Unique Clinicopathologic Subclassifiers of Cryptogenic Cerebral Emboli

James E Siegler; Lauren Thau; Taryn Hester; Terri Yeager; Nicholas Vigilante; Scott Kamen; Mark Heslin; Ryan Shannon; Linda Zhang; Miriam Butler; Christopher Higham; Solomon Oak; Jared Wolfe; Parth Patel; Pratit Patel; Jesse M Thon

doi:10.1016/j.jstrokecerebrovasdis.2022.106427

Unique Clinicopathologic Subclassifiers of Cryptogenic Cerebral Emboli

J Stroke Cerebrovasc Dis. 2022 May;31(5):106427. doi: 10.1016/j.jstrokecerebrovasdis.2022.106427. Epub 2022 Mar 9.

Authors

James E Siegler¹, Lauren Thau², Taryn Hester³, Terri Yeager⁴, Nicholas Vigilante⁵, Scott Kamen⁶, Mark Heslin⁷, Ryan Shannon⁸, Linda Zhang⁹, Miriam Butler¹⁰, Christopher Higham¹¹, Solomon Oak¹², Jared Wolfe¹³, Parth Patel¹⁴, Pratit Patel¹⁵, Jesse M Thon¹⁶

Affiliations

¹ Cooper Neurological Institute, Cooper University Hospital, Camden, NJ, USA. Electronic address: Siegler.james@gmail.com.
² Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: Thaula85@rowan.edu.
³ Cooper Neurological Institute, Cooper University Hospital, Camden, NJ, USA. Electronic address: Hester-taryn@cooperhealth.edu.
⁴ Cooper Neurological Institute, Cooper University Hospital, Camden, NJ, USA. Electronic address: Yeager-terri@cooperhealth.edu.
⁵ Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: Vigila82@rowan.edu.
⁶ Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: Kamens32@rowan.edu.
⁷ Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: Markheslin1@gmail.com.
⁸ Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: Shannon-ryan@cooperhealth.edu.
⁹ Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: Zhangl38@rowan.edu.
¹⁰ Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: Butler19@rowan.edu.
¹¹ Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: Higham37@rowan.edu.
¹² Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: Oaksol97@rowan.edu.
¹³ Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: Wolfej23@rowan.edu.
¹⁴ Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: Patelp92@rowan.edu.
¹⁵ Cooper Neurological Institute, Cooper University Hospital, Camden, NJ, USA. Electronic address: Patel-pratit@cooperhealth.edu.
¹⁶ Cooper Neurological Institute, Cooper University Hospital, Camden, NJ, USA. Electronic address: Thon-jesse@cooperhealth.edu.

PMID: 35279004
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106427

Abstract

Introduction: Ipsilateral nonstenotic (<50%) internal carotid artery (ICA) plaque, cardiac atriopathy, and patent foramen ovale (PFO) may account for a substantial proportion of embolic stroke of undetermined source (ESUS).

Methods: Consecutive stroke patients at our center (2019-2021) with unilateral, anterior circulation ESUS were categorized into the following mutually exclusive etiologies: (1) nonstenotic ipsilateral ICA plaque (NSP, ≥3mm in maximal axial diameter), (2) sex-adjusted mod-to-severe left atrial enlargement (LAE), (3) PFO, and (4) "occult ESUS" (patients who failed to meet criteria for these 3 groups). Descriptive statistics and multivariable logistic regression were used to model group characteristics.

Results: Of 132 included patients, the median age was 65 (IQR 56-73), 74 (56%) of whom were White, and 54 (41%) were female. Twenty-one patients (16%) had NSP proximal to the infarct territory, 17 (13%) had LAE, 9 (7%) had a PFO, and 85 (64%) had no other mechanism. Patients with LAE were older (p=0.004), and had more frequent intracranial occlusions of the internal carotid and proximal middle cerebral artery (p=0.048), while tobacco use was most commonly found among patients with NSP (75%) when compared to other ESUS groups (p=0.02). Five of 9 patients with LAE who underwent outpatient telemetry had paroxysmal atrial fibrillation (56%), while zero patients with PFO or NSP had paroxysmal atrial fibrillation (p=0.005). Older age (adjusted OR [aOR] 1.05, 95%CI 1.03-1.07), coronary artery disease (aOR 3.22, 95%CI 1.61-6.44) and hypertension (aOR 2.16, 95%CI 1.14-4.06) were independently associated with LAE, while only tobacco use was associated with NSP when compared to other ESUS subclassifiers (OR 3.18, 95%CI 1.08-0.42). Age and tobacco use were both inversely associated with PFO (aOR 0.93, 95%CI 0.88-0.98, and aOR 0.10, 95%CI 0.02-0.90, respectively).

Conclusions: Certain clinical and radiographic features may be useful in predicting the proximal source of occult cerebral emboli, and can be used for cost-effective outpatient diagnostic testing.

Keywords: atherosclerosis; cryptogenic stroke; embolic stroke of undetermined source; paroxysmal atrial fibrillation; patent foramen ovale; plaque.

MeSH terms

Aged
Atrial Fibrillation* / complications
Embolic Stroke*
Female
Foramen Ovale, Patent* / complications
Foramen Ovale, Patent* / diagnostic imaging
Humans
Intracranial Embolism* / complications
Intracranial Embolism* / etiology
Male
Plaque, Atherosclerotic* / complications
Risk Factors
Stroke* / diagnosis