Clinical Neurology and Neurosurgery 114 (2012) 1019–1020 Contents lists available at SciVerse ScienceDirect Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro Case report Recurrent cerebral infarction in Klippel-Trenaunay–Weber syndrome Dimitri Renard a,∗ , Aurore Larue a , Guillaume Taieb a , Luc Jeanjean b , Pierre Labauge a a b Department of Neurology, CHU Nîmes, Hôpital Caremeau, Place du Pr Debré, 30029 Nîmes Cedex 4, France Department of Ophthalmology, CHU Nîmes, Hôpital Caremeau, Place du Pr Debré, 30029 Nîmes Cedex 4, France a r t i c l e i n f o Article history: Received 10 August 2011 Received in revised form 22 December 2011 Accepted 16 January 2012 Available online 17 February 2012 Keywords: Klippel-Trenaunay–Weber syndrome Stroke Cerebral infarction Fibromuscular dysplasia Patent foramen ovale 1. Case report KTWS is characterised by capillary hemangioma, varicose veins, and bone and soft tissue hypertrophy. We present a 53-year-old woman with sporadic congenital Klippel-Trenaunay–Weber syndrome (KTWS) with involving asymmetrically the four limbs (i.e. bone and soft tissue hypertrophy predominant in the right-sided limbs, and varicose veins in both lower limbs), the trunk (large capillary hemagioma on the left-sided trunk, Fig. 1), and the head. In absence of cardiovascular risk factors, she had a history of transient ischemic attack (aphasia) at the age of 9 years, ischemic stroke at the age of 20 years with right-sided hemiparesis lasting for days without leaving permanent deficit, and another ischemic stroke at the age of 29 years leaving a permanent right-sided hemiplegia. No underlying cause for these cerebral infarctions was identified at that time. Age 53, she presented with acute vertigo, nausea, dysarthria, and gait ataxia. MRI revealed two chronic ischemic left middle cerebral artery infarctions, and a recent ischemic right superior cerebellar artery infarction. CT angiography showed an aspect of fibromuscular dysplasia in both extracranial internal carotid arteries (in absence of pseudoaneurysm, aneurysm, atheromatous plaque, or signs of acute dissection), and several intra- and extracranial venous malformations (Fig. 1). Duplex ultrasound and CT angiography showed no renal artery abnormalities. Carotid angiography ∗ Corresponding author. Tel.: +33 4 66 68 32 61; fax: +33 4 66 68 40 16. E-mail address: dimitrirenard@hotmail.com (D. Renard). 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2012.01.024 was not performed because of the associated risk (although small) for potential complications, especially when a connective tissue disease is suspected. Moreover, in absence of acute dissection, angiography would probably not have changed treatment options. Fundoscopy showed retinal vascular tortuosities (Fig. 2), often seen on KTWS, in absence of choroidal hemangioma. Blood analysis showed slight thrombopenia (103 × 109 /l). Routine coagulation tests, immunological tests, cholesterol levels, antiphospholipid antibodies, special diagnostic tests in search for a protrombotic cause (including antithrombin III, protein C, protein S, D-dimer, fibrin degradation products, Factor V Leiden and prothrombin gene mutation), and serological tests for HIV, syphilis, and hepatitis B/C were all normal. Urine toxicologic screening was negative. Transoesophageal echocardiography showed the presence of a patent foramen ovale and atrial septum aneurysm. Thoracic CT scan, in search for silent pulmonary embolism, was normal. Holter monitoring was normal. Lower limb duplex ultrasound examination showed absence of venous thrombosis. Treatment with oral acetylsalicylic acid was started. One month later, she had another – this time right middle cerebral artery – cerebral infarction (Fig. 2) provoking left hemiplegia (and thus she became tetraplegic). CT angiography and echocardiography were unchanged, and Holter monitoring was normal. Differential diagnoses, in our KTWS-patient, of recurrent infarctions included multifocal arterial dissection (although not visualised on arterial imaging) associated with fibromuscular dysplasia, and recurrent paradoxal cerebral embolism (in presence of patent foramen ovale and atrial septum aneurysm) although leg or pelvic deep venous thrombosis was not visualised on leg duplex 1020 D. Renard et al. / Clinical Neurology and Neurosurgery 114 (2012) 1019–1020 Fig. 1. A large capillary hemagioma can be seen on the left-sided trunk (A). CT angiography showing an aspect of fibromuscular dysplasia, with a pattern of string of beads, in both extracranial internal carotid arteries (B and C), and an intracranial venous malformation (D). Fig. 2. Bilateral retinal vascular tortuosities can be seen on eye fundus examination (A). Brain MRI FLAIR sequences showing a subacute infarction in the right superior cerebellar artery (B), two chronic ischemic infarctions in the left middle cerebral artery territory (C and D, arrowheads), and a recent ischemic infarction in the right middle cerebral artery territory (D, arrow). ultrasound and pelvic CT scan. Antiplatelet therapy was changed for oral anticoagulant treatment. 2. Discussion KTWS is characterised by capillary hemangioma, varicose veins, and bone and soft tissue hypertrophy. The exact cause of KTWS is unknown. The etiopathogenesis, however, may be genetic in view of recent discoveries of RASA1 gene mutations in some patients, although most cases are sporadic. If large enough, cutaneous hemangioma may sequester platelets leading to thrombopenia, as seen in our patient. Brain abnormalities reported in KTWS include hemorrhage, infarction, hemimegalencephaly, venous malformation, arteriovenous malformations, cavernoma, aneurysm, hydrocephalus, choroid plexus abnormalities, atrophy, calcifications, leptomeningeal enhancement, cortical dysplasia, and seizures. In contrast to frequently described pulmonary embolism (secondary to venous limb thrombosis), cases of cerebral infarction related to KTWS are very rare [1–5]. One patient had patent foramen ovale. In that patient, paradoxal embolism was suspected although deep venous thrombosis was not detected. One patient had antithrombin III deficiency. However, antithrombine III is an established risk factor for venous but probably not for arterial cerebrovascular disease. One KTWS-related medullary infarction has been reported. In 3 out of 5 KTWS-related stroke patients, arterial vascular deformities were described, i.e. one patient with aneurysmal dilatation of the terminal part of the basilar artery and ectasis at the vertebrobasilar artery, one patient had several intracranial aneurysms, and one patient had carotid artery dissection. In the 2 other reported KTWS-related stroke patients, only duplex scanning was performed, and so subtle arterial abnormalities might have been overlooked. In our patient, carotid arteries had an aspect of fibromuscular dysplasia. Cerebrovascular complications in fibromuscular dysplasia are most frequently arterial dissection, and less often aneurysm or carotid-cavernous fistula. There were no arguments in favour of acute dissection in our patient. In presence of patent foramen ovale and atrial septum aneurysm, recurrent paradoxal cerebral embolism was suspected, but could not be proved. It is unclear if KTWS is a risk factor for stroke. Fibromuscular dysplasia, seen in our patient, has never been described in KTWS. Patent foramen ovale and atrial septum aneurysm, also seen in our patient, have been earlier reported in KTWS-patients. Cervical and intracranial arterial imaging and transoesophageal echocardiography has to be performed in more KTWS patients with stroke in order to analyse if these associated abnormalities are risk factors for stroke in KTWS. Disclosure We have no conflict of interest to declare. References [1] Star A, Fuller CE, Landas SK. Intracranial aneurysms in Klippel-Trenaunay/Weber syndromes: case report. Neurosurgery 2010;66:E1027–8. [2] Alberti E. Ischaemic infarct of the brain stem combined with bisymptomatic Klippel-Trénaunay–Weber syndrome and cutis laxa. J Neurol Neurosurg Psychiatry 1976;39:581–5. [3] Brunaud V, Delerue O, Muller JP, Destée A. Klippel-Trenaunay syndrome and ischemic neurologic complications. Rev Neurol 1994;150: 50–4. [4] Grira M, Ben-Jemaa H, Lammouchi T, Benammou S. 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