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Mechanical thrombectomy for middle cerebral artery occlusion suspected of ovarian
hyperstimulation syndrome.
Atsushi Kuwano, Yuichi Kubota, Taku Nonaka, Satoru Miyao, Hidetoshi Nakamoto,
Takakazu Kawamata
PII:

S1878-8750(19)32453-2

DOI:

https://doi.org/10.1016/j.wneu.2019.09.023

Reference:

WNEU 13322

To appear in:

World Neurosurgery

Received Date: 28 July 2019
Revised Date:

4 September 2019

Accepted Date: 5 September 2019

Please cite this article as: Kuwano A, Kubota Y, Nonaka T, Miyao S, Nakamoto H, Kawamata T,
Mechanical thrombectomy for middle cerebral artery occlusion suspected of ovarian hyperstimulation
syndrome., World Neurosurgery (2019), doi: https://doi.org/10.1016/j.wneu.2019.09.023.
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Mechanical thrombectomy for middle cerebral artery occlusion suspected of ovarian
hyperstimulation syndrome.
Atsushi Kuwano1)2), Yuichi Kubota1)2), Taku Nonaka1)2), Satoru Miyao1)2), Hidetoshi
Nakamoto1)2), Takakazu Kawamata2)
1)Department of Neurosurgery, stroke and Epilepsy Center, TMG Asaka Medical Center,

Saitama, Japan
2)Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan

*Corresponding author

Yuichi Kubota, MD., D.Med.Sci
Department of Neurosurgery, stroke and Epilepsy Center, TMG Asaka Medical Center
1-134- Mizonuma, Asaka, Saitama
Phone: +81-48-466-2055
Fax: +81-48-466-2059
Email: kubota.yuichi@twmu.ac.jp
Atsushi Kuwano, MD
Department of Neurosurgery, stroke and Epilepsy Center, TMG Asaka Medical Center
1-134- Mizonuma, Asaka, Saitama
Phone: +81-48-466-2055
Fax: +81-48-466-2059
Email: cho_hunseki@yahoo.co.jp
Taku Nonaka, MD
Department of Neurosurgery, stroke and Epilepsy Center, TMG Asaka Medical Center
1-134- Mizonuma, Asaka, Saitama
Phone: +81-48-466-2055
Fax: +81-48-466-2059
Email: taku.nonaka7@gmail.com
Satoru Miyao, MD
Department of Neurosurgery, stroke and Epilepsy Center, TMG Asaka Medical Center
1-134- Mizonuma, Asaka, Saitama
Phone: +81-48-466-2055

Fax: +81-48-466-2059
Email: satoru.miyao14@gmail.com
Hidetoshi Nakamoto, MD
Department of Neurosurgery, stroke and Epilepsy Center, TMG Asaka Medical Center
1-134- Mizonuma, Asaka, Saitama
Phone: +81-48-466-2055
Fax: +81-48-466-2059
Email: hidetossimo@yahoo.co.jp
Takakazu Kawamata, MD., PhD
Department of Neurosurgery, Tokyo Women’s Medical University
8-1 Kawada cho, Shinjuku, Tokyo
Phone: +81-3-3353-8111
Fax: +81-48-466-2059
Email: tkawamata@twmu.ac.jp

Highest academic degrees for all authors
Atsushi Kuwano, M.D.
Yuichi Kubota, M.D., D.Med.Sci .
Taku Nonaka, M.D.
Satoru Miyao, M.D.
Hidetoshi Nakamoto, M.D.
Takakazu Kawamata, M.D., Ph.D.

Keywords
ovarian hyperstimulation syndrome; thrombectomy; cerebral infarction

Mechanical thrombectomy for middle cerebral artery occlusion suspected of ovarian
hyperstimulation syndrome. Case report and review of literature.

Atsushi Kuwano1)2), Yuichi Kubota1)2), Taku Nonaka1)2), Satoru Miyao1)2), Hidetoshi
Nakamoto1)2), Takakazu Kawamata2)
1)Department of Neurosurgery, stroke and Epilepsy Center, TMG Asaka Medical Center,

Saitama, Japan
2)Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan

*Corresponding author:

Yuichi Kubota
Department of Neurosurgery, stroke and Epilepsy Center, TMG Asaka Medical Center
1-134- Mizonuma, Asaka, Saitama
Phone: +81-48-466-2055
Fax: +81-48-466-2059
Email:

Highest academic degrees for all authors
Yuichi Kubota, M.D., Ph.D : kubota.yuichi@twmu.ac.jp
Hidetoshi Nakamoto, M.D. : hidetossimo@yahoo.co.jp
Satoru Miyao, M.D. : satoru.miyao14@gmail.com
Takakazu Kawamata, M.D., Ph.D. : tkawamata@twmu.ac.jp
Keywords: antiepileptic drugs; poststroke epilepsy; seizure; vagal nerve stimulation
Short title: Mechanical thrombectomy for ovarian hyperstimulation syndrome.

Abstract

Background
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic disorder associated with
infertility treatment. The main pathology of OHSS is intravascular dehydration and
hyperestrogenemia. In mild cases, abdominal symptoms are the main symptoms, but in
severe cases, thrombosis such as cerebral infarction may occur.
Case Description
A 36-year-old woman was undergoing infertility treatment in obstetrics and
gynecology for infertility. She received HMG-HCG therapy and artificial insemination
one week before onset, and on the day of onset she had mild abdominal distension and
was suspected of OHSS. She was prescribed aspirin for prevention of thrombosis. She
presented with right upper hemiparesis and aphasia. MRI showed left middle cerebral
artery occlusion. We performed mechanical thrombectomy and finally got Thrombolysis
in Cerebral Infarction scale (TICI) 3 recanalization. We suspected embolism as the
etiology

of

cerebral

infarction

and

started

anticoagulation

therapy.

Various

examinations were conducted to investigate the embolism source, but no anatomical
abnormality or thrombophilia factors were observed. The patient had admitted OHSS
since admission, we concluded that OHSS was suspected as the cause of this stroke.
Conclusions
We experienced the first case of mechanical thrombectomy for middle cerebral artery
occlusion suspected to be caused by OHSS. It is necessary to suspect OHSS involvement
if young women, especially those on infertility treatment, show neurological deficits.

Keywords

ovarian hyperstimulation syndrome; thrombectomy; cerebral infarction
Abbreviations and Acronyms
DWI-ASPECTS, diffusion weighted image-Alberta Stroke Programme Early Score
MCA, Middle Cerebral Artery
MRA, Magnetic Resonance Angiography
MRI, Magnetic Resonance Image
mRS, modified Rankin Scale
NIHSS, National Institutes of Health Stroke Scale
OHSS, Ovarian hyperstimulation syndrome
TICI, Thrombolysis in Cerebral Infarction scale
t-PA, tissue plasminogen activator

Introduction

Ovarian hyperstimulation syndrome (OHSS) is a rare and serious complication of
infertility treatment. OHSS is an iatrogenic disorder caused by using an ovulation
inducer. 1 The pathologies are intravascular dehydration and hyperestrogenemia.
Moderate cases may be only electrolyte abnormality, but severe cases may cause
thrombosis. Although multiple cases of cerebral infarction associated with OHSS have
been reported so far, middle cerebral artery occlusion has occurred in a pregnant woman
caused by OHSS, and there are almost no cases where thrombectomy has been
performed. We report a case of middle cerebral artery occlusion suspected of OHSS and
successfully treated with mechanical thrombectomy.
Case Report
A 36-year-old woman was undergoing infertility treatment in obstetrics and
gynecology for infertility. She received HMG-HCG therapy and artificial insemination
one week before onset, and on the day of onset she had mild abdominal distension and
was suspected of OHSS. She was prescribed aspirin for prevention of thrombosis. She
presented with right upper hemiparesis and aphasia and was transferred to another
hospital for emergency department. The doctor diagnosed her as left middle cerebral
artery occlusion and she was referred to our hospital for further treatment. Five hours
have passed from the onset of this hospital transportation. Physical examination
showed disturbance of consciousness (Glasgow Coma Scale E2V1M5), right hemiparesis
(Manual Muscle Testing upper limbs 2/5, lower limbs 1/5), global aphasia, National
Institutes of Health Stroke Scale (NIHSS) 27. Estradiol was 4599 pg./mL by blood test.
MRI showed left middle cerebral artery M1 occlusion (Figure 1), and Diffusion Weighted
Image-Alberta Stroke Programme Early Score (DWI-ASPECTS) 8/11. At the time of
transportation to our hospital, five hours had passed since onset, so we could not
perform tissue plasminogen activator (t-PA). In addition to being at an early onset,
clinical image mismatch was recognized, so we decided to perform mechanical
thrombectomy. We consulted with the family before treatment and confirmed that the
treatment was given with maternal priority, although the patient may be pregnant.
Angiography showed occlusion in the left middle cerebral artery at proximal region. We
performed thrombectomy and finally got Thrombolysis in Cerebral Infarction scale
(TICI) 3 recanalization (Figure 2). After 24 hours of treatment, right hemiparesis
improved to MMT4 and aphasia moderately remained, resulting in NIHSS score 14. We
suspected embolism as the etiology of cerebral infarction and started anticoagulation
therapy.

We

performed

various

physiological

examinations

including

holter

electrocardiography, carotid artery ultrasound, ultrasonography of the lower limbs,

transesophageal echocardiography, and also checked blood tests such as tumor markers,
coagulation function, and autoantibodies of collagen diseases to investigate the embolic
sources. But no anatomical abnormality or thrombophilia factors were observed. An
examination of abdominal distension, which had been observed since admission,
resulted in swelling of the ovaries and ascites, leading to a diagnosis of ovarian
hyperstimulation syndrome.
About a week after treatment, she fainted during rehabilitation. Ascites was markedly
increased, and exacerbation of ovarian hyperstimulation syndrome was noted. She was
referred to another hospital for OHSS management. She turned out to be pregnant at
the next hospital, eventually she aborted for OHSS control. Then OHSS stabilized and
she finally recovered to about modified Rankin Scale (mRS) 2 at six months of
treatment.
Discussion
OHSS is an iatrogenic disorder associated with infertility treatment. 1 By using
follicle stimulating agents and ovulation stimulating agents, the follicle overgrown and
OHSS is triggered. According to previous reports, OHSS is estimated to develop in 0.3%
to 6% of infertility treatments.2 OHSS is classified as mild, moderate or severe from
clinical symptoms. Mild cases are mainly abdominal symptoms such as diarrhea,
vomiting and abdominal distension, but severe cases may show thrombosis. Risk factors
reported to be associated with OHSS include young age, polycystic ovary-like patients,
low body mass index, polycystic ovarian syndrome, history of previous OHSS, and
estradiol high.3 The pathophysiology of thrombosis has not been accurately elucidated,
it is thought that intravascular dehydration and hyperestrogenemia are involved.
Ovary is stimulated by administering HMG, and hyperestrogenemia occurs. In addition,
luteinizing hormone is secreted by HMG administration, and ovulation is promoted by
HCG administration, so that the follicle is luteinized and VEGF and angiotensin are
secreted. VEGF and angiotensin enhance permeability and are thought to contribute to
intravascular dehydration.4-6 Treatment of OHSS is usually symptomatic therapy.
Antiplatelets may be given to pregnant thrombosis, but no cure for thrombosis has been
established. If symptomatic treatment cannot control OHSS, abortion may eventually
be required.7
In this case, it was a cerebral infarction of a young woman with a low vascular risk,
and the cause was carefully examined. She was free of thrombophilia factors, atrial
fibrillation and other anatomical abnormalities such as shunt disease. Risk factors for
OHSS include youth, elevated estradiol, and hCG administration. Since OHSS was

recognized from the time of admission after having conducted various cause tests, it was
finally determined that OHSS could be considered as the cause of cerebral infarction.
In

the

first

place,

thrombosis

due

to

intravascular

dehydration

and

hyperestrogenemia tends to cause venous thrombosis. However, this time she developed
a cerebral infarction. The thrombosis associated with OHSS is said to be 75% for venous
thrombosis and 25% for arterial thrombosis.8 We performed transesophageal
echocardiography in the cause search and confirmed that she had no patent foramen
ovale, but shunt disease such as pulmonary arteriovenous fistula may have been hidden.
In fact, the thrombus recovered was a red thrombus, so the vein thrombus has passed
through the shunt site, which may cause cerebral infarction. The thrombus was a red
thrombus, but the component was mainly platelets. Generally, arterial thrombus is said
to be mainly platelets, and venous thrombus is said to be mainly fibrin. However, there
is also a report that venous thrombus is rich in platelets as well as arterial thrombosis,
and it is difficult to determine whether the thrombus is arterial thrombosis or venous
thrombosis with the thrombus component alone.9
There are several reports of thrombectomy for pregnant women as in this case.10 The
prognosis of the pregnant woman who had thrombectomy was as good as mRS2 or more
at the stage after half a year of treatment as in this case. Among reports, few reports
have been found that OHSS is considered to be the cause of cerebral infarction in
pregnant women. This report is the first report of thrombectomy for a cerebral
infarction suspected to be caused by OHSS.
With regard to OHSS aggravation after thrombectomy and eventually termination for
OHSS control, it is necessary to always consider the possibility of pregnancy during the
course. Although the frequency of abortion is not high, abortion may be necessary to
protect the mother as in this case.
Conclusion
We experienced the first case of mechanical thrombectomy for middle cerebral artery
occlusion suspected to be caused by OHSS. It is necessary to suspect OHSS involvement
if young women, especially those on infertility treatment, show neurological deficits. In
addition, even if the patient is a pregnant woman, if it is indicated, we should perform
thrombectomy. To clarify the pathogenesis thrombus formation associated with OHSS,
we need to accumulate more cases. This case tells us that this condition is more
commonly seen in the current era of aggressive infertility management.

Figure legends
Figure 1.
MRA (Magnetic Resonance Angiography) shows left MCA (Middle Cerebral Artery)
occlusion. (A)
DWI shows infarct images in MCA area. (B and C)
Figure 2
Angiography shows left MCA occlusion. (A)
The recanalization of TICI3 was obtained by thrombectomy. (B)

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Abbreviations and Acronyms
DWI-ASPECTS, diffusion weighted image-Alberta Stroke Programme Early Score
MCA, Middle Cerebral Artery
MRA, Magnetic Resonance Angiography
MRI, Magnetic Resonance Image
mRS, modified Rankin Scale
NIHSS, National Institutes of Health Stroke Scale
OHSS, Ovarian hyperstimulation syndrome
TICI, Thrombolysis in Cerebral Infarction scale
t-PA, tissue plasminogen activator