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 ::  Abstract
 ::  Introduction
 ::  Case Report
 ::  Discussion
 ::  References
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Year : 2010  |  Volume : 56  |  Issue : 3  |  Page : 206-208

Paradoxical embolism causing stroke and migraine

Department of Cardiology, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester, United Kingdom

Date of Submission30-Apr-2008
Date of Decision30-Oct-2009
Date of Acceptance19-Feb-2010
Date of Web Publication23-Aug-2010

Correspondence Address:
S Nightingale
Department of Cardiology, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester
United Kingdom
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0022-3859.68630

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 :: Abstract 

This case report describes a lady who underwent investigations as a part of a clinical study. A 32-year-old woman with a history of episodes of severe migraine with aura, deep vein thrombosis and recurrent epistaxis, presented with two episodes of stroke with no particular cause evident on routine investigations. A contrast echocardiogram demonstrated a patent foramen ovale (PFO). She was found to be positive for the Factor V Leiden mutation. The PFO was closed percutaneously. However, a substantial right to left shunt of 14% persisted. Pulmonary angiography revealed multiple arterio-venous malformations (AVMs) and she was diagnosed with hereditary hemorrhagic telangiectasia. The AVMs were embolized and she has had no further cerebral events. Interestingly, her episodes of 'migraine' have also improved dramatically following the closure of the PFO and the embolization of the AVMs. This case demonstrates the complex relationship between right to left shunts, cryptogenic stroke and migraine.

Keywords: Cryptogenic stroke, hereditary hemorrhagic telangiectasia, migraine, patent foramen ovale

How to cite this article:
Nightingale S, Ray G S. Paradoxical embolism causing stroke and migraine. J Postgrad Med 2010;56:206-8

How to cite this URL:
Nightingale S, Ray G S. Paradoxical embolism causing stroke and migraine. J Postgrad Med [serial online] 2010 [cited 2023 May 30];56:206-8. Available from:

 :: Introduction Top

This case report illustrates the complex relationship between right to left shunts, cryptogenic stroke and migraine and demonstrates some of the treatment options available.

 :: Case Report Top

A 32-year-old right-handed non-smoking, non-alcoholic housewife had first presented in 1996 with sudden onset right hemiparesis and expressive dysphasia. Computerized tomographic (CT) scanning of the brain showed a left-sided, anterior circulation thrombo-embolic stroke. Direct questioning revealed that over the preceding months she had experienced symptoms consistent with anterior circulation transient ischemic attacks (TIAs) affecting motor function bilaterally. She had not reported these symptoms at the time and no investigations had been performed. Her past medical history included frequent episodes of migraine with aura; at her worst she suffered daily attacks. She was not using oral contraceptives. She had suffered a deep vein thrombosis (DVT) during pregnancies in 1989 and 1999. She had also suffered recurrent epistaxis since childhood. She reported that her brother had also suffered a stroke, possibly hemorrhagic, as a young man. He also suffered from recurrent epistaxis. Routine clinical assessment and investigation had revealed no risk factors for stroke. However, at that time, the workup did not include thrombophilia screen or contrast echocardiogram. She made a good functional recovery from the stroke with minimal residual neurological deficit. Following the DVT in her second pregnancy she was commenced on long-term warfarin therapy.

In 2004, she was investigated further as part of a study looking at the role of paradoxical embolism in cryptogenic stroke in young people. A contrast trans-thoracic echocardiogram revealed rapid appearance of a large volume of bubbles in the left side of the heart when bubble contrast was injected into the venous circulation confirming a large right to left shunt. Such was the volume of bubbles in the systemic circulation that she experienced transient visual loss and the test was not repeated. Trans-esophageal echocardiogram showed clear evidence of a significant patent foramen ovale (PFO). Bubble contrast was not given due to the risk of further amourosis fugax. A thrombophilia screen revealed she was heterozygous for the Factor V Leidin mutation.

She underwent PFO closure under local anesthetic with an 18-mm Amplatzer PFO occluder. [Figure 1] shows the device in situ. Locally injected contrast is seen in the right side of the heart with minimal residual passage across the intra-atrial septum.
Figure 1 :Amplatzer PFO occluder in situ with minimal residual flow of contrast across intra-atrial septum immediately after implantation

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Re-study with venous agitated saline following PFO closure demonstrated a persistently large shunt at atrial level despite the seemingly adequate closure of the PFO. Her pO2 was low at 6.1 kPA (normal range 10-13). She underwent an isotope scan which demonstrated a 14% shunt of venous blood into the arterial circulation (normal range <3.5%). An additional site for right to left shunting was investigated by pulmonary angiography, which revealed several large pulmonary arterio-venous malformations (AVMs) within both lung fields [Figure 2].
Figure 2 :Pulmonary angiography showing bilateral AVM

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Review of her clinical examination then revealed several telangiectasia on her lips and oropharynx, leading to a diagnosis of hereditary hemorrhagic telangiectasia (Osler Weber Rendu syndrome). She went on to have successful coil embolization of the pulmonary AVMs with minimal residual flow across one AVM only. Her Po 2 improved to 9.1 kPA (normal range 10-13) and isotope scan shunt fraction was reduced to 4.7% (normal range <3.5%).

Three years on, she has had no further strokes or symptoms suggestive of TIAs. Interestingly, her migraine with aura has also improved. Before treatment, she suffered attacks on most days. However, following PFO closure the frequency reduced to approximately once a week. Since the embolization of her pulmonary AVMs, she has not had a single episode of migraine headache or the associated aura.

 :: Discussion Top

This lady had three separate disorders: Factor V Leiden mutation, hereditary hemorrhagic telengiectasia (HHT) and a large PFO. A literature review did not reveal an association amongst these conditions and their coexistence in our patient's case is probably coincidental.

Factor V Leiden mutation is a relatively common cause of venous thrombophilia, particularly in pregnancy and it is therefore likely that this condition was responsible for DVT episodes during her pregnancies in 1989 and 1999. The history of DVTs, her known venous thrombophilia, two possible routes for paradoxical embolism and the absence of any other cause of premature stroke make it very likely that both the strokes were due to paradoxical embolism.

HHT is autosomal dominant and it seems likely that her brother who suffered recurrent epistaxis, also had this condition. His presumed intracranial hemorrhage may have been secondary to cerebral AVMs. Pulmonary AVMs (through paradoxical embolism) are a well-recognized cause of stroke in patients with HHT. [1] These patients have also been shown to have an increased prevalence of migraine of up to 50%. [2] In contrast to HHT, the association of PFO with stroke and migraine remains the source of much debate.

A meta-analysis has shown a threefold increase in young (<55 years) stroke patients with PFO. [3] However, this meta-analysis was based on case-control studies which had methodological limitations and several prospective studies have failed to demonstrate an increased stroke risk in populations with PFO. [4],[5],[6],[7]

Similarly, the association with migraine has been hard to demonstrate conclusively. The proposed mechanism is that a substance usually filtered out by the lungs is allowed to pass into the systemic circulation, where it has 'migrainogenic' properties in susceptible individuals. Although PFOs are common in the population with an overall prevalence of 27%, [8] approximately half of patients with migraine with aura have a PFO. [9] Indeed, this patient had dramatic improvements in her migraine symptoms following both PFO closure and pulmonary AVM embolization. Although, there are reports of similar outcomes in other patients, the recently reported MIST trial has failed to show the anticipated reduction in migraine following PFO closure. [10] Another interesting aspect of this case is the unusual event of amaurosis fugax following venous bubble injection during the echocardiogram. The fact that a substance in the venous circulation can cause a neurological deficit, albeit transient, adds further weight to the argument that paradoxical emboli may be implicated in the etiology of stroke and migraine.

 :: References Top

1.Moussouttas M, Fayad P, Rosenblatt M, Hashimoto M, Pollak J, Henderson K, et al. Pulmonary arteriovenous malformations: Cerebral ischemia and neurologic manifestations. Neurology 2000;55:959-64.   Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Steele JG, Nath PU, Burn J, Porteous ME. An association between migrainous aura and hereditary haemorrhagic telangiectasia. Headache 1993;33:145-8.   Back to cited text no. 2  [PUBMED]    
3.Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: A meta-analysis of case-control studies. Neurology 2000;55:1172-9.  Back to cited text no. 3      
4.Lamy C, Giannesini C, Zuber M, Arquizan C, Meder JF, Trystram D, et al. Clinical and imaging findings in cryptogenic stroke patients with and without patent foramen ovale: The PFO-ASA Study: A trial Septal Aneurysm. Stroke 2002;33:706-11.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP. Effect of medical treatment in stroke patients with patent foramen ovale: Patent foramen ovale in Cryptogenic Stroke Study. Circulation 2002;105:2625-31.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]  
6.Mas JL, Arquizan C, Lamy C, Zuber M, Cabanes L, Derumeaux G, et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 2001;345:1740-6.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]  
7.Burger AJ, Sherman HB, Charlamb MJ. Low incidence of embolic strokes with atrial septal aneurysms: A prospective, long-term study. Am Heart J 2000;139:149-52.  Back to cited text no. 7  [PUBMED]    
8.Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: An autopsy study of 965 normal hearts. Mayo Clin Proc 1984;59:17-20.  Back to cited text no. 8  [PUBMED]    
9.Anzola GP, Magoni M, Guindani M, Rozzini L, Dalla Volta G. Potential source of cerebral embolism in migraine with aura: A transcranial Doppler study. Neurology 1999;52:1622-5.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]  
10.Dowson A, Mullen MJ, Peatfield R, Muir K, Khan AA, Wells C, et al. Migraine Intervention With STARFlex Technology (MIST) trial: A prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache. Circulation 2008;117:1397-404.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  


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2004 - Journal of Postgraduate Medicine
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