Stroke Mechanisms in Intracranial Atherosclerotic Disease: A Modified Classification System and Clinical Implications

Abstract

Background: In patients with symptomatic intracranial atherosclerotic stenosis (sICAS), recent evidence has suggested an association between artery-to-artery embolism (AAE) and cortical borderzone (CBZ) infarcts.

Methods: We recruited patients with 50-99% anterior-circulation sICAS in this cohort. 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 and CBZ infarcts were both hypoperfusion, which were respectively hypoperfusion and AAE in Classification II. Other classification criteria were the same. We investigated and compared the predictive values of the two systems in predicting 90-day and 1-year recurrent ischemic stroke in the same territory (SIT).

Results: Among 145 patients (median age 62 years), 101 (69.7%) were males. We found significant difference in the proportions of baseline stroke mechanisms between these two systems (p < 0.001). Eleven (7.6%) and 19 (13.1%) patients respectively had 90-day or 1-year recurrent SIT. Classification II better predicted the risk of 90-day recurrent SIT than Classification I, when patients were divided into 4 groups according to baseline stroke mechanisms (p = 0.029), or by the presence of hypoperfusion (p < 0.001). The two classification systems had comparable predictive values for 1-year recurrent SIT.

Conclusions: In medically treated sICAS patients, considering AAE rather than hypoperfusion as the stroke mechanism for CBZ infarcts could better predict early recurrent SITs.

Keywords: Diffusion-weighted imaging; Intracranial atherosclerotic stenosis; Ischemic stroke; Stroke mechanisms; Stroke recurrence.

Fig. 1

Two stroke mechanism classification systems based on infarct topography. Stroke mechanisms are classified as isolated parent artery atherosclerosis occluding penetrating artery (PAO), isolated artery-to-artery embolism (AAE), isolated hypoperfusion and mixed mechanisms, in both Classifications I and II. The difference between the two classification systems is the classification of cortical borderzone infarcts respectively as hypoperfusion and AAE in the two systems, hence the differences in the classifications in cases C&E. A: An isolated subcortical infarct in the penetrating artery territory, classified as isolated PAO in both classification systems. B: Small, multiple cortical infarcts, classified as isolated AAE in both classifications. C: Wedge-shaped infarct in the posterior cortical borderzone, respectively classified as isolated hypoperfusion and isolated AAE in Classification I and Classification II. D: Small chain-like infarcts in the internal borderzone, classified as isolated hypoperfusion in both classification systems. E1&E2: Wedge-shaped infarcts in the anterior and posterior cortical borderzone (E1&E2) and small infarcts in the internal borderzone (E2), respectively classified as isolated hypoperfusion in Classification I and mixed mechanisms of AAE + hypoperfusion in Classification II

Fig. 2

Flow chart of patient screening for this study. sICAS, symptomatic intracranial atherosclerotic stenosis; DWI, diffusion-weighted imaging

Fig. 3

Cumulative probabilities of recurrent ischemic stroke in the same territory (SIT) within 90 days and 1 year by different baseline stroke mechanisms. A&B: In Classification I, cumulative probability of recurrent SIT was higher in patients with artery-to-artery embolism (AAE) + hypoperfusion than those with isolated hypoperfusion or other mechanisms (log-rank p = 0.024) within 1 year, but not in the first 90 days (log-rank p = 0.120). C&D: In Classification II, cumulative risks of recurrent SITs were significantly different by the 4 categories of baseline stroke mechanisms in both 90 days (log-rank p = 0.009) and 1 year (log-rank p = 0.009). E&F: The area under the curve of Classification II was significantly larger than that of Classification I (0.776 vs 0.698, Z = 2.18, p = 0.029), in predicting the risk of 90-day SIT, while the two classifications had comparable AUCs in predicting the 1-year SIT risk (0.731 vs 0.709, Z = 0.57, p = 0.572). PAO, parent artery atherosclerosis occluding penetrating artery

Fig. 4

Cumulative probabilities of recurrent ischemic stroke in the same territory (SIT) within 90 days and 1 year by the presence of hypoperfusion as a baseline stroke mechanism. A&B: In Classification I, patients with hypoperfusion as a baseline stroke mechanism had a significantly higher stroke risk of recurrent SIT in 90 days (11.1% versus 0.0%; log-rank p = 0.020) and 1 year (18.2% versus 2.2%; log-rank p = 0.009). C&D: In Classification II, patients with hypoperfusion had a significantly higher stroke risk in both 90 days (14.8% versus 0.0%; log-rank p = 0.001) and 1 year (21.6% versus 4.2%; log-rank p = 0.002). E&F: The area under curve of Classification II by presence of hypoperfusion was significantly larger than Classification I in predicting the risk of 90-day SIT (0.765 vs 0.672, Z = 5.52, p < 0.001), which were similar for 1-year SIT (0.691 vs 0.652, Z = 0.96, p = 0.335)