The Unseen Causes of Cryptogenic Stroke: From Patent Foramen Ovale to Arterial Dissections

Lura Javan^*
*Correspondence: Lura Javan, Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, USA, Email:

Introduction

Cryptogenic stroke, which accounts for 25-40% of ischemic strokes, refers to cases where no clear or identifiable cause can be determined despite comprehensive diagnostic testing. This diagnosis often leads to a sense of uncertainty both for clinicians and patients, as the absence of a clear etiology complicates treatment and management decisions. Cryptogenic stroke is especially concerning in younger individuals, where it may occur in the absence of traditional risk factors such as hypertension, diabetes, or atherosclerosis, making its origins even more difficult to uncover.

While many cryptogenic strokes are assumed to be embolic in nature, the exact source of the embolism often remains unknown. However, a growing body of research suggests that some cryptogenic strokes may be linked to specific, though under-recognized, conditions such as Patent Foramen Ovale (PFO) and arterial dissections. These conditions, often undiagnosed, can predispose individuals to the formation of blood clots that can embolize to the brain, leading to ischemic events. This article explores these lesser-known causes of cryptogenic stroke, focusing on the role of PFO and arterial dissections in the pathogenesis of cryptogenic stroke, as well as current diagnostic and therapeutic strategies.

Description

A Patent Foramen Ovale (PFO) is a small hole in the heart that connects the right and left atria. This hole is typically present in fetal development, allowing blood to bypass the lungs, which are not functional in the womb. After birth, the foramen ovale usually closes. However, in about 25% of the population, it remains open, leading to a PFO. In most individuals, a PFO is asymptomatic and does not cause health problems. However, in certain circumstances, a PFO can act as a conduit for blood clots to pass from the right atrium to the left atrium, bypassing the lungs' filtration system. From there, the clot can enter the systemic circulation and embolize to the brain, resulting in a stroke. The connection between PFO and cryptogenic stroke has been well established, as it is estimated that up to 40% of individuals with cryptogenic stroke have a PFO. The most significant concern is that blood clots, often originating in the veins of the legs (deep vein thrombosis, or DVT), may travel through the PFO, leading to embolization. In some cases, PFO has been implicated in stroke recurrence and refractory embolic events, as the presence of PFO increases the risk of paradoxical embolism. Although PFO is common, it is still unclear whether it is the primary cause of stroke or merely a contributing factor. Diagnosis of PFO typically involves imaging techniques such as Transesophageal Echocardiography (TEE) or bubble contrast echocardiography, which can detect the right-to-left shunt caused by the PFO. However, due to the asymptomatic nature of PFO in many individuals, the presence of a PFO is often not recognized until after a stroke occurs.

Treatment strategies for cryptogenic stroke patients with PFO typically involve the use of anticoagulants or antiplatelet therapy to reduce the risk of clot formation. In some cases, PFO closure via catheter-based intervention or surgery may be recommended, especially in younger patients or those with recurrent strokes, although this approach remains controversial due to mixed results in clinical trials. Arterial dissections refer to a tear in the arterial wall, which leads to the formation of a false lumen that can trap blood and form clots. These dissections most commonly occur in the vertebral artery or carotid artery, which supply blood to the brain. When a dissection occurs, the torn arterial wall can lead to the formation of a clot that may travel to the brain, causing an ischemic stroke. Although arterial dissections are a well-known cause of stroke in younger individuals, they remain underappreciated and often underdiagnosed as a cause of cryptogenic stroke. The mechanisms by which arterial dissections contribute to stroke are twofold. First, the tear in the arterial wall leads to thrombus formation, which can then embolize to the brain. Second, the dissection can cause a reduction in blood flow to the affected area of the brain, leading to ischemia. Trauma is the most common cause of arterial dissection, particularly in the cervical spine or neck region. However, arterial dissections can also occur spontaneously, without any obvious injury or trauma, making them even harder to diagnose. The clinical presentation of a stroke due to arterial dissection may include neck pain, headache, or local tenderness along the affected artery, symptoms that may not always be recognized as indicative of a dissection. As a result, these strokes may be misdiagnosed as cryptogenic, particularly in individuals without traditional risk factors or clear etiology.

Diagnosis of arterial dissections typically involves magnetic resonance angiography (MRA) or CT angiography (CTA), which can visualize arterial abnormalities. These imaging studies are crucial for detecting the location and extent of the dissection. However, arterial dissections can sometimes be missed, particularly if the dissection is not severe or if imaging is not performed promptly. Treatment of strokes caused by arterial dissections generally involves anticoagulation therapy (e.g., warfarin or direct oral anticoagulants), which helps prevent further thromboembolic events. In some cases, antiplatelet therapy may be used, depending on the location of the dissection and the patient's clinical condition. If a dissection is associated with severe stenosis or narrowing of the artery, surgical interventions or stenting may be considered to restore blood flow to the brain. In addition to PFO and arterial dissections, several other conditions may contribute to cryptogenic stroke, although they are less commonly recognized. Fibromuscular Dysplasia (FMD): A vascular condition that causes abnormal growth within the artery wall, increasing the risk of stroke due to narrowing or dissection of the arteries. Genetic or acquired conditions that increase the risk of clot formation, such as antiphospholipid syndrome, Factor V Leiden mutation, or protein C or S deficiency. These conditions can lead to venous thromboembolism and, in some cases, paradoxical embolism through a PFO. Some strokes may result from emboli originating from unknown sources within the body, such as embolism from the venous system or atherosclerotic plaques that are not detected by standard imaging [1-5].

Conclusion

Cryptogenic stroke remains a diagnostic challenge, particularly as its underlying causes are often elusive and may be due to conditions that are not immediately apparent. Patent Foramen Ovale (PFO) and arterial dissections, though relatively under recognized, are two important contributors to cryptogenic stroke that warrant closer attention. The presence of PFO may facilitate paradoxical embolism, while arterial dissections can lead to thrombus formation and ischemic events in the brain. Advances in imaging and diagnostic techniques have improved the identification of these conditions, but challenges remain in diagnosing these subtle causes of stroke, particularly in younger patients without traditional risk factors.

Further research into the pathophysiology and optimal management of cryptogenic stroke is essential, with a focus on improving diagnostic accuracy, treatment protocols, and prevention strategies. For patients with cryptogenic stroke, early identification and management of underlying conditions such as PFO and arterial dissections can significantly reduce the risk of recurrence and improve long-term outcomes. By addressing the unseen causes of cryptogenic stroke, clinicians can better understand the mechanisms of stroke in younger patients and provide more effective, targeted treatments.

Acknowledgement

None.

Conflict of Interest

None.

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