Embolic stroke of undetermined source (ESUS)

Individual risk factors

laboratory work-up

Hypercoagulable profile

Evaluation for malignancy

Genetic considerations for cryptogenic stroke

Substance use and abuse

Infectious considerations

Summary

Disclosure

References

INTRODUCTION

The diagnosis of cryptogenic stroke (CS) is made by exclusion. There are a variety of stroke definitions, advancements in diagnostic technologies, along with differing thoughts on appropriate etiologic investigations, and there are more than 200 known causes of ischemic stroke (IS) requiring elimination. Despite an extensive evaluation the cause of CS cannot be determined in 30% to 40% of cases. It is important to determine the cause of CS to understand the functional prognosis and eliminate the risk of stroke recurrence by providing appropriate secondary stroke prevention. In clinical practice, the diagnosis of CS is considered when the diagnostic assessment is not complete, when a single cause cannot be determined because there are several potential causes, or there is no identifiable cause despite an extensive evaluation. Understanding stroke subtype is essential for managing acute interventions and secondary prevention. One prominently used classification system, designed for the TRIAL of ORG-10172 for Acute Stroke Treatment (TOAST), defined an undetermined stroke as a “brain infarction that is not attributable to a cardio-embolic source, large artery atherosclerosis, or small-vessel disease, despite an extensive vascular, cardiac and serologic evaluation.” As such, the definition is thought of in negative terms, based on the absence of findings.

SUMMARY

The specific cause of stroke in a large number of patients continues to challenge clinicians despite efforts to arrive at a CS diagnosis. Approximately 30% to 40% of ischemic strokes do not have a definitive cause despite specialized, costly testing, that often results in diminishing yield. Understanding the pathogenic mechanism of stroke, lack of Class I evidence, the workup and treatment strategies often vary considerably. CS incorporates a heterogenous group of patients leading to therapeutic implications based on the potential mechanism. In the absence of AFib, antiplatelet therapy continues to be the mainstay of treatment, though scientific evidence to support this is limited. In addition, risk factor management and lifestyle modifications, lead to improved stroke prevention strategies in patients with CS.