The Evolving Concept of Cryptogenic Stroke

Hooman Kamel, MD Cerebrovascular Disease p. 353-362 April 2020, Vol.26, No.2 doi: 10.1212/CON.0000000000000832
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PURPOSE OF REVIEW This article discusses cryptogenic stroke and the results of recent randomized trials that can inform its evaluation and management.

RECENT FINDINGS Most cryptogenic strokes appear embolic, leading to the term embolic stroke of undetermined source. It was previously thought that embolic stroke of undetermined source was a single, therapeutically relevant entity, the underlying sources of which would respond to anticoagulant therapy; however, two large randomized trials found no benefit with anticoagulation compared to antiplatelet therapy for secondary stroke prevention after embolic stroke of undetermined source. A single antiplatelet drug remains the recommended long-term antithrombotic treatment for secondary stroke prevention in embolic stroke of undetermined source. However, three caveats should be considered with regard to cryptogenic stroke. First, those with minor stroke symptoms presenting early after onset should receive 3 weeks of dual antiplatelet therapy. Second, all patients with cryptogenic stroke should be monitored for atrial fibrillation. Third, patients 60 years of age or younger with a patent foramen ovale (PFO) should be carefully evaluated to determine whether the PFO may have caused the stroke and whether they might benefit from PFO closure.

SUMMARY More personalized strategies may soon be available to guide treatment of cryptogenic stroke. In the meantime, it is hoped that the application of recent findings from clinical trials will reduce stroke recurrence in this important population.

Address correspondence to Dr Hooman Kamel, Weill Cornell Medicine, 420 E 70th St, LH-413, New York, NY 10021,

RELATIONSHIP DISCLOSURE: Dr Kamel has served on an end point adjudication committee for Boehringer Ingelheim International GmbH, on a steering committee for a stroke/atrial fibrillation trial for Medtronic (uncompensated), as a deputy editor for JAMA Neurology, and on an advisory board for Roivant Sciences Ltd. Dr Kamel receives research/grant support from the Michael Goldberg Stroke Research Fund; the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (R01HL144541); the NIH/National Institute of Neurological Disorders and Stroke (U01NS095869, U01NS106513, R01NS097443); and as co–principal investigator of the NIH-funded ARCADIA trial, which receives in-kind study drugs from Bristol-Myers Squibb–Pfizer Alliance and in-kind study assays from Roche Diagnostics, North America.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Dr Kamel discusses the class of anticoagulant drugs, specifically, direct-acting oral anticoagulant drugs, for various indications related to cryptogenic stroke.

© 2020 American Academy of Neurology.