Patient description: A 62-year-old African-American man presented with left upper and lower extremity weakness, associated with dark visual spot in right eye, right facial numbness, facial drop and slurred speech. He denied dyspnea, headache, palpitations, chest pain, fever, dizziness, bowel or urinary incontinence, loss of consciousness. His medical history was significant for hypertension, hyperlipidemia and hypothyroidism. He smokes cigarette 1 pack per day for 40 years and alcohol consumption of 5 to 6 beers per week. He is not aware about his family history. He is using Levothyroxine, Atorvastatin and HTCZ. His vital signs were stable in the primary evaluation. Left-sided facial droop, dysarthria, and left-sided hemiplegia were seen in the physical exam. His National Institutes of Health Stroke Scale (NIHSS) score was calculated as 7. Initial CT angiogram of head and neck reported no acute intracranial findings. Intravenous recombinant tissue plasminogen activator (t-PA) was administered as well as high-dose statin therapy. The patient was admitted to the intensive care unit to be monitored for 24 hours. MRI of the head revealed an acute 1.7-cm infarct of the right periventricular white matter and posterior right basal ganglia.

Clinical trial eligibility criteria: eligible ages (years): 18.0-55.0,  Migraine With Aura Patent Foramen Ovale Age 18-55 years 2. Ability to speak, read, and understand English 3. Documented diagnosis of migraine aura (MA) for a ≥2 year period preceding enrollment, confirmed by a neurology healthcare provider (MD, DO, ARNP, PA-C) using the International Classification of Headache Disorders criteria. Focal neurologic symptoms must precede or accompany the headache (aura) for at least one headache in the 12 months prior to enrollment. 4. Average of 4 to 14 migraine days per month for the 3-month period preceding enrollment 5. Migraine prevention regimen stable for at least 30 days prior to enrollment. This criterion does not pertain to acute medications or aspirin or non-steroidal anti-inflammatory (NSAID) containing medications, which will be held (wash-out) prior to blood draw. See below. 6. Able and willing to complete a washout of aspirin, NSAIDs (including ibuprofen, naproxen sodium, ketorolac), combination drugs containing these compounds, or dietary supplements containing willow bark (salicylate) prior to blood collection. 7. Experimental group: Documented large right-to-left shunt (RLS) with >100 embolic tracks (ET) at rest or following calibrated or uncalibrated respiratory strain by TCD (whichever yields largest number of ET). 8. Control group: Documented absence of right-to-left shunt (RLS) with <11 ET at rest and following calibrated and uncalibrated respiratory strain by TCD (whichever yields largest number of ET). 9. Adequate correction of hearing and/or vision deficits  Pregnancy 2. Postmenopausal female 3. Documented right-to-left shunt (RLS) with 11 to 100 ET at rest or following calibrated or uncalibrated respiratory strain by TCD (whichever yields largest number of ET) 4. History of stroke or neurological condition associated with cognitive dysfunction such as multiple sclerosis, epilepsy, brain tumor or brain injury 5. Chronic migraine or medication overuse headache 6. Prescription use of warfarin or antiplatelet drug such as clopidogrel or aspirin 7. Inability or unwillingness to complete a washout of aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), combination drugs containing these compounds, or dietary supplements containing willow bark (salicylate) 8. Evidence of carotid, vertebral, or basilar artery stenosis >50% on duplex imaging 9. Evidence of fetal origins or >50% stenosis of intracranial blood vessels on TCD imaging 10. Inadequate temporal bone windows (signals) for TCD insonation 11. Daily treatment regimen includes topiramate and/or other medication that causes significant cognitive or psychomotor impairment based on provider assessment and/or self-report (e.g., amitryptiline, divalproex sodium) 12. Use of continuous positive-airway pressure (CPAP) instrumentation within 6 months of study enrollment 13. Status post PFO or RLS closure/repair 14. Beck Depression Inventory score ≥29 15. State-Trait Anxiety Inventory score exceeding cutoff for age and sex