Bischoff, C

Conrad, B

Petzold, A

English

UCL Discovery

Repetitive cerebral bleeding in an adult withKlippel–Trénaunay SyndromeA. Petzold∗† Ch. Bischoff† B. Conrad†doi: 10.1007/s004150050609SIRS: Klippel–Trénaunay Syndrome (KTS) is a congenital anomaly of un-known aetiology, characterised by vascular (98 %), cutaneous (72 %) and skele-tal (67 %) symptoms [8]. Brain involvement has been described but is ex-tremely rare [20] and is due to either bleeding or ischaemia. The underlyingcauses of cerebral bleeding are capillary or venous malformations [1] whichusually occur in the hemisphere ipsilateral to the body involvement. To ourknowledge this is the first reported case of KTS with repetitive cerebral bleed-ing without apparent macroscopic arterio venous malformations (AVM).A 44 year old man with right hemispheric bleeding of unknown cause pre-sented to the clinic on 2 February 1998. He was disorientated in time andspace and quite aggressive. Vital parameters were all normal: 1.70 m, 71kg, blood pressure 130/90, resting pulse 88/min, respiratory rate 12/min.He suffered from reduced verbal fluency, presevaration, impaired abstraction,poor judgement, poor memory and reduced sustained attention. No focal neu-rological symptoms could be detected. A large capillary malformation (port–wine stain) with telangiectasia, petechiae and varicose veins involved the entireright leg (see figure 1). No limb asymmetry or lymphangioma were seen onclinical examination. Abdominal examination revealed a hepatomegaly of ap-proximately 16 cm.The CT brain scan showed a hyperdense contrast–enhancing lesion in theright temporal lobe with surrounding oedema and slight mass effect, marked byenhanced choroid plexi and occipital cerebral calcifications (see figure 2). OnMRI the lesion was T1/T2 hyperdense and enhanced with contrast. A t2* spin–echo–gradient sequence showed haemosiderin deposits rostral to the currentbleeding, suggestive of a former haemorrhage in the same region. Cerebral an-giography revealed no macroscopic AVM or abnormality of the venous system.A control MRI two months later showed no signs of a cavernoma, which couldhave been the origin of such a presentation.∗Institute of Neurology, Department of Neuroimmunology, Queen Square, London, WC1N3BG, UK, Tel: ++44-171-83736114204, Fax: +44-171-8378553, 0000-0002-0344-9749;URL@UCL; Email: a.petzold@ucl.ac.uk†Department of Neurology, Technical University of Munich, Klinikum rechts der Isar, Munich,Germany1JOON 2000 Klippel–Trénaunay SyndromeFigure 1: Cutaneous capillary malformations (port–wine stain) and dilated vari-cose veins in Klippel–Trénaunay Syndrome.An EEG was abnormal with a right parieto–occipital δ focus without signs ofelevated cerebral excitability. Transcranial Doppler sonography was normal.Opthalmological examination showed an asymptomatic weakness of the rightinferior oblique muscle and papillary drusen, but no vascular abnormalities ofthe retina.Laboratory investigation revealed a platelet count of 68,000/µL, reducedfibrinogen (87.0 mg/dL), elevated AT III (123 %) and reduced factor XIII (63%). However the platelet aggregation (Born) was normal with collagen, risto-cetin and ADP.The presentation of this patient is consistent with a cerebral haemorrhagein KTS. According to Jacob this patient fits the diagnositc criteria for KTS [8].He had capillary malformations (port–wine stain on the right leg), soft tissuehypertrophy (hepatosplenomegaly) and varicose veins (right leg).In fact this patient’s medical history dates back to early childhood, wherea birth mark had been noted on his right lower leg. He suffered from fre-quent gingival bleeding and haematomas following minor trauma. Removal ofvaricose veins in the right leg became necessary in January 1987. The patientunderwent a bone marrow examination due to the marked hepatosplenomegalyand pancytopenia. Histology showed myelofibrosis, activated haematopoesisdue to peripheral haemolysis and a low–grade non–Hodgkin lymphoma (NHL)was suspected.In June 1994 the patient had sudden onset of Broca’s aphasia and agraphiadue to right dorsofrontal bleeding, as indicated by CT scan. At this time periph-eral blood analysis revealed thrombocytopenia (90,000 µL), reduced factorPage 2JOON 2000 Klippel–Trénaunay SyndromeFigure 2: Intracerebral bleeding in Klippel–Trénaunay Syndrome. The CT scanreveals a hyperdense contrast enhancing lesion in the right temporal lobe withsurrounding edema and slight mass effect, marked enhanced choroid plexusesand occipital cerebral calcifications.XIII (44 %), reduced maximal amplitude and prolonged k time in thrombelas-togram and prolonged bleeding time < 10 min (Marx). Detailed neuropsycho-logical testing showed severe reduced attention span and constructive abili-ties, poor memory, decreased reaction time, perseveration and reduced verbalfluency. All language impairments recovered within a year.Progression of the NHL made polychemotherapy (CHOP-I) necessary, andthis was started in June 1996. In the subsequent aplastic phase he developeda gram–positive sepsis and lower gastrointestinal bleeding caused by dissem-inated intravascular coagulation and severe thrombocytopenia (9,000/µL). Anabdominal CT scan showed splenomegaly (28 cm) with multiple infarctionsand hepatomegaly (24 cm) with a haemangioma in segment 7. The blood countimproved after splenectomy in August 1996. The spleen (1,600 g) showed asoft, dark red cut surface and several subcapsular blister–like defects, whichwere caused by splenic infarctions. Histology of the spleen revealed distendedsinusoids of the red pulp which were filled with atypical lymphoblasts andthis together with the immunohistological findings suggested a monoclonalhepato–splenic Tγ–δ cell lymphoma, which was confirmed by polymerase chainreaction analysis [23].What is unusual in this patient is the repetitive cerebral bleeding withoutany visible macroscopic AVM. Seven cases of KTS with haemorrhagic strokehave been published, all of them with an apparent AVM (see table 1). Ourpatient differs from this group by age, 44 years compared to a mean age of 21Page 3JOON 2000 Klippel–Trénaunay SyndromeTable 1: Cerebral bleeding in Klippel–Trénaunay syndrome. Age in y = years,w = weeks. Gender: f = female, m = male.Author Lesion/mechanism Age Gender n=8Jaksch 1986 [9] Rupture of angioma 34 y m n=1Oyesiku 1988 [18] AV–fistula 12 y f n=1Taira 1991 [21] Aneurysm 8 w m n=1Dunn 1993 [4] AV–fistula, occlusion of the straight sinus 34 y f n=1Suga 1994 [20] Multiple angiomata (left cerebellar and pontine) 24 y m n=1Makiyama 1994 [14] Rupture of AVM 8 y f n=1Spallone 1996 [19] Fusiform aneurysm 28 y f n=1Own case 1998 Coagulopathy, suspected microscopic AVM, repeti-tive right cerebral haemorrhage (1994, 1998)44 y m n=1years. In addition he suffers from deficient clotting due to the NHL. These fac-tors together with the suspected co–existence of microscopic AVM increasethe risk of bleeding. The occurrence of microscopic arteriovenous fistulae inKTS is controversial [12, 15, 16, 26]. A distinction between KTS and Parkes–Weber Syndrome has been suggested depending on the existence of suchhaemodynamically irrelevant AVM. Co–existence of microvascular AVM ren-der cerebral bleeding in the affected hemisphere more likely if additional riskfactors are present. Histologically the affected vessels in KTS show markedthickening of the medial vessel layer, hyaline degeneration of the lamina muscu-laris and patchy sclerosis of the intima [6]. In general, patients with peripheralbleeding suffer from spontaneous haemorrhages from dilated veins [1]. Pe-ripheral bleeding can however be caused without apparent AVM [7, 22, 24,25]. Reduced factor XIII, as been in this case, has been described with KTS[5]. Change in coagulation is mostly related to thrombocytopenia and low fib-rinogen caused by their continous consumption in the altered vessels [3, 5, 11,25]. Vascular abnormalities occasionaley involve the retina [2, 13, 17]. Se-vere haemorrhage is a risk in KTS patients and splenectomy might reduce thethrombocytopenia. In acute haemorrhage tranexamic acid has been reported tostop bleeding [10].Our case has clinical features compatible with KTS involving the right hemi-corps and repetitive right cerebral bleeding. This together with the underlyingclotting defect raises the question of co–existent microvascular AVM, as dis-cussed in the literature [12, 15, 16, 26]. Although KTS is not uncommon fordermatologists and pediatricians it is rare for neurologists. In all KTS patientswith neurologic symptoms brain involvement should be thought of. MRI, MRI–angio or conventional angiography may lead to diagnosis of cerebral AVM. Lab-oratory screening of haemostatic parameters may reveal additional risk factorsfor haemorrhagic events.Page 4JOON 2000 Klippel–Trénaunay SyndromeReferences[1] P. Baskerville et al. “The Klippel–Trenaunay Syndrome: clinical radi-ological and haemodynamic features and management”. Br J Surg 72(1985), pp. 232–236. DOI: 10.1002/bjs.1800720331.[2] R. Brod, J. Shields, C. Shields, et al. “Unusual retinal and renal vascularlesions in the Klippel–Trenaunay–Weber Syndrome”. Retina 12 (1992),pp. 355–358. DOI: 10.1097/00006982-199212040-00011.[3] J. A. D’Amico, G. C. Hoffman, and P. G. Dyment. “Klippel-Trenaunaysyndrome associated with chronic disseminated intravascular coagula-tion and massive osteolysis”. Cleve Clin Q 44 (1977), pp. 181–188.DOI: 10.3949/ccjm.44.4.181.[4] W. Dunn and T. Jaspan. “Case report: cerebral arteriovenous fistulain the Klippel–Trenaunay–Weber syndrome”. Clin Radiol 48 (1993),pp. 134–136. DOI: 10.1016/s0009-9260(05)81089-x.[5] Y. Endo, K. Takahasi, S. Mamiya, et al. “Factor XIII deficiency associ-ated with Klippel–Weber disease, platelet dysfunction and cryfibrino-genemia”. Acta Haematol 69 (1983), pp. 398–403. DOI: 10.1159/000206928.[6] S. Goldstein et al. “Aplasia of the cervical internal carotid artery andmalformation of the circle of Willis associated with Klippel–Trenaunaysyndrome Case report”. 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Repetitive cerebral bleeding in an adult with Klippel-Trénaunay Syndrome

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Repetitive cerebral bleeding in an adult with Klippel-Trénaunay Syndrome

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