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Cryptogenic strokes

Account for 25-40% of acute ischemic strokes.

Cryptogenic strokes occur in patients who are younger than those with identifiable causes of ischemic stroke.

Cryptogenic strokes are less severe, less disabling, and less likely to occur than other ischemic strokes.

The two most frequently causes of cryptogenic stroke are silent atrial fibrillation , and paradoxical embolism.

Most cryptogenic strokes are considered to be embolic and of undetermined source.

Cryptogenic stroke refers to stroke of unknown etiology and accounts for approximately 15–40% of all ischemic strokes.

Patent foramen ovales present in 35-45% of patients with cryptogenic stroke, compared with 25% in the general population.

An ischemic stroke without evidence of cardiac or cerebrovascular disease, and occurs in approximately 200,000 cases per year.

From 70-90,000 of cryptogenic strokes occur from a patent foramen ovale.

The diagnosis traditionally based on the exclusion of other well-established causes of stroke.

Evaluation requires brain imaging, with computed tomography (CT) or magnetic resonance imaging (MRI), neurovascular imaging with CT angiography (CTA), MR angiography (MRA) or cervical carotid duplex and transcranial Doppler, cardiac evaluation with echocardiography, and, in select patients, rapid plasmin reagin (RPR), erythrocyte sedimentation rate (ESR), hypercoagulable testing, genetic analysis, or other tests for atypical causes.

New defined term, embolic strokes of undetermined source (ESUS), defines cryptogenic stroke based on established criteria, rather than due to the lack of an explanation.

ESUS is defined is an cute ischemic stroke in patients who have an embolic or non-lacunar brain infarct pattern on brain CT or MRI without extra or intracranial ipsilateral vessel narrowing of greater than 50% or without an identifiable cardio embolic source associated with a major risk for acute ischemic stroke such as atrial fibrillation or left ventricular thrombi.

Diagnostic criteria for ESUS include brain CT or MRI to demonstrate non-lacunar stroke, extracranial and intracranial imaging to exclude ≥50% proximal stenosis, and electrocardiography, echocardiography, and cardiac rhythm monitoring for ≥24 hours to exclude cardioembolic source.

The ESUS definition remains heterogeneous and includes cardiac abnormalities of uncertain risk such as covert paroxysmal atrial fibrillation [AF], mitral annular calcification, aortic valve disease, or atrial pathology, arteriogenic embolism, paradoxical embolism from patent foramen ovale or pulmonary arteriovenous malformation, and unknown prothrombotic disorders.

The frequency of ESUS in acute ischemic stroke etiology ranges from 7-42% with an average prevalence of 17%.
Patients with ESUS tend to be younger than patients with acute ischemic stroke with an identifiable cause.
Patients with ESUS have a lower incidence of traditional risk factors: hypertension, diabetes, and hypercholesterolemia.

The risk of recurrent stroke on patients with ESUS mostly treated with antiplatelet drugs ranges from 2.3-6.8% per year with the average of 4.5% per year.

Fitness reduces the risk for insulin resistance and may be most beneficial among obese  individuals.
Levels of BNP and NT-proBNP may be significantly elevated in patients with cardioembolic stroke.

Acutely elevated levels of BNP in patients with cryptogenic stroke may harbor an underlying or occult cardioembolic mechanism.

Acutely elevated D-dimer levels after a stroke may implicate a hypercoagulable state secondary to an occult malignancy.

Cancer is associated with a higher prevalence of unidentified strokes as well as higher levels of D-dimer.

The major challenge in managing cryptogenic stroke is secondary stroke prevention, specifically in choosing antithrombotic therapy.

There are currently no well-founded guidelines for optimal long-term anticoagulant treatment for cryptogenic strokes.

Antiplatelet agents are preferred for noncardioembolic ischemic strokes.

There is growing evidence that cryptogenic stroke patients may benefit from anticoagulation.

Oral anticoagulants are no more effective than aspirin and preventing recurrent stroke after a presumed embolic stroke from an undetermined source.

In patients with the recent cryptogenic embolic stroke, dabigatran was not superior to aspirin and preventing recurrent stroke (RE-SPECT ESUS Investigators).

The use of an implantable cardiac monitor increases the rate of AF detection significantly compared to standard monitoring at 6 months (8.9% vs. 1.4%.

The use of a 30-day loop recorder increases the yield of AF detection in patients diagnosed with cryptogenic stroke (16.1% vs. 3.2%.

The detection of occult AF in cryptogenic stroke may warrant treatment with anticoagulation.

Presently a prospective study assessing whether anticoagulation reduces risk of stroke and systemic embolism in patients with device-detected subclinical AF.

AF is a risk factor or marker for other comorbidities that increase the risk of stroke, rather than the sole or primary etiology.

Turakhia et al. reported an episode of AF that was at least 5.5 hours in a day increased the short-term risk of stroke by 4- to 5-fold in the 5 to 10 days after the AF event and decreased over time.

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