Embolic stroke of undetermined source (ESUS) is an embolic stroke, a type of

ischemic stroke Stroke is a medical condition in which poor blood flow to a part of the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop ...

, with an unknown origin, defined as a non- lacunar brain infarct without proximal

arterial An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...

stenosis Stenosis () is the abnormal narrowing of a blood vessel or other tubular organ or structure such as foramina and canals. It is also sometimes called a stricture (as in urethral stricture). ''Stricture'' as a term is usually used when narrowing ...

or cardioembolic sources. As such, it forms a subset of cryptogenic stroke, which is part of the TOAST-classification. The following diagnostic criteria define an ESUS: * Stroke detected by CT or

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...

that is not lacunar * No major-risk cardioembolic source of

embolism An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (air embolism, gas embolism), amniotic ...

* Absence of extracranial or intracranial

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

causing 50% luminal stenosis in arteries supplying the area of

ischaemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...

* No other specific cause of stroke identified (e.g., arteritis,

dissection Dissection (from Latin ' "to cut to pieces"; also called anatomization) is the dismembering of the body of a deceased animal or plant to study its anatomical structure. Autopsy is used in pathology and forensic medicine to determine the cause of ...

migraine Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...

vasospasm Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia (insufficient blood flow) and tissue death (necrosis). Along with physical resistance, vasospasm is a main cause of ischemi ...

, drug misuse)

Signs and symptoms

Causes

The following factors are suggested as

pathogenesis In pathology, pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes . Descript ...

of ESUS: *

Subclinical Asymptomatic (or clinically silent) is an adjective categorising the medical conditions (i.e., injuries or diseases) that patients carry but without experiencing their symptoms, despite an explicit diagnosis (e.g., a positive medical test). P ...

atrial fibrillation Atrial fibrillation (AF, AFib or A-fib) is an Heart arrhythmia, abnormal heart rhythm (arrhythmia) characterized by fibrillation, rapid and irregular beating of the Atrium (heart), atrial chambers of the heart. It often begins as short periods ...

: Detectable in ~2.7-30% of ESUS patients, depending on duration and modality of ECG monitoring. * Patent foramen ovale (PFO):

Deep vein thrombosis Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enl ...

may result in paradoxical embolism in patients with PFO. About 40% of patients with cryptogenic stroke have PFO compared with 25% of the general population. However, the actual embolic source can often not be identified. * Non-stenotic arterial plaques: Complicated plaques with signs indicative of intra-plaque haemorrhage in an

ipsilateral Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...

carotid artery Carotid artery may refer to: * Common carotid artery, often "carotids" or "carotid", an artery on each side of the neck which divides into the external carotid artery and internal carotid artery * External carotid artery, an artery on each side of ...

are detected in 1 in 4 of patients with cryptogenic stroke. Aortic arch atherosclerosis is believed to be a specific cause of ESUS, particularly with plaques >4 mm diameter. * Further cardiopathies: the risk of ischaemic stroke is increased by

supraventricular tachycardia Supraventricular tachycardia (SVT) is an umbrella term for fast heart rhythms arising from the upper part of the heart. This is in contrast to the other group of fast heart rhythms – ventricular tachycardia, which start within the lower cham ...

s. This also applies to patients with elevated NT-proBNP levels and patients with atrial enlargement in cardiac ultrasound. * Other causes: Arterial dissections,

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

-related vasculopathies (esp.

Varicella zoster virus Varicella zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting children and young adults, and shingles (herpes zos ...

thrombophilia Thrombophilia (sometimes called hypercoagulability or a prothrombotic state) is an abnormality of blood coagulation that increases the risk of thrombosis (blood clots in blood vessels). Such abnormalities can be identified in 50% of people who ...

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

-related thrombosis, migraine, Fabry disease and other genetic,

autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease" ...

rheumatic Rheumatology () is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatology covers more than 100 different complex diseases, c ...

causes.

Diagnosis

ESUS is a

diagnosis of exclusion A diagnosis of exclusion or by exclusion (''per exclusionem'') is a diagnosis of a medical condition reached by a process of elimination, which may be necessary if presence cannot be established with complete confidence from history, examination o ...

based on

radiological In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or a material medium. This includes: * ''electromagnetic radiation'' consisting of photons, such as radio waves, microwaves, infr ...

and cardiological examinations. For exclusion of haemorrhagic or lacunar strokes CT or MRI imaging is needed. Both procedures also allow detection of embolic pattern of ischemic lesions. 12-lead ECG and cardiac monitoring for at least 24 h with automated rhythm detection are mandated to exclude atrial fibrillation; echocardiography (TTE and/or TEE) is used to detect other major-risk cardioembolic sources (e.g., intracardiac thrombi, or

ejection fraction An ejection fraction (EF) is the volumetric fraction (or portion of the total) of fluid (usually blood) ejected from a chamber (usually the heart) with each contraction (or heartbeat). It can refer to the cardiac atrium, cardiac ventricle, gall ...

<30%). For imaging of both the extracranial and intracranial arteries supplying the area of brain ischaemia, examination methods like

catheter In medicine, a catheter ( ) is a thin tubing (material), tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. ...

, MR/CT angiography or cervical duplex plus transcranial

Doppler ultrasonography Doppler ultrasonography is medical ultrasonography that employs the Doppler effect to perform imaging of the movement of tissues and body fluids (usually blood), and their relative velocity to the probe. By calculating the frequency shift of a ...

are required. They allow an exclusion of large vessel stenosis (≥ 50%).

Cryptogenic stroke vs ESUS

Cryptogenic stroke is also an ischemic stroke with more than one probable cause or strokes with incomplete diagnostic workup. ESUS has a clearer definition, with an established minimum diagnostic requirements; this is not required in defining a cryptogenic stroke. ESUS is an embolic stroke for which no probable cause can be identified after a standard diagnostic evaluation.

Management

Due to the lack of data, there are no specific treatment guidelines for ESUS. Current guidelines recommend antiplatelet therapy for patients with non-cardioembolic ischemic stroke. However, it is widely believed that there is a substantial overlap between ESUS and cardioembolic stroke, clinical trials have assessed the benefit of

anticoagulation An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which h ...

versus antiplatelet agents for preventing recurrent stroke. Although the existing data does not favor the use anticoagulation in patients with ESUS, current hypotheses suggest there may be subgroups who do benefit from anticoagulation.

Epidemiology

On average, ESUS accounts for about 1 in 6 ischemic strokes (17% (range 9 – 25%)) according to a systematic literature review of 9 studies.

Patient A patient is any recipient of health care services that are performed by Health professional, healthcare professionals. The patient is most often Disease, ill or Major trauma, injured and in need of therapy, treatment by a physician, nurse, op ...

s with ESUS tend to be relatively young and experience mild strokes. However, ESUS is associated with high recurrence rates. Of 2045 ESUS patients (identified by 8 studies) * 58% were

male Male (Planet symbols, symbol: ♂) is the sex of an organism that produces the gamete (sex cell) known as sperm, which fuses with the larger female gamete, or Egg cell, ovum, in the process of fertilisation. A male organism cannot sexual repro ...

, * the mean age was 65 years, * the average annualized rate of stroke recurrence was 4.5% * mean NIHSS at stroke onset was 5. The stroke recurrence rate was 29.0% over 5 years in patients with ESUS, which is similar to patients with cardioembolic stroke (26.8%), but significantly higher than all types of non-cardioembolic stroke. However, mortality was significantly lower in patients with ESUS than cardioembolic stroke.