Intern. J. Neuroscience, 115:119–127, 2005 Copyright  Taylor & Francis Inc. ISSN: 0020-7454 / 1543-5245 online DOI: 10.1080/00207450490512687 Int J Neurosci Downloaded from informahealthcare.com by CDL-UC Davis on 10/27/14 For personal use only. Case Report CLOSURE OF A PATENT FORAMEN OVALE: EFFECTIVE THERAPY OF MIGRAINE AND OCCIPITAL STROKE JOSEF FINSTERER Neurological Hospital Rosenhügel Vienna, Austria OLIVER SOMMER MICHAEL STISKAL Radiological Department Municipal Hospital Lainz Vienna, Austria CLAUDIA STÖLLBERGER Medical Department Krankenanstalt Rudolfstiftung Vienna, Austria HELMUT BAUMGARTNER Cardiological Department University of Vienna School of Medicine Vienna, Austria Received 10 March 2004. Address correspondence to Univ. Doz. DDr. J. Finsterer, Postach 20, 1180, Vienna, Austria. E-mail: duarte@aonmail.at 119 Int J Neurosci Downloaded from informahealthcare.com by CDL-UC Davis on 10/27/14 For personal use only. 120 J. Finsterer et al. Whether stroke in a patient with migraine and patent foramen ovale (PFO) is due to PFO or migraine is difficult to decide. In a 33-year-old woman with migraine with aura, a visual field defect developed acutely. Neurological investigation revealed double vision when looking to the left and exaggerated patella tendon reflexes. Since then the patient complained about permanent visual impairment. CT- and MRI-scans of the brain showed a right occipital ischemic stroke. Intensive search for risk factors revealed cigarette smoking and chronic hypovolemia. On transesophageal echocardiography an inter-atrial hypermobile septum and a PFO were detected. The patient underwent closure of the PFO by means of an Amplatzer PFO occluder nine weeks after the stroke. Since then she did not experience a further cerebrovascular event or migraine attack. This case shows that in a patient with PFO and migraine with aura, stroke may be attributable to migraine rather than to PFO. Occlusion of the PFO may reduce the frequency and intensity of migraine attacks. Keywords cerebrovascular ischemia, echocardiography, ophthalmologic impairment, stroke-prevention, therapy, vision Migraine with aura (Buring et al., 1995; Chang et al., 1999; Del Sette et al., 1998; Merikangas et al., 1997) and patent foramen ovale (PFO) (Anzola et al., 1999; Cabanes et al., 1993; DiTullio et al., 1992; Lechat et al., 1988; Webster et al., 1988) are considered risk factors for stroke in the young. Because patients with migraine have an increased prevalence of PFO, their risk for stroke is regarded particularly high (Del Sette et al., 1998; Lamy et al., 2002; Ries et al., 1996; Sztajzel, 2002). Whether stroke in a patient with migraine and PFO is due to the PFO or due to migraine is difficult to decide. This article reports a patient in whom stroke was attributable to migraine rather than PFO. CASE REPORT The patient is a 33-year-old (May 2002) woman with a history of a cervical branchiogenic cyst, successfully resectioned in 1987, recurrent infections with herpes genitalis since 1995, and tension headache. Within approximately 10 years she additionally had experienced 10–15 attacks of scintillating scotomas for 60 min maximally. Three quarters of these attacks were followed by bifrontal and sometimes pulsatory headache in the right temporal region. One or two times Int J Neurosci Downloaded from informahealthcare.com by CDL-UC Davis on 10/27/14 For personal use only. Migraine, Stroke, and Patent Foramen Ovale 121 these attacks were accompanied by vomiting. Because clinical neurologic examination, ultrasonography of the extracranial cerebral arteries, electroencephalography (EEG), and MRI of the brain were normal in September 1999, these attacks were interpreted as migraine with aura and migraine sans migraine, according to the International Headache Society classification. (Headache Classification, 1988). In August 2002 she was admitted because of acute defects in the left lower visual field for 4 days without headache or other abnormalities prior to visual impairment. Concerning the cardiovascular risk factors, she was drinking only up to 1000 ml of non-alcoholic liquids/day and was smoking 20 cigarettes/day. The personal history was negative for oral contraceptives, hypertension, diabetes, or previous thromboembolism, and ankle edema on standing or varicosity. The family history was noteworthy for epileptic seizures, her mother had experienced them 3 or 4 times so far. Clinical neurologic examination revealed double vision when looking to the left, but no visual field defects on confrontational perimetry, and exaggerated patella tendon reflexes. The latter were no longer present on the second hospital day. She had no symptoms or signs of a deep venous thrombosis (DVT). Blood pressure was 110/70 mmHg. Blood chemical investigations, thyroid function tests, and screening for cardiovascular risk factors, including anti-streptolysin-O-titer, rheuma factors, circulatory immune complexes, clotting tests, anti-nuclear antibodies, and anti-neutrophilic antibodies were all normal. ECG was uninformative. X-ray of the lung showed a lobus venae azygos in the right upper field exclusively. Ultrasound of the extracranial cerebral arteries and transcranial Doppler sonography (TCD) were normal. A CT-scan of the brain showed a small subcortical hypodense area in the right occipital paramedian region, being interpreted as recent ischemic stroke. An MRI scan of the brain confirmed the vascular nature of this lesion (Figure 1). The EEG was slightly and diffusely abnormal without any nonspecific focal or paroxysmal activity. Ophthalmologic investigation on the 2nd hospital day, including visual acuity, globe tension, fundi, visual fields, lens, and pupils, was normal. On transesophageal echocardiography (TEE), an inter-atrial hypermobile septum and a small PFO were detected. FIGURE 1. Hyperintense small expansive lesion in the right occipital pole shown on a transverse fluid attenuated inversion recovery (FLAIR) MR image (left panel). The correlating diffusion weighted sequence depicts a diffusion disturbance supporting the diagnosis of a small ischemic infarction (right panel). Int J Neurosci Downloaded from informahealthcare.com by CDL-UC Davis on 10/27/14 For personal use only. 122 J. Finsterer et al. 122 Migraine, Stroke, and Patent Foramen Ovale 123 Int J Neurosci Downloaded from informahealthcare.com by CDL-UC Davis on 10/27/14 For personal use only. Acetylsalicylic acid was prescribed. Because of the increased risk of stroke in patients with PFO and migraine (Del Sette et al., 1998; Lamy et al., 2002; Ries et al., 1996; Sztajzel et al., 2002), she underwent closure of the PFO by means of an Amplatzer PFO occlusion device (AGA Medical, Minneapolis, Minnesota, USA) nine weeks after the stroke. Since then she did not experience a further cerebrovascular event or migraine attack. Since the stroke she refrained from smoking and was regularly drinking 21 of liquids/day. DISCUSSION The foramen ovale, a remnant from the fetal circulation, remains patent through adulthood in approximately one quarter of the general population. PFO with right-to-left shunt (RLS) is a well-established risk factor for ischemic stroke due to paradoxical embolism in the young without other risk factors for stroke/embolism (Anzola et al., 1999; Cabanes et al., 1993; DiTullio et al., 1992, Lechatet al., 1988; Webster, 1988). Several studies have found that PFO is about twice as frequent in patients with stroke than in unselected healthy controls (Del Sette et al., 1998). On the contrary, other studies found a relation between PFO and stroke only if the amount of shunt was considerable (Serena et al., 1998). Anzola et al. (1999) revealed PFO as an independent predictor of stroke only in those patients in whom >10 microbubbles were tracked by TCD. PFO is usually diagnosed by TEE or TCD (Del Sette et al., 1998). Paradoxical embolism may occur through a PFO. In patients with suspected paradoxical embolism DVT is usually not easy to diagnose, despite extensive investigation (Khiani et al., 2002). Failure to document a DVT after stroke, however, does not exclude paradoxical embolism, considering the origin of paradoxical embolism a small DVT. Despite the growing recognition of PFO in the etiology of embolism, the optimal treatment for symptomatic patients is unknown. Therapeutic options are no treatment, anticoagulation, or surgical or interventional closure of the PFO. Side effects of interventional PFO occlusion may be dislocation of the device, thrombus formation at the device, pericardial effusion and tamponade, induction of arrhythmias, and endocarditis. Furthermore, PFO occlusion may have a strong placebo effect. Int J Neurosci Downloaded from informahealthcare.com by CDL-UC Davis on 10/27/14 For personal use only. 124 J. Finsterer et al. Although under debate, migraine with aura is considered a risk factor for ischemic stroke, at least in women >35 years (Buring et al., 1995; Chang et al., 1999; Del Sette et al., 1998; Merikangas et al., 1997). Migraine with aura is, like transient global amnesia, a paroxysmal disturbance in which a sudden dysfunction of cortical areas, fed by the terminal branches of the cerebral arteries, is believed to trigger the attack (Anzola et al., 1999). Focal areas of hypoperfusion (low blood flow) close to the ischemic threshold may be found in occipital regions during the aura phase (Sztajzel et al., 2002; Woods et al., 1994). Furthermore, platelet activation (hyperaggreagability) has been demonstrated in patients with migraine with aura (Kitano et al., 1994). Additionally, endothelial abnormalities are assumed to be involved in the pathogenesis of migraine (Kitano, 1994). This explains why oral anticoagulation reduces the frequency of migraine attacks (Fragoso, 1997). Cerebral infarction in migraine may be due to severe and prolonged vasoconstriction (vasospasm) and activation of the clotting cascade, leading to prolonged hypoperfusion and lastly infarction (Ries et al., 1996; Caplan, 1996). Furthermore, alterations in the arterioles and capillaries are made responsible for stroke in migraine (Ries, 1996). Indications that the simultaneous occurrence of PFO and migraine further enhances the risk of stroke (Del Sette et al., 1998; Lamy et al., 2002; Ries et al., 1996; Sztajzel et al., 2002) are the following: (1) Migraine is more prevalent in cryptogenic stroke patients with PFO than in those without PFO (Lamy et al., 2002; Wilmshurst et al., 2000). Among 44 stroke patients with PFO, 36% had migraine with aura (Sztajzel, 2002). Rather migraine with aura than migraine without aura harbors the chance of a cerebrovascular event. The increased risk of stroke in patients with migraine with aura and PFO is explained by the increased propensity to paradoxical embolism (Anzola et al., 1999). (2) A PFO is twice as frequent in migraine patients than in healthy controls (Del Sette et al., 1998; Anzola, 1999). In a study of 44 patients with migraine with aura, 41% had a PFO, diagnosed by TCD (Del Sette et al., 1998). This prevalence is similar to that of PFO in young patients with stroke and significantly higher than that of normal individuals (Del Sette et al., 1998). (3) In 7 of 15 patients with migraine and PFO, oral anticoagulation Int J Neurosci Downloaded from informahealthcare.com by CDL-UC Davis on 10/27/14 For personal use only. Migraine, Stroke, and Patent Foramen Ovale 125 or surgical closure of the PFO led to complete disappearance of the migraine attacks (Fragoso, 1997). To explain migraine in patients with PFO the following speculations were raised: (1) showers of microemboli crossing a PFO cause cerebral vasospasms and thus migraine (Khiani et al., 2002). (2) A particular genetic substrate determines bath the PFO and migraine (Del Sette et al., 2002). (3) PFO allows migraine triggers (vasoactive agents) in venous blood to bypass the pulmonary filter and reach the systemic circulation (Wilmshurst et al., 2000). Whether the degree of shunt is related to the severity of migraine is controversially discussed. In a study by Wilmshurst et al. (2000) patients with large PFO had an increased prevalence of migraine with aura compared to patients with small PFO. Another study found that there is no increased prevalence of migraine with the degree of shunt (Lamy et al., 2002). However, there may be a subgroup of patients with severe migraine and large PFO in whom closure of the atrial defect improves or abolishes migraine (Wilmshurst et al., 2000). The presented case is noteworthy because the visual aura was attributable to the same cerebral region in which the ischemic stroke occurred. Arguments against a causal relation between PFO and stroke in the presented patient are: (1) PFO is a frequent finding also in the general population (27% at autopsy). (2) PFO is related to stroke only when the amount of RLS is considerable (Serena, 1998). Normally, there is no RLS across the PFO because the atrial septal flaps are closed due to the higher pressure in the left compared to the right atrium. Only during the Valsalva maneuver or in the diastole during normal breathing, a transient reversal of the intra-atrial pressure gradient may occur and open the connection between the atria (Anzola et al., 1999). (3) There were no symptoms or signs of a DVT prior to the stroke, although a DVT may remain undetected. DVT could have occurred due to hypovolemia. Arguments for migraine to have caused the stroke in the presented patient are that migraine and stroke were accompanied by transient visual field defects, both attributable to impairment of the occipital cortex and that it is rather unlikely that embolization through the PFO affected the same cerebral regions that were involved in the migraine attack. Whether the PFO closure or acteylsalicylic acid Int J Neurosci Downloaded from informahealthcare.com by CDL-UC Davis on 10/27/14 For personal use only. 126 J. Finsterer et al. was responsible for the therapeutic success during almost one year remains speculative. Limitations of this study were that no conventional cerebral angiography was carried out, that no search for DVT was initiated, and that the follow-up period to assess the effect of PFO occlusion was short. This case shows that in a patient with PFO and migraine with aura and migraine sans migraine, respectively, a stroke may occur in that region, which is involved in the migraine attack. Closure of the PFO reduces frequency and intensity of the migraine attacks and prevents further paradoxical embolism. REFERENCES Auzola, G. P., Magoni, M., Guindani, M., Rozzini, L., Dalia Volta, G. (1999). Potential source of cerebral embolism in migraine with aura: A transcranial Doppler study. Neurology, 52, 1622–1625. Buring, J. E., Hebert, P., Romero, J., Kittors, A., Cook, N., Manson, J., Peto, R., & Hennekens, C. (1995). Migraine and subsequent risk of stroke in the Physicians Health Study. Archives in Neurology, 52, 129–134. Cabanes, L., Mas, J. L., Cohen, A., Amarenco, P., Cabanes, P. A., Oubary, P., Chedru, F., Guerin, F., Bousser, M. G., & de Recondo, J. (1993). Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age. A study using transesophageal echocardiography. Stroke, 24, 1865–1873. Caplan, L. R. (1996). Migraine and posterior circulation stroke. In L. R. Caplan (Ed.), Posterior circulation diseases: clinical findings, diagnosis and management (pp. 544– 568). Cambridge: Blackwell Science. Chang, C. L., Donaghy, M., Poulter, N., & World Health Organisation Collaborative study of cardiovascular disease and steroid hormone contraception. (1999). Migraine and stroke in young women: Case control study. British Medical Journal, 318, 13–18. Del Sette, M., Angeli, S., Leandri, M., Ferriero, G., Bruzzone, G. L., Finocchi, C., & Gandolfo, C. (1998). Migraine with aura and right-to-left shunt on transcranial Doppler: A casecontrol study. Cerebrovascular Disease, 8, 327–330. DiTullio, M., Sacco, R. L., Gopal, A., Mohr, J. P., & Homma, S. (1992). Patent foramen ovale as a risk factor for cryptogenic stroke. Annals of Internal Medicine, 117, 461–465. Fragoso, Y. D. (1997). Reduction of migraine attacks during the use of warfarin. Headache, 37, 667–668. Headache classification committee of the International Headache Society. (1988). Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia, 8(suppl 7), 1–93. Khiani, R., Daly, K., & McCollum, C. (2002). Clinical and imaging findings in cryptogenic stroke patients with and without patent foramen ovale. Stroke, 33, 2149–2150. Kitano, A., Shimomura, T., Takeshima, T., & Takahashi, K. (1994). Increased 11-dehydrothromboxane B2 in migraine: Platelet hyperfunction in patients with migraine during headache-free periods. Headache, 34, 515–518. Lamy, C., Giannesini, C., Zuber, M., Arquizan, C., Meder, J. F., Txystram, D., Coste, J., & Mas, J. L. (2002). Clinical and imaging findings in cryptogenic stroke patients with and without patent foramen ovale: The PFO-ASA Study. Atrial Septal Aneurysm. Stroke, 33, 706–711. Int J Neurosci Downloaded from informahealthcare.com by CDL-UC Davis on 10/27/14 For personal use only. Migraine, Stroke, and Patent Foramen Ovale 127 Lechat, P., Mas, J. L., Lascault, G., Klimczac, M., Drobinski, G., Thomas, D., & Grosgogeat, Y. (1988). Prevalence of patent foramen ovale in patients with stroke. New England Journal of Medicine, 318, 1148–1152. Merikangas, K. R., Fenton, B. T., Cheng, S. H., Stolar, M. J., & Risch, N. (1997). Association between migraine and stroke in a large-scale epidemiological study of the United States. Archives of Neurology, 54, 362–368. Ries, S., Steinke, W., Neff, W., Schindlmayr, C., Meairs, S., & Hennerici, M. (1996). Ischemia-induced migraine from paradoxical cardioembolic stroke. European Neurology, 36, 76–78. Serena, J., Segura, T., Perez-Ayuso, M. J., Bassaganyas, J., Molins, A., & Davalos, A. (1998). The need to quantify right-to-left shunt in acute ischemic stroke. A case controlled study. Stroke, 29, 1322–1328. Sztajzel, R., Genoud, D., Roth, S., Mermillod, B., & Le Floch-Rohr, J. (2002). Patent foramen ovale, a possible cause of symptomatic migraine: A study of 74 patients with acute ischemic stroke. Cerebrovascular Disease, 13, 102–106. Webster, M. W., Chancellor, A. M., Smith, H. J., Swift, D. L., Sharpe, D. N., Bass, N. M., & Glasgow, G. L. (1988). Patent foramen ovale in young stroke patients. Lancet, 2, 11–12. Wilmshurst, P. T., Nightingale, S., Walsh, K. P., & Morrison, W. L. (2000). Effect on migraine of closure of cardiac right-to-left shunts to prevent recurrence of decompression illness or stroke or for haemodynamic reasons. Lancet, 356, 1648–1651. Woods, R. P., Iacoboni, M., & Mazinotta, J. C. (1994). Bilateral spreading cerebral hypoperfusion during spontaneous migraine headache. New England Journal of Medicine, 331, 1689– 1692.