• George Ntaios and Mayank Dalakoti.
• Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa 41110, Greece. Electronic address: gntaios@med.uth.gr.
• Eur. J. Intern. Med. 2024 Oct 23.

AbstractFor any physician treating a patient with a medical condition of unclear etiology, the differential diagnosis aims to identify the actual most probable cause among various potential etiologies, in order to tailor treatment options. In patients with embolic stroke of undetermined source (ESUS), this can be challenging due to the frequent presence of multiple potential embolic sources, raising difficulties to identify the most likely cause. Additionally, despite targeted preventive measures for the presumed embolic source, patients may remain at risk for stroke and cardiovascular events due to other unrecognized or underestimated pathologies. The multi-level complexity and multimorbidity typically associated with ESUS, represents a challenge that requires broad knowledge of the cardiovascular pathophysiology, deep expertise of the available diagnostic and therapeutic options, and interdisciplinary approach. At the same time, it is an ideal opportunity to assess thoroughly the overall cardiovascular status of the patient, which in turn can allow us to optimize therapeutic and preventive strategies in a holistic approach, and prevent future strokes, cardiovascular events and disability through different parallel pathways. In this context, rather than narrowing our perspective on identifying the specific embolic source presumed to be the most likely cause of ESUS, it is crucial to shift our focus from the disease to the patient, and evaluate the overall cardiovascular profile by assessing the risk of all cardiovascular comorbidities present, no matter if causally associated with ESUS or not. In order to bring across these points and more, this article is centred around a clinical case that serves as a starting point to illustrate the holistic approach to the management of patients with ESUS. After all, this is the beauty, the magic and the art of Internal Medicine: to treat the patient, not the disease, the system or the organ.Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

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