Embolic stroke of undetermined source (ESUS) is an embolic stroke, a type of ischemic stroke, with an unknown origin,[1] defined as a non-lacunarbrain infarct without proximal arterialstenosis or cardioembolic sources.[2] As such, it forms a subset of cryptogenic stroke, which is part of the TOAST-classification.[3] The following diagnostic criteria define an ESUS:[2]
Patent foramen ovale (PFO): Deep vein thrombosis 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 ipsilateralcarotid artery are detected in 1 in 4 of patients with cryptogenic stroke.[5][6]Aortic arch atherosclerosis is believed to be a specific cause of ESUS, particularly with plaques >4 mm diameter.[4][7]
ESUS is a diagnosis of exclusion based on radiological 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 <30%). For imaging of both the extracranial and intracranial arteries supplying the area of brain ischaemia, examination methods like catheter, MR/CT angiography or cervical duplex plus transcranial Doppler ultrasonography are required. They allow an exclusion of large vessel stenosis (≥ 50%).[2]
Cryptogenic stroke vs ESUSedit
Cryptogenic stroke is also an ischemic stroke with more than one probable cause or strokes with incomplete diagnostic workup.[3] 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.[citation needed]
Managementedit
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.[8][9][10] However, it is widely believed that there is a substantial overlap between ESUS and cardioembolic stroke, clinical trials have assessed the benefit of anticoagulation versus antiplatelet agents for preventing recurrent stroke.[2][11] 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.[12]
Epidemiologyedit
On average, ESUS accounts for about 1 in 6 ischemic strokes (17% (range 9 – 25%)) according to a systematic literature review of 9 studies.[13]Patients 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)
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.[14][15]
^ abcdHart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O'Donnell MJ, Sacco RL, Connolly SJ (April 2014). "Embolic strokes of undetermined source: the case for a new clinical construct". The Lancet. Neurology. 13 (4): 429–38. doi:10.1016/S1474-4422(13)70310-7. PMID 24646875. S2CID 36116833.
^ abAdams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE (January 1993). "Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment". Stroke. 24 (1): 35–41. doi:10.1161/01.STR.24.1.35. PMID 7678184.
^ abNouh A, Hussain M, Mehta T, Yaghi S (2016). "Embolic Strokes of Unknown Source and Cryptogenic Stroke: Implications in Clinical Practice". Frontiers in Neurology. 7: 37. doi:10.3389/fneur.2016.00037. PMC4800279. PMID 27047443.
^Freilinger TM, Schindler A, Schmidt C, Grimm J, Cyran C, Schwarz F, et al. (April 2012). "Prevalence of nonstenosing, complicated atherosclerotic plaques in cryptogenic stroke". JACC: Cardiovascular Imaging. 5 (4): 397–405. doi:10.1016/j.jcmg.2012.01.012. PMID 22498329.
^Gupta A, Gialdini G, Lerario MP, Baradaran H, Giambrone A, Navi BB, et al. (June 2015). "Magnetic resonance angiography detection of abnormal carotid artery plaque in patients with cryptogenic stroke". Journal of the American Heart Association. 4 (6): e002012. doi:10.1161/JAHA.115.002012. PMC4599540. PMID 26077590.
^Amarenco P, Cohen A, Tzourio C, Bertrand B, Hommel M, Besson G, et al. (December 1994). "Atherosclerotic disease of the aortic arch and the risk of ischemic stroke". The New England Journal of Medicine. 331 (22): 1474–9. doi:10.1056/NEJM199412013312202. PMID 7969297.
^European Stroke Organisation (ESO) Executive Committee, Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, et al. (July 2014). "Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association". Stroke. 45 (7): 2160–236. doi:10.1161/STR.0000000000000024. PMID 24788967.
^Lansberg MG, O'Donnell MJ, Khatri P, Lang ES, Nguyen-Huynh MN, Schwartz NE, et al. (February 2012). "Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e601S–e636S. doi:10.1378/chest.11-2302. PMC3278065. PMID 22315273.
^European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee, Ringleb PA, Bousser MG, Ford G, Bath P, Brainin M, et al. (2008). "Guidelines for management of ischaemic stroke and transient ischaemic attack 2008". Cerebrovascular Diseases. 25 (5): 457–507. doi:10.1159/000131083. PMID 18477843.