Chinese Researchers Challenge Traditional View: Lacunar Stroke May Not Stem from Large Vessel Narrowing

A landmark study by Peking Union Medical College Hospital (PUMCH) neurologists, published in Circulation, overturns decades of assumptions about lacunar stroke - revealing that tortuous and dilated blood vessels, not narrowed arteries, may be the true culprit behind this common stroke type.

CT scan showing lacunar stroke in brain

The Discovery: A Paradigm Shift
Understanding Lacunar Stroke
The Tortuous Vessel Connection
Clinical Implications
Ongoing Clinical Trials
Sources

The Discovery: A Paradigm Shift {#discovery}

Brain imaging for stroke diagnosis

On June 4, 2026, Peking Union Medical College Hospital announced groundbreaking research published in Circulation (IF=38.7), one of the world’s most prestigious cardiovascular journals. Led by Professor Zhu Yicheng, Director of the Neurology Department, and Dr. Han Fei, Associate Chief Physician, in collaboration with Professor Joanna Wardlaw’s team at the University of Edinburgh, the study challenges the long-held belief that lacunar stroke is primarily caused by large artery stenosis.

Using a long-term stroke follow-up cohort, the researchers examined two types of large vessel changes - stenosis (narrowing) and tortuosity with dilation - and their relationship with cerebral small vessel disease (cSVD). Their findings were unexpected: large artery atherosclerotic stenosis is not the main cause of lacunar stroke or cerebral small vessel disease, nor can it predict the progression of cSVD-related brain damage.

Instead, patients with tortuous and dilated large arteries were more likely to experience lacunar strokes, had a heavier burden of cerebral small vessel disease, faster progression of brain damage, and a higher risk of asymptomatic new cerebral infarction. Notably, despite receiving standard secondary stroke prevention treatment, more than one-quarter of patients still developed asymptomatic new cerebral infarcts during the one-year follow-up period.

Understanding Lacunar Stroke {#understanding}

Doctor consulting with elderly patient about stroke

Lacunar stroke, also known as lacunar cerebral infarct (LACI), is the most common type of ischemic stroke, accounting for approximately 25% of all ischemic stroke cases. It results from the occlusion of small penetrating arteries that supply blood to the brain’s deep structures, including the basal ganglia, thalamus, pons, and internal capsule.

According to a comprehensive review published in the Journal of Clinical Investigation in 2024 by Dupré et al., cerebral small vessel disease encompasses a heterogeneous group of age-related small vessel pathologies that affect multiple brain regions. Disease manifestations range from incidental neuroimaging findings to severe disability and cognitive impairment.

Traditional understanding, based largely on the work of C. Miller Fisher’s cadaver dissections, suggested two primary mechanisms: microatheroma and lipohyalinosis. However, the PUMCH-Edinburgh collaboration provides new evidence that challenges this conventional wisdom.

The Tortuous Vessel Connection {#mechanism}

Blood vessel research in laboratory

The study’s key finding - that tortuous and dilated arteries are more closely associated with lacunar stroke than narrowed arteries - aligns with emerging research on cerebral hemodynamics. A 2025 study published in Frontiers in Aging Neuroscience by Sun et al. demonstrated that tortuous extracranial arteries contribute to white matter hyperintensities in aging brains, suggesting that morphological changes in large brain-feeding arteries can alter intracranial hemodynamics.

The PUMCH research indicates that lacunar stroke is more likely caused by pathology of the small blood vessels themselves rather than large artery narrowing or occlusion. This finding helps explain why current secondary prevention approaches, centered on antiplatelet therapy and statins, have limited effectiveness for some lacunar stroke patients.

The mechanism appears to involve endothelial dysfunction and increased permeability of the blood-brain barrier, which first allow leakage of blood contents, promoting gliosis and white matter hyperintensities. Focal narrowing of brain vessels and impairment of their ability to dilate in response to various stimuli may lead to decreased cerebral blood flow and ultimately lacunar stroke.

Clinical Implications {#implications}

Medical research on blood vessels

The discovery has profound implications for stroke treatment and prevention. Current stroke prevention guidelines emphasize controlling traditional risk factors such as hypertension, diabetes, and smoking. While these remain important, the new findings suggest that targeting small vessel injury directly may be more effective for lacunar stroke patients.

The study reveals a critical gap in current treatment approaches: over 25% of patients in the study developed asymptomatic new cerebral infarcts despite receiving standard secondary prevention therapy. This highlights the urgent need for new therapeutic strategies that address small vessel pathology rather than focusing primarily on large vessel disease.

For clinicians, the findings suggest that patients with evidence of arterial tortuosity and dilation may require closer monitoring and potentially different treatment approaches than those with traditional atherosclerotic risk factors.

Ongoing Clinical Trials {#ongoing}

Brain imaging technology

Peking Union Medical College Hospital is currently leading a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial for acute lacunar stroke. This trial aims to provide new evidence-based medical guidance for the precise treatment of cerebral small vessel disease and offer new directions for slowing disease progression.

The research was supported by the Central High-level Hospital Clinical Research Special Project and PUMCH’s “Hundred Talents Program.” The international collaboration with the University of Edinburgh’s world-renowned stroke research team, led by Professor Joanna Wardlaw, brings together expertise from two leading institutions in cerebrovascular disease research.

As the global population ages, cerebral small vessel disease and lacunar stroke are becoming increasingly important public health concerns. This Chinese-led research contributes to a growing body of evidence that is reshaping our understanding of stroke mechanisms and pointing toward more effective, targeted treatments.

Sources {#sources}

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