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Stroke after prolonged air travel associated with a pulmonary arteriovenous malformation
Journal of the Neurological Sciences 292 (2010) 99–100
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Stroke after prolonged air travel associated with a pulmonary arteriovenous malformation Isabel Pareés a,⁎, Alejandro Horga a, Estevo Santamarina a, Maite Mendióroz b, Israel Fernández-Cádenas b, Alberto del Río-Espínola b, José Álvarez-Sabín a a b
Department of Neurology, Hospital Vall d'Hebron, Barcelona, Spain Neurovascular Research Laboratory, Hospital Vall d'Hebron, Barcelona, Spain
a r t i c l e
i n f o
Article history: Received 1 December 2009 Received in revised form 19 February 2010 Accepted 22 February 2010 Available online 16 March 2010 Keywords: Stroke Pulmonary arteriovenous malformation Thrombolysis Hereditary haemorrhagic telangiectasia
a b s t r a c t Several reports describe a potential association between prolonged flights and stroke. However, causes of travel-related stroke due to paradoxal embolism other than patent foramen ovale have not been previously reported. We here describe the case of a 44-year-old woman who presented with an acute anterior circulation stroke after a transoceanic flight. The patient received intravenous thrombolytic therapy, with complete recanalization of the anterior and middle cerebral arteries. Contrast transthoracic echocardiography was suggestive of an extracardiac right-to-left shunt. Both cardiothoracic CT and MR angiography revealed a single pulmonary arteriovenous malformation (PAVM) in the lower lobe of the right lung. No cardiac abnormalities were identified. Careful examination of the patient revealed telangiectatic skin lesions, and recurrent epistaxis was reported to occur in first-grade relatives. Genetic testing for hereditary haemorrhagic telangiectasia revealed no mutations in the endoglin and activin receptor-like kinase 1 genes. Intravascular embolization of the PAVM was performed and effective occlusion was later confirmed. To our knowledge, this is the first reported case of travel-related stroke associated with a PAVM. These should be considered in patients with stroke after prolonged flights, particularly when right-to-left shunt is detected and patent foramen ovale is ruled out. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Venous thrombotic events are well-established complications of long-haul air travels. Prolonged immobilization with flexed lower limbs, dehydration and hypobaric hypoxia are probable contributing factors [1,2]. In contrast, arterial thromboembolism and ischemic stroke are extremely rare in this context. Several reports describe a potential association between prolonged flights and stroke due to paradoxal embolism through patent foramen ovale (PFO) or due to cervicocephalic arterial dissection [3,4]. However, causes of paradoxal embolism other than PFO have not been previously described. We here report a case of stroke after a prolonged flight associated with a pulmonary arteriovenous malformation (PAVM).
2. Case report In July, 2006, a 44-year-old woman was admitted to the hospital because of an acute stroke. Her medical history was unremarkable. Five days before the admission, she had travelled by airplane from San ⁎ Corresponding author. Department of Neurology, Hospital Vall d'Hebron, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. Tel.: +34 932746607; fax: +34 932746235. E-mail address: [email protected] (I. Pareés). 0022-510X/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2010.02.019
José, Costa Rica, to Barcelona, Spain (8961 km). Initial neurological examination revealed a complete right middle cerebral artery syndrome. Results of chest radiography, electrocardiography and laboratory tests were unremarkable. Cerebral MRI disclosed an acute ischemic infarction in the territory of the right middle and anterior cerebral arteries with perfusion–diffusion mismatch. MR angiography confirmed the occlusion of both arteries and no signs of cervicocephalic arterial dissection. Intravenous thrombolysis with recombinant tissue plasminogen activator was initiated 2 h after symptoms onset. Transcranial Doppler sonography confirmed middle cerebral artery recanalization 15 min after treatment administration. Twenty-four hours later, the patient was asymptomatic, and a second cerebral MRI showed complete recanalization of the anterior and middle cerebral arteries with no residual intracranial arterial stenosis. Paradoxical embolism was suspected because of recent air travel. A right-to-left shunt was detected by contrast transthoracic echocardiography. Following peripheral injection of agitated saline, echo contrast first appeared in the right atrium and ventricle and then subsequently appeared in the left atrium after approximately five cardiac cycles, suggesting an extracardiac shunt. No arrhythmias were observed on 24 h Holter monitoring. An extensive thrombophilia screening including homocysteine plasma levels and the search for factor V Leiden, the G20210A prothrombin mutation, lupus anticoagulant, anticardiolipin antibodies and deficiencies of antithrombin,
100
I. Pareés et al. / Journal of the Neurological Sciences 292 (2010) 99–100
Fig. 1. Cardiothoracic CT angiography of the patient showing a pulmonary arteriovenous malformation, with a feeding artery (arrow) and draining vein (arrowhead), in the lower lobe of the right lung.
protein C, protein S and plasminogen revealed no abnormalities. Deep venous thrombosis (DVT) was not demonstrated by vascular ultrasound assessment of the limbs and abdominopelvic CT venography performed two days after thrombolytic therapy. Both cardiothoracic CT and MR angiography revealed a single PAVM in the lower lobe of the right lung (Fig. 1). No cardiac abnormalities were identified on either echocardiography or MRI, and gasometric and spirometric parameters were within normal limits. Careful physical examination revealed several telangiectatic skin lesions, and hereditary haemorrhagic telangiectasia (HHT) was suspected. Recurrent epistaxis was reported to occur in patient's mother and son. Genetic testing of the patient detected no mutations in the endoglin and activin receptorlike kinase 1 genes. Possible HHT diagnosis was made according to consensus criteria [5]. Intravascular embolization of the PAVM was performed, and occlusion was later confirmed by transcranial Doppler sonography and echocardiography following intravenous injection of agitated saline contrast. The patient remains asymptomatic since then. 3. Discussion Since Beighton and Richards described stroke as a complication of long-haul air travel for the first time in 1968, several cases were subsequently reported [6,7]. More recently, an observational study investigated the frequency of positive travel history in patients with acute stroke as well as related risk factors, stroke patterns and presence of PFO. Positive travel history was defined as a travel, mainly in a sitting position, of at least 4 h in duration, and median delay between travel and stroke was 7 days. Patients with positive travel history more frequently had PFO and cardioembolic or cryptogenic strokes, and less frequently conventional stroke risk factors compared with those without travel history [8]. These findings suggest that paradoxal embolism through PFO may be a major cause for travelassociated stroke, and supports previous observations. However, causes of paradoxal embolism in patients with stroke after prolonged flights other than PFO have not been described to date.
In the present case, an extracardiac shunt through a PAVM was confirmed, while cardiac sources and other potential aetiologies were excluded after an extensive investigation. Therefore, we consider that paradoxal embolism through the PAVM was the most probable pathophysiological mechanism of stroke. Similar to previous reports, no evidence of DVT was found. This fact, however, does not necessarily diminish the probability of flight-associated paradoxal cerebral embolism, since DVT is found in only 31% of patients with this condition [7]. In our case, previous administration of systemic thrombolytic therapy might explain the normal findings of venous imaging studies. Nevertheless, the possibility of an undetected thrombus, particularly in the pelvic veins or originated from the PAVM, cannot be completely excluded. Paradoxal embolism through PAVM is an uncommon but welldocumented mechanism of stroke [9,10]. PAVM is a vascular anomaly consisting of direct communications between pulmonary artery and veins without an intervening capillary bed. More than 80% of PAVM are congenital. Of these, 70% are associated with HHT. The fundamental pathophysiological defect in PAVM is a right-to-left shunt, and clinical features are related to hypoxemia, malformation rupture and paradoxal embolism to the systemic circulation [9]. The prevalence of stroke in patients with PAVM is variable, depending on whether they have single or multiple malformations (radiological evidence of cortical infarctions in 14% and 27% of patients, respectively) [10]. Although the most appropriate treatment of PAVM is a matter of debate, percutaneous transcatheter coil vasoocclusion of the feeding artery is currently regarded as the treatment of choice [11]. To our knowledge, this is the first reported case of stroke in a patient with recent history of a prolonged flight associated with a PAVM. This should be strongly considered when PFO and cervicocephalic arterial dissection are ruled out, and right-to-left shunt is detected by echocardiography or transcranial Doppler sonography. Moreover, this observation emphasizes the need for extensive etiological investigation not only in patients with travel-associated stroke, but also in those with other risk factors for venous thrombosis. In this era of frequent air travel, identification of those disorders may be critical for prevention of further thromboembolic events.
References [1] Kuipers S, Cannegieter SC, Middeldorp S, Robyn L, Büller HR, Rosendaal FR. The absolute risk of venous thrombosis after air travel: a cohort study of 8,755 employees of international organisations. PLoS Med 2007;4:e290. [2] Bendz B, Rostrup M, Sevre K, Andersen TO, Sandset PM. Association between acute hypobaric hypoxia and activation of coagulation in human beings. Lancet 2000;356:1657–8. [3] Belvís R, Masjuan J, García-Barragán N, Cocho D, Martí-Fàbregas J, Santamaría A, et al. Stroke and pulmonary thromboembolism after a long flight. Eur J Neurol 2005;12:732–4. [4] Lewis MJ, Greenwood RJ, Brew S, Jager HR. Economy class stroke syndromes: vertebral artery dissection revisited. J Neurol Neurosurg Psychiatry 2003;74: 1594–5. [5] Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu–Osler– Weber syndrome). Am J Med Genet 2000;91:66–7. [6] Beighton PH, Richards PR. Cardiovascular disease in air travellers. Br Heart J 1968;30:367–72. [7] Kakkos SK, Geroulakos G. Economy class stroke syndrome: case report and review of the literature. Eur J Vasc Endovasc Surg 2004;27:239–43. [8] Heckmann JG, Stadter M, Reulbach U, Duetsch M, Nixdorff U, Ringwald J. Increased frequency of cardioembolism and patent foramen ovale in patients with stroke and a positive travel history suggesting economy class stroke syndrome. Heart 2006;92:1265–8. [9] Khurshid I, Downie GH. Pulmonary arteriovenous malformation. Postgrad Med J 2002;78:191–7. [10] 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. [11] Grosso M, Groppo Marchisio F, Testa F, Gallarato G, Balderi A, Lingua G, et al. Pulmonary arteriovenous malformations: percutaneous treatment preserving parenchyma in high-flow fistulae. Radiol Med 2008;113:395–413.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Stroke after prolonged air travel associated with a pulmonary arteriovenous malformation Isabel Pareés a,⁎, Alejandro Horga a, Estevo Santamarina a, Maite Mendióroz b, Israel Fernández-Cádenas b, Alberto del Río-Espínola b, José Álvarez-Sabín a a b
Department of Neurology, Hospital Vall d'Hebron, Barcelona, Spain Neurovascular Research Laboratory, Hospital Vall d'Hebron, Barcelona, Spain
a r t i c l e
i n f o
Article history: Received 1 December 2009 Received in revised form 19 February 2010 Accepted 22 February 2010 Available online 16 March 2010 Keywords: Stroke Pulmonary arteriovenous malformation Thrombolysis Hereditary haemorrhagic telangiectasia
a b s t r a c t Several reports describe a potential association between prolonged flights and stroke. However, causes of travel-related stroke due to paradoxal embolism other than patent foramen ovale have not been previously reported. We here describe the case of a 44-year-old woman who presented with an acute anterior circulation stroke after a transoceanic flight. The patient received intravenous thrombolytic therapy, with complete recanalization of the anterior and middle cerebral arteries. Contrast transthoracic echocardiography was suggestive of an extracardiac right-to-left shunt. Both cardiothoracic CT and MR angiography revealed a single pulmonary arteriovenous malformation (PAVM) in the lower lobe of the right lung. No cardiac abnormalities were identified. Careful examination of the patient revealed telangiectatic skin lesions, and recurrent epistaxis was reported to occur in first-grade relatives. Genetic testing for hereditary haemorrhagic telangiectasia revealed no mutations in the endoglin and activin receptor-like kinase 1 genes. Intravascular embolization of the PAVM was performed and effective occlusion was later confirmed. To our knowledge, this is the first reported case of travel-related stroke associated with a PAVM. These should be considered in patients with stroke after prolonged flights, particularly when right-to-left shunt is detected and patent foramen ovale is ruled out. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Venous thrombotic events are well-established complications of long-haul air travels. Prolonged immobilization with flexed lower limbs, dehydration and hypobaric hypoxia are probable contributing factors [1,2]. In contrast, arterial thromboembolism and ischemic stroke are extremely rare in this context. Several reports describe a potential association between prolonged flights and stroke due to paradoxal embolism through patent foramen ovale (PFO) or due to cervicocephalic arterial dissection [3,4]. However, causes of paradoxal embolism other than PFO have not been previously described. We here report a case of stroke after a prolonged flight associated with a pulmonary arteriovenous malformation (PAVM).
2. Case report In July, 2006, a 44-year-old woman was admitted to the hospital because of an acute stroke. Her medical history was unremarkable. Five days before the admission, she had travelled by airplane from San ⁎ Corresponding author. Department of Neurology, Hospital Vall d'Hebron, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. Tel.: +34 932746607; fax: +34 932746235. E-mail address: [email protected] (I. Pareés). 0022-510X/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2010.02.019
José, Costa Rica, to Barcelona, Spain (8961 km). Initial neurological examination revealed a complete right middle cerebral artery syndrome. Results of chest radiography, electrocardiography and laboratory tests were unremarkable. Cerebral MRI disclosed an acute ischemic infarction in the territory of the right middle and anterior cerebral arteries with perfusion–diffusion mismatch. MR angiography confirmed the occlusion of both arteries and no signs of cervicocephalic arterial dissection. Intravenous thrombolysis with recombinant tissue plasminogen activator was initiated 2 h after symptoms onset. Transcranial Doppler sonography confirmed middle cerebral artery recanalization 15 min after treatment administration. Twenty-four hours later, the patient was asymptomatic, and a second cerebral MRI showed complete recanalization of the anterior and middle cerebral arteries with no residual intracranial arterial stenosis. Paradoxical embolism was suspected because of recent air travel. A right-to-left shunt was detected by contrast transthoracic echocardiography. Following peripheral injection of agitated saline, echo contrast first appeared in the right atrium and ventricle and then subsequently appeared in the left atrium after approximately five cardiac cycles, suggesting an extracardiac shunt. No arrhythmias were observed on 24 h Holter monitoring. An extensive thrombophilia screening including homocysteine plasma levels and the search for factor V Leiden, the G20210A prothrombin mutation, lupus anticoagulant, anticardiolipin antibodies and deficiencies of antithrombin,
100
I. Pareés et al. / Journal of the Neurological Sciences 292 (2010) 99–100
Fig. 1. Cardiothoracic CT angiography of the patient showing a pulmonary arteriovenous malformation, with a feeding artery (arrow) and draining vein (arrowhead), in the lower lobe of the right lung.
protein C, protein S and plasminogen revealed no abnormalities. Deep venous thrombosis (DVT) was not demonstrated by vascular ultrasound assessment of the limbs and abdominopelvic CT venography performed two days after thrombolytic therapy. Both cardiothoracic CT and MR angiography revealed a single PAVM in the lower lobe of the right lung (Fig. 1). No cardiac abnormalities were identified on either echocardiography or MRI, and gasometric and spirometric parameters were within normal limits. Careful physical examination revealed several telangiectatic skin lesions, and hereditary haemorrhagic telangiectasia (HHT) was suspected. Recurrent epistaxis was reported to occur in patient's mother and son. Genetic testing of the patient detected no mutations in the endoglin and activin receptorlike kinase 1 genes. Possible HHT diagnosis was made according to consensus criteria [5]. Intravascular embolization of the PAVM was performed, and occlusion was later confirmed by transcranial Doppler sonography and echocardiography following intravenous injection of agitated saline contrast. The patient remains asymptomatic since then. 3. Discussion Since Beighton and Richards described stroke as a complication of long-haul air travel for the first time in 1968, several cases were subsequently reported [6,7]. More recently, an observational study investigated the frequency of positive travel history in patients with acute stroke as well as related risk factors, stroke patterns and presence of PFO. Positive travel history was defined as a travel, mainly in a sitting position, of at least 4 h in duration, and median delay between travel and stroke was 7 days. Patients with positive travel history more frequently had PFO and cardioembolic or cryptogenic strokes, and less frequently conventional stroke risk factors compared with those without travel history [8]. These findings suggest that paradoxal embolism through PFO may be a major cause for travelassociated stroke, and supports previous observations. However, causes of paradoxal embolism in patients with stroke after prolonged flights other than PFO have not been described to date.
In the present case, an extracardiac shunt through a PAVM was confirmed, while cardiac sources and other potential aetiologies were excluded after an extensive investigation. Therefore, we consider that paradoxal embolism through the PAVM was the most probable pathophysiological mechanism of stroke. Similar to previous reports, no evidence of DVT was found. This fact, however, does not necessarily diminish the probability of flight-associated paradoxal cerebral embolism, since DVT is found in only 31% of patients with this condition [7]. In our case, previous administration of systemic thrombolytic therapy might explain the normal findings of venous imaging studies. Nevertheless, the possibility of an undetected thrombus, particularly in the pelvic veins or originated from the PAVM, cannot be completely excluded. Paradoxal embolism through PAVM is an uncommon but welldocumented mechanism of stroke [9,10]. PAVM is a vascular anomaly consisting of direct communications between pulmonary artery and veins without an intervening capillary bed. More than 80% of PAVM are congenital. Of these, 70% are associated with HHT. The fundamental pathophysiological defect in PAVM is a right-to-left shunt, and clinical features are related to hypoxemia, malformation rupture and paradoxal embolism to the systemic circulation [9]. The prevalence of stroke in patients with PAVM is variable, depending on whether they have single or multiple malformations (radiological evidence of cortical infarctions in 14% and 27% of patients, respectively) [10]. Although the most appropriate treatment of PAVM is a matter of debate, percutaneous transcatheter coil vasoocclusion of the feeding artery is currently regarded as the treatment of choice [11]. To our knowledge, this is the first reported case of stroke in a patient with recent history of a prolonged flight associated with a PAVM. This should be strongly considered when PFO and cervicocephalic arterial dissection are ruled out, and right-to-left shunt is detected by echocardiography or transcranial Doppler sonography. Moreover, this observation emphasizes the need for extensive etiological investigation not only in patients with travel-associated stroke, but also in those with other risk factors for venous thrombosis. In this era of frequent air travel, identification of those disorders may be critical for prevention of further thromboembolic events.
References [1] Kuipers S, Cannegieter SC, Middeldorp S, Robyn L, Büller HR, Rosendaal FR. The absolute risk of venous thrombosis after air travel: a cohort study of 8,755 employees of international organisations. PLoS Med 2007;4:e290. [2] Bendz B, Rostrup M, Sevre K, Andersen TO, Sandset PM. Association between acute hypobaric hypoxia and activation of coagulation in human beings. Lancet 2000;356:1657–8. [3] Belvís R, Masjuan J, García-Barragán N, Cocho D, Martí-Fàbregas J, Santamaría A, et al. Stroke and pulmonary thromboembolism after a long flight. Eur J Neurol 2005;12:732–4. [4] Lewis MJ, Greenwood RJ, Brew S, Jager HR. Economy class stroke syndromes: vertebral artery dissection revisited. J Neurol Neurosurg Psychiatry 2003;74: 1594–5. [5] Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu–Osler– Weber syndrome). Am J Med Genet 2000;91:66–7. [6] Beighton PH, Richards PR. Cardiovascular disease in air travellers. Br Heart J 1968;30:367–72. [7] Kakkos SK, Geroulakos G. Economy class stroke syndrome: case report and review of the literature. Eur J Vasc Endovasc Surg 2004;27:239–43. [8] Heckmann JG, Stadter M, Reulbach U, Duetsch M, Nixdorff U, Ringwald J. Increased frequency of cardioembolism and patent foramen ovale in patients with stroke and a positive travel history suggesting economy class stroke syndrome. Heart 2006;92:1265–8. [9] Khurshid I, Downie GH. Pulmonary arteriovenous malformation. Postgrad Med J 2002;78:191–7. [10] 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. [11] Grosso M, Groppo Marchisio F, Testa F, Gallarato G, Balderi A, Lingua G, et al. Pulmonary arteriovenous malformations: percutaneous treatment preserving parenchyma in high-flow fistulae. Radiol Med 2008;113:395–413.