Brain & Development xxx (2017) xxx–xxx
www.elsevier.com/locate/braindev

Case Report

Atypical moyamoya syndrome with brain calcification and stenosis
of abdominal aorta and renal arteries
Hideki Uchikawa a,b,⇑, Katsunori Fujii a, Mayuko Fujita a, Tomoko Okunushi a,
Naoki Shimojo a
a

Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan
b
Department of Pediatrics, Eastern Chiba Medical Center, Togane, Japan

Received 7 November 2016; received in revised form 27 February 2017; accepted 3 April 2017

Abstract
Moyamoya syndrome is a progressive cerebrovascular disease that is characterized by stenosis of the terminal portion of the
internal carotid artery and its main branches, in combination with an accompanying disease. We herein describe an 8-year-old
boy exhibiting transient loss of consciousness, who had recurrent seizures in infancy with progressive brain calcification. On admission, he was alert but magnetic resonance angiography showed bilateral stenosis of the whole internal carotid artery and proliferation of vascular collaterals, and brain CT revealed calcification on bilateral putamen. Given that this fulfilled diagnostic criteria, we
finally diagnosed him as having moyamoya syndrome, though the etiology was unclear. Interestingly, a whole vessel survey revealed
vascular stenosis of abdominal aorta and renal arteries, in which the former has not been reported in moyamoya syndrome. We
considered that brain calcification was gradually formed by decreased cerebral vascular flow from infancy, and stenosis of abdominal aorta was possibly extended from renal arteries. This is, moyamoya syndrome with brain calcification and stenosis of abdominal
aorta, suggesting that morphological screening of whole vessels containing cerebral and abdominal arteries should be considered in
cases of slowly progressive brain calcification.
Ó 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Keywords: Moyamoya; Infantile; Calcification; Seizure; Abdominal aorta

1. Introduction
Moyamoya disease is characterized by progressive
occlusion of the internal carotid artery or its terminal
branches, which is accompanied by the formation of a
collateral vascular network called as ‘‘moyamoya vessels” at the base of the brain [1]. Other vascular stenosis
includes coronary artery, pulmonary artery, abdominal
⇑ Corresponding author at: Department of Pediatrics, Eastern Chiba
Medical Center, 3-6-2 Okayamadai, Togane 283-8686, Japan. Fax:
+81 475 50 1356.
E-mail address: uchikawa@chiba-u.jp (H. Uchikawa).

artery, and renal artery, which occasionally causes renal
hypertension [2]. However, to our knowledge, abdominal aorta has not been reported as an involvement of
moyamoya disease.
Some of the angiographic and clinical features of
moyamoya disease are sometimes observed in conjunction with congenital or acquired systemic disorders. This
condition is known as moyamoya syndrome or quasimoyamoya disease [3,4].
We herein describe an 8-year-old boy with progressive moyamoya syndrome, which is atypical case as
moyamoya disease exhibiting increasing brain calcification and unusual stenosis of abdominal aorta.

http://dx.doi.org/10.1016/j.braindev.2017.04.002
0387-7604/Ó 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Please cite this article in press as: Uchikawa H et al. Atypical moyamoya syndrome with brain calcification and stenosis of abdominal aorta and
renal arteries. Brain Dev (2017), http://dx.doi.org/10.1016/j.braindev.2017.04.002

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H. Uchikawa et al. / Brain & Development xxx (2017) xxx–xxx

2. Case report
An 8-year-old Japanese boy was admitted to our hospital because of recurrent episodes of transient loss of
consciousness during awake status. His delivery was
unremarkable. At the age of 4 months, he exhibited
unprovoked seizures, and revealed slight bilateral calcification in basal ganglia and temporal lobes on computed tomography (CT), which was gradually
increased by 4 years (Fig. 1A, B). He was diagnosed as
having epilepsy at that time, and phenobarbital was prescribed for 4 years without any additional epileptic
seizure.
At the age of 8 years, he exhibited sudden loss of consciousness at school and admitted to our hospital. On
admission, general physical examinations revealed unremarkable results. He also had no neurological deficit,
but seemed to have mildly intellectual disability. His
total intelligence quotient examination gave him the
score of 78, indicating that he had mild mental retardation. Blood examinations including coagulating system
(PT, APTT, TAT), inflammation (WBC, CRP, ANCA),
amino acid analysis, autoimmune antibodies and calcium metabolism (intact-PTH, Ca, P) were all within
normal limits.
Brain CT revealed increased bilateral calcification in
basal ganglia, and frontal and temporal lobes, compared
to those of 4 months and 2 years old (Fig. 1). Brain magnetic resonance angiography revealed prominent stenosis and disappearance of the whole internal carotid
arteries and proliferation of vascular collaterals, which
were typical for moyamoya vessels (Fig. 2A, B). Magnetic resonance imaging revealed flow voids in basal
ganglia and ivy sign on the brain surface (Fig. 2B).
Fluid-attenuated inversion recovery (FLAIR) image
showed high intensities on deep white matter region
(Fig. 2C).
We also investigated extra-cerebral systematic vascular involvements of this patient. We found moderate
stenosis of abdominal aorta and renal arteries on con-

trast CT (Fig. 3A). The diameter of abdominal aorta
was apparently narrow compared to the normal control
that was already reported (Fig. 3B). The stenosis was
limited to the range of abdominal aorta and renal arteries, and no other stenosis was identified. Single-photon
emission computerized tomography (SPECT) of the
brain revealed relatively preserved intracranial circulation (data not shown). The c.14429 G > A variant of
RNF213, which are known to cause familial moyamoya
disease [5], was investigated but failed to identify any
mutation. Furthermore, although whole exome sequencing was performed, no pathological mutation was
detected.
Though this patient fulfilled diagnostic criteria, he
was unique case showing increased brain calcification
and rare involvement of abdominal aorta as well as
renal arteries. Therefore we finally diagnosed him as
having moyamoya syndrome. Cerebral blood flow has
been maintained and no other neurological findings
were confirmed, so we have not performed vascular surgery for him, and currently maintained close observation at outpatient clinic.
3. Discussion
We described for the first time an 8-year-old Japanese
boy with progressive moyamoya syndrome, exhibiting
increasing brain calcification and unusual stenosis of
abdominal aorta and renal arteries. This is, to our
knowledge, a first report of progressive cerebral calcification and the involvement of abdominal aorta, possibly
those being developed from infancy.
Extracranial vascular involvements of moyamoya
disease have been widely reported, most often in the
renal artery about 5% [2,6]. Renal artery stenosis tends
to be located in the proximal region of the main branch.
In addition to the renal artery, the coronary, pulmonary, hepatic, splenic, superior mesenteric, pancreatic, iliac, and peripheral arteries are also involved in
moyamoya disease [2]. The stenosis of abdominal aorta

Fig. 1. Brain CT showing an increasing calcification of basal ganglia, and frontal and temporal cerebral regions at the age of (A) 4 months, (B)
2 years, and (C) 8 years, respectively.

Please cite this article in press as: Uchikawa H et al. Atypical moyamoya syndrome with brain calcification and stenosis of abdominal aorta and
renal arteries. Brain Dev (2017), http://dx.doi.org/10.1016/j.braindev.2017.04.002

H. Uchikawa et al. / Brain & Development xxx (2017) xxx–xxx

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Fig. 2. Brain MRI and MR angiography at the age of 8 years. (A) MR angiography revealed moyamoya vessels and stenosis of the proximal region
of the anterior and the middle cerebral arteries. (B) MR angiography indicated stenosis and disappearance (arrows) of the whole internal cerebral
arteries. (C) Fluid attenuated inversion recovery images showed ivy sign (arrow heads) and high intensity lesions in the deep white matter.

Fig. 3. Contrast CT showing a stenosis of the abdominal aorta and renal arteries. (A) Reconstruction image of the abdominal aorta and renal
arteries. Arrows indicate the stenotic portion. (B) The diameter of abdominal aorta of this patient indicated less than 3SD compared to agematched control described by Hegde et al. [12]. Filled circle depicts this patient.

might be extended from adjust renal arteries, as well as
extending stenosis from the end portion of internal carotid arteries as observed in the progressed stage.
Calcification of the brain is not usually associated
with moyamoya disease and syndrome. There have been
some reports to exhibit calcification associated with
moyamoya vessels. Moyamoya disease with RNF 213
could show bilateral calcification in the basal ganglia
[7]. Down syndrome is a chromosomal abnormality of
trisomy-21, occasionally associated with moyamoya
syndrome with brain calcification [8]. Systemic lupus
erythematosus due to C1q deficiency is known to cause
moyamoya syndrome with brain calcification [9]. Keutel
syndrome is a hereditary disease to show abnormal cartilage calcification and moyamoya syndrome with brain
calcification [10]. Hence, although etiology of calcification remains to be elucidated, brain calcification could
be associated with not only moyamoya disease but also
moyamoya syndrome.

A causative disease as homocystinuria, Down syndrome, fibromuscular dysplasia, sickle cell anemia, generalized arterial calcification of infancy, cerebral
arteriopathy associate with ACTA2, vasculopathy,
thrombophilia, neurofibromatosis type 1 and congenital
internal carotid artery (ICA) agenesis should be discussed [3]. Most possible candidate disease is fibromuscular dysplasia, which is a congenital vascular dysplasia
showing brain infarction or other ischemia of the organ.
Although fibromuscular dysplasia usually shows ‘string
of beads’ signs on MR angiography, which should be
confirmed in 80% patients [11], and stenosis of renal
arteries, which are typically recognized in distal portion,
we could not confirm these findings in this patient. In
addition, disease onset of fibromuscular dysplasia is usually early adulthood in women, we considered this disease seemed not to be likely for diagnosis of this
patient. Congenital ICA agenesis also should be discussed. Congenital ICA agenesis is usually unilateral,

Please cite this article in press as: Uchikawa H et al. Atypical moyamoya syndrome with brain calcification and stenosis of abdominal aorta and
renal arteries. Brain Dev (2017), http://dx.doi.org/10.1016/j.braindev.2017.04.002

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H. Uchikawa et al. / Brain & Development xxx (2017) xxx–xxx

associated with unilateral closure of foramen lacerum.
However, in this patient, the occlusion of ICA was bilateral, and the skull CT confirmed bilateral intact foramen
lacerum, suggesting this congenital ICA agenesis is
unlikely.
In conclusion, we demonstrated an 8-year-old boy
with moyamoya syndrome accompanied with stenosis
of the abdominal aorta with progressive brain calcification, suggesting that systematic vascular review containing brain arteries should be tried in cases with slowly
progressive brain calcification in infancy.

Acknowledgement
We thank to Prof. Kure in the Department of Pediatrics, Tohoku University for RNF213 gene analysis
and Dr. Hata in the Department of Maternal-Fetal Biology, National Research Institute for Child Health and
Development for whole exome sequencing.
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Please cite this article in press as: Uchikawa H et al. Atypical moyamoya syndrome with brain calcification and stenosis of abdominal aorta and
renal arteries. Brain Dev (2017), http://dx.doi.org/10.1016/j.braindev.2017.04.002