Intracranial non-stenosing atherosclerotic plaques assessed with vessel wall MRI in patients with Embolic Stroke of Undetermined Source

Background and Objectives: artery-to-artery embolization from vulnerable intracranial non-stenosing atherosclerotic plaques (vNSPs) has been proposed as a major contributor to Embolic Stroke of Undetermined Source (ESUS). Vessel wall magnetic resonance imaging (VWMRI) offers the potential to identify culprit vNSPs, yet prospective studies in ESUS populations are lacking. This study aimed to assess the role of vNSPs in single-territory ESUS and to evaluate the utility of intracranial VWMRI in the diagnostic workup. Methods: We prospectively evaluated consecutive patients admitted to the IRCCS Mondino Foundation (Pavia, Italy) Stroke Unit between June 1, 2022, and August 31, 2024. Patients were included if they had a confirmed diagnosis of ESUS following a complete etiological workup. Patients with multi-territorial ischemic lesions were excluded. Intracranial VWMRI at 3-Tesla was performed within one month of the index event. Atherosclerotic lesions were considered culprit if demonstrating post-contrast enhancement on T1-weighted images and a location consistent with ischemic lesions’ distribution. Quantitative radiological features of vNSPs were also analyzed. Results: A total of 80 patients [mean age: 65.6 years, 34 (42.5%) females] were included. VWMRI identified a potentially culprit vNSP in 23 of 80 patients (28.8%, 95% CI: 20-39.5). Patients with symptomatic vNSPs were older (72.7 vs 62.8 years, p = 0.002) and more frequently current (43.5 vs 35.1%) or former (30.4 vs 8.8%) smokers (p = 0.014). In a multivariable logistic regression model including major risk factors of intracranial atherosclerosis (age, smoking, hypertension, diabetes, and dyslipidemia), both age (adjusted odds ratio [aOR] 1.12, 95% CI 1.05-1.22, p = 0.002) and smoking status (active smokers: aOR 7.99, 95% CI 1.18-47.8, p = 0.011; former smokers: aOR 8.79, 95% CI 1.73-55.0, p = 0.012) were significantly associated with symptomatic vNSP. Discussion: Intracranial vNSPs may represent a significant underlying cause of single-territory ESUS, and VWMRI could provide an added value in the diagnostic workup of these patients. Older age and smoking exposure were found to be independently associated with the presence of culprit intracranial vNSPs.