Evaluation of the patient with unexplained stroke

Despite increasing sophistication of brain imaging, neurovascular evaluation, and laboratory testing, a sizable proportion of ischemic strokes defy etiologic classification. Many, if not most, of such 'cryptogenic' strokes may stem from unrecognized cardiac or aortic embolism, with a bimodal pathophysiology potentially dominated by interatrial septal abnormalities in young adults, and by subclinical aortic and large-artery atherothrombotic embolism in older individuals. Echocardiography is the centerpiece of the diagnostic evaluation of unexplained ischemic stroke, and unless contraindicated, transesophageal echocardiography is currently the modality of choice. Comprehensive and timely evaluation is essential to identify the potential emboligenic substrate, and, pending randomized trial data, to institute appropriate therapy based on best clinical judgment.