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Sudden One-Sided Weakness in a Young Woman


Cerebrovascular accidents occur in a small but significant number of young persons, many of whom do not have traditional risk factors for vascular disease.

An otherwise healthy woman in her mid-30s is brought to the emergency department with left-sided weakness of acute onset. Weakness developed first in her hand, then in her face and leg. She also exhibits facial numbness, and dysarthria without aphasia. No visual field abnormalities, incontinence, seizures, headaches, or other focal neurologic deficits are evident.

About 10 minutes after the episode began, her condition started to improve. After about 6 hours, all symptoms have completely resolved; the facial numbness is the last symptom to abate.

The patient had a similar episode about 9 years earlier: she experienced identical symptoms for about 5 minutes, followed by their spontaneous and complete resolution. She did not seek medical attention.

She has no other significant medical history and no known drug allergies. Her family history is positive for peripheral vascular disease and stroke. Long-term medications include an oral contraceptive and low-dose testosterone for libido enhancement. She does not smoke or use illicit drugs, and she drinks alcohol only occasionally. She is married and has 2 healthy children.

Results of a neurologic examination and comprehensive laboratory evaluation (including liver function tests, basic chemistry panel, complete blood cell count, and coagulation profile) are normal. Doppler ultrasonography of the carotid arteries shows a high-resistance signal and flow characteristics that suggest distal obstruction of the right internal carotid artery. Intravenous heparin is initiated for probable carotid dissection.

CT scanning reveals no focal abnormalities. CT venography and angiography show normal, open circulation, with no obstruction from the aorta to the small cerebral branches; all dural venous sinuses are unoccluded. A transesophageal echocardiogram (TEE) shows normal cardiac function and no clots but reveals a small right-to-left shunt from a patent foramen ovale (PFO); there is no associated aneurysmal dilatation (Figure). MRI of the brain shows a very small focus of diffusion restriction in the right motor cortex, in a region to which her symptoms could be attributed. Magnetic resonance angiography confirms normal, unoc-cluded intracranial and extracranial vasculature.

The patient's testosterone supplementation and oral contraceptive are stopped. Daily low-dose aspirin and full anticoagulation with low molecular weight heparin are started. Her symptoms do not return, and she is discharged after 1 week with a prescription for warfarin. Results of a hypercoagulability workup are negative. After 3 months, the patient is switched from warfarin to aspirin. After 1 month of aspirin prophylaxis, she has had no significant bleeding problems and no recurrent thrombotic events.


Cerebrovascular accidents (CVAs) typically occur in persons with either traditional risk factors for atherosclerosis or established cardiovascular disease (CVD). Because the prevalence of these risk factors and the incidence of CVD are highest in persons older than 65 years, stroke has been largely regarded as a disease of the elderly. However, CVAs also occur in a small but significant number of young persons: 12% of all patients with stroke are younger than 45 years.1

Because younger patients with stroke only rarely have traditional risk factors for vascular disease, sources (cardiac and otherwise) of presumed embolism are often considered early in the differential diagnosis. Sources of embolism are definitively identified in only about half of younger patients2; the other half are said to have "cryptogenic" stroke.

Early studies showed that roughly half of younger patients with cryptogenic stroke had a PFO,3,4 although the prevalence of PFO in younger patients in general was only slightly higher than its prevalence in the population as a whole (about 25%).5 However, the unblind interpretation of echocardiograms, which were often done for indications other than stroke, was a possible source of bias in these early studies and significantly limits their power.


Early in normal infancy, after the first few inspirations of extrauterine life cause the left atrial pressure to overcome the right atrial pressure, the embryonic septum primum and septum secundum fuse to permanently close an opening in the fossa ovalis. However, this opening (PFO) can persist into adulthood and may allow the passage of blood (and emboli) from the right-sided circulation into the left-sided circulation when appropriate circumstances are present (see Figure). Indeed, there have been descriptions of the "paradoxical embolus," in which arterial thrombosis, venous thrombosis, a cardiac septal defect with right-to-left shunting pressure, and a visualized "straddling" thrombus were all found in the same patient.6

Such a thrombus is rarely found in younger patients with stroke and a PFO. Moreover, the right-to-left shunting pressures required to propel an embolus across the septum are not normally present in younger patients with stroke; conditions that encourage such shunting (eg, Valsalva maneuver) have also not typically been reported.7,8 The management of younger patients with stroke and a PFO thus represents an unresolved clinical problem.9


Identification of a cardioembolic cause of stroke is best made by TEE, which detects such sources in just under 60% of patients with cryptogenic stroke.10 This imaging modality is superior to transthoracic echocardiography, which has a relatively low yield (lower than 10%) in patients without known prior cardiac disease.10 A simultaneous "bubble study," in which saline and a small amount of air are administered intravenously during echocardiography-and which facilitates direct visualization of shunted air bubbles in the left-sided circulation-may increase the chances of detecting a right-to-left shunt. However, no large prospective studies have evaluated the ideal diagnostic algorithm in younger patients with stroke.


Randomized prospective data on the treatment of patients with PFO and stroke are sparse; however, at least 3 principles can be gleaned from the available evidence. First, young patients with CVA and a PFO generally have a good prognosis. One prospective study of 140 patients with cryptogenic stroke and a PFO who were randomly assigned to be treated either medically or surgically demonstrated an overall annual stroke recurrence rate of 1.9%, with no discernible difference between therapies.11 In a second study of 581 young patients with cryptogenic stroke who were treated with aspirin, the 4-year recurrence rate was only 4.2%. The rate was only 2.3% in those with a PFO, although those with simultaneous PFO and atrial septal aneurysm fared worse, with a 4-year recurrence rate of 15.2%.12

Second, although aspirin and warfarin may each be more beneficial than no treatment, they are about equally effective in preventing recurrent stroke. A retrospective study of 90 young patients with CVA (over half of whom also had a PFO) suggested that warfarin was somewhat more effective than aspirin (or no therapy).13 Subgroup analysis of a randomized trial of 98 patients with PFO and CVA demonstrated a greater reduction in 2-year stroke recurrence rates with warfarin (9.5%) than with aspirin (17. 9%), but this difference was not statistically significant.14

Finally, closure of the PFO remains an option, but surgery is indicated in few circumstances. Older case series that evaluated surgical closure found low mortality rates (below 1.5%) and estimated 2-year stroke recurrence rates of 3.5% or less.15-17 However, significant nonfatal cardiac morbidity was reported, and postoperative hemorrhage occurred. A more recent review of more than 1000 patients treated by percutaneous closure found a 1-year rate of stroke/transient ischemic attack recurrence of 4.9% or lower.18 Minor (7.9%) and serious (1.5%) complications were uncommon but significant. Currently, most authorities would reserve surgical closure for patients who experience recurrence despite anticoagulation.

The optimal treatment strategy for young patients with CVA and a TEE-verified PFO has not been fully defined; indeed, several professional societies either disagree or find insufficient convincing evidence to make a recommendation.9 Because antithrombotic therapy is relatively well tolerated in young patients, a short course of warfarin therapy is reasonable, based on the premise that a deep venous thrombosis might have caused paradoxical embolism and that warfarin is the optimal initial treatment for this condition.

Certainly, if an additional indication for longer-term warfarin therapy were discovered (eg, a hypercoagulable state), this therapy could-and probably should-continue. Otherwise, after a 3- to 6-month course of warfarin, switching to aspirin seems safest, given the undocumented efficacy of long-term warfarin in this patient population and the cumulative risk of bleeding events later in life. Aspirin probably provides a benefit over placebo in this setting (similar to that seen in general CVA literature), although ongoing trials may provide stronger data.

Surgical closure should probably be reserved for patients who cannot take warfarin. Percutaneous closure, although a very appealing option, is currently indicated only for patients who have a recurrent CVA despite adequate anticoagulation.




Bogousslavsky J, Van Melle G, Regli F. The Lausanne Stroke Registry: analysis of 1000 consecutive patients with first stroke.




Leys D, Bandu L, Henon H, et al. Clinical outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke.




Lechat P, Mas J, Lascault G, et al. Prevalence of patent foramen ovale in patients with stroke.

N Engl J Med.



Overell J, Bone I, Less K. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies.




Hagen P, Scholz D, Edwards W. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts.

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Kerut E, Norfleet W, Plotnick G, et al. Patent foramen ovale: a review of associated conditions and the impact of physiologic size.

J Am Coll Cardiol.



Meacham R, Headley A, Bronze M, et al. Impending paradoxical embolism.

Arch Intern Med.

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Falk R. PFO or UFO? The role of a patent foramen ovale in cryptogenic stroke.

Am Heart J.



Kizer J, Devereux R. Patent foramen ovale in young adults with unexplained stroke.

N Engl J Med.



Rahmatullah A, Rahko P, Stein J. Transesophageal echocardiography for the evaluation and management of patients with cerebral ischemia.

Clin Cardiol.



Bogousslavsky J, Garazi S, Jeanrenaud X, et al. Stroke recurrence in patients with patent foramen ovale: the Lausanne study.


1996;46: 1301-1305.


Mas JL, Arquizan C, Lamy C, et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both.

N Engl J Med.



Cujec B, Mainra R, Johnson D. Prevention of recurrent cerebral ischemic events in patients with patent foramen ovale and cryptogenic strokes or transient ischemic attacks.

Can J Cardiol.

1999;15: 57-64.


Homma S, Sacco R, DiTullio M, et al. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in cryptogenic stroke study.




Devuyst G, Bogousslavsky J, Ruchat P, et al. Prognosis after stroke followed by surgical closure of patent foramen ovale: a prospective follow-up study with brain MRI and simultaneous transesophageal and transcranial Doppler ultrasound.




Homma S, DiTullio M, Sacco R, et al. Surgical closure of patent foramen ovale in cryptogenic stroke patients.




Dearani J, Ugurlu B, Danielson G, et al. Surgical patent foramen ovale closure for prevention of paradoxical embolism-related cerebrovascular ischemic events.


1999;100(suppl II): II-171-II-175.


Khairy P, O'Donnell C, Landzberg M. Transcatheter closure versus medical therapy of patent foramen ovale and presumed paradoxical thromboemboli: a systematic review.

Ann Intern Med.

2003; 139:753-760.

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