Researchers following mild stroke patients found that abnormal widening and distortion of cerebral arteries, not traditional large-artery narrowing, was more strongly associated with progressive small-vessel brain damage and latent stroke.
Study: Implications of cranial arterial stenosis and dolichoectasis for the etiology of cerebral small vessel disease: Findings from a mild stroke cohort perspective. Image credit: Hamara/Shutterstock.com
A recent study published in the journal Traffic reports that dolichoectasia and intracranial arterial enlargement are independently associated with cerebral small vessel disease and cerebrovascular accident.
Cerebral artery narrowing and widening show distinct effects
Scientists consider stenosis (narrowing) and dolichoectasia (abnormal lengthening, twisting, and widening) of the cranial arteries as distinct entities that affect the large arteries of the brain. Large artery stenosis (LAS) results from the deposition of atherosclerotic plaque, which causes focal stenosis. In contrast, dolichoectasia apparently arises due to non-atherosclerotic mechanisms.
These conditions affect the downstream small vessels differently and are associated with different types of stroke. Aberrant stroke accounts for 20%-30% of ischemic stroke. Such strokes are thought to result primarily from intrinsic cSVD, specifically, segmental arterial disorganization.
In addition, approximately 15% of patients with latent stroke have potential sources of embolism, including atheroma in large arteries. However, it remains uncertain whether these directly contribute to the erratic stroke. Furthermore, the relative importance of LAS and dolichoectasis in the etiology of cSVD remains unclear.
Multimodal imaging study
Researchers recruited 229 patients with latent (131 patients) or mild non-lacunose stroke and compared multimodality imaging at baseline and after one year. Magnetic resonance imaging (MRI) or computed tomography (CT) was used to assess brain tissue at baseline at the time the stroke occurred.
Cerebrovascular imaging was performed to identify intracranial or carotid artery stenosis, basilar artery dolichoectasis, and intracranial carotid and middle cerebral artery diameters.
LAS is associated with non-laconic but not missense stroke
They found that LAS occurred in 20.5% of patients, while dolichoectasia was present in 15.7%. LAS was associated with nonlacunular stroke and a higher number of index infarcts at presentation.
In contrast, LAS was associated with approximately 50% lower odds of latent stroke compared with non-latent stroke. There was no consistent association with cSVD. Cortical infarcts were more common with LAS, but subcortical infarcts were more common with dolichoectasia.
Subcortical infarcts in patients with LAS they were more likely to involve the corona ciliary, centrum semiovale, and internal border zone, whereas subcortical infarcts in patients without LAS more frequently affected the basal ganglia, thalamus, and brainstem.
Dolichoectasia associated with latent stroke
Basilar artery dolichoectasia was associated with a 4.7-fold likelihood of latent stroke and a 2.6-fold likelihood of cSVD, compared with patients without this finding. Heart attacks were 2.3 times more likely, mainly in the subcortical region.
Incident infarcts were more often cortical when caused by embolism, but subcortical when associated with dolichoectasia. LAS was associated with downstream cortical infarcts, but this was not the case with subcortical infarcts. These subcortical infarcts occurred mainly in the cerebral white matter. White matter hyperintensities showed greater progression over the year of follow-up.
Intracranial carotid and middle cerebral artery enlargement was associated with similar changes to those seen in basilar artery dolichoectasia.
Neither LAS nor dolichoectasia was associated with impaired cognitive tests, mobility, or functional outcomes after adjustment for age, sex, baseline cSVD burden, and vascular risk factors. Further analyzes confirmed the validity of these associations.
Hypothesized mechanisms underlying these associations
According to the authors, proposed mechanisms for the association of dolichoectasia and cSVD, as well as latent stroke, include genetic susceptibility to weak basement membrane proteins. common abnormalities of the connective tissue of the vessel wall. and remodeling of the walls of small vessels with mechanical stress due to dolichoectasis of the large arteries, resulting in microvascular damage.
These may contribute to diffuse cerebrovascular degeneration, altered vascular elasticity, and abnormal hemodynamic stress, which account for the association with cSVD.
The systematic review supports these findings
The researchers also conducted a systematic review. Their findings confirmed that the associations between LAS and latent stroke were inconsistent, whereas cross-sectional studies showed that cSVD and latent stroke were associated with dolichoectasia.
Factors that negate the causative role of LAS in latent stroke include stroke location, which is as likely to be contralateral as ipsilateral to the stenotic artery.
Strengths and limitations
The study is among the first to examine two different large-artery disease processes, LAS and dolichoectasia, within the same well-characterized prospective stroke cohort. Its strengths included its prospective design, standardized data acquisition on a global scale, and blinded assessment.
Despite this, limitations include the use of contrast-enhanced dynamic phase MRI instead of exclusive angiography to evaluate intracranial atherosclerotic stenosis. the inability to detect plaque at the beginning of perforating arteries, which are affected in latent stroke. and inclusion of patients from a single center, limiting generalizability.
conclusions
Taken together, these findings do not support an important causative role for LAS in the pathogenesis of latent stroke. In contrast, dolichoectasia and dilation of intracranial arteries are independently associated with cSVD, particularly latent stroke. This supports the primary contribution of intrinsic microvascular disease rather than large artery embolic disease.
These findings support a non-atherosclerotic, intrinsic microvascular pathology, particularly segmental arterial disorganization, as the primary mechanism of latent stroke and cSVD.
Consequently, the authors suggest that, in addition to secondary prevention targeting atherosclerotic disease of the large cerebral arteries, microvascular function should also be improved to reduce the risk of progressive brain damage due to cSVD. However, because this was an observational study, the findings demonstrate associations rather than definitive proof of causation.
