Hidden Causes of Cryptogenic Stroke: The Role of Patent Foramen Ovale and Arterial Dissection

Arvizur Nugar^*
*Correspondence: Arvizur Nugar, Department of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan, Email:

Introduction

Cryptogenic stroke, which accounts for approximately 25-40% of all ischemic strokes, is a perplexing condition where no definitive cause for the stroke can be identified despite a thorough evaluation. This diagnosis is particularly troubling, especially when it affects younger individuals who lack the usual risk factors such as hypertension, diabetes, and atherosclerosis. In these cases, clinicians often find themselves struggling to determine the origin of the stroke, which complicates treatment decisions and long-term care.

Recent research has increasingly pointed to two often-overlooked factors that may contribute to cryptogenic strokes: Patent Foramen Ovale (PFO) and arterial dissection. Both of these conditions can create pathways for blood clots to travel to the brain, but their subtle nature often makes them difficult to diagnose. Understanding the role of PFO and arterial dissections in cryptogenic stroke can help clinicians more accurately pinpoint the underlying causes of stroke and improve patient outcomes. This article explores the hidden causes of cryptogenic stroke, focusing on the contribution of PFO and arterial dissection, the diagnostic challenges associated with these conditions, and the current approaches to treatment.

Description

The Patent Foramen Ovale (PFO) is a small, often asymptomatic hole between the right and left atria of the heart. In fetal development, the foramen ovale allows blood to bypass the non-functional lungs, and it typically closes after birth. However, in around 25% of the adult population, the foramen ovale remains open. Most of these individuals will never experience any health issues due to the PFO. However, in some cases, this opening can become a pathway for blood clots, which usually originate from the veins, to travel from the right side of the heart to the left side. Once in the left atrium, these clots can be pumped into the systemic circulation and eventually reach the brain, resulting in an ischemic stroke. The role of PFO in cryptogenic stroke has been well-documented, especially among younger patients who lack the usual stroke risk factors. It is estimated that up to 40% of cryptogenic stroke patients may have an undiagnosed PFO. The primary concern with PFO is that it can facilitate paradoxical embolism, where a clot that would typically be filtered by the lungs bypasses this filtration system and enters the brain, causing a stroke. This condition is often undiagnosed until a stroke occurs, as PFO itself is asymptomatic in many cases.

Diagnosis of PFO typically involves advanced imaging techniques, including transesophageal echocardiography (TEE) or bubble contrast echocardiography, which are highly effective in detecting a right-to-left shunt. However, due to the asymptomatic nature of PFO in many individuals, it is often not discovered until after a stroke has occurred. The management of cryptogenic stroke in patients with PFO includes the use of anticoagulants or antiplatelet medications to reduce the risk of further clot formation. In some patients, particularly those with recurrent strokes, PFO closure through catheter-based procedures or surgery may be recommended, although this approach remains controversial. Some studies have shown benefits in stroke recurrence reduction after closure, while others have raised concerns about its efficacy and long-term outcomes. Arterial dissection refers to a tear in the inner lining of an artery, often affecting the carotid or vertebral arteries, which supply blood to the brain. When an arterial dissection occurs, it can cause a blood clot to form in the false lumen created by the tear. This clot can then embolize to the brain, resulting in an ischemic stroke. Arterial dissections are particularly important in the context of younger patients and are often a leading cause of stroke in individuals under 50. They are frequently associated with trauma (e.g., neck or head injury), but they can also occur spontaneously without any obvious precipitating factors, making them difficult to diagnose in the absence of a clear clinical history.

The pathophysiology of arterial dissections involves two main mechanisms: the formation of blood clots within the dissected artery and a reduction in blood flow to the brain. Both mechanisms increase the risk of ischemic stroke. Trauma, including motor vehicle accidents or chiropractic manipulation, is the most common cause of arterial dissection, but it can also occur spontaneously, often due to underlying vascular abnormalities like fibromuscular dysplasia or connective tissue disorders. The clinical symptoms of arterial dissection-related stroke may include neck pain, headache, or local tenderness along the affected artery. These symptoms are often nonspecific and may be confused with other conditions, leading to misdiagnosis as cryptogenic stroke. Because arterial dissections may be subtle or only detectable with advanced imaging techniques, they are frequently missed in initial assessments.

Diagnosis of arterial dissection typically involves high-resolution imaging, such as Magnetic Resonance Angiography (MRA) or CT Angiography (CTA), which can reveal the dissection and its impact on blood flow. However, early detection is crucial, as arterial dissections may not always be visible on standard imaging or may evolve over time, complicating the diagnostic process. Treatment of arterial dissection-related strokes generally involves anticoagulation or antiplatelet therapy to prevent further clot formation and minimize the risk of stroke recurrence. In more severe cases, surgical interventions or stenting may be required to restore normal blood flow through the affected artery. A condition that affects the walls of arteries, leading to abnormal growth and narrowing or dissection of the arteries, which increases the risk of stroke. Conditions such as antiphospholipid syndrome or Factor V Leiden mutation, which make the blood more prone to clotting, can lead to venous thromboembolisms and paradoxical embolisms through a PFO. Although not commonly associated with younger patients, small or overlooked atherosclerotic plaques in arteries can cause emboli to travel to the brain, particularly when there are vascular anomalies or dissections. Embolic events originating from the heart, such as left atrial thrombus in individuals with undiagnosed atrial fibrillation (AF), can also lead to cryptogenic stroke [1-5].

Conclusion

Cryptogenic stroke remains a challenging diagnosis, particularly when the underlying cause is not readily apparent. However, growing evidence suggests that Patent Foramen Ovale (PFO) and arterial dissection play significant roles in the pathogenesis of many cryptogenic strokes. PFO acts as a conduit for paradoxical embolism, while arterial dissections can directly lead to thrombus formation and embolization. The subtle nature of these conditions, combined with their ability to cause stroke without clear symptoms, often leads to their underdiagnosis. Improvements in diagnostic techniques, such as advanced echocardiography for PFO and high-resolution imaging for arterial dissections, are crucial for identifying these hidden causes of cryptogenic stroke. Furthermore, while treatment for these conditions often includes anticoagulation therapy, PFO closure and surgical interventions may be considered in certain cases, although their efficacy remains a topic of debate.

Acknowledgment

None.

Conflict of Interest

None.

References

1. Schneider, Birke, Thomas Hofmann, Maria H. Justen and Thomas Meinertz. "Chiari's network: Normal anatomic variant or risk factor for arterial embolic events?." J Am Coll Cardiol 26 (1995): 203-210.

Google Scholar        Cross Ref                Indexed at

2. Kent, David M., Jeffrey L. Saver, Scott E. Kasner and Jason Nelson, et al. "Heterogeneity of treatment effects in an analysis of pooled individual patient data from randomized trials of device closure of patent foramen ovale after stroke." JAMA 326 (2021): 2277-2286.

Google Scholar        Cross Ref                Indexed at

3. Lechat, P. H., Jean-Louis Mas, Gilles Lascault and P. H. Loron, M. et al. "Prevalence of patent foramen ovale in patients with stroke." N Engl J Med 318 (1988): 1148-1152.

Google Scholar        Cross Ref                Indexed at

4. Overell, J. R., I. Bone and K. R. Lees. "Interatrial septal abnormalities and stroke: A meta-analysis of case-control studies." Neurology 55 (2000): 1172-1179.

Google Scholar        Cross Ref                Indexed at

5. Pristipino, Christian, Peter Germonpré, Danilo Toni and Horst Sievert, et al. "European position paper on the management of patients with patent foramen ovale. Part II-Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions." Eur Heart J 42 (2021): 1545-1553.

Google Scholar        Cross Ref                Indexed at