Surgical Neurology 67 (2007) 273 – 282
www.surgicalneurology-online.com

Vascular

Temporary neurologic deterioration due to cerebral hyperperfusion
after superficial temporal artery-middle cerebral artery anastomosis
in patients with adult-onset moyamoya disease
Miki Fujimura, MDa,4, Tomohiro Kaneta, MDb, Shunji Mugikura, MDb,
Hiroaki Shimizu, MDc, Teiji Tominaga, MDa
Departments of aNeurosurgery and bRadiology, Tohoku University School of Medicine, Sendai 980-8574, Japan
c
Department of Neurosurgery, Kohnan Hospital, Sendai, Japan
Received 10 April 2006; accepted 3 July 2006

Abstract

Background: Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks
by improving CBF, but little is known about the change in CBF and its effect on neurologic status
during the acute stage after revascularization.
Methods: 123I-IMP-SPECT was performed 1 and 7 days after STA-MCA anastomosis on 34 sides of
27 consecutive patients with adult-onset moyamoya disease (6 men, 21 women; 22-62 years old).
The follow-up period ranged from 5 to 28 months (mean, 17.6 months).
Results: Thirteen patients (13 sides, 38.2%) suffered temporary neurologic deterioration due to
hyperperfusion several days after surgery, which was sustained for several days (7.4 days in
average). Postoperative magnetic resonance imaging/angiography showed the STA as a higher
intensity signal than the preoperative finding without ischemic changes in all 13 patients.
Postoperative SPECT revealed focal intense increase in CBF at the sites of anastomosis in all 13
patients. Eleven patients (32.4%) had transient focal neurologic deficit mimicking ischemic attack.
Two patients (5.9%) had cerebral hyperperfusion syndrome associated with subarachnoid
hemorrhage extending to the ipsilateral sylvian cistern. Symptoms were relieved by intensive blood
pressure control, and no patients had permanent neurologic deficit or delayed neurologic
deterioration during the follow-up period.
Conclusions: Surgical revascularization including STA-MCA anastomosis is a safe and effective
treatment for moyamoya disease, although temporary neurologic deterioration due to hyperperfusion
could occur at a substantial rate. Routine CBF measurement is recommended for accurate diagnosis
of postoperative hyperperfusion in moyamoya disease because its treatment is contradictory to that
for ischemia.
D 2007 Elsevier Inc. All rights reserved.

Keywords: Cerebral blood flow; Cerebral hyperperfusion; Moyamoya disease; Superficial temporal artery-middle cerebral artery anastomosis; Hyperperfusion;
Single-photon emission computed tomography

Abbreviations: CBF, cerebral blood flow; CT, computed tomography;
3DSRT, 3-dimensional stereotactic region of interest template; DTA, deep
temporal artery; DWI, diffusion-weighted imaging; EDMS, encephaloduromyosynangiosis; FLAIR, fluid-attenuated inversion recovery; 123I-IMPSPECT, N-isopropyl-p-[123I]iodoamphetamine single-photon emission
computed tomography; MRI, magnetic resonance imaging; MRA, magnetic
resonance angiography; PWI, perfusion-weighted imaging; ROS, reactive
oxygen species; STA-MCA anastomosis, superficial temporal artery-middle
cerebral artery anastomosis.
4 Corresponding author. Tel.: +81 22 717 7230; fax: +81 22 717 7233.
E-mail address: fujimur@nsg.med.tohoku.ac.jp (M. Fujimura).
0090-3019/$ – see front matter D 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.surneu.2006.07.017

1. Introduction
Moyamoya disease is a chronic, occlusive cerebrovascular
disease with unknown etiology characterized by bilateral
steno-occlusive changes at the terminal portion of the internal
carotid artery and an abnormal vascular network at the base of
the brain [20]. Surgical revascularization for moyamoya
disease is believed to be beneficial to prevent cerebral
ischemic attacks by improving CBF, and STA-MCA anastomosis with or without indirect bypass is generally used as

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M. Fujimura et al. / Surgical Neurology 67 (2007) 273 – 282

the standard surgical treatment of moyamoya disease
[3,6,7,9,17]. However, little is known about the change in
CBF and its effect on neurologic status during the acute stage
after direct bypass for moyamoya disease [3,4,13].
Cerebrovascular reconstruction surgery including carotid
endarterectomy or extracranial-intracranial bypass in
patients with atherosclerotic cerebral steno-occlusive diseases can cause a rapid increase in CBF in the chronic
ischemic brain, resulting in complications such as cerebral
hyperperfusion syndrome. Cerebral hyperperfusion syndrome is characterized by unilateral headache, facial and
ocular pain, seizures, and focal symptoms that occur
secondary to cerebral edema or intracerebral hemorrhage
[15,18,19]. Patients with poorer cerebrovascular reactivity
are known to have potentially higher risk for hyperperfusion
syndrome [10,11,23]. It was reported that STA-MCA
anastomosis as a treatment for moyamoya disease could
result in transient neurologic deterioration due to an
unknown mechanism [5,21]. However, it remains undetermined whether STA-MCA anastomosis for moyamoya
disease, which usually provides low-flow revascularization
due to the anatomy of their recipient arteries, can result in
neurologic deterioration due to hyperperfusion postoperatively. To address this issue, we prospectively performed
123
I-IMP-SPECT 1 and 7 days after STA-MCA anastomosis
on 34 sides of 27 consecutive patients with adult-onset
moyamoya disease treated in our institute. Comprehensive
evaluation of postoperative CBF and its comparison with
neurologic status in patients with adult-onset moyamoya
disease allowed us to reveal the possible contribution of
focal intense increase in CBF to the transient focal
neurologic deterioration after STA-MCA anastomosis.
2. Patients and methods
The correlation between postoperative changes in CBF
and clinical course was investigated in 27 consecutive
patients (6 men, 21 women; 22-62 years old) with adult-

onset moyamoya disease on 34 sides, treated by the same
surgeon (M.F.) in Tohoku University Hospital from March
2004 to February 2006. All patients were strictly followed up
in our institute with a mean follow-up period of 17.6 months.
All patients satisfied the criteria of the Research Committee
on Spontaneous Occlusion of the Circle of Willis, of the
Ministry of Health, Labor, and Welfare, Japan, except for
3 patients with bprobable moyamoya diseaseQ with unilateral
involvement. All patients underwent STA-MCA anastomosis with or without EDMS and dural pedicle insertion
[17,22]. The CBF was routinely measured by 123I-IMPSPECT 1 and 7 days after surgery in all patients. The CBF
was quantified by the autoradiographic method, and the CBF
in each subregion of the cerebral cortex was automatically
calculated by 3DSRT software (version 2) provided by
Daiichi Radio-Isotope (Tokyo, Japan). The 1.5-T MRI and
MRA were routinely performed 2 and 8 days after surgery.
MRI includes DWI, FLAIR, T1-/T2-weighted images, and
T2*-weighted images.
3. Results
Among the 27 consecutive patients with 34 surgeries, no
patients had perioperative cerebral infarction, and in all
patients who had transient ischemic attack, the ischemic
attack disappeared or improved during the follow-up period.
One hemorrhagic-onset patient had cerebral hemorrhage on
the contralateral side 3 months after surgery, which did not
affect his neurologic status. The patency of STA-MCA
bypass was confirmed in all 27 patients with 34 surgeries by
MRA during the follow-up period. Thirteen patients
(13 sides, 38.2%) had temporary neurologic deterioration
due to hyperperfusion from 2 to 7 days after surgery, which
was sustained for several days (Table 1). Postoperative
MRI/MRA showed no ischemic changes, and the thick, high
signal of STA-MCA anastomosis was evident in all
13 patients. Postoperative SPECT revealed focal intense
increase in CBF at the sites of anastomosis in all 13 patients.

Table 1
Summary of 13 patients with temporary neurologic deterioration due to hyperperfusion
Case No.

Age/sex

Type of onset

Side of operation

Symptoms

Period of deficit

Hyperperfusion by SPECT

1
2
3
4
5
6
7
8
9
10
11
12
13

55/F
38/F
36/F
37/M
36/F
26/F
62/M
42/F
47/F
40/F
36/M
29/F
36/M

Hemorrhage
Infarction
TIA, seizure
Infarction
Infarction
TIA
Hemorrhage
TIA
TIA
TIA
TIA
Infarction
TIA

Right
Left
Left
Rightb
Right
Right
Right
Right
Rightb
Right
Left
Right
Left

Dysarthria, SensD, SZ
Aphasia
Aphasia, SensD
Aphasia, SensD
HA, SAH
Dysarthria, SensD, FP
Dysarthria, FP
HA, SAH
Aphasia, SensD
Dysarthria, SZ
Aphasia
Dysarthria, SensD
Aphasia, SensD

POD 7-20
POD 2-6
POD 2-10
POD 3-30
POD 2
POD 3-13
POD 9
POD 2-4
POD 2-11
POD 5-10
POD 5-16
POD 3-6
POD 3-6

POD 6
POD 1, 5, 7
POD 1,a 7
POD 2, 7
POD 1
POD 1, 7
POD 1, 7
POD 1, 7
POD 1, 7
POD 1, 7
POD 1, 7
POD 2, 7
POD 1, 7

M indicates male; F, female; POD, postoperative day; TIA, transient ischemic attack; HA, headache; SAH, subarachnoid hemorrhage; FP, facial palsy; SensD,
sensory disturbance (numbness) at upper limb and/or face on the contralateral side; SZ, seizure.
a
Slight increase at the site of the anastomosis.
b
Language dominancy in the right hemisphere as shown by functional MRI or by Edinburgh test.

M. Fujimura et al. / Surgical Neurology 67 (2007) 273 – 282

Eleven patients (11 sides, 32.4%) had transient focal
neurologic deficit due to hyperperfusion that mimicked
ischemic attack, which started from 2 to 9 days after surgery
and was sustained for several days (7.4 days, on average).
The anatomical location and the temporal profile of hyperperfusion were completely in accordance with the transient
neurologic deficits in these 11 patients (Table 1). Two
patients (2 sides, 5.9%) complained of severe headache and
had cerebral hyperperfusion syndrome associated with
subarachnoid hemorrhage extending to the ipsilateral
sylvian cistern. Symptoms were relieved by intensive blood
pressure control with the use of the free radical scavenger,
edaravone (Mitsubishi Pharma Co, Tokyo, Japan), and no
patients had permanent neurologic deficit or delayed
neurologic deterioration during the follow-up period.
4. Representative cases
4.1. Case 1
A 55-year-old woman presented with left hemiparesis
due to right putaminal hemorrhage in October 2002 and was
admitted to another hospital where she was treated
conservatively. The diagnosis was stage III moyamoya
disease according to the criteria of the Research Committee
on Spontaneous Occlusion of the Circle of Willis of the
Ministry of Health, Labor, and Welfare, Japan. She was
discharged without neurologic deficit and was introduced to
our service in December 2003.
She was admitted to our hospital to undergo bypass
surgery for moyamoya disease in July 2004. SPECT showed
her bilateral CBF and cerebrovascular reserve capacities

275

were markedly affected, so bilateral bypass surgery was
planned. The first-stage surgery on the right side was
performed in July 2004. After exploration of the frontal
branch of the right STA, frontotemporoparietal craniotomy
was performed. The recipient artery at the M4 segment of
the anterior parietal branch of the MCA was explored and
anastomosis was performed between the stump of the STA
(1.0 mm in diameter) and the M4 segment (0.8 mm in
diameter) that supplied the parietal lobe. Then, EDMS and
dural pedicle insertion were performed. The patient showed
no neurologic deficit immediately after surgery.
123
I-IMP-SPECT 1 day after surgery showed no apparent
change in CBF on the right side (Fig. 1B) compared with the
preoperative findings (Fig. 3A), but focal intense increase in
CBF at the site of anastomosis was evident 6 days after
surgery (Fig. 1C, arrows). Postoperative MRA showed the
apparently patent STA-MCA bypass as a higher intensity
signal than the opposite side STA (Fig. 2A and B, arrows),
and diffusion-weighted MRI showed no evidence of ischemic
change (Fig. 2C). She had dysarthria, numbness in the left
upper limb, and emotional incontinence 7 days after surgery.
She had a simple partial seizure on her left limbs 10 days after
surgery. Intensive blood pressure control and the use of free
radical scavenger relieved her symptoms that completely
disappeared 20 days after surgery, when focal intense
increase in CBF disappeared as shown by SPECT (Fig. 1D).
She was discharged without neurologic deficit on August 22,
2004. Three months later, STA-MCA anastomosis with
EDMS was performed on the left side, and she was
discharged without neurologic deficit after an uneventful
postoperative course. Postoperative external carotid angiography 3 months after the second surgery showed that the

Fig. 1. Case 1. 123I-IMP-SPECT scans before surgery (A) and 1 (B), 6 (C), and 20 days (D) after surgery. The focal intense increase in CBF at the site of
anastomosis (arrows in C) was evident as early as 6 days after surgery and preceded the manifestation of dysarthria and sensory disturbance on the left hand
7 days after surgery.

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M. Fujimura et al. / Surgical Neurology 67 (2007) 273 – 282

Fig. 2. Case 1. Postoperative MRA showing the apparently patent STA-MCA bypass as a higher intensity signal than the opposite side STA (arrows in A and
B). C: Diffusion-weighted MR images 2 days after surgery, showing no evidence of ischemic change.

bilateral MCA territories were supplied by the thick STAMCA bypass (data not shown). She did not experience
neurologic deterioration during the follow-up period.
4.2. Case 2
A 38-year-old woman was admitted to our hospital for
second-stage bypass surgery for moyamoya disease in April
2004. She experienced repeated numbness in the left upper
extremity after hyperventilation for the previous 18 years.
She had sudden onset of left hemiparesis due to cerebral
infarction at the posterior limb of the right internal capsule
in November 2003 and was admitted to another hospital.
She was treated conservatively and was discharged without

neurologic deficit. However, she had repeated transient
ischemic attacks of the left upper limb and was introduced
to our service.
Cerebral angiography delineated steno-occlusive changes
at the terminal portions of the bilateral internal carotid
arteries, and abnormal networklike vessels were apparent at
the bilateral basal ganglia. The diagnosis was stage III
moyamoya disease according to the criteria of the Research
Committee on Spontaneous Occlusion of the Circle of
Willis of the Ministry of Health, Labor, and Welfare, Japan.
STA-MCA anastomosis with EDMS and dural pedicle
insertion was performed on the right side in December
2003. The postoperative course was uneventful and she was

Fig. 3. Case 2. 123I-IMP-SPECT scans before surgery (A) and 1 (B), 5 (C), 7 (D), and 88 days (E) after surgery. The transient focal intense increase in CBF at
the site of anastomosis (arrows in B-D) was evident as early as 1 day after surgery and preceded the manifestation of motor aphasia on postoperative day 2.

M. Fujimura et al. / Surgical Neurology 67 (2007) 273 – 282

discharged without neurologic deficit in January 2004.
Because her CBF and cerebrovascular reserve capacity were
markedly affected on both sides (data not shown), secondstage surgery was carried out on the left side in April 2004.
After exploration of the frontal branch of the left STA,
frontotemporoparietal craniotomy was performed. The
recipient artery at the M4 segment of the MCA was then
explored and anastomosis was performed between the
stump of the STA (1.0 mm in diameter) and the proximal
portion of the M4 segment (1.2 mm in diameter) that
supplied the temporal lobe. Then, EDMS and dural pedicle
insertion were performed. She showed no neurologic deficit
immediately after surgery.
123
I-IMP-SPECT 1 day after surgery showed focal
intense increase in CBF at the site of anastomosis (Fig. 3B,
arrows) compared with the preoperative findings (Fig. 3A).
Postoperative diffusion-weighted MRI showed no evidence
of ischemic change, and MRA showed the apparently patent
STA-MCA bypass as a higher intensity signal than the
preoperative finding. She developed fluctuating aphasia on
the next day (postoperative day 2), which persisted until
postoperative day 6. The focal intense increase in CBF
persisted until postoperative day 7 (Fig. 3C and D, arrows),
but she recovered from the aphasia and was discharged
without neurologic deficit. Focal intense increase in CBF
was not evident by SPECT 88 days after surgery (Fig. 3E).
She did not experience neurologic deterioration during the
follow-up period.
4.3. Case 3
A 36-year-old woman presented with transient left
hemiparesis and subsequent generalized convulsion in

277

December 2003 and was introduced to our service. Stage
III moyamoya disease was identified. She had had transient
ischemic attacks in the bilateral upper extremities. SPECT
showed her bilateral CBF and cerebrovascular reserve
capacities were markedly affected. Therefore, bilateral
bypass surgery was planned. STA-MCA anastomosis with
EDMS was performed on the right side in March 2004, and
she was discharged without neurologic deficit after an
uneventful postoperative course.
Second-stage surgery on the left side was performed in
August 2004. After exploration of the parietal branch of the
left STA, frontotemporoparietal craniotomy was performed.
The recipient artery at the M4 segment of the anterior
parietal branch of the MCA was explored and anastomosis
was performed between the stump of the STA (1.2 mm in
diameter) and the M4 segment (1.0 mm in diameter) that
supplied the temporal lobe. Then EDMS and dural pedicle
insertion were performed. The patient showed no neurologic
deficit immediately after surgery.
123
I-IMP-SPECT 1 day after surgery showed a slight
increase in CBF in the left hemisphere (Fig. 4B, arrow)
compared with the preoperative findings (Fig. 4A). Postoperative diffusion-weighted MRI showed no evidence of
ischemic change, and MRA demonstrated the apparently
patent STA-MCA bypass as a higher intensity signal than
the preoperative finding. Several hours later, she had
fluctuating aphasia and numbness in the right upper limb.
123
I-IMP-SPECT showed focal intense increase in CBF at
the site of anastomosis 7 days after surgery (Fig. 4C,
arrows). Intensive blood pressure control and the use of free
radical scavenger relieved her symptoms gradually, which
completely disappeared 14 days after surgery. She was

Fig. 4. Case 3. 123I-IMP-SPECT scans before surgery (A) and 1 (B) and 7 days (C) after surgery. Mild increase in CBF was detected on the side of anastomosis
1 day after surgery (arrow in B). The focal intense increase in CBF at the site of anastomosis (arrows in C) was evident 7 days after surgery, in accordance with
the manifestation of aphasia and sensory disturbance on the right hand.

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M. Fujimura et al. / Surgical Neurology 67 (2007) 273 – 282

Fig. 5. Case 6. 123I-IMP-SPECT scans before surgery (A) and 1 (B) and 7 days (C) after surgery. Mild increase in CBF was detected at the site of anastomosis
1 day after surgery (arrow in B). The focal intense increase in CBF at the site of anastomosis (arrows in C) was evident 7 days after surgery, in accordance with
the manifestation of dysarthria and sensory disturbance on the left hand.

discharged without neurologic deficit, and she did not show
neurologic deterioration during the follow-up period.
4.4. Case 6
A 26-year-old woman who has had transient weakness
at the left upper extremity since August 2005 was
introduced to our service. Stage III moyamoya disease
was identified, and SPECT showed her bilateral CBF and
cerebrovascular reserve capacities were markedly affected.
Therefore, bilateral bypass surgery was planned. STA-

MCA anastomosis with EDMS was performed on the right
side in March 2005. After exploration of the parietal
branch of the right STA, frontotemporoparietal craniotomy
was performed. The recipient artery at the M4 segment of
the anterior parietal branch of the MCA was explored and
anastomosis was performed between the stump of the STA
(1.0 mm in diameter) and the M4 segment (0.8 mm in
diameter). Then EDMS and dural pedicle insertion were
performed. She showed no neurologic deficit immediately
after surgery.

Fig. 6. Case 8. 123I-IMP-SPECT scans before surgery (A) and 1 (B) and 7 days (C) after surgery. Significant increase in CBF was detected on the side of
anastomosis 1 day after surgery (arrows in B). The increase in CBF was sustained (arrows in C) 7 days after surgery.

M. Fujimura et al. / Surgical Neurology 67 (2007) 273 – 282
123

I-IMP-SPECT 1 day after surgery showed a slight
increase in CBF on the right side (Fig. 5B, arrow) compared
with the preoperative findings (Fig. 5A). Postoperative
diffusion-weighted MRI showed no evidence of ischemic
change, and MRA demonstrated the apparently patent STAMCA bypass as higher intensity signal than the opposite
side STA. One day later, she had fluctuating dysarthria, left
facial palsy, and numbness in the left upper limb. 123I-IMPSPECT showed focal intense increase in CBF at the site of
anastomosis 7 days after surgery (Fig. 5C, arrows).
Intensive blood pressure control and the use of free radical
scavenger relieved her symptoms, which completely disappeared 13 days after surgery. She was discharged without
neurologic deficit 13 days after surgery.
We performed second-stage surgery on the left side
1 month later. She was discharged uneventfully after
successful STA-MCA anastomosis and EDMS, which
resulted in disappearance of her ischemic attack as well as
the significant improvement of CBF on the bilateral cerebral
hemisphere. She did not have neurologic deterioration
during the follow-up period.
4.5. Case 8
A 42-year-old woman with transient dysarthria and
weakness at the left upper extremity since November 2004
was introduced to our service. Cerebral angiogram revealed

279

stage II (right)/III (left) moyamoya disease, and SPECT
showed her bilateral CBF and cerebrovascular reserve
capacities were markedly affected. Bilateral bypass surgery
was planned, and STA-MCA anastomosis with EDMS was
performed on the right side in June 2005. After exploration
of the frontal branch of the right STA, frontotemporoparietal
craniotomy was performed. The recipient artery at the M4
segment of the anterior parietal branch of the MCA was
explored and anastomosis was performed between the
stump of the STA (1.0 mm in diameter) and the M4
segment (1.0 mm in diameter). Then, EDMS and dural
pedicle insertion were performed. She showed no neurologic deficit immediately after surgery.
123
I-IMP-SPECT 1 day after surgery showed a significant increase in CBF on the right (Fig. 6B, arrows)
compared with the preoperative findings (Fig. 6A). One
day later, she had progressive headache, and postoperative
FLAIR by MRI showed subarachnoid hemorrhage around
the site of anastomosis, extending to the ipsilateral sylvian
cistern and the basal cistern (Fig. 7A), which was not evident
1 day after surgery by CT scan (data not shown). Diffusionweighted MRI showed no evidence of ischemic change, and
MRA demonstrated the apparently patent STA-MCA bypass
as a higher intensity signal than the opposite side STA
(Fig. 7B). Significant visualization of the branches of MCA
around the site of the anastomosis was also evident

Fig. 7. Case 8. FLAIR by MRI 2 days after surgery demonstrating subarachnoid hemorrhage around the site of anastomosis, extending to the ipsilateral sylvian
cistern and the basal cistern (asterisks in A). Postoperative MRA showing the apparently patent bypass as a higher intensity signal than the opposite side STA
(arrow in B). Significant visualization of the branches of MCA around the site of anastomosis was also evident compared with the preoperative state.

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M. Fujimura et al. / Surgical Neurology 67 (2007) 273 – 282

compared with the preoperative state (Fig. 7B). Intensive
blood pressure control and the use of free radical scavenger
relieved her symptoms, and the subarachnoid hemorrhage
disappeared 10 days after surgery as shown by MRI. She was
discharged without neurologic deficit 25 days after surgery.
We performed the second-stage surgery on the left side
4 months later. She was discharged uneventfully after
successful STA-MCA anastomosis and EDMS, which
resulted in disappearance of her ischemic attack as well as
the significant improvement of CBF on the bilateral cerebral
hemisphere. She did not experience neurologic deterioration
during the follow-up period.

5. Discussion
Postoperative cerebral hyperperfusion syndrome has
been considered to be less common in patients with
moyamoya disease [6,8,16] because of the relatively low
flow revascularization obtained by surgery for moyamoya
disease. Furthermore, it was undetermined how rapid
increase in CBF affects the chronic ischemic brain in
moyamoya disease because comprehensive CBF study
during the acute stage has not been done after revascularization for moyamoya disease, except for case reports
[4,13]. The present study demonstrated for the first time
that STA-MCA anastomosis in patients with adult-onset
moyamoya disease can result in temporary neurologic
deterioration due to transient focal intense increase in
CBF at the site of anastomosis at a substantial rate (13/34,
38.2%) and that intensive blood pressure control can relieve
this pathology. Clinical presentation due to focal hyperperfusion in the present series involved not only
bhyperperfusion syndromeQ (2/34, 5.9%) but also transient
focal neurologic deficit mimicking ischemic attack (11/34,
32.4%). Despite the relatively high incidence of the
temporary neurologic deterioration due to hyperperfusion
(38.2%), no patients had permanent neurologic deficit or
delayed neurologic deterioration during the follow-up
period. Based on our findings, it was suggested that STAMCA anastomosis is considered to be a safe and effective
treatment of moyamoya disease as long as the deleterious
effects of cerebral hyperperfusion during the acute stage are
counteracted by intensive blood pressure control. Routine
CBF measurement is recommended for accurate diagnosis
of postoperative hyperperfusion in moyamoya disease
because its treatment is contradictory to that for ischemia.
Because SPECT is not available in all the institutions or all
of the time, perfusion CT or PWI by MRI can be the
alternative modality for the diagnosis of postoperative
hyperperfusion. In fact, we recently conducted PWI in
patients with moyamoya disease postoperatively, and our
preliminary results indicate that PWI is also useful for the
diagnosis of hyperperfusion state (unpublished data).
Besides the CBF study, the characteristic finding of MRA
that demonstrated STA-MCA bypass as a higher intensity

signal than the opposite side STA as shown in all cases with
hyperperfusion may support the diagnosis of a hyperperfusion state. In addition to this finding, significant
visualization of the branches of the MCA around the site
of anastomosis was also evident in some cases compared
with the preoperative state. Reversibility of these findings
after the recovery of transient neurologic deterioration in all
13 cases further supported the idea that these characteristic
findings of MRA reflect a hyperperfusion state. However,
some of the patients without postoperative symptomatic
hyperperfusion also presented a similar MRA finding of the
STA, and further evaluation is needed to verify the
specificity and the mechanism of these findings in future
studies. Alternatively, we do not completely rule out the
possibility that surgical manipulation of the STA might
affect, at least in part, the MRA finding of STA.
On one hand, 2 patients (cases 5 and 8) manifested the
cerebral hyperperfusion syndrome compatible to that seen
after carotid endarterectomy or STA-MCA anastomosis for
atherosclerotic cerebral occlusive disease, which is characterized by unilateral headache, facial and ocular pain,
seizures, and focal symptoms secondary to cerebral edema
or intracerebral hemorrhage [15,18,19]. Because our
procedure includes single anastomosis at the distal M4
with a diameter less than 1 mm, it is conceivable that
patients with moyamoya disease are more vulnerable to
cerebral hyperperfusion after STA-MCA anastomosis. On
the other hand, the clinical manifestations due to hyperperfusion in the other 11 patients were distinct from the
cerebral hyperperfusion syndrome. The clinical presentation
of the 11 cases was characterized by fluctuating aphasia,
numbness in the contralateral side of the face and upper
limb, facial palsy, and dysarthria, in accordance with the
anatomical location of the site of anastomosis. Headache
was associated with these focal neurologic signs only in
limited cases, and seizure was seen only in 2 cases.
Furthermore, case 1 showed delayed increase in localized
CBF 6 days after surgery and subsequently presented focal
neurologic deficit the next day, and such temporal profile
seems to be unusual after carotid endarterectomy or STAMCA anastomosis for atherosclerotic cerebral occlusive
disease. Taken together, the clinical presentation mimicking
ischemic attack seen in 11 patients is likely to be the
characteristic pattern of focal hyperperfusion in patients
with moyamoya disease [3,4,13]. In another similar case, a
39-year-old patient with moyamoya disease had transient
aphasia 2 days after left STA-MCA anastomosis [4].
Technetium 99m hexamethyl propylene amine oxime
SPECT detected focal hyperperfusion at the left frontal
operculum during the course of aphasia [4].
The underlying mechanism of such specific manifestations of hyperperfusion in patients with moyamoya
disease remains undetermined. Certain specific biological
conditions such as the overexpression of proteins including
angiogenic factors and extracellular matrix proteins, which
not only contribute to angiogenesis but also affect vascular

M. Fujimura et al. / Surgical Neurology 67 (2007) 273 – 282

permeability in the chronic ischemic cortex, may be
involved in these intrinsic responses to vascular reconstruction against the chronic ischemic brain in moyamoya
disease. It is conceivable that increased vascular permeability by such mechanism resulted in subarachnoid hemorrhage
after revascularization for moyamoya disease in our 2 cases
(cases 5 and 8), although the exact mechanism is unclear.
Because ROS has been implicated in cerebral ischemia/
reperfusion injury [1,2], differences in ROS production after
vascular reconstruction, vulnerability to ROS, and the
expression of antioxidant enzymes in the chronic ischemic
cortex may also participate in this pathology. In fact,
antioxidant agents are reported to prevent hyperperfusion
syndrome after carotid endarterectomy in patients with
atherosclerotic occlusive disease and markedly affect
cerebrovascular reserve capacity [12]. Therefore, we treated
our patients with edaravone, a novel free radical scavenger,
to ameliorate the unfavorable effects of hyperperfusion on
the affected brain. Long-term follow-up of the neurologic
function including cognitive functions and histologic
changes in the affected brain is needed, because exposure
to sublethal levels of ROS can affect organelles, and thus
lead to delayed neuronal damage by apoptosis [2]. In fact,
postoperative cerebral hyperperfusion is reported to be
associated with impairment of cognitive function in patients
undergoing carotid endarterectomy [14]. In our series, no
patients had delayed neurologic deterioration or delayed
radiologic changes of the affected cortex including changes
in signal intensity on MRI and marked regionally specific
cortical atrophy [13].
Identification of the predictors for cerebral hyperperfusion in patients with moyamoya disease is clinically
important. Preoperative cerebrovascular reserve capacity
[10,11,23], severity of ischemia during surgery, and
anatomical vascular structures around the site of the
anastomosis may affect postoperative cerebral hyperperfusion. In our series, most of the patients showed preoperative
cerebrovascular reserve capacity of less than 0% (steal
phenomenon), which may contribute to the high incidence
of symptomatic hyperperfusion postoperatively. Regarding
intraoperative ischemic insult during anastomosis, which
may facilitate postischemic hyperperfusion, most of the
cases were subjected to temporary occlusion at distal M4
within 30 minutes in our series. Patient age may also affect
postoperative cerebral hyperperfusion. It is totally unclear
how rapid increase in CBF affects the ischemic brain in
childhood moyamoya disease, although a substantial number of children with moyamoya disease, as much as 59.3%
of patients with STA-MCA anastomosis, were reported to
suffer transient neurologic deterioration due to an unknown
mechanism [21]. The limited number of pediatric cases
evaluated by SPECT did not allow us to evaluate the effect
of patient age, and this issue remains to be elucidated in
future study.
In conclusion, surgical revascularization including STAMCA anastomosis is a safe and effective treatment of

281

moyamoya disease, although temporary neurologic deterioration due to hyperperfusion could occur at a substantial
rate. Routine CBF measurement is recommended for
accurate diagnosis of postoperative hyperperfusion in
moyamoya disease because its treatment is contradictory
to that for ischemia.

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