Primary stroke mechanism identification helps predict recurrent stroke risk

In medically treated symptomatic intracranial atherosclerotic stenosis (sICAS) patients, considering artery-to-artery embolism (AAE) rather than hypoperfusion as the stroke mechanism for cortical borderzone (CBZ) infarcts could better predict early recurrent stroke in the same territory (SIT), a study by the Chinese University of Hong Kong (CUHK) has found.

The study, a substudy of the prospective, longitudinal Stroke Risk and Hemodynamics in Intracranial Atherosclerotic Disease (SOpHIA) cohort study, recruited 145 patients (median age, 61 years; males, 69.7 percent) with 50–99 percent anterior-circulation sICAS from the main cohort. Subjects of the studies, who were on guideline-directed medical therapy including antiplatelet agents, statins and vascular risk management, were enrolled from the Prince of Wales Hospital in Hong Kong and the First Affiliated Hospital of Zhengzhou University in China. Predictive values of two stroke mechanism classification systems for 90-day and 1-year recurrent SIT were investigated and compared. [Transl Stroke Res 2025; https://doi.org/10.1007/s12975-025-01338-0]

Stroke mechanisms were categorized as isolated parent artery atherosclerosis occluding penetrating artery (PAO), isolated AAE, isolated hypoperfusion, and mixed mechanisms, using two classification systems. In Classification I, the probable stroke mechanisms of internal borderzone (IBZ) and CBZ infarcts were both hypoperfusion. These were hypoperfusion and AAE, respectively, in Classification II (Classification I modified based on the authors’ previous study, to more accurately stratify recurrent stroke risks by stroke mechanism). Other classification criteria were the same. [Stroke 2019;50:2692-2699]

 “The modified system [Classification II] did exhibit higher predictive values for short-term [3-month] recurrent SITs than the previous version [Classification I], while the two systems had comparable predictive values for long-term [1-year] recurrent SITs,” the authors reported. “Since most recurrent strokes in sICAS patients occur in the first few weeks or months after the index stroke, Classification II may yield higher values in identifying high-risk patients and informing early interventions.”

“However, regardless of classification methods, identifying the stroke mechanisms in sICAS is crucial, as different mechanisms are associated with different stroke risks,” they emphasized.

The authors postulated that the different predictive values of the two classification systems for 3-month SITs may be explained in part by the different trajectories of stroke recurrence in sICAS patients with true “hypoperfusion” and “AAE” while on medical treatment. Those with true “hypoperfusion” at baseline might be more prone to recurrent SIT early after an index stroke, if no interventional or medical treatment was given to restore or improve cerebral perfusion. In particular, blood pressure control, usually initiated within a few days after an index stroke, may further impair cerebral perfusion in such patients and increase stroke risk in the first few months. On the other hand, short-term (up to 90 days) dual antiplatelet therapy in some patients and high-intensity statin therapy in all patients without contraindications may effectively prevent SITs in sICAS patients with true “AAE” as a stroke mechanism, particularly within the first few months when medication compliance is usually better than later.

“This study provided a probably more reasonable stroke mechanism classification system [Classification II] for more accurate stroke risk stratification in sICAS patients than previous classification systems. With further validation of this classification system, studies are warranted to test for more effective secondary stroke prevention strategies [depending on stroke mechanism] for sICAS patients,” the authors concluded.