doi: 10.2169/internalmedicine.9326-22
Intern Med 62: 617-621, 2023
http://internmed.jp

【 CASE REPORT 】

Enhancement of the Ivy Sign during an Ischemic Event in
Moyamoya Disease
Yuki Hamada 1, Ayano Shigehisa 1, Yoshiki Kanda 1, Mei Ikeda 1, Go Takaguchi 1,
Hideki Matsuoka 1 and Hiroshi Takashima 2

Abstract:
We herein report a case of increased and expanded ipsilateral ivy sign paralleling the expansion of cerebral
infarction in a patient with moyamoya disease. A 67-year-old woman visited our hospital with symptoms of
left hemiplegia, left homonymous hemianopia, and left unilateral spatial neglect. Magnetic resonance imaging
of the head showed cerebral infarction in the right parietal lobe. In addition, ivy signs were evident on fluidattenuated inversion recovery imaging. These findings were enhanced by the expansion of cerebral infarction
and disappeared once the ischemia resolved, implying hemodynamic changes. As a result of continuing medical treatment without antithrombotic therapy, the patient obtained a good outcome. Treatment for moyamoya
disease in the acute phase is considered to require complex knowledge of multiple factors, such as the anatomical background of the individual patient and the progression grade of ischemia.
Key words: moyamoya disease, ivy sign, ischemic event
(Intern Med 62: 617-621, 2023)
(DOI: 10.2169/internalmedicine.9326-22)

Introduction

Case Report

Moyamoya disease is a progressive cerebrovascular disease that causes stenosis at the ends of the bilateral internal
carotid arteries and formation of an abnormal vascular network (moyamoya blood vessels) at the bottom of the brain
as collateral circulation (1-3). Occlusion of the main artery
may cause ischemic events, while cerebral and intraventricular hemorrhaging may occur due to the development or disruption of the fragile collateral circulation. Characteristic
linear hyperintensities along the sulcus on fluid-attenuated
inversion recovery (FLAIR) imaging are called the leptomeningeal ivy sign and are considered to represent a slow
retrograde flow in the engorged pial vasculature via leptomeningeal anastomosis (4).
We herein report a case of ipsilateral ivy sign that enhanced and expanded with expansion of the cerebral infarction in a patient with moyamoya disease.

A 67-year-old woman presented to our hospital with the
sudden onset of left hemiparesis (manual muscle testing: 4/
5), left homonymous hemianopia, and left unilateral spatial
neglect. She had a medical history of hypertension and type
2 diabetes mellitus. The patient was being treated by her
family physician with amlodipine (5 mg/day) and metformin
(1,000 mg/day), and home blood pressure was in the 120/80
mmHg range. Vital signs on admission were as follows:
blood pressure, 155/82 mmHg; heart rate, 78 beats/min;
temperature, 36.3°C; respiratory rate, 16 breaths/min; and
Glasgow Coma Scale score, 14 (E4V5M5). Laboratory findings showed hyperglycemia (fasting blood glucose level, 165
mg/mL; hemoglobin A1c, 7.8%). Other laboratory findings
were unremarkable, including coagulation activity and autoimmune system disease. She had no retinopathy or nephropathy. Echocardiography showed no regional left ventricular
motion abnormalities.
Emergent magnetic resonance imaging (MRI) demon-

１

Department of Strokology, Stroke Center, National Hospital Organization Kagoshima Medical Center, Japan and ２ Department of Neurology and
Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Japan
Received: January 5, 2022; Accepted: May 5, 2022; Advance Publication by J-STAGE: July 29, 2022
Correspondence to Dr. Yuki Hamada, sunamushi.elmonkichi@gmail.com

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DOI: 10.2169/internalmedicine.9326-22

Figure 1. A) DWI of the head shows cerebral infarction from the right parietal lobe to the right
occipital lobe. B) On FLAIR imaging, linear hyperintensities of the sulci are evident in the right cerebral hemisphere. C) MRA shows occlusion of the terminal portions of the bilateral internal carotid
arteries (white arrows) and right PCA (white arrowhead). D) Angiography of the right internal carotid artery shows steno-occlusive changes at the terminal portion of the internal carotid artery and
moyamoya blood vessels at the base of the brain. Micro-aneurysm is observed at the periphery of the
lenticulostriate artery (black arrow). E) Angiography of the right vertebral artery shows occlusion of
the PCA (black arrowhead).

strated signal hyperintensity involving the right parietal lobe
on diffusion-weighted imaging (DWI) (Fig. 1A). Magnetic
resonance angiography (MRA) revealed occlusion of the terminal portions of the bilateral internal carotid arteries and
the right posterior cerebral artery (Fig. 1C). FLAIR imaging
showed multiple hyperintensities in the subarachnoid space
(Fig. 1B). After admission, edaravone was administered by
drip infusion, but we did not start antithrombotic drugs, considering the possibility of subarachnoid hemorrhaging. In
addition, considering the possibility of hemodynamic
ischemic stroke, amlodipine was discontinued, and the blood
pressure was controlled to around 160/80 mmHg with continuous intravenous infusion of dopamine hydrochloride at
5-7 μg/kg/min.
However, the neurological deficits were exacerbated, and
follow-up MRI one day after admission showed expansion
of the infarction territory and prominent signal enhancement
of hyperintensities in the subarachnoid space (Fig. 2). We
therefore started concentrated glycerin and fructose (200
mL) 3 times a day to prevent the spread of cerebral edema.
Five days after admission, angiography showed steno-

occlusive changes at the terminal portions of the internal carotid arteries and an abnormal vascular network at the base
of the brain, in addition to posterior cerebral artery (PCA)
occlusion (Fig. 1D, E). Based on these findings, we diagnosed the patient with moyamoya disease.
Contrast-enhanced MRI revealed enhancement in the
subarachnoid space corresponding to the area of hyperintensity on FLAIR imaging (Fig. 3A, B), explaining the ivy
sign. Brain single photon emission computed tomography
(SPECT) with 123I-N-isopropyl-p-iodoamphetamine showed
decreased regional cerebral perfusion in the right parietal
lobe on admission and an increase in the hypo-perfused area
around the ischemic lesion five days after admission
(Fig. 4A, B). Since a micro-aneurysm was observed on angiography (Fig. 1D), we decided not to perform antithrombotic therapy for secondary prevention, considering the risk
of aneurysm rupture. No abnormalities were detected on
electrocardiography or Holter electrography. The cause of
cerebral infarction in the PCA territory was considered to be
progression of moyamoya disease.
Following the exacerbation of neurological symptoms, the

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DOI: 10.2169/internalmedicine.9326-22

Figure 2. The comparison of FLAIR and DWI on admission and at 3, 5, and 23 days after admission. These comparisons show increased and expanded ipsilateral ivy sign paralleling expansion of the
cerebral infarction. Five days after admission, progression of cerebral infarction had stopped on
DWI, and the ivy sign was also diminished 23 days after admission. All immediate MRI studies were
performed on a 1.5-T scanner (Siemens Healthcare, Erlangen, Germany) to examine patients with
suspected stroke, including DWI, FLAIR, and MRA. DWI was performed with a standard protocol
using the following parameters: field of view (FOV), 220 mm; spatial resolution, 1.7×1.7×5.5 mm; and
b-values of 0 and 1,000 s/mm2. FLAIR was performed in the axial plane (FOV, 220 mm) with a common spatial resolution of 0.9×0.9×5.5 mm.

Figure 3. Gd-enhanced T1-weighted MRI (A, B) five days after admission reveals enhancement in
the subarachnoid space corresponding to hyperintensity on FLAIR imaging.

blood pressure was controlled to around 180/90 mmHg with
the continuous intravenous infusion of dopamine hydrochloride at 7-10 μg/kg/min. Five days after admission, the progression of the neurological exacerbation stopped, and the
progression of cerebral infarction appeared to have stopped
as well based on DWI. Concentrated glycerin and fructose
were administered for 14 days, and the dose of dopamine
hydrochloride was gradually reduced and discontinued by 14
days after admission. The blood pressure was subsequently

controlled to around 150/80 mmHg, and no new neurological symptoms appeared. The ivy sign also diminished 23
days after admission (Fig. 2). Finally, the left homonymous
hemianopia and left unilateral spatial neglect gradually improved, but the left hemiparesis remained moderate (manual
muscle testing: 4/5).
The patient was transferred to a rehabilitation hospital
with a modified Rankin Scale score of 3 at 24 days after admission.

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Figure 4. SPECT on admission (A) and five days after admission (B). Regional cerebral perfusion
in the right parietal lobe is decreased. Five days after admission, there was an increased hypo-perfused area around the ischemic lesion.

Discussion
We described an interesting case of increased and expanded ipsilateral ivy sign paralleling the expansion of cerebral infarction in a patient with moyamoya disease. The ivy
sign is reportedly found in 31-66% of cases of moyamoya
disease and often appears in symptomatic cases (5). In terms
of clinical significance, one report suggests that this sign reflects a state of decreased cerebral circulatory reserve (6).
However, the ivy sign is also reportedly unrelated to the
oxygen intake rate or collateral circulation (7). Other studies
have speculated that only dilated leptomeningeal vessels,
which act to supply blood during ischemia, are visualized (4, 7).
The relationship between the presence of an ivy sign and
the expansion of cerebral infarction in the acute phase of
cerebral infarction has not been clarified. Interestingly, the
presence of the ivy sign has been reported to be a predictor
of recurrent cerebral infarction in adults with moyamoya
disease (8). This suggests that chronic hypoperfusion may
be prone to progress to hemodynamic ischemic stroke. In
addition, staging in moyamoya disease is associated with the
appearance of ischemic disease. The appearance of infarction in the PCA territory reportedly reflects an increased
risk of ischemic stroke as the stage progresses (9). Based on
these findings, this case was considered to have involved
ischemic stroke because of the presence of the PCA lesion
and resulting disease progression. In addition, we speculated
that the cerebral infarction expanded because the presence of
the ivy sign showed chronic hypoperfusion, which failed to
suppress the progression of hemodynamic cerebral infarction.
In this case, the ivy sign was enhanced by the expansion
of cerebral infarction, and it disappeared once ischemia resolved. In particular, three days after admission, the cerebral
infarction on DWI appeared to have expanded, paralleling

the expansion of the ivy sign, and five days after admission,
SPECT findings showed an increased area of hypo-perfusion
around the ischemic lesion in the right parietal temporal
lobe compared to SPECT on admission. The reason for the
enhancement of the ivy sign was presumed to involve reactive dilation of pial blood vessels due to increased flow demands resulting from expansion of the cerebral infarction (10). Furthermore, after the progression of cerebral infarction stopped, the ivy sign was considered to have diminished due to decreased flow demands in the ischemic territory. The patient had an expanded cerebral infarction due to
an insufficient blood flow supply from the pial arteries. We
considered that the ivy sign had weakened as a result of an
increased blood flow from the pial arteries as a result of
maintaining the blood pressure at a high level by means of
the continuous intravenous infusion of dopamine hydrochloride.
No consensus has been reached regarding the medical
treatment for moyamoya disease. In general, pediatric cases
often develop with cerebral ischemic symptoms, whereas
adult cases often develop with intracranial hemorrhaging in
addition to cerebral ischemic symptoms. In the acute phase
of ischemia and bleeding, medical treatment, such as blood
pressure control and management for increased intracranial
pressure, is performed. Although evidence is lacking, the use
of edaravone, ozagrel sodium, argatroban, and aspirin is recommended for the treatment of acute ischemic moyamoya
disease based on the treatment for acute-onset atherosclerotic cerebral infarction (3).
In the present case, the ischemic lesion expanded despite
sufficient blood pressure control and intracranial pressure
control with concentrated glycerin and fructose. The accumulation of ischemic cores may have been avoidable with
the addition of antithrombotic therapy. However, in this
case, due to concerns about subarachnoid hemorrhaging and
the presence of micro aneurysm, we were hesitant to use antithrombotic therapy in combination. As a result of continu-

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ing medical treatment without antithrombotic therapy, the
spread of ischemia was minimized, and poor outcomes were
avoided. If antithrombotic therapy had been used in combination, cerebral hemorrhaging might have developed, and
the outcome might have been poor. Furthermore, if enhancement of the ivy sign is associated with progression of ischemia, small-molecular-weight dextran may have been useful
for preventing progression of ischemia, in terms of increasing circulating plasma volume.
Based on the anatomical considerations, such as the localization of aneurysms at the periphery of the lenticulostriate
artery making clipping difficult to perform directly and coil
embolization being difficult because of the small vessel diameter, no surgery was performed. Treatment for moyamoya
disease is thus considered to require complex knowledge of
multiple factors, such as the anatomical background of each
patient and the progression grade of ischemia.
Conclusion

The ivy sign in moyamoya disease with ischemic onset
might enhance and diminish in response to hemodynamic
changes, indicating flow demands in the ischemic territory.
In particular, enhancement of the ivy sign may be associated
with expansion of the ischemic area and warrants personalized medical treatment according to the patient background.
The authors state that they have no Conflict of Interest (COI).

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Ⓒ 2023 The Japanese Society of Internal Medicine
Intern Med 62: 617-621, 2023

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