Abstract

Introduction: Intracranial atherosclerotic disease (ICAD) remains a major source of stroke worldwide, with high recurrence risk. Prior evaluation of posterior circulation ICAD patients enrolled in the prospective VERiTAS and MYRIAD studies revealed regional hypoperfusion, assessed by large vessel flow measurements using quantitative MRA (QMRA), predicts subsequent vertebrobasilar stroke risk. We examined whether a similar approach to regional flow assessment using QMRA predicted stroke risk in anterior circulation ICAD patients enrolled in MYRIAD. Methods: MYRIAD enrolled patients with recent TIA or stroke attributable to 50-99% stenosis of proximal intracranial artery; the primary outcome was ischemic stroke in the territory of the stenotic artery with 1 year of follow-up. Secondary outcomes included new in-territory infarcts on MRI at 6-8 weeks. Flow was measured in the major intracranial arteries at baseline using QMRA. We designated patients as low- or normal-flow status based on an algorithm assessing distal flow and collateral capacity using age-normalized MCA and hemispheric (aggregate of ipsilateral ACA, MCA, and PCA) flows. Different thresholds for flow status categorization were tested to determine the optimal algorithm for stroke risk prediction. Results: Of 73 enrolled subjects with symptomatic anterior circulation ICAD, 7 (9.6%) patients had recurrent stroke. Z-score thresholds for age-normalized flow ranging from -0.5 to -1.5 were examined. The optimal thresholds identified were as follows: -1 for the MCA and -0.75 for hemispheric flow. 24 (33%) patients were categorized as low-flow status based on these thresholds; recurrent stroke occurred in 21% of low-flow patients vs. 4% of normal-flow patients (OR 6.2 (95% CI 1.1-34.7, p=0.04). However, flow status was not predictive of recurrent infarct on imaging among 61 patients with 6-8 week MRI (32% in low-flow vs. 26% in normal-flow patients). Conclusions: Similar to the predictive value in the posterior circulation, distal flow status assessed through QMRA regional flow measurement appears to be predictive for recurrent clinical (but not imaging-based) stroke. Identification of high-risk patients has implications for future investigation of therapeutic interventions.

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