Accepted Manuscript
A pediatric case of reversible cerebral vasoconstriction syndrome with similar
radiographical findings to posterior reversible encephalopathy syndrome
Tomoya Kamide, Taishi Tsutsui, Kouichi Misaki, Hiroki Sano, Masanao Mohri,
Naoyuki Uchiyama, Mitsutoshi Nakada
PII:

S0887-8994(16)30725-1

DOI:

10.1016/j.pediatrneurol.2017.02.008

Reference:

PNU 9089

To appear in:

Pediatric Neurology

Received Date: 24 September 2016
Revised Date:

8 February 2017

Accepted Date: 12 February 2017

Please cite this article as: Kamide T, Tsutsui T, Misaki K, Sano H, Mohri M, Uchiyama N, Nakada
M, A pediatric case of reversible cerebral vasoconstriction syndrome with similar radiographical
findings to posterior reversible encephalopathy syndrome, Pediatric Neurology (2017), doi: 10.1016/
j.pediatrneurol.2017.02.008.
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A pediatric case of reversible cerebral vasoconstriction syndrome with similar

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radiographical findings to posterior reversible encephalopathy syndrome

Tomoya Kamidea, Taishi Tsutsuia, Kouichi Misakia, Hiroki Sanob, Masanao Mohria,

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Naoyuki Uchiyamaa, Mitsutoshi Nakadaa

Department of Neurosurgery, Graduate School of Medical Sciences, Kanazawa

University, Kanazawa, Ishikawa, Japan
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Department of Neurosurgery, Kanazawa Municipal Hospital, Kanazawa, Ishikawa,

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Japan

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Corresponding author: Tomoya Kamide

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Department of Neurosurgery, Graduate School of Medical Science, Kanazawa
University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan
Phone: +81-76-265-2384,
Fax: +81-76-234-4262
E-mail: kamide@med.kanazawa-u.ac.jp

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Word count: 2,013

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Running title: Pediatric thunderclap headache

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Abstract

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Background: Reversible cerebral vasoconstriction syndrome predominantly occurs in
middle-aged women. Only 9 pediatric cases of this syndrome have ever been reported.

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Case report: Here we present a pediatric case of reversible cerebral vasoconstriction

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syndrome (RCVS) with similar radiographical findings to posterior reversible
encephalopathy syndrome (PRES). A 10-year-old healthy boy developed thunderclap
headache with no neurological deficit. Brain magnetic resonance angiography (MRA)
revealed multifocal narrowing of the cerebral arteries, while magnetic resonance

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imaging (MRI) with diffusion-weighted imaging and fluid-attenuated inversion
recovery demonstrated hyperintense lesions in the bilateral occipital lobes and the left

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cerebellum. The patient’s clinical symptoms resolved spontaneously after a few hours

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and no recurrence was reported thereafter. MRA on the 2nd day showed a complete
normalization of the affected arteries and MRI after 1 month demonstrated a significant
improvement in the abnormal findings, leading to a diagnosis of RCVS with similar
radiographical findings to PRES. Conclusions: This report suggests that, although rare,
RCVS with or without PRES, should be considered in pediatric patients if they present
with a thunderclap headache.

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syndrome, posterior reversible encephalopathy syndrome

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Key words: pediatric, thunderclap headache, reversible cerebral vasoconstriction

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Introduction

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Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico-radiological
condition characterized by severe, often thunderclap, headaches with or without

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concomitant neurological signs and symptoms, in the context of reversible

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vasoconstriction of the cerebral arteries [1]. RCVS may occur spontaneously or may be
provoked by various precipitating factors, such as pregnancy-related factors, drugs,
headache disorders, medical problems, surgical procedures, and blood product
transfusions [2]. The clinical features of RCVS are also common to posterior reversible

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encephalopathy syndrome (PRES), which is characterized by symmetrical areas of
vasogenic edema of the white matter predominantly localized to the territories of the

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posterior circulation in patients with acute neurological symptoms (e.g., seizures,

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encephalopathy, headache, and visual disorders). PRES is diagnosed in the settings of
renal failure, blood pressure fluctuations, cytotoxic drugs, autoimmune disorders, and
pre-eclampsia or eclampsia, but has also been reported to occur in individuals with
RCVS [3].
RCVS is mostly observed in middle-aged women. In fact, only 9 pediatric
cases of RCVS have ever been reported [1, 4-9]. Among the pediatric cases, only 1

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patient with Loeys-Dietz syndrome, which is an autosomal dominant connective tissue
disease, exhibited RCVS together with PRES [1]. In this report, we describe an

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extremely rare case of a healthy pediatric patient diagnosed with RCVS with similar

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radiographical findings to PRES.

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Case report

A 10-year-old boy presented with a sudden-onset, throbbing, severe, diffuse headache
with a verbal numeric pain scale of 10/10 intensity without other neurological deficits

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after mild exercise. He developed several moderate to severe headaches after karate,
which is a traditional Japanese system of unarmed combat, in the two weeks prior to his

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visit. He was born through Caesarean section at 32 weeks’ gestation and weighed 1,600

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g, but his development was normal. He had no history of headache and his family
history was negative for headache, migraine, or premature vascular disease, although his
mother was diagnosed with antiphospholipid syndrome. He was not taking medication
and denied alcohol, tobacco, or substance misuse. He went to the emergency department
of another hospital and was referred to our hospital because his brain imaging results
had abnormal findings.

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Upon admission, the patient’s headache had completely disappeared and his
neurological examination was unremarkable. His blood pressure was 140/92 mmHg and

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laboratory findings, including blood cell counts and chemistries, were normal. Serology
demonstrated normal inflammatory markers, autoimmune profile, complement and

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immunoglobulin levels, and procoagulant screen results. Cerebrospinal fluid (CSF)

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examination indicated normal opening pressure and no abnormal findings. Brain
magnetic resonance angiography (MRA) showed multiple, segmental, mild to moderate
narrowings of the bilateral middle cerebral arteries (MCAs) and the right posterior
cerebral artery (PCA) (Fig. 1a). Brain magnetic resonance imaging (MRI) revealed
large

bilateral

hyperintense

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relatively

lesions

of

the

occipital

lobes

on

diffusion-weighted images (DWI, Fig. 2c) and fluid-attenuated inversion recovery

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(FLAIR, Fig. 2d), in addition to a lesion that was not visualized on DWI (Fig. 2a), but

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was visible on the left cerebellum on FLAIR (Fig. 2b). This lesion corresponded to a
cerebral infarction. After admission, the patient’s blood pressure returned to the normal
range (90-100/60-70 mmHg) spontaneously and he was carefully observed without
medication.
A follow-up MRA on day 2 revealed a complete resolution of the vascular
stenosis of the MCAs and the PCA (Fig. 1b), although DWI and FLAIR images

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revealed maturation of the hyperintense lesions. Furthermore, contrast high-resolution
MRI demonstrated no findings of vessel wall thickening or enhancement. No additional

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headaches occurred and the patient was discharged on day 9 without any neurological
deficits. Follow-up MRI after 1 month showed notable improvement of the DWI and

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FLAIR hyperintense lesions (Figs. 2e-h). Further repeat MRI and MRA after 3 and 6

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months remained unchanged and the patient remained headache-free for >6 months.

Discussion

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RCVS is characterized by thunderclap headaches with or without neurological deficits,
benign CSF analysis, and multifocal segmental areas of cerebral arterial narrowing or

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vasoconstriction that usually resolve within weeks. We observed all of the above

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characteristics in our case. Ischemic infarctions are the most common complicated
lesions found in several cohort analyses, and occur in 6-39% of cases. These infarctions
tend to occur in arterial watershed areas [2]. RCVS mainly occurs in middle-aged adults
and only 9 pediatric cases have ever been reported (Table 1) [1, 4-9]. The majority of
the pediatric cases are in boys, while adult cases mainly occur in women [1, 4].
Pediatric arterial ischemic stroke also occurs predominantly in boys. Normann et al.

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have reported that testosterone levels above the 90th percentile for age and sex are
documented in 16.7% of pediatric patients with stroke, when compared to 1.8% in

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control patients [10]. In fact, Probert et al. have discussed the possibility that
testosterone affects the male dominance of pediatric RCVS cases [8]. However, it is

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unclear whether this association is indeed present.

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PRES is a clinical syndrome with acute neurological findings resulting from
the disruption of the blood-brain barrier and accompanies evidence of vasogenic edema
on brain imaging [11]. Endothelial dysfunction is a key factor in PRES, but vascular
stenosis is not a major finding [3]. The radiological features of PRES include

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subcortical vasogenic edema that predominantly involves the bilateral parieto-occipital
regions and resolves within days or weeks. The presence of restricted diffusion is

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compatible with a diagnosis of PRES. Moreover, Fugate et al. have reported that brain

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edema is not uncommon in cases of PRES affecting regions other than the classic
parieto-occipital areas [3]. For example, edema can affect the cerebellum in up to half of
the patient population, as observed in the present case. A diagnosis of PRES should be
considered in several different settings, although cases such as ours have similar
radiological findings.
Hypertension is common in pediatric PRES, although blood pressure at the

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onset of PRES is lower because the cerebral blood flow autoregulation threshold is
lower in children than in adults [3]. In fact, Siebert et al. have reported that the mean

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blood pressure at the time of presentation in pediatric patients with PRES in three
medical centers in Germany was 140/85 mmHg, as in our case [12]. It is unclear

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whether our patient can be diagnosed with PRES without typical clinical symptoms,

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such as seizure, encephalopathy, and visual disturbance, although PRES has been
reported in 17-38% of patients with RCVS [3]. Pediatric cases of PRES occur
occasionally [11], although pediatric patients with both RCVS with PRES are extremely
rare, probably due to the fact that RCVS mainly occurs in middle-aged adults. Akazawa

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et al. reported the first pediatric case of RCVS with PRES [1]. However, the patient may
have also had endothelial dysfunction associated with an underlying condition, which

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was diagnosed genetically as Loeys-Dietz syndrome. Therefore, this is the first healthy

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pediatric case diagnosed with RCVS, with similar radiographical findings to PRES.
In our case, cerebral arterial narrowing was completely resolved within 1 day

of the initial evaluation, although the vascular changes may have begun when the
patient had the mild headaches before admission. Since the affected arteries may
improve within a few days, a large number of patients with RCVS may be undiagnosed.
Furthermore, many more pediatric patients with RCVS with or without PRES may exist,

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as the diagnosis of pediatric cases is particularly difficult given the need for MRI and
MRA [5, 13]. This is especially true for healthy children without neurological deficits.

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In conclusion, we report the first healthy pediatric case of RCVS with similar
radiographical findings to PRES. Pediatric cases of RCVS are rare, but a larger number

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of cases may be detected as more and more MRIs and MRAs are performed in pediatric

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patients with severe headaches. We emphasize that RCVS with or without PRES should

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be considered in pediatric patients with thunderclap headaches.

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Funding: none.

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Informed consent

The parent of the patient has consented to the submission of this case report to the

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Conflicts of interest: none.

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journal.

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Figure legends

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FIGURE 1. (a) Brain magnetic resonance angiography (MRA) on the 1st day of
admission showing multiple, bilateral segmental narrowings of the middle cerebral

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artery and the right posterior cerebral artery (arrow). (b) Follow-up MRA on the 2nd

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day showing complete resolution of the cerebral artery constrictions.

FIGURE 2. Brain magnetic resonance imaging (MRI) on the 1st day of admission
showing relatively large hyperintense lesions of the left cerebellum on fluid-attenuated

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inversion recovery (FLAIR), (b) but not on diffusion-weighted imaging (DWI) (a). The
bilateral occipital lobes contain hyperintense lesions on both DWI (c) and FLAIR (d).

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Follow-up MRI DWI (e, g) and FLAIR (f, h) after 1 month showing marked

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improvements in the bilateral occipital lobe and the left cerebellum lesions.

Table 1. Clinical and radiological features of pediatric cases with reversible cerebral
vasoconstriction syndrome in published literature

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References

Akazawa Y, Inaba Y, Hachiya A, et al. Reversible cerebral vasoconstriction

2.

syndrome and posterior reversible encephalopathy syndrome in a boy with
Loeys-Dietz syndrome. Am J Med Genet A 2015;167:2435-2439.
Mehdi A, Hajj-Ali RA. Reversible cerebral vasoconstriction syndrome: a
comprehensive update. Curr Pain Headache Rep 2014;18:443.
Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome:
clinical and radiological manifestations, pathophysiology, and outstanding
questions. The Lancet Neurology 2015;14:914-925.

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3.

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1.

Ghosh PS, Rothner AD, Zahka KG, Friedman NR. Reversible Cerebral
Vasoconstriction Syndrome: A Rare Entity in Children Presenting With
Thunderclap Headache. J Child Neurol. 2011;26:1580-1584.

5.

Kazato Y, Fujii K, Oba H, et al. Reversible cerebral vasoconstriction syndrome
associated with brain parenchymal hemorrhage. Brain Dev 2012;34:696-699.
Kirton A, Diggle J, Hu W, Wirrell E. A Pediatric Case of Reversible Segmental
Cerebral Vasoconstriction. Can J Neurol Sci 2006;33:250-253.

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11.

12.

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8.

Liu HY, Fuh JL, Lirng JF, Chen SP, Wang SJ. Three paediatric patients with
reversible cerebral vasoconstriction syndromes. Cephalalgia 2010;30:354-359.
Probert R, Saunders DE, Ganesan V. Reversible cerebral vasoconstriction
syndrome: rare or underrecognized in children? Dev Med Child Neurol
2013;55:385-389.
Yoshioka S, Takano T, Ryujin F, Takeuchi Y. A pediatric case of reversible
cerebral vasoconstriction syndrome with cortical subarachnoid hemorrhage.
Brain Dev 2012;34:796-798.
Normann S, de Veber G, Fobker M, et al. Role of endogenous testosterone

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6.

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4.

concentration in pediatric stroke. Ann Neurol 2009;66:754-758.
Chen TH, Lin WC, Tseng YH, Tseng CM, Chang TT, Lin TJ. Posterior
Reversible Encephalopathy Syndrome in Children: Case Series and Systematic

Review. J Child Neurol 2013;28:1378-1386.
Siebert E, Spors B, Bohner G, Endres M, Liman TG. Posterior reversible
encephalopathy syndrome in children: radiological and clinical findings - a
retrospective analysis of a German tertiary care center. Eur J Paediatr Neurol
2013;17:169-175.
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Singhal AB. Diagnostic challenges in RCVS, PACNS, and other cerebral

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arteriopathies. Cephalalgia 2011;31:1067-1070.

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Table 1 : Clinical and radiological features of pediatric cases with reversible cerebral vasoconstriction syndrome in published literature

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Age
(y)

Sex

Angiographical
improvement

Outcome

1

13

M

CT : normal (day 1, 5), MRI : normal (day 5)

Smooth narrowing of bilateral proximal vessels
(day 6)

day16

Headache free >
18 months

2

10

M

MRI : small hyperintense lesion of the left occipital lobe and
hyperintensities in the sulci of the bilateral posterior temporal
and the occipital lobes on FLAIR (day 12)

Multiple segmental narrowing in MCA and PCA
bilaterally (day 4)

day 44

Headache free >
3 months

3

16

M

Not described

Multiple segmental narrowing over bilateral
PCAs and irregularity of left MCA

2 months

Headache free >
2 years

4

10

M

Not described

Multiple segmental narrowing over bilateral
MCAs and PCAs

day 31

Headache free >
2 years

5

15

M

CT : normal (day 2), MRI : normal (day 2)

Multifocal vascular irregularities of posterior and
anterior circulation (day 4, 6)

6 weeks

Headache free >
3 months

6

12

M

CT : normal (day 1), MRI : cortical SAH of the right occipital,
the left frontal, and the bilateral parietal lobes (day 5)

Multifocal narrowing of cerebral arteries (day 5)

3 months

Headache free >
3 months

7

7

F

CT : parenchymal hemorrhage of the left occipital and
parietal lobes (day 2), MRI : post hemorrhagic (day 28)

Diffuse cerebral vasoconstriction (day 28)

day 60

Not described
(Aplastic anemia)

8

13

M

CT : normal (day 5), MRI : multiple acute infarcts in the
territory of the posterior circulation (day 12)

Beading and stenosis of both VAs, ICAs, and
MCAs (day 18)

5 weeks

Headache free >
3 years

9

9

M

MRI : cortical SAH of the right parietal lobe (day 1), hyper
lesions of the left posterior lobe, the right temporal lobe, and
the bilateral cerebellum on FLAIR (day 6)

Mild narrowing of bilateral ICAs (day 1)
Significant narrowing of bilateral ICAs (day 5)

2 months

Not described
(Loeys-Dietz
syndrome)

Present
case

10

M

MRI : large hyper lesions of the bilateral posterior lobes and
the left cerebellum on DWI and FLAIR (day 1)

Multiple, segmental, mild to moderate narrowing
of bilateral MCAs and right PCA (day 1)

day 2

Headache free >
6 months

Cerebrovascular imaging

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Brain imaging

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Case

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M, male; F, female; CT, computed tomography; MRI, magnetic resonance imaging; FLAIR, fluid-attenuated inversion recovery; MCA, middle cerebral artery; PCA, posterior cerebral
artery; SAH, subarachnoid hemorrhage; VA, vertebral artery; ICA, internal carotid artery; DWI, diffusion weighted imaging.

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