Recurrent stroke risk in intracranial atherosclerotic disease

Abstract

Recurrent stroke risk secondary to intracranial atherosclerotic disease remains high despite aggressive medical treatment. This risk is further amplified in subgroups possessing biomarkers of hemodynamic insufficiency and potential for embolization, which have been shown to be independently and synergistically predictive of recurrent stroke. Luminal stenosis was predominantly used as entry criteria in major treatment trials, discounting the potential role of hemodynamics from primary analyses, limiting the strength of evidence and conclusions of these biomarkers to post-hoc analyses and other natural history studies. Future treatment trials should consider stratifying patients using a combination of these high-risk biomarkers. In the absence of trials, risk stratifying patients based on the presence of these markers may lend to more individualized clinical decisions. We aimed to summarize the studies that have investigated the relationship between biomarkers and their role in predicting recurrent stroke risk in intracranial atherosclerotic disease.

Association Between the Degree of Vertebrobasilar Stenosis, Location, Infarction Pattern and QMRA Flow State

“…[2][3][4][5] Recurrent stroke rates, however, remain high, and likely substantially higher in patients with markers of hemodynamic insufficiency. 7,13,[19][20][21] Furthermore, there appears to be a positive relationship between hemodynamic markers in predicting recurrent stroke risk, 19 as the presence of multiple imperfect markers likely increases the probability of a hemodynamically compromised state. This is likely due to the inherent limitations of our current imaging (QMRA, perfusion studies, infarction patterns), since none of these unimodal imaging modalities fully reflect the complex hemodynamic environment surrounding atherosclerotic lesions as each imaging modality likely depicts a piece of the complicated hemodynamic picture.…”

“…Intracranial atherosclerotic disease is the leading cause of stroke worldwide 1 with high recurrent stroke rates despite aggressive medical therapies. [2][3][4][5] Challenges in stroke prevention have been attributed to the heterogeneity of disease 6,7 as multiple interrelated stroke mechanisms exist, such as thromboembolism, hypoperfusion, and branch atheromatous disease. [8][9][10] Despite the complexity of stroke mechanisms, randomized treatment trials have focused primarily on luminal stenosis as entry criteria, [2][3][4][5] discounting the potential role of hemodynamics, plaque morphology, and potential for embolization.…”

“…[8][9][10] Despite the complexity of stroke mechanisms, randomized treatment trials have focused primarily on luminal stenosis as entry criteria, [2][3][4][5] discounting the potential role of hemodynamics, plaque morphology, and potential for embolization. Although luminal stenosis correlates strongly with single-vessel hemodynamics 11,12 and recurrent stroke risk, 7 its influence on regional and downstream blood flow is greatly influenced by collateral status and anatomical variability. Attempts to account for these differences in the posterior circulation have been introduced by VERiTAS investigators by devising an algorithm focused on distal-flow status measured on quantitative magnetic resonance angiography (QMRA), derived from flow in the basilar and both non-fetal posterior cerebral arteries.…”

The Role of High-Resolution Magnetic Resonance Imaging in Cerebrovascular Disease: A Narrative Review

“…Previous studies on carotid plaques showed that the hyperintensity of the T1WI often represented IPH or lipid nucleation, which increased the risk of plaque rupture and the occurrence of arterial embolism resulting in stroke recurrence. Plaque enhancement is a reliable imaging biomarker [ 3 , 44 ]. The degree of plaque enhancement may reflect the level of inflammatory activity caused by increased endothelial permeability and new blood vessels [ 46 ].…”

“…The degree of luminal stenosis in the head and carotid arteries has been considered the traditional measure of the severity of atherosclerotic disease. However, recent evidence has shown that this criterion alone may not accurately assess the risk of adverse events associated with vulnerable plaques [ 3 ]. Therefore, component analysis of atherosclerosis has been utilized to evaluate the extent and mechanism of stenosis and predict the recurrence of ischemic events such as stroke and transient ischemic attack.…”