Case Report

Symptomatic Cerebral Hyperperfusion After Cerebral Vasospasm Associated with
Aneurysmal Subarachnoid Hemorrhage
Hiroyuki Sakata1,2, Hidenori Endo2, Miki Fujimura2, Kuniyasu Niizuma2,3, Teiji Tominaga2

Key words

- BACKGROUND: Cerebral hyperperfusion syndrome, which carries a potential

- Cerebral aneurysm

risk of intracranial hemorrhage, is a rare and overlooked condition in the setting
of subarachnoid hemorrhage (SAH).

- Cerebral blood flow
- Cerebral hyperperfusion syndrome
- Cerebral vasospasm
- Subarachnoid hemorrhage

Abbreviations and Acronyms
123
I-IMP: N-isopropyl[123I]-p-iodoamphetamine
CBF: Cerebral blood flow
CT: Computed tomography
FLAIR: Fluid-attenuated inversion recovery
MRA: Magnetic resonance angiography
SAH: Subarachnoid hemorrhage
SPECT: Single-photon emission computed
tomography
From the 1Department of Neurosurgery, Shirakawa Kousei
General Hospital, Shirakawa, Fukushima; 2Department of
Neurosurgery, Tohoku University Graduate School of
Medicine, Sendai, Miyagi; and 3Department of Neurosurgical
Engineering and Translational Neuroscience, Tohoku
University Graduate School of Biomedical Engineering,
Sendai, Miyagi, Japan
To whom correspondence should be addressed:
Hiroyuki Sakata, M.D., Ph.D.
[E-mail: sakata@nsg.med.tohoku.ac.jp]

- CASE DESCRIPTION: A 72-year-old female presenting with SAH underwent

clipping of a ruptured aneurysm of the left middle cerebral artery. On post-SAH
day 7, the patient exhibited motor aphasia due to cerebral vasospasm of the left
middle cerebral artery. After recovery from symptomatic cerebral vasospasm, the
patient became restless and suffered from right hemiparesis on post-SAH day 12.
Initially, recurrence of cerebral vasospasm was suspected; however, cerebral
blood flow measurement using single-photon emission computed tomography
revealed apparently increased perfusion in the same territory of the left middle
cerebral artery. Hypertensive therapy was not induced during the postoperative
period. Her neurologic symptoms and signs of cerebral hyperperfusion gradually
improved with intensive blood pressure lowering.
- CONCLUSIONS: This

is the first report to describe postischemic cerebral
hyperperfusion syndrome after symptomatic vasospasm detected using
sequential single-photon emission computed tomography during the acute stage
of SAH. Early diagnosis of this rare phenomenon is crucial given the necessity to
lower blood pressure for preventing hemorrhagic complications, which is
contrary to the usual management of patients with vasospasm.

Citation: World Neurosurg. (2020) 137:379-383.
https://doi.org/10.1016/j.wneu.2020.02.092
Journal homepage: www.journals.elsevier.com/worldneurosurgery
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª 2020 Elsevier Inc. All
rights reserved.

not
treated
properly,
cerebral
hyperperfusion syndrome can result in
severe
brain
edema,
intracranial
hemorrhage, and death. It is generally
induced by the excessive resupply of CBF

after chronic or temporary ischemia with
dysautoregulation of the central vascular
system. Surprisingly, serial single-photon
emission computed tomography (SPECT)
measurements have revealed that >50% of

INTRODUCTION
Cerebral hemodynamics dramatically
change during the acute stage of subarachnoid hemorrhage (SAH),1,2 and the
most
common
and
devastating
consequence is hypoperfusion due to
cerebral vasospasm, which leads to
delayed ischemic neurologic deficits.3
Conversely, cerebral hyperperfusion in
the setting of SAH is a rare and
overlooked condition. Hyperperfusion is
defined as a significant increase in
cerebral blood flow (CBF) relative to the
homologous area of the contralateral
hemisphere, which occasionally leads to
cerebral
hyperperfusion
syndrome
characterized by ipsilateral headache,
seizures, and focal neurologic deficits.4 If

Figure 1. Preoperative head computed tomography (CT). (A) CT showing diffuse subarachnoid
hemorrhage, especially in the left sylvian fissure. (B) Three-dimensional CT angiography revealing a
4-mm aneurysm with a bleb in the left middle cerebral artery.

WORLD NEUROSURGERY 137: 379-383, MAY 2020

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379

CASE REPORT
HIROYUKI SAKATA ET AL.

CEREBRAL HYPERPERFUSION POST VASOSPASM

patients with SAH experience regional
mild
hyperperfusion
after
initial
hypoperfusion.1 Moreover, 6% of patients
with SAH suffer from hemorrhagic
complications
following
cerebral
vasospasm,
although
the
causal
relationship
between
intracranial
hemorrhage and cerebral hyperperfusion
syndrome is undetermined because of
the lack of serial CBF measurements in
previous reports.5,6
Here we present a rare case of cerebral
hyperperfusion
syndrome
following
symptomatic vasospasm in a patient with
SAH. Serial CBF measurements in this
case led to the early diagnosis of cerebral
vasospasm and subsequent symptomatic
hyperperfusion, which was successfully
treated by lowering blood pressure.
CASE DESCRIPTION
History and Examination
A 72-year-old female with a history of
arterial hypertension presented with transient loss of consciousness followed by
severe headache. She was drowsy and
restless without focal abnormalities (Hunt
and Hess grade III). Computed tomography (CT) of the head revealed SAH
(modified Fisher grade 3) with a thick clot
in the left sylvian fissure (Figure 1A).
Three-dimensional (3D)-CT angiography
revealed a 4-mm left middle cerebral artery
aneurysm with a bleb (see Figure 1B).
Operation
On post-SAH day 1, the aneurysm was
surgically clipped via left frontotemporal
craniotomy. Temporary occlusion of M1
was performed for 2 minutes, 21 seconds
under brain protection with edaravone and
mannitol.
Postoperative Course
The patient awoke from anesthesia relatively soon without apparent neurologic
deficits. Diffusion-weighted and fluidattenuated inversion recovery (FLAIR)
imaging on post-SAH day 3 showed no
abnormalities. Postoperatively, her neurologic status was monitored closely with
serial clinical examinations. On post-SAH
day 2, she was started on intravenous
fasudil hydrochloride, a Rho kinase
inhibitor to prevent cerebral vasospasm.
Induced hypertension was not performed

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Figure 2. Postoperative magnetic resonance imaging. Magnetic resonance angiography showing
severe cerebral vasospasm in the left middle cerebral artery on day 7 (arrows in A) and resolution of
cerebral vasospasm on day 12 (arrows in B). Fluid-attenuated inversion recovery imaging on day 12
demonstrating cortical hyperintensity in the territory of the left middle cerebral artery (arrows in C) in
the absence of abnormal findings on diffusion-weighted imaging (D).

during the postoperative period, and her
systolic blood pressure ranged between
120 mm Hg and 140 mm Hg. However, on
post-SAH day 7, she exhibited fluctuating
motor aphasia. Diffusion-weighted and
fluid-attenuated inversion recovery imaging showed no cerebral infarctions,
whereas magnetic resonance angiography
(MRA) demonstrated severe cerebral
vasospasm at the left middle cerebral
artery (Figure 2A), accompanied by
hypoperfusion in the left frontal region
confirmed
by
N-isopropyl[123I]123
p-iodoamphetamine ( I-IMP) SPECT
(Figure 3A). Delayed cerebral ischemia
due to cerebral vasospasm was strongly
suspected, and she was initiated on
intravenous administration of edaravone
and hypervolemic therapy, which led to
the complete disappearance of motor

aphasia. However, on post-SAH day 12,
the patient became restless and suffered
from right hemiparesis. Initially, recurrence of cerebral vasospasm was
123
suspected;
however,
I-IMP-SPECT
revealed apparently increased perfusion in
the left middle cerebral artery territory (see
Figure 3B), whereas resolution of
vasospasm was observed in the left
middle cerebral artery by MRA (see
Figure 2B). FLAIR imaging demonstrated
cortical hyperintensity in the left middle
cerebral artery territory (see Figure 2C)
without any abnormal findings by
diffusion-weighted
imaging
(see
Figure 2D). The neurologic symptoms and
increased CBF were not caused by epilepsy
because electroencephalogram showed no
epileptic abnormal waves. These results
suggested postischemic hyperperfusion

WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2020.02.092

CASE REPORT
HIROYUKI SAKATA ET AL.

CEREBRAL HYPERPERFUSION POST VASOSPASM

Figure 3. Postoperative images of single-photon
emission computed tomography with N-isopropyl
[123I]-p-iodoamphetamine. Note that the cerebral

due to cerebral vasospasm-mediated
ischemic insult led to the cerebral hyperperfusion syndrome.
Chronologic CBF data by 123I-IMP-SPECT
are shown in Figure 4. Briefly, CBF was
quantified by autoradiographic methods,
and the CBF in each subregion was
automatically calculated by software for
3-dimensional stereotactic regions of
interest templates provided by Daiichi

blood flow is decreased in the left middle cerebral
artery territory on day 7 (arrows in A), followed by an
apparent increase on day 13 (arrows in B).

Radio-Isotope (Tokyo, Japan). The
regional CBF of the left frontal lobe was
decreased (ratio, 0.80) on post-SAH day 7
but suddenly increased prominently (ratio,
1.61) on post-SAH day 13. The systemic
blood pressure was strictly controlled to
stay in a range from 110 mm Hg to 130 mm
Hg using continuous intravenous drip
infusion of nicardipine hydrochloride.
Hyperperfusion of the affected cortex

WORLD NEUROSURGERY 137: 379-383, MAY 2020

gradually improved and returned to normal
on post-SAH day 76. The cortical hyperintensity on FLAIR imaging peaked between post-SAH days 12 and 17 and
gradually decreased in intensity and
returned to normal on post-SAH day 54.
Neither hemorrhagic transformation nor
atrophic changes were noted in the affected
regions on CT scans and FLAIR imaging
throughout the observation period.

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CASE REPORT
HIROYUKI SAKATA ET AL.

CEREBRAL HYPERPERFUSION POST VASOSPASM

Figure 4. Line graph depicting chronological changes
in regional cerebral blood flow (rCBF) by single-photon
emission computed tomography (SPECT) with
N-isopropyl[123I]-p-iodoamphetamine. rCBF in the left
frontal lobe (affected side) and right frontal lobe

Follow-Up
The patient’s hemiparesis and restlessness
gradually
improved
starting
from
post-SAH day 27. The patient had no
neurologic deficits at the time of discharge
from the hospital on post-SAH day 57.
DISCUSSION
Cerebral hyperperfusion syndrome in the
setting of SAH is a rare phenomenon;
however, recognition of this unusual
complication is critical given the potential
risk of intracranial hemorrhage.7 Previous
reports found that the risk of hemorrhagic
complications (6%) following cerebral
vasospasm was relatively high possibly
due to postischemic hyperperfusion,
although the actual mechanism of
hemorrhage remained unclear.5,6 In the
present
case,
the
serial
CBF
measurements by 123I-IMP-SPECT have
outlined the drastic change in cerebral
hemodynamics during the acute stage of
SAH, which aids in the potential
identification of the trigger underlying
cerebral hyperperfusion syndrome.

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(unaffected side) are plotted against days after the
onset of subarachnoid hemorrhage. Corresponding
images of SPECT with N-isopropyl
[123I]-p-iodoamphetamine are shown above the line
graph.

We speculate the mechanism underlying cerebral hyperperfusion syndrome
post SAH as follows. First, loss of
autoregulation (i.e., vasoparalysis) due to
a preexisting ischemic insult is reported
to induce postischemic hyperperfusion.8,9
Serial CBF studies revealed that
vasospasm-induced hypoperfusion preceded symptomatic hyperperfusion in the
corresponding area, which lends strong
support for this possibility. Therefore
ischemic damage caused by cerebral
vasospasm potentially induced vasoparalysis in the affected cortex, resulting
in cerebral hyperperfusion syndrome.
Moreover, ischemic insult due to temporary clipping of a parent artery during
aneurysm surgery is also known to lead to
postischemic hyperperfusion, especially if
the temporary clipping lasts for >20 minutes of the total duration.10,11 However,
since the temporary occlusion time was
<3 minutes, the influence of temporary
clipping was considered minimal in the
present case. Second, increased CBF at
the epileptogenic site has been
consistently reported during seizure

activity.12 However, epilepsy-induced
hyperperfusion is unlikely in the present
case, since the electroencephalogram obtained immediately after the onset of
symptoms revealed no epileptic abnormal
waves. Third, hypertensive therapy for
SAH-induced vasospasm was reported to
cause hypertensive encephalopathy such
as posterior reversible encephalopathy
syndrome, resulting in symptomatic
hyperperfusion.13 Indeed, hypertensive
therapy was not induced in the present
case throughout the postoperative
period, and systolic blood pressure was
maintained between 120 mm Hg and
140 mm Hg before the onset of
symptoms.
Therefore
hypertensive
encephalopathy might not be the trigger
for symptomatic hyperperfusion. Taken
together, postischemic hyperperfusion
due to vasospasm-induced ischemic
insult is considered the most reasonable
trigger of cerebral hyperperfusion syndrome in the present case.
Because therapeutic strategies against
symptomatic cerebral hypoperfusion and
hyperperfusion are complete opposites,

WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2020.02.092

CASE REPORT
HIROYUKI SAKATA ET AL.

accurate evaluation of cerebral hemodynamics before starting treatment is critical
in patients who develop neurologic deficits in the acute stage of SAH. As treatment against cerebral vasospasm,
including hypertensive therapy and
administration of vasodilators, may lead to
worsening of deficits and even permanent
injury, the possibility of cerebral hyperperfusion syndrome should be considered
during the postoperative period of SAH,
especially in patients with preceding
symptomatic vasospasm. In the present
case, we performed repeat 123I-IMP-SPECT
imaging to assess cerebral hemodynamics
after SAH, which led to the early diagnosis
of cerebral vasospasm and subsequent
cerebral
hyperperfusion
syndrome.
Increased cortical intensity on FLAIR
imaging in the affected area indicated
reversible vasogenic edema caused by
cerebral hyperperfusion syndrome.14 In
addition, MRA served as a noninvasive
and useful tool to determine whether
worsening of the neurologic signs were
due to cerebral vasospasm. Therefore
serial
angiography
and
CBF
measurements are useful in identifying
patients with hyperperfusion, as well as
in distinguishing those with cerebral
vasospasm.
Delayed intracranial hemorrhage due to
cerebral hyperperfusion after revascularization surgery was reported previously4;
therefore symptomatic hyperperfusion
after SAH is considered to entail
substantial risk of morbidity and
mortality
due
to
hyperperfusion.
Therefore
rapid
counteraction
of
hyperperfusion is essential after the
accurate
diagnosis
of
cerebral
hyperperfusion. Because intensive blood
pressure lowering in patients with
evidence of hyperperfusion by flow
studies is the standard management of
cerebral
hyperperfusion
after
revascularization surgery for carotid
artery stenosis, as well as Moyamoya
disease,15 the systemic blood pressure in
the present patient was managed strictly
to stay below 130 mm Hg using
continuous intravenous drip infusion of
nicardipine hydrochloride. Postoperative
use of a free-radical scavenger is an

CEREBRAL HYPERPERFUSION POST VASOSPASM

acceptable additional approach to
ameliorate secondary brain damage due to
cerebral hyperperfusion, as reported in
patients undergoing carotid endarterectomy.16 Fortunately, symptomatic cerebral
hyperperfusion was resolved completely by
blood
pressure
lowering
and
administration of a free-radical scavenger
without the development of permanent
neurologic deficits in the present case.
CONCLUSIONS
This is the first report to present postischemic cerebral hyperperfusion syndrome following symptomatic vasospasm
detected by sequential 123I-IMP-SPECT
during the acute stage of SAH. Early
diagnosis of this rare phenomenon is
crucial given the necessity to lower blood
pressure for prevention of hemorrhagic
complications, which is contrary to the
usual management of patients with
vasospasm.
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Conflict of interest statement: This work was supported by
JSPS KAKENHI Grant Number JP19K18414.

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WORLD NEUROSURGERY 137: 379-383, MAY 2020

Received 12 December 2019; accepted 16 February 2020
Citation: World Neurosurg. (2020) 137:379-383.
https://doi.org/10.1016/j.wneu.2020.02.092
Journal homepage: www.journals.elsevier.com/worldneurosurgery
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª 2020 Elsevier Inc. All
rights reserved.

www.journals.elsevier.com/world-neurosurgery

383