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Journal of the Neurological Sc

Short communication

Cerebral arteriopathy with extracranial artery involvement in a patient with

ulcerative colitis

Tatsuya Nomoto a,b,*, Takehiko Nagao a, Kyugo Hirabayashi a, Takehiro Seta b,

Masayuki Yokochi a, Ken-ichiro Katsura b, Yasuo Katayama b

a Department of Neurology, Tokyo Metropolitan Ebara Hospital, Tokyo 145-0065, Japanb The Second Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan

Received 6 June 2005; received in revised form 12 October 2005; accepted 11 November 2005

Available online 20 December 2005

Abstract

Arteriopathy of the central nervous system (CNS) complicated with ulcerative colitis is a rare condition, moreover the involvement of

extracranial arteries has not been documented. An 18-year-old female complained of a severe pulsatile headache and nausea. She had been

diagnosed and treated for ulcerative colitis for four years. Magnetic resonance imaging of the brain showed normal results; however,

magnetic resonance angiography (MRA) revealed severe irregularity of the intracerebral arteries. After treatment with prednisolone, the

patient fully recovered and the irregularity of the intracerebral arteries was dramatically improved. Vasculitis was strongly suggested as the

cause of arteriopathy of the CNS in the present case. Involvement of extracranial arteries such as the carotid artery was also incidentally

discovered by duplex ultrasonography and the HLA typing suggested genetic susceptibility to Takayasu’s arteritis. Findings from our patient

suggest that extracranial arterial involvement should be considered in the case of arteriopathy of the CNS associated with ulcerative colitis.

D 2005 Elsevier B.V. All rights reserved.

Keywords: CNS; MRI; HLA; Takayasu’s arteritis; Ulcerative colitis

1. Introduction

Ulcerative colitis is a chronic, relapsing, remitting

gastrointestinal disease characterized by chronic inflamma-

tion of the intestine. Recent reports about the possible role of

mucosal immune activation, and low-grade inflammatory

mucosal changes have supported a pathophysiologic concept

of ulcerative colitis as an inflammatory disorder [1].

Ulcerative colitis is a condition that primarily affects the

superficial layer of the colon mucosa, and histological

analysis has shown ulceration of the mucosa, blunting and

loss of crypts, and an inflammatory infiltrate. The cellular

composition of the inflammatory infiltrate in the colon is

characterized by increased numbers of CD4+ T lymphocytes,

0022-510X/$ - see front matter D 2005 Elsevier B.V. All rights reserved.

doi:10.1016/j.jns.2005.11.004

* Corresponding author. The Second Department of Internal Medicine,

Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603,

Japan. Tel.: +81 3 3822 2131; fax: +81 3 3822 4865.

E-mail address: nomotatsu@jichi.ac.jp (T. Nomoto).

mast cells, neutrophils, and eosinophils [2]. Ulcerative colitis

is associated with intestinal and extra-intestinal clinical

manifestations. Among these, strokes, generalized seizures,

and coma have been reported as cerebral complications of

ulcerative colitis. On the basis of clinical, angiographic, and

laboratory data, these manifestations have been attributed to

arteritis or thromboembolic disease [3,4]. Here, we report the

arteriopathy of the central nervous system (CNS) associated

with ulcerative colitis. Duplex ultrasonography of the carotid

artery and cerebral angiography indicated the involvement of

extracranial arteries. Interestingly, the HLA type of this

patient suggested the possible clinical association with

Takayasu’s arteritis.

2. Case report

A 15-year old female was suffered from low-grade fever

and bloody diarrhea. Colonoscopy was performed and the

iences 243 (2006) 87 – 89

T. Nomoto et al. / Journal of the Neurological Sciences 243 (2006) 87–8988

colon biopsy showed crypt abscesses with epithelial ulcera-

tion. Subsequently, she was diagnosed with ulcerative colitis.

At the age of 18, she was referred to our department because

of severe pulsatile headache and nausea for 3 days. In this

period, the disease activity of ulcerative colitis was sup-

pressed with 1500 mg mesalazine and 20 mg prednisolone.

Initially, she was treated as an outpatient clinic for the

headache. Although several medications, including nonste-

roidal anti-inflammatory drug were prescribed, her headache

gradually increased and the nausea was not improved at all.

She was admitted for further evaluation of refractory

headache 10 days after medication. On admission, her blood

pressure was 92/64 mm Hg and she had no fever and no

neurological deficit. Head computed tomography (CT) scan

and magnetic resonance imaging (MRI) with gadolinium-

diethylenetriamine pentaacetic acid was normal. Cerebrospi-

nal fluid (CSF) showed mild pleocytosis (36 cells/Al), normal

protein (40 mg/dl), and glucose (57 mg/dl). No bacteria,

fungi, or viruses were identified in the CSF. Admission

laboratory data included hemoglobin 12 g/dl, white count

11,000 per mm3, C-reactive protein of 2.2 mg/dl, and normal

sedimentation rate, electrolytes, liver function studies,

prothrombin time, and partial thromboplastin time. Magnetic

Fig. 1. Vascular alternation of the 3-dimensional time-of-flight magnetic resonanc

the cerebral arteries (arrows) are evident 8 days after admission (A). Vascular irreg

prednisolone (B). Bilateral carotid angiography (C and D) demonstrates wall irreg

subclavian (F) angiograms reveals the long segmental narrowing without wall irr

resonance angiography (MRA) on day 8 showed diffusely

narrowed cerebral arteries with multiple segmental stenosis

(Fig. 1A). Subsequent cerebral digital subtraction angiogra-

phy also demonstrated diffuse irregularities of the intracere-

bral arteries (Fig. 1C, D). Common carotid artery (Fig. 1E)

and subclavian artery (Fig. 1F) showed subtle narrowing

without wall irregularities. Duplex ultrasonography of

carotid arteries revealed significant thickening of the inti-

ma-media complex. Extensive laboratory tests including

antinuclear antibodies, rheumatoid factor, immunoglobulin

level, myeloperoxidase (MPO)-anti-neutrophil cytoplasmic

antibodies (ANCA), proteinase-3 (PR3)-ANCA , protein C

and protein S activity, lupus anticoagulant, and anti-h2-glycoprotein I antibodies were within normal range. HLA

studies showed HLA-A24, Bw52, and DR2. The patient

developed transient confusion and disorientation 11 days

after admission. However, she recovered from the confu-

sional state spontaneously, but the severe headache and

nausea continued. Therapy with 60 mg of oral prednisolone

was initiated 13 days after admission followedwith a tapering

of oral prednisolone. Two days later, a rapid improvement of

the refractory headache and nausea was observed. Follow-up

MRA, 3 weeks after 1st MRAmeasurement, showed marked

e angiogram (A and B). Several arterial dilatations and segmental stenosis of

ularities were significantly improved 3 weeks after treatment with increased

ularities of the M1 segment (arrowheads). Left common carotid (E) and left

egularities (arrows).

T. Nomoto et al. / Journal of the Neurological Sciences 243 (2006) 87–89 89

improvement in the irregularities of the intracerebral arteries

(Fig. 1B) and normalized thickening of the intima-media

complex of the carotid arteries was also confirmed by duplex

ultrasonography. There was no recurrence of subjective

symptoms associated with cerebral vascular abnormality

such as pulsatile headache during a follow-up period of 2.5

years.

3. Discussion

The patient reported here was suffering from a severe

headache, which would be the most common symptom of

vasculitis of the CNS. Arteriopathy of the CNS was

diagnosed with MRA and remarkable thickening of the

intima-media complex of carotid arteries was also discovered

with duplex ultrasonography. Our patient was successfully

treated with an immediate increase of the dosage of

prednisolone.

Although a brain biopsy was not performed in our patient,

vasculitis was considered as the most probable cause of

arteriopathy of the CNS based on the following reasons. First,

she had no underlying disease, such as hypertension,

hyperlipidemia, or diabetes mellitus. Second, MRA imaging

of the multiple arterial dilatations and segmental stenosis is

consistent with vasculitis. Third, rapid improvement of

clinical symptoms and the irregularity ofMRAwith increased

prednisolone indicated the involvement of inflammatory

mechanism in this arteriopathy.

Patients with ulcerative colitis occasionally have extra-

colonic complication, such as arthritis, uveitis erythema

nodosum, and sclerosing spondylitis. Thromboembolic

diseases are also recognized as serious extra-intestinal

complications of inflammatory bowel diseases and there

have been many reports of thromboembolic complications

associated with ulcerative colitis. However there have been

only two reports that described vasculitis of the CNS

complicated by ulcerative colitis [3,4].

Interestingly, we found that this patient had HLA-A24,

Bw52, and DR2. HLA-A24, Bw52, Dw12 and DR2 have

been associated with Japanese Takayasu patients [5,6].

Similarly, a significant association between ulcerative colitis

and HLA-B52 and DR2 has been shown in Japanese

populations [7]. The pathogenic relevance of HLA-B52 and

DR2 to concomitant Takayasu’s arteritis and ulcerative colitis

was also emphasized [8,9]. In our patient, arteriopathy was

initially believed to be restricted to the CNS, however diffuse

thickening of intima-media complexes of the common carotid

arteries was identified, suggesting extracranial vascular

involvement. Furthermore, her HLA typing indicated a

genetic susceptibility for Takayasu’s arteritis.

Approximately 10% to 15% of patients with Takayasu’s

arteritis will have ischemic stroke or transient ischemic

attacks. These strokes have mainly been attributed to

stenotic extracranial vessels [10,11], but few reports have

described intracranial arteritis in a patient with Takayasu’s

arteritis [12–14]. Recently, Ringleb et al showed the

involvement of intracranial arteries in the seven patients of

Takayasu’s arteritis with MRA [12]. At least one case report

has described intracranial arteritis in a patient with

Takayasu’s arteritis at autopsy [13]. They emphasized the

intracranial arterial involvement in a patient with Takayasu’s

arteritis, however they could not show the simultaneous

involvement of extracranial arteries.

Although this case does not fulfill the criteria of

Takayasu’s arteritis, similar genetic influences susceptible

to Takayasu’s arteritis might have contributed to the

pathogenesis of the intracranial and extracranial vascular

involvement in our patient.

In conclusion, we report the arteriopathy of the CNS

in a patient of ulcerative colitis. The vasculitis was

considered the probable cause of arteriopathy of the CNS.

Extracranial arterial involvement and HLA analysis

indicated a similar genetic susceptibility for Takayasu’s

arteritis. In the case of arteriopathy of the CNS, the

possibility of associated extracranial arterial involvement

should always be entertained.

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