Ultrasound and Clinical Predictors of Recurrent Ischemia in Symptomatic Internal Carotid Artery Occlusion
Background and Purpose—Occlusion of the internal carotid artery puts patients at risk of recurrent ischemic events because of hemodynamic compromise. Our goal was to characterize clinical and duplex parameters indicating patients at risk of recurrent ischemia.
Methods—We retrospectively identified patients with symptomatic internal carotid artery occlusion. Clinical characteristics and ultrasound parameters, including collateral networks, were analyzed. Predictors for recurrent ipsilateral ischemia were investigated by Cox regression analysis.
Results—Of 68 patients, at least 1 recurrent ischemic event within the same vascular territory was observed in 14 patients (20.6%) within 2 to 92 days (median, 29.5 days). The median follow-up period was 6 months. Diabetes mellitus and previous transient ischemic attack were associated with recurrence, as was activation of the maximum number of collateral pathways on transcranial ultrasound (28.6% versus 5.6%; P=0.03). Furthermore, flow in the posterior cerebral arteries was higher in patients with recurrence in ipsilateral and contralateral posterior cerebral artery P2 segments (76 IQR 37.5 versus 59, IQR 22.5 cm/s and 68, IQR 35.6 versus 52, IQR 21 cm/s; P<0.01 and 0.02).
Conclusions—Flow increases in both posterior cerebral artery P2 segments suggest intensified compensatory efforts when other collaterals are insufficient. Together with the presence of diabetes mellitus and a history of transient ischemic attack, this duplex parameter indicates that patients with internal carotid artery are at particular risk of recurrent ischemia.
Patients with symptomatic internal carotid artery occlusion (ICAO) are at an increased risk of recurrent stroke, which has been estimated to be between 5.5% and 10% per year.1–5 The risk is likely increased if collateral supply is insufficient resulting in hemodynamic compromise.6–8 Collateral pathways activated in response to ICAO have been categorized as either primary or secondary. Primary collateral pathways involve the circle of Willis, either through cross flow from the anterior communicating artery or the posterior communicating artery. Reversed flow through the ophthalmic artery and enhanced flow within leptomeningeal collaterals are considered secondary collateral pathways.9 Secondary collaterals may have a limited capacity, and activation of secondary collaterals has been linked to impaired cerebral vasoreactivity.10,11 However, there are studies suggesting that the type of collateral network does not affect cerebrovascular reserve but that the activation of more collateral pathways indicates a higher risk of stroke recurrence in ICAO.12,13 This study aimed to define clinical and ultrasound predictors for recurrent ipsilateral ischemia or early vascular death in patients with symptomatic ICAO.
Study Design and Cohort Description
In this retrospective analysis, patients with symptomatic proximal ICAO treated at the University Hospital Zurich Department of Neurology between 2009 and 2014 were included if they had received an extracranial and intracranial duplex investigation at our site within 30 days and a clinical follow-up of at least 1 month (Methods in the online-only Data Supplement). Patient demographics, stroke severity on the National Institute of Health Stroke Scale, and medical history before stroke were obtained.
Analyses were performed using nonparametric and semiparametric methods. Group comparisons were performed using Fisher exact test (categorical measurements) and 2-tailed Mann–Whitney U test (continuous measurements) both yielding conservative P values by ignoring the censoring. Predictors for recurrent ischemia were investigated using a univariate Cox regression model. Multiple testing corrections were omitted.
Sixty-eight patients with symptomatic ICAO were included in this study (Table). At least 1 recurrent ischemic event within the same vascular territory was observed in 14 patients (20.6%) at a median time of 29.5 days (interquartile range, 8–89) during the median follow-up of 6 months (interquartile range, 4–24). In the group with an observed recurrent ischemic event, there were significantly more patients with diabetes mellitus and previous transient ischemic attack, as well as statin and antiplatelet use in their medical history. First duplex ultrasound was performed within a median time of 1 day (interquartile range, 0.25–3) after the ischemic event (Figure). In patients with a recurrent event, activation of all 4 collateral pathways (anterior communicating artery, posterior communicating artery, leptomeningeal collaterals, and ophthalmic artery) was more frequently detected by transcranial Doppler ultrasound, but the type of pathway (type I or II) was not different between groups. Higher flow values within both posterior cerebral artery P2 segments were observed in patients with recurrence (Figure I and Tables I and II in the online-only Data Supplement).
According to univariate Cox regression analysis (Table III the online-only Data Supplement), diabetes mellitus and previous transient ischemic attack with the use of platelet inhibitors or statins, as well as the presence of 4 activated collateral pathways, were univariately associated with a recurrent ischemic event. Flow in the posterior cerebral arteries was higher in patients who experienced a recurrent event. All other investigated duplex parameters were not significantly different between patient groups.
Our data indicate that after symptomatic ICAO, the risk of a recurrent ipsilateral ischemic event is high, particularly in the early phase. We found that the activation of all 4 transcranial Doppler ultrasound–assessable collateral systems (anterior communicating artery, ophthalmic artery, posterior communicating artery, and leptomeningeal collateral) and increased flow in both posterior cerebral artery P2 segments were more common in patients with a recurrent event. This suggests that recruitment of more collateral systems, particularly the vertebrobasilar vessels, implies impaired collateral capacity. Middle cerebral arterial flow velocities were not predictive of ischemia recurrence.14
Previous transient ischemic attack and diabetes mellitus are clinical parameters associated with an increased risk of recurrence after symptomatic ICAO. The presence of 4 activated collateral systems in transcranial ultrasound and increased flow in the posterior cerebral artery-P2 segments are further indicators of hemodynamic failure and the risk of ischemia recurrence. Prospective validation in larger patient groups is needed. However, transcranial Doppler ultrasound has the potential to strengthen clinical prediction algorithms because of its unique capability to assess collateral flow pathways.
Sources of Funding
This work was supported by the Swiss National Science Foundation Marie Heim-Vögtlin program and the P&K Pühringer Foundation.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.115.011269/-/DC1.
- Received August 21, 2015.
- Revision received August 21, 2015.
- Accepted August 24, 2015.
- © 2015 American Heart Association, Inc.
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