- Email: [email protected]
Coincidence of ischemic stroke and recurrent brain haemorrhage in a patient with Klippel-Trenaunay Syndrome
1454
Case Reports / Journal of Clinical Neuroscience 20 (2013) 1454–1455
Coincidence of ischemic stroke and recurrent brain haemorrhage in a patient with Klippel-Trenaunay Syndrome Lena A. Beume ⇑, Silke C. Fuhrmann, Matthias Reinhard, Andreas Harloff Department of Neurology, University Hospital Freiburg, Breisacherstrasse 64, Freiburg 79106, Germany
a r t i c l e
i n f o
Article history: Received 26 June 2012 Accepted 15 October 2012
Keywords: Amyloid angiopathy Intracerebral bleeding Ischemic stroke Klippel-Trenaunay Syndrome
a b s t r a c t Cerebrovascular manifestations in Klippel-Trenaunay Syndrome (KTS) have been reported but are extremely rare. Case reports describe brain embolism in KTS-associated coagulopathy as well as bleeding due to arteriovenous malformations. We describe a 45-year-old patient with KTS and both acute ischemic stroke and repeated cerebral haemorrhage. The underlying aetiology of both events remained undetermined despite extensive diagnostic work-up, including coagulation tests and dynamic MR angiography. It is most likely that both a pathological coagulation and increased vessel fragility comparable to amyloid angiopathy were responsible for the combined brain lesions in this patient. We conclude that KTS is a very rare but relevant aetiology of cerebral ischemia and that anticoagulation treatment in these cases should be carefully considered as the risk of cerebral haemorrhage is probably elevated. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Klippel-Trenaunay syndrome (KTS)1 is a rare sporadic congenital mesodermal phakomatosis and is characterized by a clinical triad of venous malformations (especially varicosity, seen in 72% of patients), cutaneous capillary malformations (especially portwine stains, seen in 98% of patients) and bone and soft tissue hypertrophy (seen in 67% of patients) of one limb.2 The closely related Klippel-Trenaunay-Weber-Syndrome includes the KTS-triad and arteriovenous fistulas.3 In general, a polygenic aetiology is considered involving defects in angiogenesis and growth regulation of vessels and tissue.4 Venous malformation is the main pathology in KTS leading to venous thromboembolism, thrombophlebitis and dermal varicose veins as well as hyperpigmentation.5,6 Single cases of disseminated intravascular coagulation have been reported.7,8 The incidence of stroke, however, is low in KTS; capillary or venous malformation may result in predisposition to brain haemorrhage and hypercoagulability may induce ischemic stroke.9
2. Case report A 45-year-old man was admitted to our stroke unit with acute facial palsy and sensory-motor deficit in his left arm. His medical history included sporadic congenital KTS with port-wine stains and hypertrophy of the right upper extremity (Fig. 1a). Brain MRI showed acute infarction of the right hemisphere, minimal cerebral small-vessel disease and an old subcortical haemorrhage of the left parietal lobe (Fig. 1b,c). The diagnostic work-up revealed slightly elevated blood pressure. Extra- and intracranial ultrasound (including the bubble-test, transthoracic and transesophageal echocardiography), Holter-echocardiogram, and extended screening for coagulation (antithrombin III, fibrinogen, protein C/S, factor II and factor V mutation) and immunological disorders (immunoglobulins, phospholipid antibodies, rheumatoid factors) were normal. Sonography of the right arm showed no signs of prior thrombosis. The patient received 100 mg of acetylsalicylic acid and 10 mg of amlodipine per day as anti-hypertensive medication. On discharge he still had slight hypaesthesia and a fine motor deficit in his left hand. ⇑ Corresponding author. Tel.: +49 761 2705 0010; fax: +49 761 2705 3700. E-mail address: [email protected] (L.A. Beume).
Four months later he was readmitted due to severe nausea, dizziness and blurred vision. Brain MRI showed acute cerebellar haemorrhage (2.1 2.6 2.0 cm3) with surrounding oedema (Fig. 1d). Clotting factors were normal. Treatment with acetylsalicylic acid was stopped and anti-hypertensives were expanded to include 735.8 mg eprosartan and 12.5 mg hydrochlorothiazide per day due to intermittent hypertensive blood pressure values. MRI, including time-resolved MR angiography, 5 months later did not reveal any arteriovenous malformation or venous abnormality.
3. Discussion Cerebral symptoms of KTS have been reported but they are extremely rare. In contrast to our patient, previous reports describe only single cerebral events either related to infarction or haemorrhage. In the latter, venous malformation, cavernoma or aneurysms were usually found as the cause for intracerebral bleeding. Even though pulmonary embolism secondary to deep vein thrombosis is frequent, brain embolism in KTS is rare and aetiology is usually cryptogenic.10 Patent foramen ovale and atrial septum aneurysm have been reported in KTS but their incidence is no higher than in the general population. One stroke patient had antithrombin III deficiency11 and recently, Renard et al. described a single case of KTS with recurrent cerebral infarctions and fibromuscular dysplasia suggesting multiple dissections as the aetiology of stroke.12 In view of all reports on KTS and cerebral effects we assume a predisposition to thromboembolic events despite normal tests for coagulation in our patient. Although we did not entirely exclude a small arteriovenous malformation (AVM) by time-resolved MR angiography, an associated AVM appears improbable. Rather, a diminished integrity of arterial vessels comparable to amyloid angiopathy may have predisposed the patient to the recurrent bleeding, including two microbleeds, that were visible on T2weighted MRI. In summary, KTS constitutes a rare aetiology of stroke and, as this case report demonstrates, can present with both cerebral ischemia and bleeding. Thus, indication for anticoagulation needs to be carefully balanced due to the potentially increased risk of brain haemorrhage in these patients. Also, patients with cryptogenic stroke should be screened for typical skin lesions or extremity hypertrophy in order to detect KTS as the underlying cause.
Case Reports / Journal of Clinical Neuroscience 20 (2013) 1455–1457
1455
Fig. 1. (a) Photograph of the patient showing port-wine stains and hypertrophy (3.4 cm length difference measured from elbow to the tips of the fingers) of the right arm and hand. (b) Axial diffusion weighted imaging of the brain showing acute infarction of the right hemisphere. (c) Axial T2-weighted MRI showing the old subcortical haemorrhage of the left parietal lobe. (d) Axial T2-weighted fluid attenuated inversion recovery dark fluid imaging showing acute cerebellar haemorrhage with surrounding oedema.
References 1. Klippel M. Du Naevus variquex osteohypertrophique. Arch Gen Med 1900;3:641–72. 2. Jacob AG et al. Klippel-Trenaunay syndrome: spectrum and management. Mayo Clin Proc 1998;73:28–36. 3. Lindenauer SM. Congenital arteriovenous fistula and the Klippel-Trenaunay syndrome. Ann Surg 1971;174:248–63. 4. Oduber CE, van der Horst CM, Hennekam RC. Klippel-Trenaunay syndrome: diagnostic criteria and hypothesis on etiology. Ann Plast Surg 2008;60:217–23. 5. Star A, Fuller CE, Landas SK. Intracranial aneurysms in Klippel-Trenaunay/ Weber syndromes: case report. Neurosurgery 2010;66:E1027–1028. 6. Petzold A, Bishoff C, Conrad B. Repetitive cerebral bleeding in an adult with Klippel-Trénaunay syndrome. J Neurol 2000;247:389–91.
7. Samuel M, Spitz L. Klippel-Trenaunay syndrome: clinical features, complications and management in children. Br J Surg 1995;82:757–61. 8. Neubert AG, Golden MA, Rose NC. Kasabach-Merritt coagulopathy complicating Klippel-Trenaunay-Weber syndrome in pregnancy. Obstet Gynecol 1995;85(5):831–3. 9. Brunaud V et al. Klippel-Trenaunay syndrome and ischemic neurologic complications. Rev Neurol 1994;150:50–4. 10. Baskerville PA, Ackroyd JS, Lea Thomas M, et al. The Klippel–Trenaunay syndrome: clinical, radiological and haemodynamic features and management. Br J Surg 1985;72:232–6. 11. Grira M, Ben-Jemaa H, Lammouchi T, et al. Klippel-Trenaunay syndrome associated with antithrombin III deficiency. Rev Neurol 2008;164:855–8. 12. Renard D, Larue A, Taieb G, et al. Recurrent cerebral infarction in KlippelTrenaunay-Weber syndrome. Clin Neurol Neurosurg 2012;114:1019–120.
doi:http://dx.doi.org/10.1016/j.jocn.2012.10.039
Clopidogrel effective for frequent transient monocular blindness caused by vulnerable plaque Hong-Kyun Park a, Hang Rai Kim a, Beom Joon Kim a, Jihoon Kang a, Cheolkyu Jung b, Byung Se Choi b, Jae Hyoung Kim b, Moon-Ku Han a, Seong-Ho Park a, Hee-Joon Bae a,⇑ a
Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
b
a r t i c l e
i n f o
Article history: Received 17 June 2012 Accepted 28 October 2012
Keywords: Clopidogrel loading Free-floating thrombus Transient monocular blindness Vulnerable plaque
a b s t r a c t Transient monocular blindness (TMB) is a well-known warning symptom of impending cerebral or retinal infarction, which suggests vulnerable ipsilateral carotid disease. Instability of free-floating thrombus may cause recurrent artery-to-artery embolism. A recent study showed that a combination of clopidogrel and aspirin might reduce microthromboembolisms. Here, we report a patient with frequent TMB despite aspirin monotherapy whose symptom disappeared after the addition of clopidogrel. This is the first report of aspirin-resistant frequent TMB caused by thromboembolism from vulnerable plaque that remitted after the addition of clopidogrel. These findings highlight the need for a randomized controlled trial to illustrate the most efficacious treatment strategy in this situation. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
⇑ Corresponding author. Tel.: +82 31 787 7467; fax: +82 31 719 7985. E-mail address: [email protected] (H.-J. Bae).
Transient monocular blindness (TMB), or amaurosis fugax, is a well-known warning symptom of imminent retinal or cerebral infarction. The most common cause of TMB is ipsilateral internal carotid artery (ICA) disease, which can result in hemodynamic
Case Reports / Journal of Clinical Neuroscience 20 (2013) 1454–1455
Coincidence of ischemic stroke and recurrent brain haemorrhage in a patient with Klippel-Trenaunay Syndrome Lena A. Beume ⇑, Silke C. Fuhrmann, Matthias Reinhard, Andreas Harloff Department of Neurology, University Hospital Freiburg, Breisacherstrasse 64, Freiburg 79106, Germany
a r t i c l e
i n f o
Article history: Received 26 June 2012 Accepted 15 October 2012
Keywords: Amyloid angiopathy Intracerebral bleeding Ischemic stroke Klippel-Trenaunay Syndrome
a b s t r a c t Cerebrovascular manifestations in Klippel-Trenaunay Syndrome (KTS) have been reported but are extremely rare. Case reports describe brain embolism in KTS-associated coagulopathy as well as bleeding due to arteriovenous malformations. We describe a 45-year-old patient with KTS and both acute ischemic stroke and repeated cerebral haemorrhage. The underlying aetiology of both events remained undetermined despite extensive diagnostic work-up, including coagulation tests and dynamic MR angiography. It is most likely that both a pathological coagulation and increased vessel fragility comparable to amyloid angiopathy were responsible for the combined brain lesions in this patient. We conclude that KTS is a very rare but relevant aetiology of cerebral ischemia and that anticoagulation treatment in these cases should be carefully considered as the risk of cerebral haemorrhage is probably elevated. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Klippel-Trenaunay syndrome (KTS)1 is a rare sporadic congenital mesodermal phakomatosis and is characterized by a clinical triad of venous malformations (especially varicosity, seen in 72% of patients), cutaneous capillary malformations (especially portwine stains, seen in 98% of patients) and bone and soft tissue hypertrophy (seen in 67% of patients) of one limb.2 The closely related Klippel-Trenaunay-Weber-Syndrome includes the KTS-triad and arteriovenous fistulas.3 In general, a polygenic aetiology is considered involving defects in angiogenesis and growth regulation of vessels and tissue.4 Venous malformation is the main pathology in KTS leading to venous thromboembolism, thrombophlebitis and dermal varicose veins as well as hyperpigmentation.5,6 Single cases of disseminated intravascular coagulation have been reported.7,8 The incidence of stroke, however, is low in KTS; capillary or venous malformation may result in predisposition to brain haemorrhage and hypercoagulability may induce ischemic stroke.9
2. Case report A 45-year-old man was admitted to our stroke unit with acute facial palsy and sensory-motor deficit in his left arm. His medical history included sporadic congenital KTS with port-wine stains and hypertrophy of the right upper extremity (Fig. 1a). Brain MRI showed acute infarction of the right hemisphere, minimal cerebral small-vessel disease and an old subcortical haemorrhage of the left parietal lobe (Fig. 1b,c). The diagnostic work-up revealed slightly elevated blood pressure. Extra- and intracranial ultrasound (including the bubble-test, transthoracic and transesophageal echocardiography), Holter-echocardiogram, and extended screening for coagulation (antithrombin III, fibrinogen, protein C/S, factor II and factor V mutation) and immunological disorders (immunoglobulins, phospholipid antibodies, rheumatoid factors) were normal. Sonography of the right arm showed no signs of prior thrombosis. The patient received 100 mg of acetylsalicylic acid and 10 mg of amlodipine per day as anti-hypertensive medication. On discharge he still had slight hypaesthesia and a fine motor deficit in his left hand. ⇑ Corresponding author. Tel.: +49 761 2705 0010; fax: +49 761 2705 3700. E-mail address: [email protected] (L.A. Beume).
Four months later he was readmitted due to severe nausea, dizziness and blurred vision. Brain MRI showed acute cerebellar haemorrhage (2.1 2.6 2.0 cm3) with surrounding oedema (Fig. 1d). Clotting factors were normal. Treatment with acetylsalicylic acid was stopped and anti-hypertensives were expanded to include 735.8 mg eprosartan and 12.5 mg hydrochlorothiazide per day due to intermittent hypertensive blood pressure values. MRI, including time-resolved MR angiography, 5 months later did not reveal any arteriovenous malformation or venous abnormality.
3. Discussion Cerebral symptoms of KTS have been reported but they are extremely rare. In contrast to our patient, previous reports describe only single cerebral events either related to infarction or haemorrhage. In the latter, venous malformation, cavernoma or aneurysms were usually found as the cause for intracerebral bleeding. Even though pulmonary embolism secondary to deep vein thrombosis is frequent, brain embolism in KTS is rare and aetiology is usually cryptogenic.10 Patent foramen ovale and atrial septum aneurysm have been reported in KTS but their incidence is no higher than in the general population. One stroke patient had antithrombin III deficiency11 and recently, Renard et al. described a single case of KTS with recurrent cerebral infarctions and fibromuscular dysplasia suggesting multiple dissections as the aetiology of stroke.12 In view of all reports on KTS and cerebral effects we assume a predisposition to thromboembolic events despite normal tests for coagulation in our patient. Although we did not entirely exclude a small arteriovenous malformation (AVM) by time-resolved MR angiography, an associated AVM appears improbable. Rather, a diminished integrity of arterial vessels comparable to amyloid angiopathy may have predisposed the patient to the recurrent bleeding, including two microbleeds, that were visible on T2weighted MRI. In summary, KTS constitutes a rare aetiology of stroke and, as this case report demonstrates, can present with both cerebral ischemia and bleeding. Thus, indication for anticoagulation needs to be carefully balanced due to the potentially increased risk of brain haemorrhage in these patients. Also, patients with cryptogenic stroke should be screened for typical skin lesions or extremity hypertrophy in order to detect KTS as the underlying cause.
Case Reports / Journal of Clinical Neuroscience 20 (2013) 1455–1457
1455
Fig. 1. (a) Photograph of the patient showing port-wine stains and hypertrophy (3.4 cm length difference measured from elbow to the tips of the fingers) of the right arm and hand. (b) Axial diffusion weighted imaging of the brain showing acute infarction of the right hemisphere. (c) Axial T2-weighted MRI showing the old subcortical haemorrhage of the left parietal lobe. (d) Axial T2-weighted fluid attenuated inversion recovery dark fluid imaging showing acute cerebellar haemorrhage with surrounding oedema.
References 1. Klippel M. Du Naevus variquex osteohypertrophique. Arch Gen Med 1900;3:641–72. 2. Jacob AG et al. Klippel-Trenaunay syndrome: spectrum and management. Mayo Clin Proc 1998;73:28–36. 3. Lindenauer SM. Congenital arteriovenous fistula and the Klippel-Trenaunay syndrome. Ann Surg 1971;174:248–63. 4. Oduber CE, van der Horst CM, Hennekam RC. Klippel-Trenaunay syndrome: diagnostic criteria and hypothesis on etiology. Ann Plast Surg 2008;60:217–23. 5. Star A, Fuller CE, Landas SK. Intracranial aneurysms in Klippel-Trenaunay/ Weber syndromes: case report. Neurosurgery 2010;66:E1027–1028. 6. Petzold A, Bishoff C, Conrad B. Repetitive cerebral bleeding in an adult with Klippel-Trénaunay syndrome. J Neurol 2000;247:389–91.
7. Samuel M, Spitz L. Klippel-Trenaunay syndrome: clinical features, complications and management in children. Br J Surg 1995;82:757–61. 8. Neubert AG, Golden MA, Rose NC. Kasabach-Merritt coagulopathy complicating Klippel-Trenaunay-Weber syndrome in pregnancy. Obstet Gynecol 1995;85(5):831–3. 9. Brunaud V et al. Klippel-Trenaunay syndrome and ischemic neurologic complications. Rev Neurol 1994;150:50–4. 10. Baskerville PA, Ackroyd JS, Lea Thomas M, et al. The Klippel–Trenaunay syndrome: clinical, radiological and haemodynamic features and management. Br J Surg 1985;72:232–6. 11. Grira M, Ben-Jemaa H, Lammouchi T, et al. Klippel-Trenaunay syndrome associated with antithrombin III deficiency. Rev Neurol 2008;164:855–8. 12. Renard D, Larue A, Taieb G, et al. Recurrent cerebral infarction in KlippelTrenaunay-Weber syndrome. Clin Neurol Neurosurg 2012;114:1019–120.
doi:http://dx.doi.org/10.1016/j.jocn.2012.10.039
Clopidogrel effective for frequent transient monocular blindness caused by vulnerable plaque Hong-Kyun Park a, Hang Rai Kim a, Beom Joon Kim a, Jihoon Kang a, Cheolkyu Jung b, Byung Se Choi b, Jae Hyoung Kim b, Moon-Ku Han a, Seong-Ho Park a, Hee-Joon Bae a,⇑ a
Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
b
a r t i c l e
i n f o
Article history: Received 17 June 2012 Accepted 28 October 2012
Keywords: Clopidogrel loading Free-floating thrombus Transient monocular blindness Vulnerable plaque
a b s t r a c t Transient monocular blindness (TMB) is a well-known warning symptom of impending cerebral or retinal infarction, which suggests vulnerable ipsilateral carotid disease. Instability of free-floating thrombus may cause recurrent artery-to-artery embolism. A recent study showed that a combination of clopidogrel and aspirin might reduce microthromboembolisms. Here, we report a patient with frequent TMB despite aspirin monotherapy whose symptom disappeared after the addition of clopidogrel. This is the first report of aspirin-resistant frequent TMB caused by thromboembolism from vulnerable plaque that remitted after the addition of clopidogrel. These findings highlight the need for a randomized controlled trial to illustrate the most efficacious treatment strategy in this situation. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
⇑ Corresponding author. Tel.: +82 31 787 7467; fax: +82 31 719 7985. E-mail address: [email protected] (H.-J. Bae).
Transient monocular blindness (TMB), or amaurosis fugax, is a well-known warning symptom of imminent retinal or cerebral infarction. The most common cause of TMB is ipsilateral internal carotid artery (ICA) disease, which can result in hemodynamic