J Neurol (2014) 261:632–634 DOI 10.1007/s00415-014-7286-y
LETTER TO THE EDITORS
Successful thrombolysis of stroke with intravenous alteplase in the third trimester of pregnancy Laura Mantoan Ritter • A. Schu¨ler • R. Gangopadhyay • L. Mordecai • O. Arowele N. Losseff • P. O’ Brien • B. Dewan
•
Received: 18 December 2013 / Revised: 10 February 2014 / Accepted: 12 February 2014 / Published online: 26 February 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Dear Sirs, Pregnancy and the puerperium are associated with haemostatic and haemodynamic changes resulting in an increased risk of stroke [1, 2]. As this group of patients was excluded from randomised trials, the only evidence currently available to guide the use of intravenous recombinant tissue plasminogen activator (rt-PA, Alteplase) in pregnant patients with acute ischaemic stroke consists of case series and reports. Only nine cases of intravenous L. Mantoan Ritter (&) N. Losseff The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK e-mail: [email protected] L. Mantoan Ritter O. Arowele N. Losseff B. Dewan Hyperacute Stroke Unit, University College London Hospital, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, UK A. Schu¨ler Department of Accident and Emergency, University College London Hospital, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, UK R. Gangopadhyay P. O’ Brien Department of Obstetrics and Gynaecology, Elizabeth Garrett Anderson Wing, Institute for Women’s Health, University College London Hospitals NHS Foundation Trust, 25 Grafton Way, London WC1E 6BD, UK L. Mordecai Department of Anaesthetics, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, UK B. Dewan Royal Free Neurosciences Department, Royal Free London NHS Foundation Trust, Pond Street, London NW3 2QG, UK
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thrombolysis in stroke occurring in the first two trimesters of pregnancy have been described to date [1, 3–6]. Here we report the first use and successful outcome of intravenous thrombolysis for acute ischaemic stroke in the third trimester of pregnancy. A 32-year-old Caucasian woman, at 36 weeks gestation into her first pregnancy, was admitted out of hours and within 40 min of a witnessed, sudden onset left middle cerebral artery syndrome consisting of receptive and expressive dysphasia, dysarthria, right-sided hemianopia, neglect to multiple modalities, a dense right-sided hemiplegia, and hemisensory loss. A day prior she had experienced short-lived symptoms suggestive of a left-sided amaurosis fugax. She had migraine with aura, but past medical, family, and social history was otherwise unremarkable . She had no risk factors for stroke apart from her pregnancy, which had been classified as ‘low risk’ at the booking in the first trimester. On admission, her Glasgow Coma Scale was 14/15 (E4 V4 M6). She was in sinus rhythm, normotensive, and normoglycaemic. Her National Institutes of Health Stroke Scale score (NIHSS) was 22/42. Continuous cardiotocographic recordings excluded any foetal distress. A CT head and CT angiogram (CTA) confirmed occlusion of the left lower M2 segment with infarction of the left posterior insula and inferior temporal lobe (Fig. 1a). Following agreement among the clinical teams (stroke, obstetrics, and neonatology) and the patient‘s husband, our patient was thrombolysed with 0.9 mg/kg intravenous rt-PA within 2 h from stroke onset. At 2 h post-thrombolysis her NIHSS score had improved significantly (13/42). Magnetic resonance imaging (MRI) performed subsequently showed an acute left posterior capsular infarct (Fig. 1b) with restricted diffusion (Fig. 1c, d). Further investigations revealed a haemoglobin level of 10.6 g/dl and a total cholesterol of 5.4 mmol/l. Other tests,
J Neurol (2014) 261:632–634
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Fig. 1 Intracranial imaging. a Admission CT showing subtle, low density and loss of grey-white differentiation in the posterior left insular and inferior left temporal lobe (arrow). b Post-thrombolysis T2 MRI sequence showing an acute left posterior capsular infarct with restricted diffusion on diffusion-weighted sequences (c) and
ADC map (d). e, f Formal 2-vessel angiography showing a smooth, focal, tear-shaped, partially occlusive intravascular filling defect within the left M2 bifurcation (arrows). g MR angiogram showing complete recanalization of the artery 3 months post-thrombolysis
including full blood count, clotting screen, electrolytes, renal and liver function tests, C-reactive protein, and auto-immune profile, were normal. A thrombophilia screen including antithrombin III, fibrinogen, Factor V Leiden mutation, protein C, free protein S, and Lupus Anticoagulant screen was unremarkable. Carotid Doppler and Magnetic Resonance Angiography with fat-saturated sequences were normal and ruled out extracranial dissection as a potential aetiology. A normal transoesophageal echocardiogram and CT pulmonary angiogram excluded right-to-left shunts and a two-vessel angiogram did not show changes suggestive of intracranial vasculitis (Fig. 1e, f). After thrombolysis, antiplatelet treatment with 150 mg Aspirin was started and continued until
delivery, when this was changed to Clopidogrel 75 mg, which she was advised to continue for life. Ecographic examination of the foetus after thrombolysis was normal, and no uterine or placental haemorrhages were detected. At term, she was delivered of a healthy male infant by an uncomplicated Caesarean section. On discharge from rehabilitation, 4 months after symptom onset, she was assessed by the Neurology Registrar (LMR) who admitted and thrombolysed her: her cognition and speech were normal, she had a mild residual right sided hemiplegia but was fully independent in walking and all activities of daily living, achieving a final modified Rankin Scale score of 2.
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The use of intravenous (iv) rt-PA in pregnancy continues to be a controversial topic, without trial evidence to guide treatment decisions [7, 8]. Only a few published cases report its use for ischaemic stroke either in early stages of pregnancy or by using intra-arterial thrombolysis [1, 3–6]. Further supportive evidence in favour of using iv rt-PA in later stages of pregnancy can be found in reports of thrombolysis used for treating massive pulmonary embolism [9], venous embolism, myocardial infarction, or embolism from cardiac prosthetic valves, with no increased risk of an adverse outcome compared to the normal population [10]. Due to its large molecular weight, rt-PA does not cross the blood-placenta barrier and is thought to be of low risk to the foetus. After careful evaluation, we felt that our patient’s case fulfilled a number of thrombolysis eligibility criteria [7, 8]: she presented at a centre with hyperacute stroke, anaesthetic, obstetric, and neonatal facilities and expertise (No endovascular team was available out-of hours to consider intra-arterial rt-PA). Her stroke was severe, she had no other medical co-morbidities, and she presented early. The location of the arterial occlusion was identified and confirmed by CTA. Finally, her pregnancy was in the third trimester, allowing for an emergency Caesarean section in case of complications and for CT scanning without risk of teratogenicity. Whilst thrombolysis of strokes in pregnancy should continue to be evaluated on a case-by-case basis, this is the first report describing its safe intravenous use in the third trimester of pregnancy. Acknowledgments L. Mantoan Ritter wrote the manuscript. B. Dewan revised and supervised the preparation of the manuscript. A. Schu¨ler, R. Gangopadhyay, L. Mordecai, O. Arowele, N. Losseff, and P. O’Brien revised the manuscript.
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J Neurol (2014) 261:632–634 Ethical standards The patient gave informed consent to the publication of this case report. Conflicts of interest of interest.
The authors declare that they have no conflict
References 1. Del Zotto E, Giossi A, Volonghi I et al (2011) Ischemic stroke during pregnancy and puerperium. Stroke Res Treat. Article ID 606780. doi:10.4061/2011/606780 2. Davie CA, O’Brien P (2008) Stroke and pregnancy. J Neurol Neurosurg Psychiatry 79(3):240–245 3. Yamaguchi Y, Kondo T, Ihara M et al (2010) Intravenous recombinant tissue plasminogen activator in an 18-week pregnant woman with embolic stroke. Rinsho Shinkeigaku 50(5):315–319 4. Hori H, Yamamoto F, Ito Y et al (2013) Intravenous recombinant tissue plasminogen activator therapy in a 14-week pregnant woman with embolic stroke due to protein S deficiency. Rinsho Shinkeigaku 53(3):212–216 5. Tassi R, Acampa M, Marotta G et al (2013) Systemic thrombolysis for stroke in pregnancy. Am J Emerg Med 31(2):448.e1–448.e3 6. Hirano T (2013) Acute revascularization therapy in pregnant patients. Neurol Med Chir (Tokyo) 53:531–536 7. Selim MH, Molina CA (2013) The use of tissue plasminogenactivator in pregnancy. A taboo treatment or a time to think out of the box. Stroke 44:868–869 8. Broderick JP (2013) Should intravenous thrombolysis be considered the first option in pregnant women? Stroke 44:866–867 9. Fasullo S, Maringhini G, Terrazzino G et al (2011) Thrombolysis for massive pulmonary embolism in pregnancy: a case report. Int J Emerg Med 4:69 10. Leonhardt G, Gaul C, Nietsch HH et al (2006) Thrombolytic therapy in pregnancy. J Thromb Thrombolysis 21:271–276
LETTER TO THE EDITORS
Successful thrombolysis of stroke with intravenous alteplase in the third trimester of pregnancy Laura Mantoan Ritter • A. Schu¨ler • R. Gangopadhyay • L. Mordecai • O. Arowele N. Losseff • P. O’ Brien • B. Dewan
•
Received: 18 December 2013 / Revised: 10 February 2014 / Accepted: 12 February 2014 / Published online: 26 February 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Dear Sirs, Pregnancy and the puerperium are associated with haemostatic and haemodynamic changes resulting in an increased risk of stroke [1, 2]. As this group of patients was excluded from randomised trials, the only evidence currently available to guide the use of intravenous recombinant tissue plasminogen activator (rt-PA, Alteplase) in pregnant patients with acute ischaemic stroke consists of case series and reports. Only nine cases of intravenous L. Mantoan Ritter (&) N. Losseff The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK e-mail: [email protected] L. Mantoan Ritter O. Arowele N. Losseff B. Dewan Hyperacute Stroke Unit, University College London Hospital, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, UK A. Schu¨ler Department of Accident and Emergency, University College London Hospital, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, UK R. Gangopadhyay P. O’ Brien Department of Obstetrics and Gynaecology, Elizabeth Garrett Anderson Wing, Institute for Women’s Health, University College London Hospitals NHS Foundation Trust, 25 Grafton Way, London WC1E 6BD, UK L. Mordecai Department of Anaesthetics, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, UK B. Dewan Royal Free Neurosciences Department, Royal Free London NHS Foundation Trust, Pond Street, London NW3 2QG, UK
123
thrombolysis in stroke occurring in the first two trimesters of pregnancy have been described to date [1, 3–6]. Here we report the first use and successful outcome of intravenous thrombolysis for acute ischaemic stroke in the third trimester of pregnancy. A 32-year-old Caucasian woman, at 36 weeks gestation into her first pregnancy, was admitted out of hours and within 40 min of a witnessed, sudden onset left middle cerebral artery syndrome consisting of receptive and expressive dysphasia, dysarthria, right-sided hemianopia, neglect to multiple modalities, a dense right-sided hemiplegia, and hemisensory loss. A day prior she had experienced short-lived symptoms suggestive of a left-sided amaurosis fugax. She had migraine with aura, but past medical, family, and social history was otherwise unremarkable . She had no risk factors for stroke apart from her pregnancy, which had been classified as ‘low risk’ at the booking in the first trimester. On admission, her Glasgow Coma Scale was 14/15 (E4 V4 M6). She was in sinus rhythm, normotensive, and normoglycaemic. Her National Institutes of Health Stroke Scale score (NIHSS) was 22/42. Continuous cardiotocographic recordings excluded any foetal distress. A CT head and CT angiogram (CTA) confirmed occlusion of the left lower M2 segment with infarction of the left posterior insula and inferior temporal lobe (Fig. 1a). Following agreement among the clinical teams (stroke, obstetrics, and neonatology) and the patient‘s husband, our patient was thrombolysed with 0.9 mg/kg intravenous rt-PA within 2 h from stroke onset. At 2 h post-thrombolysis her NIHSS score had improved significantly (13/42). Magnetic resonance imaging (MRI) performed subsequently showed an acute left posterior capsular infarct (Fig. 1b) with restricted diffusion (Fig. 1c, d). Further investigations revealed a haemoglobin level of 10.6 g/dl and a total cholesterol of 5.4 mmol/l. Other tests,
J Neurol (2014) 261:632–634
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Fig. 1 Intracranial imaging. a Admission CT showing subtle, low density and loss of grey-white differentiation in the posterior left insular and inferior left temporal lobe (arrow). b Post-thrombolysis T2 MRI sequence showing an acute left posterior capsular infarct with restricted diffusion on diffusion-weighted sequences (c) and
ADC map (d). e, f Formal 2-vessel angiography showing a smooth, focal, tear-shaped, partially occlusive intravascular filling defect within the left M2 bifurcation (arrows). g MR angiogram showing complete recanalization of the artery 3 months post-thrombolysis
including full blood count, clotting screen, electrolytes, renal and liver function tests, C-reactive protein, and auto-immune profile, were normal. A thrombophilia screen including antithrombin III, fibrinogen, Factor V Leiden mutation, protein C, free protein S, and Lupus Anticoagulant screen was unremarkable. Carotid Doppler and Magnetic Resonance Angiography with fat-saturated sequences were normal and ruled out extracranial dissection as a potential aetiology. A normal transoesophageal echocardiogram and CT pulmonary angiogram excluded right-to-left shunts and a two-vessel angiogram did not show changes suggestive of intracranial vasculitis (Fig. 1e, f). After thrombolysis, antiplatelet treatment with 150 mg Aspirin was started and continued until
delivery, when this was changed to Clopidogrel 75 mg, which she was advised to continue for life. Ecographic examination of the foetus after thrombolysis was normal, and no uterine or placental haemorrhages were detected. At term, she was delivered of a healthy male infant by an uncomplicated Caesarean section. On discharge from rehabilitation, 4 months after symptom onset, she was assessed by the Neurology Registrar (LMR) who admitted and thrombolysed her: her cognition and speech were normal, she had a mild residual right sided hemiplegia but was fully independent in walking and all activities of daily living, achieving a final modified Rankin Scale score of 2.
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The use of intravenous (iv) rt-PA in pregnancy continues to be a controversial topic, without trial evidence to guide treatment decisions [7, 8]. Only a few published cases report its use for ischaemic stroke either in early stages of pregnancy or by using intra-arterial thrombolysis [1, 3–6]. Further supportive evidence in favour of using iv rt-PA in later stages of pregnancy can be found in reports of thrombolysis used for treating massive pulmonary embolism [9], venous embolism, myocardial infarction, or embolism from cardiac prosthetic valves, with no increased risk of an adverse outcome compared to the normal population [10]. Due to its large molecular weight, rt-PA does not cross the blood-placenta barrier and is thought to be of low risk to the foetus. After careful evaluation, we felt that our patient’s case fulfilled a number of thrombolysis eligibility criteria [7, 8]: she presented at a centre with hyperacute stroke, anaesthetic, obstetric, and neonatal facilities and expertise (No endovascular team was available out-of hours to consider intra-arterial rt-PA). Her stroke was severe, she had no other medical co-morbidities, and she presented early. The location of the arterial occlusion was identified and confirmed by CTA. Finally, her pregnancy was in the third trimester, allowing for an emergency Caesarean section in case of complications and for CT scanning without risk of teratogenicity. Whilst thrombolysis of strokes in pregnancy should continue to be evaluated on a case-by-case basis, this is the first report describing its safe intravenous use in the third trimester of pregnancy. Acknowledgments L. Mantoan Ritter wrote the manuscript. B. Dewan revised and supervised the preparation of the manuscript. A. Schu¨ler, R. Gangopadhyay, L. Mordecai, O. Arowele, N. Losseff, and P. O’Brien revised the manuscript.
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J Neurol (2014) 261:632–634 Ethical standards The patient gave informed consent to the publication of this case report. Conflicts of interest of interest.
The authors declare that they have no conflict
References 1. Del Zotto E, Giossi A, Volonghi I et al (2011) Ischemic stroke during pregnancy and puerperium. Stroke Res Treat. Article ID 606780. doi:10.4061/2011/606780 2. Davie CA, O’Brien P (2008) Stroke and pregnancy. J Neurol Neurosurg Psychiatry 79(3):240–245 3. Yamaguchi Y, Kondo T, Ihara M et al (2010) Intravenous recombinant tissue plasminogen activator in an 18-week pregnant woman with embolic stroke. Rinsho Shinkeigaku 50(5):315–319 4. Hori H, Yamamoto F, Ito Y et al (2013) Intravenous recombinant tissue plasminogen activator therapy in a 14-week pregnant woman with embolic stroke due to protein S deficiency. Rinsho Shinkeigaku 53(3):212–216 5. Tassi R, Acampa M, Marotta G et al (2013) Systemic thrombolysis for stroke in pregnancy. Am J Emerg Med 31(2):448.e1–448.e3 6. Hirano T (2013) Acute revascularization therapy in pregnant patients. Neurol Med Chir (Tokyo) 53:531–536 7. Selim MH, Molina CA (2013) The use of tissue plasminogenactivator in pregnancy. A taboo treatment or a time to think out of the box. Stroke 44:868–869 8. Broderick JP (2013) Should intravenous thrombolysis be considered the first option in pregnant women? Stroke 44:866–867 9. Fasullo S, Maringhini G, Terrazzino G et al (2011) Thrombolysis for massive pulmonary embolism in pregnancy: a case report. Int J Emerg Med 4:69 10. Leonhardt G, Gaul C, Nietsch HH et al (2006) Thrombolytic therapy in pregnancy. J Thromb Thrombolysis 21:271–276
