, even after receiving standard treatments to prevent new strokes from occurring.
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These treatments include antiplatelet drugs, medication to lower blood pressure, and drugs for controlling blood cholesterol levels.
The authors suggest that solely focusing on these conventional treatments might not be the best choice in every case:
“Although these approaches remain important and should not be discounted, accumulating evidence, consistent with our results, suggests that guideline-based secondary stroke prevention, including antiplatelet therapy and statins, has limited efficacy in preventing the progression of cSVD-related brain damage.”
Ischemic strokes like lacunar strokes occur due to reduced blood flow to parts of the brain. As a result, it may seem strange for there to be an association between lacunar strokes and the widening of small arteries.
The study authors suggest some potential mechanisms behind their findings. One is that there may be a shared genetic link between artery widening, lacunar stroke, and cSVD.
Another possible reason is that the widening and lengthening of certain arteries could result in extra stress being placed on other blood vessels. This could disrupt the flow of blood in these areas as well as damaging them.
Wardlaw explained to Medical News Today how this might work:
“One might think that wider blood vessels would give better blood flow but it can also be that the widening, as here, indicates loss of normal supporting membranes in the blood vessel wall of the large arteries, which means that the blood vessels are ‘baggy’ and less able to control flow. We think this is also what is happening to the small arterioles in the brain.”
Wardlaw said that the team had seen elsewhere that widening “was associated with worse function of the small blood vessels in the brain, which we know is a problem in lacunar stroke and small vessel disease.
“Therefore we think the large artery widening seen in our paper mirrors what is happening in the small arterioles in the brain which become baggy and lose the ability to constrict and dilate to manage blood flow,” she noted.
The authors note that their research was limited by the fact that their patient data all came from the stroke services in one single city. For the results to be generalizable to a wider population, they suggest larger studies looking at patients from a number of different locations are needed.
The researchers write that treatment for patients with lacunar stroke should aim to improve the functioning of small blood vessels in the brain rather than focusing on the potential clogging and narrowing of arteries.
Following up this research, the LACunar Intervention Trial 3 (LACI-3) is investigating whether two cardiovascular drugs — cilostazol and isosorbide mononitrate — can help target cSVD damage.
“The LACI-3 trial is testing two existing drugs used in heart and peripheral vascular disease that we think can improve the function of the small blood vessels in the brain and thus improve control of blood supply better,” Wardlaw told MNT.
By doing so, the hope is that this will “help to prevent more lacunar strokes and cognitive decline and other bad effects of small vessel disease.”
The trial is currently in its first year of recruitment at 38 different centers across the U.K. The team is aiming to recruit 1,300 people with lacunar stroke receiving treatment for 18 months, with the main outcome to assess being the effect on cognitive decline.
This trial could go some way to supporting the findings of the study and potentially alter the approach of future stroke treatment plans.
