Ischemic Stroke in Young Patients with Cardiac Abnormalities and Hypercoagulable State: 2 Case Reports and Literature Review to Assess Diagnostic and Prevention Options
Authors: Thomas Lisa , Shi Qi , Sethi Arjinder , Ramakrishnan Sathyanarayanan , Jia Jihua , Thomas-Hemak Linda 
Published: October 2019

Abstract
Abstract 4663

Background
Stroke is the third leading cause of death and the leading cause of severe, long-term disability in the United States. The incidence of cerebrovascular accident (CVA) in young adults has been increasing. Since the etiology of CVA in young adults is more heterogeneous, making a diagnosis is often a challenge requiring extensive clinical investigation. We report 2 cases of ischemic stoke in young adults with multiple risk factors.

Case Report
No. 1. A 46-year-old male presented to the ER with loss of consciousness. Past medical history was unremarkable. MRA confirmed occlusion of the left posterior cerebral artery. Transesophageal Echocardiogram (TEE) revealed a patent foramen ovale (PFO) and atrial septal aneurysm (ASA). Hypercoagulable evaluation confirmed increased IgM anticardiolipin antibody, a lupus anticoagulant, and heterozygous MTHFR (Methylenetetrahydrofolate reductase) C677T mutation. Anticoagulation therapy was started with Heparin and then switched to Coumadin. Aspirin was also initiated along with folic acid, Vitamin B6 and B12, and smoking cessation therapy. Unfortunately, the patient developed hemiparesis and dementia after stroke.
No. 2. A 50-year-old female presented to the ER with headache and blurred vision for one hour. Patient had cerebrovascular accident (CVA) 7 years prior to that event. She has been taking aspirin. MRI confirmed encephalomalacia in the left cerebellar hemisphere. TEE revealed a PFO. During the PFO closure procedure, an atrioseptal defect and a myxomatous were diagnosed. Patient was directed to use clopidogrel for at least six months after procedure, and aspirin indefinitely.

Discussion
The differential diagnosis for potential etiology in young people (under 55 years of age) of CVA is broader than that for older adults. Ischemic strokes are much more common than hemorrhagic in this group of patients. The atypical causes are more prevalent in the younger population, including cardiogenic cerebral embolus, hypercoagulable states, and autoimmune disease needs to be considered. Cardiogenic cerebral embolus is the most common cause of stroke in young adults. Stroke can be associated with abnormalities of the atrial septum, specifically PFO, atrial septal defect (ASD), aneurysm, and cardiac myxomas. Studies show that the prevalence of PFO in patients who have stroke of unknown cause (cryptogenic stroke) may be about 40 percent. More specifically, PFO increases the rate of paradoxical thromboembolic stroke that occurs by allowing blood clots from the venous system to enter the arterial system. This is particularly true in patients who have had a stroke at an age less than 55 years. PFO closure procedures may help to identify underlying causes of CVA, as was discussed in case 2. Some studies have described an association between atrial septal aneurysm (ASA) and embolic strokes. The embolus might originate in an ASA or from a clot around the edges of a PFO. The mechanism of cerebrovascular events with ASA may be platelet/thrombus formation at the site of the aneurysm. Aspirin may be effective therapy for preventing CVA. Emboli from cardiac myxomas also can lead to cerebral ischemia, infarction, and aneurysm formation. Up to half of cardiac myxomas produce systemic emboli. Consequently, studies show that inherited thrombophilic disorders in the pathogenesis of stroke might relate to congenital heart diseases. The data suggests that Factor V Leiden G1691A mutation or Prothrombin G20210A variant may be associated with PFO. An increased prevalence of right-to-left shunts in patients with cerebrovascular accident CVA and activated protein C resistance has also been documented. Antiphospholipid Antibody Syndromes (APS) are recognized as independent risks for Cerebrovascular Accident (CVA). APS are associated with a heterogeneous group of disorders that result in hypercoagulable states involving arterial and venous thrombosis. Cerebral circulation is particularly affected in APS.

Conclusion
Based on these observations, the authors conclude that hypercoagulable testing should be performed in young patients with CVA. In addition, PFO closure procedures may be an important diagnostic tool that helps to identify a subset of patients in whom the etiology of CVA was not apparent.

Disclosures:
No relevant conflicts of interest to declare.