Model Hailey Bieber announced that she had recently been hospitalized for a “mini-stroke.” In March, the 25-year-old was eating breakfast with husband, pop star Justin Bieber, when she felt a sudden shooting pain down her arm. As she explained in a YouTube video, when asked by Justin if she was OK, she was unable to respond: “I couldn’t speak. The right side of my face started drooping, I couldn’t get a sentence out,” she said.
She was taken to the hospital by ambulance, and by the time she got there her symptoms had abated. She underwent testing, which showed that she had a small blood clot in her brain, which had resolved on its own — i.e., a transient ischemic attack (TIA).
Originally doctors thought that the explanation for the TIA was a combination of birth-control pill use, a recent bout of COVID-19, a history of migraines, and a recent long flight. However, after she underwent additional testing, a more likely source was found, she related: “They found that I had a grade 5 PFO [patent foramen ovale], which is the highest grade that you can have. Mine was fairly large.”
She went on to say: “My blood clot escaped through the flap, or the hole, in my heart and traveled to my brain, and that was why I had my TIA.” Subsequently, she underwent successful surgery to close the FPO and has now been resting at home.
What Is TIA, ‘Mini-Stroke’?
A TIA is defined as “a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction.” Most symptoms of a TIA disappear within an hour, although they may persist for up to 24 hours.
TIA is considered a medical emergency. Even if symptoms have resolved, a prompt evaluation (within 60 minutes) is necessary to identify the cause of the TIA and determine appropriate therapy.
It is important to note that the above definition represents a change in the way TIAs are viewed. In the past, the classical definition of TIA included symptoms lasting as long as 24 hours. However, advances in neuroimaging suggest that many such cases represent minor strokes with resolved symptoms rather than true TIAs. In 2009 the American Heart Association and the American Stroke Association endorsed the above tissue-based definition of TIA (i.e., as an episode of focal ischemia rather than acute infarction) rather than a time-based definition.
Based on a study of subjects in the Framingham Heart Study from 1948 to 2017, the incidence of TIA is considered to be 1.19 per 1,000 person-years. The study also found that the risk of stroke was significantly greater after a TIA.
Between 200,000 and 500,000 TIAs are diagnosed annually in the United States. The incidence increases with age: 1-3 cases/100,000 in those younger than 35, to as many as 1,500 cases/100,000 in those over 85.
The symptoms of TIA can include numbness or weakness in the face, arm, or leg, especially on one side of the body; confusion or difficulty in talking or understanding speech; trouble seeing in one or both eyes; and difficulty with walking, dizziness, or loss of balance and coordination.
Risk factors for TIA are the same as those for stroke and can be divided into three categories:
- Non-modifiable (age, sex, race, and significant family history of stroke)
- Well-documented and modifiable (tobacco smoking, obesity, physical inactivity, cardiovascular, and lipid profile derangements — i.e., coronary artery disease, myocardial infarction, valvular disease, atrial fibrillation, diabetes mellitus, arterial hypertension, and peripheral arterial disease)
- Potentially modifiable (history of migraine, obstructive sleep apnea, sleep patterns, and high-risk alcohol consumption)
A 2020 “focused update” review by Mary G. George, MD, of the CDC in Stroke looked at stroke risks in younger adults (i.e., ages 18-50). These are summarized here:
- Risk factors unique to or more common among women: use of contraception containing estrogen, pregnancy, migraine with aura
- Conditions associated with or potentially associated with cryptogenic stroke: PFO
- Inherited thrombophilias and acquired prothrombotic or hypercoagulable states: protein C and S deficiency, systemic lupus erythematosus (which is more common among women and Black individuals), sickle cell disease, cancer, and metabolic syndrome
- Carotid or vertebral artery dissection
- Vasculopathy and vasculitis and related conditions
- Cardiovascular risk factors
- Lifestyle risk factors
Patent Foramen Ovale
Foramen ovale is a flap-like tunnel between the right and left atria, made up of the septum primum and septum secundum. Foramen ovale is present in utero and is necessary for flow of cardiac blood from right to left as the lungs are bypassed until birth. When the lungs become functional at birth, pulmonary vascular pressure decreases, and the left atrial pressure exceeds that of the right. This forces the septum primum against the septum secundum, functionally closing the foramen ovale. In time the septa eventually fuse in most people, but in about 25% of adults, the foramen ovale does not fuse completely and remains as a small patent foramen ovale.
PFO can be detected by several methods: transthoracic echocardiography, transesophageal echocardiography (TEE), transcranial Doppler (TCD), and intracardiac echocardiography (ICE). TTE, TEE, TCD, and ICE are all performed in conjunction with an injection of agitated saline contrast (i.e., a “bubble study”). Color Doppler imaging for TTE, TEE, and ICE is often added. All can detect a right-to-left shunt associated with a PFO.
Only TEE and ICE, however, can visualize the site of the shunt. TTE or TEE can detect other cardiac abnormalities. Studies have shown that TCD is more sensitive but less specific than TTE for the detection of PFO.
Microemboli detected in 60 seconds are used as a method of grading PFO size. They are identified as high-intensity transient signals related to the injection of bubbles (agitated saline) and can be graded as follows:
- Grade 0: no microemboli detected
- Grade 1: 1–10 microemboli
- Grade 2: 11–30 microemboli
- Grade 3: 31–100 microemboli
- Grade 4: 101–300 microemboli
- Grade 5: >300 microemboli
The majority of adults with PFO are asymptomatic. However, in some, the PFO can cause inter-atrial right-to-left shunting of deoxygenated blood, with the potential for thromboemboli to reach the arterial circulation.
PFO has been associated with cryptogenic stroke, decompression sickness, migraine (with aura), platypnea-orthodeoxia syndrome, and acute limb ischemia secondary to emboli. Cryptogenic stroke is one in which no other identifiable cause is found. It accounts for approximately 20-40% of ischemic strokes. Platypnea-orthodeoxia syndrome is an under-diagnosed condition characterized by dyspnea and deoxygenation when changing from a recumbent to an upright position.
The prevalence of PFO is significantly higher in patients with cryptogenic stroke, especially in those under age 55. Given the high prevalence of PFO in the general population, some have questioned whether PFOs are causative, a risk factor, or incidental in cryptogenic stroke.
A 2020 review in Frontiers in Neurology concluded: “PFO in stroke patients may represent an incidental finding, a risk factor for stroke occurrence or a robust cause. It is associated with cryptogenic stroke through several mechanisms; most theories support paradoxical embolism, in situ thrombus formation, and arrhythmogenesis, while other possible, yet unknown, explanations cannot be excluded. Young age, PFO morphological characteristics and factors predisposing to venous thrombosis are essential features to determine a pathogenic PFO. Further investigation is needed in order to identify the role of these characteristics in the stroke pathogenesis.”
Kent and colleagues developed a tool called RoPE (Risk of Paradoxical Embolism) to estimate a patient-specific “PFO-attributable fraction” – i.e., the probability that a documented PFO is causally related to a stroke or TIA. The score is based on whether there is a history of hypertension, diabetes, previous stroke or TIA, or smoking.
A “no” answer to these gives a patient one point each. A cortical infarct on imaging adds another point. The age at which the episode occurs adds additional points: +5 for ages 18-29, +4 for ages 30-39, +3 for ages 40-49, +2 for ages 50-59, +1 for ages 59- 69, and +0 for >70.
“A high score correlates with increased likelihood that a PFO is responsible for the index stroke,” the team explained. “The PFO‐attributable fraction of stroke for a score of 7, 8, and 9 is 72%, 84%, and 88%, respectively, and defines a subset of patients who may benefit from PFO closure.”
There are currently two FDA-approved devices for percutaneous closure of a PFO: the Amplatzer PFO Occluder and the Gore Cardioform Septal Occluder. The former consists of two expandable discs with a connecting waist, all made of a nickel-titanium metal alloy. The discs have a polyester mesh inside to enhance elimination of flow across the hole.
The Gore Cardioform Septal Occluder also uses a nickel-titanium metal alloy wire frame, covered with a thin membrane made of Gore-Tex. Once the device is passed through the catheter, it opens up to form one circular disk that covers the hole on the left side and one disc on the right side of the septum.
Michele R. Berman, MD, is a pediatrician-turned-medical journalist. She trained at Johns Hopkins, Washington University in St. Louis, and St. Louis Children’s Hospital. Her mission is both journalistic and educational: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.
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