Cryptogenic Stroke

Posted by • May 27th, 2016

2016-05-23_14-38-46Cryptogenic ischemic strokes are symptomatic cerebral infarcts for which no probable cause is identified after adequate diagnostic evaluation. In general, the percentage of ischemic strokes that are classified as cryptogenic has declined over time as diagnostic testing has advanced. However, stroke that is cryptogenic after a standard diagnostic evaluation remains a common clinical challenge, accounting for 20 to 30% of all ischemic strokes and therefore occurring in 120,000 to 180,000 patients each year in the United States. As compared with strokes of determined origin, cryptogenic ischemic strokes typically result in less severe presenting neurologic deficits, less final disability, and lower mortality.

One quarter of ischemic strokes are cryptogenic (no obvious cause). Additional investigation involves assessment for arteriopathies, cardiac sources of embolism (in particular, occult low-burden atrial fibrillation), and disturbances of coagulation. A new Clinical Practice summarizes.

Clinical Pearl

• What are some of the causes of cryptogenic stroke that may be discovered after more specialized testing?

In patients with ischemic stroke that is considered to be cryptogenic after standard evaluation, causes that are most often found after more specialized testing include occult atherosclerosis, including nonstenosing but unstable plaques at intracranial and cervical sites or stenosing plaques at the thoracic origins of the common carotid and thoracic vertebral arteries; nonatherosclerotic arteriopathies, such as dissection or vasculitis; hypercoagulable states; cardioembolism from medium-grade sources, such as low-burden paroxysmal atrial fibrillation or dilated cardiomyopathy of moderate degree; and paradoxical embolism.

Clinical Pearl

• What is the most common cause of cryptogenic stroke in young adults?

The age of the patient influences the likelihood of various causes. In young adults 18 to 30 years of age, dissection is most common, but thrombophilias and congenital cardiac disease are also noteworthy causes. In persons 31 to 60 years of age, early-onset atherosclerosis and acquired structural cardiac disease are increasingly common. In patients older than 60 years of age, occult atrial fibrillation becomes more frequent.

Morning Report Questions

Q: What patient characteristics increase the likelihood that protracted cardiac monitoring will reveal occult atrial fibrillation? 

A: Technology to detect infrequent paroxysmal atrial fibrillation has dramatically improved over the past decade, with the development of mobile cardiac telemetry systems that may be worn externally for 2 to 4 weeks, subcutaneous loop recorders with battery lives enabling detection for 1 to 3 years, and in patients needing therapeutic internal pacemakers or defibrillators, implantable therapeutic devices with the capability to detect atrial fibrillation for 3 years or more. Among patients whose ischemic strokes are cryptogenic after conventional inpatient evaluation, prolonged outpatient cardiac monitoring detects low-burden atrial fibrillation in 15%. Patients with low-burden paroxysmal atrial fibrillation have a lower risk of stroke than patients with chronic or high-burden paroxysmal atrial fibrillation. However, their risk of stroke is higher than that among persons without atrial fibrillation. As little as a single 1-hour episode of atrial fibrillation during 2 years of monitoring has been associated with a doubling in the risk of ischemic stroke. The characteristics of patients that increase the likelihood that protracted monitoring will uncover low-burden atrial fibrillation include older age and higher CHA2DS2-VASc score (on which scores range from 0 to 9, with higher scores indicating greater risk), cerebral infarct topographic features (such as multiple vascular territories and cortical location), and indexes of left atrial cardiopathy, including left atrial dilatation, strain, and reduced emptying fraction, left atrial appendage size and single-lobe morphologic features, p-wave dispersion on ECG [electrocardiogram], frequent atrial premature beats, and elevated N-terminal pro–brain natriuretic peptide serum levels.

Q: When a patent foramen ovale is found during the work up of cryptogenic stroke, how is one to know if it is causally related?

A: A patent foramen ovale is present in approximately one quarter of the general patient population but in one half of patients with cryptogenic stroke. A Bayesian attributable risk analysis of pooled data from 12 studies suggested that among patients with cryptogenic stroke who had a patent foramen ovale, the patent foramen ovale is probably causally related to the stroke in approximately half. Features that increase the likelihood of a causal relationship include younger age; Valsalva maneuver at the onset of stroke; extended plane or car travel preceding the stroke; concomitant venous thrombosis in the leg or pelvis; coexisting venous hypercoagulable state; coexisting atrial septal aneurysm; history of migraine with aura; cortical location, multiplicity, and large size of cerebral infarcts; and absence of hypertension, diabetes, and smoking.

Figure 1. Algorithm for the Identification and Diagnostic Evaluation of Patients with Cryptogenic Ischemic Stroke or Transient Ischemic Attack (TIA).

Table 1. Suggestive Findings on History and Physical Examination in Patients with Cryptogenic Stroke.

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