Infarct Recurrence in Intracranial Atherosclerosis: Results from the MyRIAD Study

Abstract

Background: Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke with a high risk of clinical stroke recurrence. Multiple mechanisms may underlie cerebral ischemia in this condition. The study's objective is to discern the mechanisms of recurrent ischemia in ICAD through imaging biomarkers of impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, and artery-to-artery embolism.

Methods: This prospective multicenter observational study enrolled patients with recent (≤21 days) ischemic stroke or transient ischemic attack (TIA) caused by ICAD with 50-99% stenosis treated medically. We obtained baseline quantitative MRA (QMRA), perfusion MRI (PWI), transcranial Doppler vasoreactivity (VMR), and emboli detection studies (EDS). The primary outcome was ischemic stroke in the territory of the stenotic artery within 1 year of follow-up; secondary outcomes were TIA at 1 year and new infarcts in the territory on MRI at 6-8 weeks.

Results: Amongst 102 of 105 participants with clinical follow-up (mean 253±131 days), the primary outcome occurred in 8.8% (12.7/100 patient-years), while 5.9% (8.5/100 patient-years) had a TIA. A new infarct in the territory of the symptomatic artery was noted in 24.7% at 6-8 weeks. A low flow state on QMRA was noted in 25.5%, poor distal perfusion on PWI in 43.5%, impaired vasoreactivity on VMR in 67.5%, and microemboli on EDS in 39.0%. No significant association was identified between these imaging biomarkers and primary or secondary outcomes.

Conclusions: Despite intensive medical management in ICAD, there is a high risk of clinical cerebrovascular events at 1 year and an even higher risk of new imaging-evident infarcts in the subacute period after index stroke. Hemodynamic and plaque instability biomarkers did not identify a higher risk group. Further work is needed to identify mechanisms of ischemic stroke and infarct recurrence and their consequence on long-term physical and cognitive outcomes.

Trial registration: ClinicalTrials.gov: NCT02121028.

Keywords: Biomarkers; Cerebral infarction; Intracranial arterial disease; Stroke.

Conflict of interest statement

Conflicting interests/Disclosures

• JG Romano reports no conflicts of interest.

• I Campo-Bustillo reports no conflicts of interest.

• DS Liebeskind reports no conflicts of interest.

• S Prabhakaran reports no conflicts of interest.

• A Nizam reports no conflicts of interest.

• G Cotsonis reports no conflicts of interest.

• R Sangha reports no conflicts of interest.

• E Feldmann reports no conflicts of interest.

• S Koch reports no conflicts of interest.

• T Rundek reports no conflicts of interest.

• MI Chimowitz reports no conflicts of interest.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Figure 1.

Treatment adherence at baseline, enrollment and during follow-up visits.

Figure 2.

Kaplan-Meier curves for ischemic stroke in the territory showing the cumulative probability of stroke versus follow-up time, stratified by the presence/absence of baseline biomarker abnormality. Log-rank test p-values comparing the strata: 2A (PWI abnormality) p=0.77; 2B (QMRA abnormality) p=0.60; 2C (TCD VMR abnormality) p=0.79; 2D (TCD EDS abnormality) p=0.18.

Figure 3.

Kaplan-Meier curves for ischemic stroke in the territory showing the cumulative probability of stroke versus follow-up time, stratified by the presence/absence of prespecified combination of baseline biomarker abnormalities. Log-rank test p-values comparing the strata: 3A (TCD VMR plus EDS abnormality) p=0.47; 3B (PWI plus QMRA abnormality) p=0.60.