The traditional model of stroke pathogenesis, which linked the disease solely to the atherosclerotic blockage of arteries and subsequent brain ischemia, has been challenged by recent research. It appears that this simplified approach completely overlooks the mechanism of lacunar stroke—one of the most common forms of this pathology.
Data from the Mild Stroke Study 3 reveals that deep, small-vessel strokes are not caused by the occlusion of major (large) blood vessels. Instead, it was found that the process originates in the primary damage of the brain’s microvascular network. This reassessment of the nature of the pathology has placed the search for entirely new concepts in clinical management and prevention at the forefront of the medical agenda.
What is a Lacunar Stroke?
Statistically, nearly one-third of all ischemic strokes are lacunar. These strokes specifically damage areas of the brain responsible for motor functions, coordination, and cognitive abilities. The development of the pathology is driven by the progressive degeneration of microscopic arteries—a phenomenon known in medical literature as Small Vessel Disease (SVD).
The etiopathogenic factors behind lacunar stroke have long been a subject of academic debate. The primary focus of research has been directed toward differentiating whether this phenomenon is exclusively the result of microvascular damage or if the obliterative processes of large arteries also play a role in its development.
Two Opposing Phenomena of Vascular Pathology
Researchers compared two types of changes occurring in the large arteries of the brain:
Large Artery Stenosis: This represents the classic picture of a stroke. An artery narrowed by fatty plaque restricts blood flow and increases the risk of blood clot formation.
Dolichoectasia: This is almost the opposite occurrence. Instead of narrowing, the artery becomes pathologically dilated, elongated, and tortuous (twisted) without the presence of atherosclerotic plaque.
These models point toward two completely different pathological mechanisms. The study demonstrated that in the case of lacunar stroke, these processes manifest with entirely unique specificities.
What Did the Study Reveal?
The study involved 229 individuals who had recently suffered a mild stroke. More than half of the participants were diagnosed with a lacunar stroke, while the remaining cases involved other types of pathologies. Patients were monitored using high-precision Magnetic Resonance Imaging (MRI) both at the start of the study and one year later.
The gathered data substantially contradicts previously established views:
While nearly 29% of patients in the non-lacunar group exhibited narrowing of the arterial lumen (stenosis), this figure was only 15% for those with lacunar strokes.
Notably, in the latter cohort, the anatomical location of the stenosis rarely coincided with the actual site of the ischemic lesion. This fact contradicts the notion that the primary etiological mechanism of lacunar stroke is the mechanical blockage of arteries.
In the case of dolichoectasia, the results showed the opposite trend. This anomaly was recorded three times more frequently in the lacunar stroke group and was directly linked to changes visualized on MRI, such as microhemorrhages and diffuse white matter degeneration. These results indicate the dynamic nature of the process; specifically, over the course of one year, the risk of forming new pathological brain lesions was significantly higher in individuals with dolichoectasia, even in asymptomatic cases.
This hypothesis is further supported by a systematic review of 27 studies based on clinical data from over 9,500 patients. The meta-analysis determined that arterial stenosis on the ipsilateral (stroke) side was recorded in only 11% of cases. Particularly significant is that the prevalence of stenosis on the affected side and the contralateral (opposite) side was nearly identical. This circumstance virtually rules out the involvement of large artery narrowing as a direct causative factor in the pathogenesis of lacunar stroke.
Why Do Dolichoectasia and Small Vessel Disease Occur Together?
This connection may be far deeper than mere coincidence. Scientists believe the cause should be sought in the shared genetic code of the blood vessel wall—specifically, the genes responsible for producing proteins that maintain the strength of the vascular framework. Certain genetic variations that weaken this primary support structure cause both the damage of microscopic vessels and the abnormal dilation of large arteries simultaneously. This suggests that both pathologies are different manifestations of the same genetic “weakness.”
Beyond genetics, the process can be explained by mechanical factors. Pathologically dilated and deformed large arteries likely exert excessive physical pressure on the small vessels branching from them. This disrupts normal blood flow, ultimately leading to the damage of microvessels located deep within the brain.
What Do These Findings Change?
The results of this study hold immense practical significance. Current methods for preventing lacunar stroke, which rely primarily on the use of statins and antiplatelet agents, have only a minimal impact on Small Vessel Disease. Since the root of the problem is not the blockage of large arteries but rather the damage to microscopic vessels, traditional treatments are less effective. Consequently, future strategies should shift their main focus toward protecting the blood-brain barrier and maintaining the structural integrity of blood vessel walls.
Source: AHA|ASA Journals
