Association of Clinical, Imaging, and Thrombus Characteristics With Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic Stroke

Abstract

Importance: Recanalization of intracranial thrombus is associated with improved clinical outcome in patients with acute ischemic stroke. The association of intravenous alteplase treatment and thrombus characteristics with recanalization over time is important for stroke triage and future trial design.

Objective: To examine recanalization over time across a range of intracranial thrombus occlusion sites and clinical and imaging characteristics in patients with ischemic stroke treated with intravenous alteplase or not treated with alteplase.

Design, setting, and participants: Multicenter prospective cohort study of 575 patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and Turkey) with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA).

Exposures: Demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics (location and permeability) defined on CTA.

Main outcomes and measures: Recanalization on repeat CTA or on first angiographic acquisition of affected intracranial circulation obtained within 6 hours of baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores from 0 [primary occlusive lesion remains the same] to 3 [complete revascularization of primary occlusion]).

Results: Among 575 patients (median age, 72 years [IQR, 63-80]; 51.5% men; median time from patient last known well to baseline CTA of 114 minutes [IQR, 74-180]), 275 patients (47.8%) received intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone, and 57 (9.9%) received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes (IQR, 79-268); median time from intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR, 62-238). Successful recanalization occurred at an unadjusted rate of 27.3% (157/575) overall, including in 30.4% (143/470) of patients who received intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% [95% CI, 10.2%-25.8%]). Among patients receiving alteplase, the following factors were associated with recanalization: time from treatment start to recanalization assessment (OR, 1.28 for every 30-minute increase in time [95% CI, 1.18-1.38]), more distal thrombus location, eg, distal M1 middle cerebral artery (39/84 [46.4%]) vs internal carotid artery (10/92 [10.9%]) (OR, 5.61 [95% CI, 2.38-13.26]), and higher residual flow (thrombus permeability) grade, eg, hairline streak (30/45 [66.7%]) vs none (91/377 [24.1%]) (OR, 7.03 [95% CI, 3.32-14.87]).

Conclusions and relevance: In patients with acute ischemic stroke, more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanalization of arterial occlusion after administration of intravenous alteplase; among patients who did not receive alteplase, rates of arterial recanalization were low. These findings may help inform treatment and triage decisions in patients with acute ischemic stroke.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Coutts reported that Boehringer Ingelheim reimburses sites for the study drug provided in her TEMPO-2 clinical trial. Dr Demchuk reported receiving honoraria for CME events from Medtronic. Dr Goyal reported that funding for the HERMES collaboration was provided by Medtronic as an unrestricted research grant to the University of Calgary; reported receiving consulting fees from Medtronic, Stryker, and Microvention; and reported holding a patent on a system of acute stroke diagnosis licensed to GE Healthcare. Dr Hill reported receiving payment for serving as a stroke outcome event adjudicator for a panel of clinical trials by Merck; receiving study drug as in-kind support for the TEMPO-1 trial from Hoffmann-La Roche Canada Ltd; grants to his institution (University of Calgary) for clinical trials from Covidien (Medtronic), Boehringer Ingelheim, Stryker, and Medtronic; reported holding a patent on a system and method for assisting in decision making and triaging for acute stroke patients (US patent 62/086,077); reported owning stock in Calgary Scientific Incorporated, a company that focuses on medical imaging software; is a director of the Canadian Federation of Neurological Sciences, a not-for-profit group; and has received grant support from Alberta Innovates Health Solutions, CIHR, Heart & Stroke Foundation of Canada, and the National Institutes of Neurological Disorders and Stroke. Dr Menon reported holding a patent on a system and method for assisting in decision making and triaging for acute stroke patients. Dr Poppe reported receiving honoraria for speaking from Medtronic and serving on the advisory board for Bayer and Bristol-Myers Squibb/Pfizer. No other disclosures were reported.

Figures

Figure 1.. The Clot Burden Score and Residual Blood Flow in the Assessment of Recanalization in Acute Ischemic Stroke

A, Computation of the clot burden score, which measures the extent of intracranial thrombus burden in patients with anterior circulation acute ischemic stroke. A score of 0 implies complete occlusion of the ipsilateral anterior circulation vessels; a score of 10 implies no occlusion. The numbers in the figure indicate points assigned to each segment when computing the score. The colors are only to differentiate arterial segments. Two points are subtracted for thrombus found on computed tomographic angiography (CTA) in the supraclinoid internal carotid artery segment and each of the proximal and distal halves of the M1 segment of MCA. One point is subtracted for thrombus seen in the infra-clinoid ICA and A1 segment of ACA and for each affected M2 branch of the middle cerebral artery (MCA). B-D, Residual flow grade on CTA, a measure of permeability of intracranial thrombus: grade 0 on axial CTA (yellow arrowheads, proximal M1 segment MCA density similar to surrounding brain parenchyma), residual flow grade 1 on axial CTA (yellow arrowheads, distal M1 segment MCA denser than surrounding brain parenchyma), and residual flow grade 2 on coronal CTA (yellow arrowheads, tiny hairline lumen or streak of well-defined contrast within the distal M1 segment MCA thrombus).

Figure 2.. Estimated Successful Recanalization From the Start of Intravenous Alteplase to Recanalization Assessment Stratified by Residual Flow (n = 470 Patients)

Results are derived from the logistic regression model reported in Table 2 with residual flow categorized as yes (grade 1 and 2; n = 93) vs no (grade 0; n = 377). The shaded areas indicate 95% CIs. Recanalization of intracranial thrombus with intravenous alteplase was assessed using the revised arterial occlusive lesion (rAOL) score on repeat computed tomographic angiography (CTA) of the head or on first angiographic acquisition of the affected intracranial circulation. Successful recanalization was defined as an rAOL score of 2b or 3. The rAOL score is described in detail in the Methods section and in eTable 1 in the Supplement.

Figure 3.. Estimated Recanalization From the Start of Intravenous Alteplase to Recanalization Assessment Stratified by Residual Flow and by Location of Intracranial Thrombus

Results are derived from individual logistic regression models, each derived from data for that site of intracranial occlusion. The shaded areas indicate 95% CIs. Residual flow is categorized as yes (grade 1 and 2) vs no (grade 0). The numbers of patients are as follows: internal carotid artery, total n = 92; proximal M1 middle cerebral artery (MCA), total n = 111 (residual flow yes = 28, no = 83); distal M1 MCA total n = 84 (residual flow yes = 29, no = 55); and M2 MCA total n = 143 (residual flow yes = 22, no = 121). Presence or absence of residual flow was not associated with recanalization prevalence in patients with intracranial internal carotid artery segment occlusion. Graphs for distal locations (M3 MCA, anterior cerebral artery, and posterior cerebral artery) are not shown because neither residual flow nor time from the start of alteplase to recanalization assessment was significantly associated with recanalization prevalence in that statistical model. Statistical models for each individual site of occlusion are in the Supplement.