Bogousslavsky, J.

Granziera, C.

Lurati, F.

Michel, P.

Reymond, S.

Rossetti, A.

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J Neurol (2005) 252 : 615–616DOI 10.1007/s00415-005-0702-6Cristina GranzieraPatrik MichelAndrea O. RossettiFloriana LuratiSitthided ReymondJulien BogousslavskyWegener Granulomatosispresenting withhaemorragic stroke in a young adultReceived: 7 May 2004Received in revised form: 8 October 2004Accepted: 19 October 2004Published online: 22 March 2005Sirs: Haemorrhagic stroke inyoung patients is primarily causedby elevated blood pressure, under-lying vascular structural abnor-malities, cardiac embolism or mi-graine [1–3]. Vasculitis may be apossible but uncommon aetiologyof ischemic stroke in patients agedless than 45 years [4] and rarelycauses brain haemorrhage [5, 6].We report on a patient who pre-sented with haemorrhagic strokeas the initial symptom of Wegenergranulomatosis (WG).In March 2003, a 42 year oldmale smoker presented with acuteonset of a right sensorimotorhemisyndrome accompanied bymotor aphasia. Magnetic resonanceimaging (MRI) revealed a haemor-rhagic stroke in the left basal gan-glia, without underlying ischaemicdamage (Figure). No vascular mal-formation, aneurysm, tumour orvenous thrombosis was observed.Acutely, blood pressure was180/90 mmHg but funduscopy aswell as urinary sediment did notshow signs of chronic hypertensivedamage. Cerebrovascular Dopplerultrasound and transthoracicechocardiography were negative.Laboratory investigations showedmild inflammatory signs and im-munological tests revealed elevatedc-ANCA and anti PR-3 antibodies(Table); p-ANCA, x-ANCA, antiMPO antibodies, as well as CSFanalysis were negative. The patienthad no symptoms or signs charac-teristic of WG: renal function, uri-nary sediment, thorax radiographyand otorhinolaryngological exami-nation were normal. Three monthslater, the patient had no symptoms,normal inflammatory parametersand still elevated autoantibodies(Table). In November 2003, he de-veloped acute respiratory distress,fever, oral ulcers, epistaxis andarthralgia. Lung CT showed sub-pleural nodules and infiltrates andbronchoscopic bronchoalveolarlavage revealed intraalveolar haem-orrhage (30 % haemosidero-phages). Microbiological analysisfor pneumocystis, nocardia, my-coses, mycobacteries and CMV wasnegative. Tongue and gingivalbiopsy specimens showed nonspecific ulcers. Glomerular micro-haematuria (95 RBC/field) andmild proteinuria (0.3 g/l proteins)were now observed. Renal biopsyrevealed an impaired immunitycrescentic extracapillary glomeru-lonephritis without granulomatouslesions; c-ANCA and anti PR-3antibodies elevation persisted andinflammatory parameters hadreappeared (Table). Three out offour ACR classification criteria [7]were positive, so the diagnosis ofWG was established. The patientwas treated with intravenoussteroids and cyclophosphamide.One month later, inflammatorysigns as well as autoantibodies nor-malised and all systemic signs andsymptoms had resolved completely.This patient presented withhaemorrhagic stroke; he did notLETTER TO THE EDITORSJON 1702Fig. T1 (left) and FLAIR (right) weighted brain MRI show predominantly hypointense lesion in the left lenticu-lar nucleus (left) with a hyperintense oedematous ring surrounding the lesion (right)Table Comparative evolution of autoantibodies levels, inflammatory parameters, and clinical featuresMarch 2003 July 2003 November 2003 December 2003Anti c-ANCA (n. r. < 1/20) 1/320* 1/320* 1/320* –Anti PR3 (n. r. < 20 U) 73U* 67U* 75U* 21UESR (n. r. < 10 mm/h) 33 mm/h* 10 mm/h 40 mm/h* 18 mm/hCRP (n. r. < 10 mg/l) 31 mg/l* < 2 mg/l 70 mg/l*Symptoms Haemorrhagic None Fever, arthralgia, ENT, Nonestroke lung, kidney disease0615_0616_Granziera_JON_1702  26.04.2005  11:00 Uhr  Seite 615616have the clinical picture of WG,but-ANCA and anti PR-3 antibod-ies were significantly elevated anda mild inflammatory syndromewas present. Eight months later, hedeveloped specific symptoms andsigns of the disease without in-volvement of the CNS. The imagingstudies excluded any vascular orcardiac abnormality, and the pa-tient had no objective signs of un-derlying arterial hypertension or ahistory of migraine. Therefore, webelieve that his haemorrhagicstroke represented an unusual ini-tial manifestation of WG.WG is a primary small vesselvasculitis. Its immunological hall-mark is a diffuse cytoplasmic pat-tern of antibodies (c-ANCA) thatare usually directed against pro-teinase 3 (anti PR3) [13]. Concomi-tant testing of c-ANCA and antiPR3 antibodies can minimize falsepositive results [14]. In our patientsboth tests were consistently highlypositive and normalised only aftertreatment. This case confirms thatWG may rarely be responsible forcerebrovascular disease in youngadults [8–12] and that intracerebralhaematoma can exceptionally oc-cur [8, 12]. Moreover, it illustratesthat WG may reveal itself exclu-sively through neurological mani-festations, without typical systemicsigns. In addition, though severeCNS involvement has been de-scribed in ANCA negative patients[15], it suggests that autoantibodies(c-ANCA/anti-PR3) represent avaluable marker of WG even beforeits clinical manifestation.For all these reasons, we suggestthat WG should be considered as apossible cause of haemorrhagicstroke in a young patient in the ab-sence of other causes. A positive c-ANCA/PR-3 testing should lead toa close clinical and paraclinical fol-low up, in order to prevent a cata-strophic outcome of this poten-tially serious disease.References1. Ruiz-Sandoval JL, Cantu C, Barinagar-rementeria F (1999) Intracerebral he-morrhage in young people: analysis ofrisk factors, location, causes, and prog-nosis. Stroke 30:537–5412. Qureshi AI, Tuhrim S, Broderick JP,Batjer HH, Hondo H, Hanley DF (2001)Spontaneous intracerebral haemor-rhage. N Engl J Med 344:1450–14603. Bogousslavsky J, Pierre P (1992)Ischemic stroke in patients under age45. Neurol Clin 10:113–1244. Ferro (1988) Vasculitis of the centralnervous system. J Neurol 245:766–7765. Futrell N, Millikan C (1989) Frequency,etiology, and prevention of stroke inpatients with systemic lupus erythe-matosus. Stroke 20:583–5916. Sigal LH (1987) The neurologic pre-sentation of vasculitic and rheumato-logic syndromes. A review. Medicine66:157–1807. Rao JK, Allen NB, Pincus T (1998)Limitations of the 1990 AmericanCollege of Rheumatology classificationcriteria in the diagnosis of vasculitis.Ann Intern Med 129:345–3528. Nishino H, Rubino FA, DeRemee RA,Swanson JW, Parisi JE (1993) Neuro-logical involvement in Wegener’s gran-ulomatosis: an analysis of 324 consec-utive patients at the Mayo Clinic. AnnNeurol 33:4–99. Mandl LA, Solomon DH, Smith EL,Lew RA, Katz JN, Shmerling RH (2002)Using antineutrophil cytoplasmic anti-body testing to diagnose vasculitis: cantest-ordering guidelines improve diag-nostic accuracy? Arch Intern Med162:1509–151410. Drachman (1963) Neurological com-plications of Wegener Granulomatosis.Arch Neurol 8:45–5511. Bares M, Muchova M, Dufek M, Litz-mann J, Krupa P, Rektor I (2002)Wegener Granulomatosis: ischemicstroke as the first clinical manifesta-tion (case study). J Neurol 249:1593–159412. Haas JP, Metzler M, Ruder H, WaldherrR, Boswald M, Rupprecht T (2002) Anunusual manifestation of Wegener’sgranulomatosis in a 4-year-old girl.Pediatr Neurol 27:71–7413. Nolle B, Specks U, Ludemann J, Rohr-bach MS, DeRemee RA, Gross WL(1998) Anticytoplasmic autoantibod-ies: their immunodiagnostic value inWegener granulomatosis. Ann InternMed 111:28–4014. Schmitt WH, van der Woude FJ (2004)Clinical applications of antineutrophilcytoplasmic antibody testing. CurrOpin Rheumatol 16:9–1715. Reinhold-Keller E, de Groot K, Holl-Ulrich K, Arlt AC, Heller M, Feller AC,Gross WL (2001) Severe CNS manifes-tations as the clinical hallmark ingeneralized Wegener’s granulomatosisconsistently negative for antineu-trophil cytoplasmic antibodies(ANCA). A report of 3 cases and areview of the literature. Clin ExpRheumatol 5:541–549Dr. C. Granziera () · P. Michel, MD · A. O. Rossetti, MD · S. Reymond, MD · J. Bogousslavsky, MDService de NeurologieCHUV BH 191011 Lausanne, SwitzerlandTel.: +41-21/314-1184Fax: +41-21/314-1256E-Mail: cristina.granziera@hospvd.chF. Lurati, MDService d’Immunologie et AllergologieCentre Hospitalier Universitaire VaudoisLausanne, Switzerland0615_0616_Granziera_JON_1702  26.04.2005  11:00 Uhr  Seite 616

Wegener Granulomatosispresenting withhaemorragic strokein a young adult

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Wegener Granulomatosispresenting withhaemorragic strokein a young adult

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