Clinical phenotypes of embolic strokes of undetermined source
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Clinical phenotypes of embolic strokes of undetermined source Simona Lattanzi 1 & Claudia Rinaldi 1 & Alessandra Pulcini 1 & Tommaso Corradetti 1 & Stefania Angelocola 1 & Maria Luisa Zedde 2 & Giuseppe Ciliberti 3 & Mauro Silvestrini 1 Received: 21 May 2020 / Accepted: 28 August 2020 # Fondazione Società Italiana di Neurologia 2020
Abstract Background and purpose The embolic stroke of undetermined source (ESUS) represents a heterogeneous clinical entity. The aim of this study was to investigate whether distinct clinical phenotypes may be identified in the ESUS population. Methods We retrospectively identified consecutive patients hospitalized for acute ischemic stroke who met the ESUS diagnostic criteria. Baseline characteristics and diagnostic workup findings were collected. Hierarchical cluster analysis was carried out to classify clinical features and identify different groups of ESUS patients. Results One hundred twenty-seven patients with a mean age of 68.6 (12.5) years were included. Three main clusters were identified. The first cluster associated young age, male sex, presence of patent foramen ovale, and posterior circulation infarct. The second phenotype linked hypertension, severe stroke, left atrial cardiopathy, diabetes mellitus, and involvement of multiple vascular territories. The third cluster gathered smoking, dyslipidemia, ipsilateral vulnerable sub-stenotic carotid plaque, and infarct of anterior vascular territory. Conclusions Distinct clinical phenotypes have been identified within the ESUS population, which may supply clues to the underlying pathogenic mechanisms. Keywords Embolic stroke of undetermined source . Cerebrovascular disease . Stroke . Cerebral ischemia
Introduction
Materials and methods
The term “embolic stroke of undetermined source” (ESUS) identifies non-lacunar stroke whose mechanism is likely to be embolic and the source remains unidentified [1]. Far from being a homogeneous entity, patients with ESUS show considerable variability in clinical presentation and etiology. We aimed to investigate the relationships between clinical features and explore whether distinct phenotypes may be identified in the ESUS population.
Participants Consecutive acute ischemic stroke patients hospitalized at the Stroke Unit of the Marche Polytechnic University, Ancona, Italy (January 2016 to December 2018), who met the ESUS diagnostic criteria, were retrospectively identified [1]. Briefly, ESUS was a brain infarct visualized by brain CT or MRI that is not lacunar, in the absence of (a) extracranial or intracranial atherosclerosis causing ≥ 50% luminal stenosis in arteries supplying the area of ischemia, (b) major-risk cardioembolic source, and (c) any other identified specific cause of stroke [1]. The assessment required for the ESUS diagnosis included brain CT or MRI, 12-lead ECG, cardiac monitoring for ≥ 24 h with automated rhythm detection, precordial echocardiography, and imaging of the extra- and intracranial arteries [1]. Two authors independently assessed patients fo
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