Symptomatic Non-stenotic Carotid Disease in Embolic Stroke of Undetermined Source : Analysis of the ESCAPE-NA1 Trial

Martha Marko; Nishita Singh; Johanna M Ospel; Kazutaka Uchida; Mohammed A Almekhlafi; Andrew M Demchuk; Raul G Nogueira; Ryan A McTaggart; Alexandre Y Poppe; Jeremy L Rempel; Michael Tymianski; Michael D Hill; Mayank Goyal; Bijoy K Menon; ESCAPE-NA1 Investigators

doi:10.1007/s00062-023-01365-0

Symptomatic Non-stenotic Carotid Disease in Embolic Stroke of Undetermined Source : Analysis of the ESCAPE-NA1 Trial

Clin Neuroradiol. 2023 Dec 18. doi: 10.1007/s00062-023-01365-0. Online ahead of print.

Authors

Martha Marko¹, Nishita Singh², Johanna M Ospel^{2

3}, Kazutaka Uchida⁴, Mohammed A Almekhlafi^{2

3

5

6}, Andrew M Demchuk^{2

3

5}, Raul G Nogueira⁷, Ryan A McTaggart⁸, Alexandre Y Poppe⁹, Jeremy L Rempel¹⁰, Michael Tymianski¹¹, Michael D Hill^{2

3

5

6

12}, Mayank Goyal^{2

3}, Bijoy K Menon^{2

3

5

6}; ESCAPE-NA1 Investigators

Affiliations

¹ Department of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. martha.marko@meduniwien.ac.at.
² Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
³ Department of Diagnostic Imaging, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁴ Department of Neurosurgery, Hyogo Medical University, Nishinomiya, Japan.
⁵ Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁶ Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁷ Emory University School of Medicine, Grady Memorial Hospital, Atlanta, USA.
⁸ Warren Alpert School of Medicine, Brown University, Providence, RI, USA.
⁹ Department of Medicine (Neurology), Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
¹⁰ University of Alberta Hospital, Edmonton, AB, Canada.
¹¹ NoNO, Toronto, ON, Canada.
¹² Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada.

PMID: 38108829
DOI: 10.1007/s00062-023-01365-0

Abstract

Purpose: Non-stenotic (< 50%) carotid disease may play an important etiological role in ischemic stroke classified as embolic stroke of undetermined source (ESUS). We aimed to assess the prevalence of non-stenotic carotid disease and its association with ipsilateral ischemic stroke.

Methods: Data are from ESCAPE-NA1, a randomized controlled trial investigating the neuroprotectant nerinetide in patients with acute ischemic stroke and large vessel occlusion (LVO). The degree of stenosis of the extracranial internal carotid artery (ICA) and high-risk plaque features were assessed on baseline computed tomography (CT) angiography. We evaluated the association of non-stenotic carotid disease and ipsilateral stroke by age-adjusted and sex-adjusted logistic regression and calculated the attributable risk of ipsilateral stroke caused by non-stenotic carotid disease.

Results: After excluding patients with non-assessable imaging, symptomatic > 50% carotid stenosis and extracranial dissection, 799/1105 (72.1%) patients enrolled in ESCAPE-NA1 remained for this analysis. Of these, 127 (15.9%) were classified as ESUS. Non-stenotic carotid disease occurred in 34/127 ESUS patients (26.8%) and was associated with the presence of ipsilateral ischemic stroke (odds ratio, OR 1.6, 95% confidence interval, CI 1.0-2.6, p = 0.049). The risk of ipsilateral ischemic stroke attributable to non-stenotic carotid disease in ESUS was estimated to be 19.7% (95% CI -5.7% to 39%), the population attributable risk was calculated as 4.3%. Imaging features such as plaque thickness, plaque irregularity or plaque ulceration were not different between non-stenotic carotids with vs. without ipsilateral stroke.

Conclusion: Non-stenotic carotid disease frequently occurs in patients classified as ESUS and is associated with ipsilateral ischemic stroke. Our findings support the role of non-stenotic carotid disease as stroke etiology in ESUS, but further prospective research is needed to prove a causal relationship.

Keywords: Atherosclerotic plaque; Carotid stenosis; Computed tomography angiography; Ischemic stroke; Stroke etiology.