European Journal of Neurology 2001, 8: 719±722 CLINICAL CORRESPONDENCE Cerebral vasculitis and ischaemic stroke in BehcËet's disease: report of one case and review of the literature Y. Krespi, G. Akman-Demir, M. Poyraz, B. Tugcu, O. Coban, R. Tuncay, P. Serdaroglu and S. Bahar Department of Neurology, Istanbul Faculty of Medicine, University of Istanbul, Istanbul, Turkey Keywords: BehcËet's disease, ischaemic stroke, vasculitis Received 23 May 2001 Accepted 5 July 2001 Introduction. BehcËet's disease (BD) is a multisystemic, recurrent, in¯ammatory disorder. Neurological involvement is well-known but cerebral vasculitis and ischaemic stroke are unusual. Case description. A 43-year-old male patient presented with acute left hemiparesis, he had recurrent oral aphthae and scrotal ulcerations. Two episodes of transient brainstem ischaemia and an episode of right hemiparesis were reported in the past 2 years. Cranial magnetic resonance (MR) imaging showed a right striatocapsular infarction and multiple segmental stenosis, fusiform enlargement and beading of the arteries of the polygone of Willis were seen on angiography. Cerebro-spinal ¯uid (CSF) examination disclosed lymphocytic pleocytosis. Skin pathergy test was positive. A diagnosis of BD with cerebral vasculitis was made and immunosuppressive therapy was started. Some improvement of the arterial lesions on MR angiography and normalization of CSF were observed after 1 year of treatment. Discussion. Low grade chronic meningo-encephalitis is the core neuropathological process in neuro-BehcËet's disease. Nevertheless BD is a systemic disease known to cause vasculitis and can exceptionally lead to cerebral vasculitis and brain infarction. While BD is usually not part of the di€erential diagnosis of cerebral vasculitis, it should be borne in mind especially in endemic areas of the disease and in patients from these areas. Introduction BehcËet's disease (BD), is a multisystemic, recurrent, in¯ammatory disorder, also a€ecting the nervous system. Neurological involvement in BD has two common features: parenchymal involvement and non-parenchymal involvement, also called cerebral angio-BehcËet's syndrome that mainly encompasses cases with dural sinus thrombosis (Akman-Demir et al., 1996). Ischaemic stroke and cerebral vasculitis are unusual manifestations during the course of BD. Case report A 43-year-old male presented in October 1997, 10 days after acute left hemiparesis and dysarthria. He reported an episode of right hemiparesis that lasted 2 days in December 1995. In January 1996 he was evaluated for acute diplopia, nausea and vomiting that regressed in 3 days. A small old left putaminal infarct, which was probably responsible for the previous episode, was seen Correspondence: Yakup Krespi MD, Department of Neurology, Istanbul Faculty of Medicine, University of Istanbul, Millet cad, 34390, CËapa, Istanbul, Turkey (fax: +90-212-533-43-93; e-mail: mykrespi@superonline.com). ã 2001 EFNS on cranial computerized tomography (CT). He also reported an episode of acute vertigo, nausea, vomiting, ataxia and diplopia that lasted 2 days in May 1997. He had a 20-year history of recurrent oral aphthae and three episodes of scrotal ulceration. No vascular risk factor other than cigarette smoking was reported. On admission his physical examination was normal. He had dysarthria and left hemiparesis with left central facial paresis. Deep tendon re¯exes were brisk on the left side with a left Babinski sign. Erythrocyte sedimentation rate was 40 mm at 1 h. Haemogram and serum chemistry were normal. Skin patergy test performed as described before (Dilsen et al., 1986) was negative. Cranial magnetic resonance imaging (MRI) showed a well delineated right basal ganglia and capsular lesion, with no mass e€ect and which was slightly enhanced after gaddinium (Gd-DTPA) injection in addition to an old left putaminal infarct (Fig. 1a). The new lesion was compatible with a striatocapsular infarction. Cerebral digital subtraction angiography (DSA) revealed multiple segmental stenosis, fusiform enlargement and beading of the arteries of the polygone of Willis (Fig. 2a±d). Cerebro-spinal ¯uid (CSF) examination disclosed lymphocytic pleocytosis (28/mm3 lymphocytes, 6/mm3 polymorphonuclear leucocytes) and high protein content (0.66 g/l). The angiographic features 719 720 Y. Krespi et al. a b Figure 1 Magnetic resonance imaging T2-weighted images in axial plane (a) show a striatocapsular infarct and a small old infarct area in the left putamen (arrow-head). (b) Control cranial computerized tomography examination shows a right frontal abscess formation with perilesional oedema in the area of biopsy (arrow). stroke mechanism. There was no clinical or serological evidence in favour of any other cause of cerebral vasculitis. A diagnostic right frontal leptomeningeal and cortical biopsy was performed at the 60th day of the hospitalization that showed normal brain and leptomeningeal tissue. During the hospital course, he developed ¯orid oral aphtae and scrotal ulcers and a repeat skin pathergy test was now positive. On the 11th day after the biopsy he had a left simple motor seizure and his left hemiparesis progressively worsened. A control cranial CT examination revealed a right frontal abscess formation with perilesional oedema in the area of biopsy (Fig. 1b). Smears prepared from the aspiration specimen disclosed a haemorrhagic exudate, which was rich in neutrophils and macrophages. Gram staining, aerobe and anaerobe cultures remained negative. Antibiotic (meropenem 6 g/day) and methylprednisolone 48 mg/ day was started and the patient showed clinical and radiological improvement. A chest CT showed bilateral pulmonary artery aneurysms that had a thrombosed appearance on the right side, pointing to asymptomatic pulmonary artery vasculitic involvement. A diagnosis of BD with presumed cerebral vasculitis and a consequent brain infarction was made. Monthly 1 g IV cyclophosphamide for 12 months was added to steroid therapy. Repeat CSF examination was normal at the 6th month of therapy. At the 12th month of therapy cranial MRI showed a residual infarct area in the right putamen and MR angiography, although less sensitive than conventional angiography, showed improvement of beading appearance of P1 and P2 segments of the left posterior cerebral artery (PCA) (Fig. 2e) and practically no change in other arteries. The patient was neurologically stable after 3.5 years of follow up. Discussion Figure 2 Digital subtraction angiography: (a) stenosis (arrowhead) and fusiform enlargement (arrow) of right middle cerebral artery (MCA) M1 segment; (b) tubular narrowing of distal left MCA M1 and proximal M2 segment (arrow); (c) slight stenosis of distal part of the V4 segment of right vertebral artery (VA) (arrowhead) and irregularities of the basilar artery (BA) (arrow); (d) ectasic appearance of proximal segment of BA (arrow-head) and beading of P1 and P2 segment of left posterior cerebral artery (PCA) (arrow). (e) On control magnetic resonance angiography 12 months later, the beading appearance of left PCA P1 and P2 segments is improved. and the lymphocytic pleocytosis were considered in favour of an indolent meningo-vasculitic process, which was probably evolving for 2 years, and was the putative Our patient ful®lled the diagnostic criteria for BD (International Study Group For BehcËet's Disease, 1990); he had more than three episodes of oral aphtae, active genital ulceration and a positive pathergy test. Moreover, he also had asymptomatic pulmonary artery aneurysms, which is considered pathognomonic of BehcËet's vasculitis (Park et al., 1984). He presented with cerebral vasculitis and the new striatocapsular lesion seen on MRI was compatible with a middle cerebral artery (MCA) deep territory infarction. This lesion was well di€erentiated from the typical basal ganglia involvement observed during acute attacks of neuro-BehcËet, which is con¯uent and not ®tting within any arterial territory (CËoban et al., 1999). We were intrigued by the appearance of a cerebral abscess after ã 2001 EFNS European Journal of Neurology 8, 719±722 Cerebral vasculitis and ischaemic stroke in BehcËet's disease the cerebral biopsy that was contemporaneous with a strongly positive skin pathergy test. Although negative bacteriological studies could not de®nitely rule out a pyogenic brain abscess, we think that this lesion might probably be the result of an aseptic focal brain in¯ammatory response to the non-speci®c physical insult of the biopsy procedure and was reminiscent of skin pathergy reaction. Concomitant appearance of ¯orid oral aphtae and scrotal ulcers were considered in favour of this second hypothesis. To our knowledge such focal reaction in the brain has not been previously described in BD. The constellation of cerebral vasculitis and brain infarction represent a particular and unusual form of cerebral angio-BehcËet's syndrome. This patient is the only case of cerebral vasculitis in our large registry including 200 neuro-BehcËet cases (Akman-Demir et al., 1999). Another patient in this series with right brainstem infarction had right extra-cranial vertebral artery (VA) dissection because of vasculitis and was previously reported (Bahar et al., 1993). During the course of BD, arterial involvement is rare (1±5%) and peripheral arteries are most commonly involved with aneurysm and pseudo-aneurysm formation or occlusion (Dilsen et al., 1993). Histological studies demonstrate a nonspeci®c vasculitis with mononuclear cells or neutrophilic in®ltration, endothelial cell proliferation, destruction of internal elastic lamina, ®brinoid necrosis and thrombus formation (Matsumoto et al., 1991). Vasculitis of vasa vasorum is generally held responsible for aneurysm or pseudo-aneurysm formation (Matsumoto et al., 1991). Cerebral vasculature can also be involved in BD. While intra- or extra-cranial isolated fusiform or saccular aneurysm formation is a rather well-known entity, intra-cranial cerebral artery stenosis or occlusion are very rare and only ®ve cases have been reported in the literature (Bienenstock and Murray, 1961; Iragui and Maravi, 1986; Buge et al., 1987; Zelenski et al., 1989; Nishimura et al., 1991). Except one patient (Zelenski et al., 1989), all these cases were neurologically symptomatic and presented with transient (Bienenstock and Murray, 1961; Iragui and Maravi, 1986) or established neurological de®cits contralateral to the a€ected artery (Bienenstock and Murray, 1961; Buge et al., 1987; Nishimura et al., 1991); hemiparesis being the most frequent manifestation (Bienenstock and Murray, 1961; Iragui and Maravi, 1986; Buge et al., 1987; Nishimura et al., 1991). In one report the neurological de®cit was considered to be the result of a cerebral infarction in the deep territory of the middle cerebral artery (MCA), but brain imaging ®ndings were not provided (Buge et al., 1987). Angiography disclosed fusiform aneurysmal dilatations (Buge et al., 1987; Zelenski et al., 1989), stenoses (Iragui and Maravi, ã 2001 EFNS European Journal of Neurology 8, 719±722 721 1986; Buge et al., 1987; Zelenski et al., 1989) or occlusions (Bienenstock and Murray, 1961; Buge et al., 1987; Nishimura et al., 1991) of proximal segments of medium sized intra-cranial vessels, usually of the MCA that was sometimes associated with more peripheral small vessel involvement (Zelenski et al., 1989). In all cases there was convincing evidence that a vasculitic process underlined the arterial changes. High protein content and/or pleocytosis of CSF were seen in all the patients. In two patients there was vasculitis elsewhere; pulmonary in one (Buge et al., 1987) and retinal in two cases (Buge et al., 1987; Zelenski et al., 1989). Spontaneous progression (Buge et al., 1987) or regression of the arterial changes under immunosuppressive therapy (Iragui and Maravi, 1986; Zelenski et al., 1989) pleaded also in favour of vasculitis in three patients. One autopsy study clearly demonstrated neuropathological ®ndings consistent with panarteritis of branches of the MCA causing occlusion and infarction in its territories (Nishimura et al., 1991). Usually rather than a true vasculitis, a low grade chronic meningoencephalitis is considered to be the principal neuropathological process in neuro-BehcËet's disease (Had®eld et al., 1997). On the other hand, BD is a systemic disease known to cause vasculitis and can rarely lead to cerebral vasculitis. This is the exception and one should always be cautious in making this diagnosis. 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