NEUROSURGICAL

FOCUS

Neurosurg Focus 46 (2):E3, 2019

Cerebral revascularization after the Carotid Occlusion
Surgery Study: what candidates remain, and can we do
better?
Timothy G. White, MD,1 Hussam Abou-Al-Shaar, MD,1 Jung Park, MD, PhD,1 Jeffrey Katz, MD,3
David J. Langer, MD,2 and Amir R. Dehdashti, MD1,2
Departments of 1Neurosurgery and 3Neurology, North Shore University Hospital, Barbara and Donald Zucker School of Medicine
at Hofstra Northwell; and 2Department of Neurosurgery, Lenox Hill Hospital, Barbara and Donald Zucker School of Medicine at
Hofstra Northwell, Manhasset, New York

OBJECTIVE Cerebral revascularization for carotid occlusion was previously a mainstay procedure for the cerebrovascular neurosurgeon. However, the 1985 extracranial-intracranial bypass trial and subsequently the Carotid Occlusion
Surgery Study (COSS) provided level 1 evidence via randomized controlled trials against bypass for symptomatic atherosclerotic carotid occlusion disease. However, in a small number of patients optimal medical therapy fails, and some
patients with flow-limiting stenosis develop a perfusion-dependent neurological examination. Therefore it is necessary to
further stratify patients by risk to determine who may most benefit from this intervention as well as to determine perioperative morbidity in this high-risk patient population.
METHODS A retrospective review was performed of all revascularization procedures done for symptomatic atherosclerotic cerebrovascular steno-occlusive disease. All patients undergoing revascularization after the publication of the
COSS in 2011 were included. Perioperative morbidity and mortality were assessed as the primary outcome to determine
safety of revascularization in this high-risk population. All patients had documented hypoperfusion on hemodynamic
imaging.
RESULTS At total of 35 revascularization procedures were included in this review. The most common indication was
for patients with recurrent strokes, who were receiving optimal medical therapy and who suffered from cerebrovascular steno-occlusion. At 30 days only 3 perioperative ischemic events were observed, 2 of which led to no long-term
neurological deficit. Immediate graft patency was good, at 94%. Long term, no further strokes or ischemic events were
observed, and graft patency remained high at 95%. There were no factors associated with perioperative ischemic events
in the variables that were recorded.
CONCLUSIONS Cerebral revascularization may be done safely at high-volume cerebrovascular centers in high-risk patients in whom optimal medical therapy has failed. Further research must be done to develop an improved methodology
of risk stratification for patients with symptomatic atherosclerotic cerebrovascular steno-occlusive disease to determine
which patients may benefit from intervention. Given the high risk of recurrent stroke in certain patients, and the fact that
patients fail medical therapy, surgical revascularization may provide the best method to ensure good long-term outcomes
with manageable up-front risks.
https://thejns.org/doi/abs/10.3171/2018.11.FOCUS18536

I

KEYWORDS COSS; Carotid Occlusion Surgery Study; carotid occlusion; cerebral bypass; cerebral revascularization

for cerebral revascularization have decreased over the last decade. Its indications fall into 2
main categories: 1) flow augmentation in the setting of
ischemia, and 2) flow replacement in the setting of complex cerebral aneurysms or tumors. Flow augmentation has
ndications

been well studied, with the recent publications of the Carotid Occlusion Surgery Study (COSS), the Japanese Adult
Moyamoya Trial, and the Japan Extracranial-Intracranial
Bypass Trial (JET).8–10 Flow augmentation may be done
in the setting of moyamoya disease, a rare steno-occlusive

ABBREVIATIONS ACA = anterior cerebral artery; COSS = Carotid Occlusion Surgery Study; CTA = CT angiography; CVR = cerebrovascular reserve; DAPT = dual-antiplatelet therapy; EDAS = encephaloduroarteriosynangiosis; ICA = internal carotid artery; MCA = middle cerebral artery; NOVA = noninvasive optimal vessel analysis; OEF =
oxygen extraction fraction; QMRA = quantitative MRA; STA = superficial temporal artery; STLCOS = St. Louis Carotid Occlusion Study; TIA = transient ischemic attack.
SUBMITTED October 1, 2018. ACCEPTED November 26, 2018.
INCLUDE WHEN CITING DOI: 10.3171/2018.11.FOCUS18536.
©AANS 2019, except where prohibited by US copyright law

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White et al.

disease of the intracranial vasculature, or for symptomatic cerebral atherosclerotic stenosis and occlusion. However, historical and recent randomized clinical trials have
whittled down the indications for bypass in the setting of
cerebrovascular atherosclerotic steno-occlusive disease.
The first trial, published in the New England Journal
of Medicine in 1985, showed no benefit for cerebral revascularization in patients with symptomatic nonmoyamoya
vasculopathy; however, it failed to stratify patients by risk
in order to determine which would receive the greatest
benefit from intervention.1 Subsequently, the St. Louis Carotid Occlusion Study (STLCOS) was able to identify patients at the highest risk for recurrent stroke in the setting
of cerebrovascular stenosis and occlusion by using PET
oxygen extraction fraction (OEF).3,5 The COSS was then
designed on this premise.7 In order to determine whether
patients with symptomatic cerebral atherosclerotic stenosis and occlusion who are at the highest risk of recurrent
stroke would benefit from revascularization, patients in the
COSS underwent PET OEF in order to stratify them by
risk. They were then randomized to best medical therapy
versus surgical revascularization. Despite numerous criticisms, the ultimate outcome showed that surgical revascularization provided no benefit over best medical therapy,
mostly due to the impressive natural history of medical
therapy and the perioperative surgical risk associated with
revascularization.6,11 That being said, more recent studies
still demonstrate that misery perfusion is a predictor of
stroke risk in patients with symptomatic atherosclerotic
cerebrovascular steno-occlusive disease, even with newer
optimal medical management.13
A small group of patients develop ischemic symptoms
and symptomatic hypoperfusion (limb shaking and/or
crescendo transient ischemic attacks [TIAs] or orthostatic
hypoperfusion) even on optimal medical therapy, due to
severe hemodynamic impairment. This group of patients
has not been well studied by prior trials. There is little
literature on their clinical syndrome and subsequent outcome and surgical risk after undergoing revascularization.
The purpose of this study was to identify this group of
patients and discuss their surgical outcomes in a single institution’s series.

Methods

A retrospective chart review of all patients who underwent cerebral revascularization for symptomatic cerebral
atherosclerotic stenosis and occlusion between January
2011 and August 2018 was done. All patients who underwent cerebral revascularization for nonmoyamoya
vasculopathy were included in the study. This study was
approved by the IRB at the Feinstein Institute under the
Northwell Health System. Clinical and demographic data
were collected for each patient. Variables studied included
patient age, sex, diagnosis, medical history, clinical course,
medical therapy, preoperative imaging, postoperative imaging, and postoperative clinical outcomes. Independent
radiologists determined bypass patency. Clinical outcomes
were gathered from date of last patient follow-up in the
medical record. Of particular concern was the perioperative morbidity associated with individual cases; therefore,
2

30-day outcomes were collected as the primary surgical
outcome in these patients.
Patient Choice and Surgical Technique
Patients were identified as possible candidates for cerebral revascularization if they showed evidence of atherosclerotic carotid or middle cerebral artery (MCA) stenoocclusive disease and optimal medical therapy had failed,
or if they had perfusion-dependent neurological examinations. Optimal medical therapy including dual-antiplatelet
therapy (DAPT), tight blood pressure control, glycemic
control, and statin use was determined by the stroke neurologist taking care of the individual patients and was
documented as part of the data that were collected. Once
identified as possible candidates, the patients underwent
conventional cerebral angiography for diagnostic purposes,
to determine the site of disease, and for presurgical planning. All patients also underwent some form of hemodynamic imaging, including either SPECT with and without
Diamox, quantitative MRA (QMRA) noninvasive optimal
vessel analysis (NOVA), MR perfusion, or CT perfusion.
SPECT was done to determine those patients with impaired cerebrovascular reserve (CVR), and QMRA NOVA
was used as an adjunct demonstrating decreased flow in
the vascular territory in question.
Surgery was subsequently performed teamed with a
trained neuroanesthesiologist and with strict blood pressure control. Direct superficial temporal artery (STA)MCA bypass was preferred in all cases because the goal
in each procedure was flow augmentation. Postoperatively,
patients were followed after 30 days had passed postdischarge in order to accurately assess perioperative morbidity. Postprocedure bypass patency was assessed using
digital subtraction angiography, CT angiography (CTA), or
QMRA NOVA.
Perioperative management focused on tight blood pressure controls and adherence to an aspirin regimen as well
as patient positioning. During the case, systolic blood pressure was maintained above 120 mm Hg during the procedure, especially for induction. Postoperative blood pressure
goals depended on graft flow but generally were from 120
to 140 mm Hg. Patients were placed on aspirin (81 mg)
prior to the procedure, given aspirin (325 mg) on the night
of the procedure, and then continued on 81 mg daily. CTA
was done on postoperative day 1. If any patient developed
a new deficit on examination, MRI and QMRA NOVA
studies were done to assess for hyperperfusion versus new
stroke.
Statistical Analysis
All data were collected and stored via a REDcap (Research Electronic Data Capture) database, and statistics
were analyzed using SPSS and Excel. All variables are
expressed as the average ± SD, and where appropriate p =
0.05 was used for statistical significance. For descriptive
statistics the average was calculated. Univariate (Student
t-test and chi-square analysis for continuous variable) and
multivariate regression were used to predict factors associated with bypass patency and clinical outcome.

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White et al.

TABLE 1. Characteristics in 35 patients who underwent
revascularization procedures
Characteristic

Value

Age, yrs (range)
Female sex
Presentation
Recurrent stroke
Recurrent TIA
Perfusion-dependent neurological exam
Hemorrhagic transformation of stroke
Headache w/ severe hypoperfusion
Vessel occluded
MCA
ICA
Bilat ICA
QMRA NOVA
Yes
Low flow in affected vessel
SPECT
Yes
Diminished CVR w/ Diamox

55 (22–74)
54% (19/35)
74% (26/35)
11% (4/35)
9% (3/35)
3% (1/35)
3% (1/35)
31% (11/35)
49% (17/35)
20% (7/35)
60% (21/35)
100% (21/21)
91% (32/35)
81% (26/32)

Results

Patient Demographics
In total, 36 patients underwent cerebral revascularization for nonmoyamoya cerebrovascular occlusive disease.
One of the 36 patients was not included in the study because the cerebrovascular occlusion and subsequent hypoperfusion was secondary to carotid sacrifice during head
and neck surgery. The average patient age was 55 years
(range 22–74 years). All patients except 1 were on at least
single-antiplatelet therapy prior to presentation. Clinical
presentation included recurrent strokes, recurrent TIA,
perfusion-dependent examination, hemorrhagic transformation of stroke, and headache with severe hypoperfusion.
The most common presentation was recurrent stroke in
74% (26/35) of patients, followed by recurrent TIA in 11%
(4/35), and perfusion-dependent examination in 9% (3/35).
Both hemorrhagic transformation of stroke as well as headache and severe hypoperfusion occurred in 1 patient each.
Of note, most patients presented with metabolic syndrome
including the combination of hypertension, hyperlipidemia, and insulin resistance. There were 3 unique cases
in which patients did not present with classic symptoms of
atherosclerosis: one patient with fibromuscular dysplasia,
one with sickle cell anemia, and one with antiphospholipid
syndrome.
Imaging Characteristics
All patients were evaluated using multimodal imaging
techniques. During the workup, patients underwent MRI
followed by vessel imaging. In 57% (20/35) of patients
MRI results demonstrated multiple watershed-area infarcts, which was the most frequent MRI finding, whereas
other patients presented with multiple MCA but no wa-

TABLE 2. Perioperative outcomes in 35 patients who underwent
revascularization procedures
Outcome
Complications
Total w/ ischemia
  Patient 1
  Patient 2

  Patient 3

Value or Description
11% (4/35)
9% (3/35)
Postop day 1: neurological change, found
to have graft occlusion; neurological
improvement by time of discharge
Postop day 2: neurological change, found
to have graft occlusion; patient taken
for revision surgery & EDAS procedure
when unable to reopen bypass
Postop day 3: patient developed a worsening neurological exam, graft found
to be patent; by discharge patient had
improved to neurological baseline
3% (1/35)
94% (33/35)

Seizure
Total w/ graft patency
Long-term graft patency
Total w/ imaging
60% (21/35)
Patency on imaging
95% (20/21)
Length of follow-up
23 mos (range 3–84)
Long-term clinical outcome
Total w/ follow-up
80% (28/35)
Length of follow-up
25.5 mos (range 3–84)
Seizure complication
4% (1/28)

tershed area strokes. All patients underwent some form
of hemodynamic imaging. Most commonly the imaging
workup included QMRA NOVA as well as SPECT with
and without Diamox. QMRA NOVA was done in 60%
(21/35) of patients, and in 100% (35/35) of those patients
flow-limiting stenosis was demonstrated when compared
to historical age-based normal values. SPECT was done in
91% of patients (32/35), and of those patients 81% (26/32)
showed decreased CVR when challenged with Diamox.
All patients without diminished CVR who received Diamox did not improve with the administration of the drug,
and at baseline had severe hypoperfusion on SPECT along
with recurrent stroke on optimal medical therapy. Patients
were categorized as having internal carotid artery (ICA)
steno-occlusion, bilateral ICA steno-occlusion, or MCA
steno-occlusion. ICA steno-occlusion was the most common, occurring in 49% of patients (17/35), followed by
MCA steno-occlusion in 31% (Table 1).
Perioperative Outcomes
Thirty-day perioperative outcomes were assessed in all
patients to accurately determine perioperative morbidity in
this theoretically high-risk population. Immediate postoperative graft occlusion occurred in 2 patients; therefore immediate graft patency was 94% (33/35). Postoperative complications occurred in 11% of patients (4/35). There were
3 cases of postoperative ischemic events (9% of patients),
which were permanent in only 1 case. Further description
of these 3 events can be seen in Table 2. All events ocNeurosurg Focus Volume 46 • February 2019

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FIG. 1. Case 1. A: MRI, diffusion-weighted imaging (DWI). B: Conventional angiography demonstrating occlusion of the right ICA.
C: QMRA NOVA demonstrating right ICA occlusion with a small amount of collateral flow from the right posterior communicating
artery. Numbers represent the volumetric flow rate (ml/min). D: Postoperative CTA showing patent bypass. BA = basilar artery;
LACA = left ACA; LCCA = left common carotid artery; LICA = left ICA; LPCA = left posterior cerebral artery; LVA = left vertebral
artery; RACA = right ACA; RCCA = right common carotid artery; RPCA = right posterior cerebral artery; RPCOM = right posterior
communicating artery; RVA = right vertebral artery.

curred within 3 days postoperatively. There was also 1 case
of postoperative seizure treated successfully with antiepileptic drugs. One patient with postoperative graft occlusion
underwent a subsequent encephaloduroarteriosynangiosis
(EDAS) procedure when postoperative angiography demonstrated the occlusion. In univariate and multivariate
analysis no factors (age, sex, preoperative hemodynamic
imaging findings, site of occlusion) were identified as being
associated with the risk of a perioperative ischemic event
or the likelihood of bypass patency (p > 0.05).
Long-Term Outcomes
Long-term clinical outcomes were assessed in 80%
(28/35) of patients, whereas long-term graft patency outcomes were assessed in 60% (21/35) of patients. Bypass
grafts were found to be patent in 95% of patients (20/21)
(Table 2). In one patient who experienced immediate graft
failure on long-term follow-up the graft was found to be
open, and in the other patient with immediate occlusion
who underwent the revision EDAS procedure long-term
patency was not assessed. Clinically, no patient experienced subsequent stroke; however, 1 patient did develop
a persistent seizure disorder postoperatively. Duration
of follow-up was on average 25.5 months (range 3–84
months).

Illustrative Cases

Case 1
A 58-year-old man with a history of stroke, TIA, hyper4

tension, hyperlipidemia, and atrial fibrillation who was on
coumadin and DAPT presented to the hospital with left facial droop, hand weakness, and numbness. MRI revealed
right MCA territory acute infarcts and angiography demonstrated right ICA occlusion with no filling of the right
ICA (Fig. 1A and B). QMRA NOVA demonstrated right
ICA occlusion with a small amount of collateral flow from
the right posterior communicating artery, and follow-up
SPECT with Diamox challenge revealed right-sided hypoperfusion with decreased CVR (Fig. 1C). Given the
imaging evidence of right-sided hypoperfusion as well as
recurrent strokes on DAPT, a right-sided STA-MCA flow
augmentation revascularization was offered and, after a
discussion of the risks and benefits, the patient chose to
undergo the procedure. Postoperatively the patient experienced no complications, with postoperative imaging
showing a patent bypass graft (Fig. 1D). One year after the
initial bypass the patient had no further evidence of stroke.
Case 2
A 60-year-old woman presented with aphasia and
right-sided weakness. MRI revealed left-sided basal ganglia and watershed zone infarcts as well as prior watershed ischemic changes (Fig. 2A). CTA and conventional
angiography showed 95% left MCA stenosis, so the patient was placed on an aspirin and Plavix regimen. However, 1 week later she presented back to the hospital with
worsening right-sided weakness and recurrence of aphasia
after initial improvement from prior admission. Follow-up
MRI showed new strokes (Fig. 2B and C). QMRA NOVA

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FIG. 2. Case 2. A: Initial MRI, DWI. B: Follow-up MRI, DWI sequence showing progression of stroke. C: Digital subtraction
angiography showing severe MCA stenosis. D: Initial QMRA NOVA showing low flow in the left MCA. E: Postbypass QMRA NOVA
showing patent bypass with significant flow.

showed low flow in the left anterior cerebral artery (ACA)
and left MCA, and SPECT with Diamox showed significant left-sided hypoperfusion with diminished CVR (Fig.
2D). Due to recurrence of stroke and hemodynamic compromise the patient underwent left-sided STA-MCA bypass. Postoperatively the patient experienced no complications and the graft was patent immediately and 1 year
postoperatively based on QMRA NOVA (Fig. 2E). At 5
years postbypass the patient had not experienced another
stroke.

Discussion

Prior randomized controlled trials have demonstrated
no benefit to surgical revascularization in patients with
symptomatic cerebrovascular atherosclerotic steno-occlusive disease.1,10 However, optimal medical management,
which includes optimization of atherosclerotic and stroke
risk factors as well as DAPT, still fails to prevent strokes
in a small number of patients. These patients may present with perfusion-dependent examinations or recurrent
TIAs and/or strokes.4,11 No randomized controlled trial
has investigated the role of bypass in this patient group.
Although the COSS did stratify patient risk by using hemodynamic imaging modalities, it did not specifically investigate patients in whom best medical therapy failed.4
The purpose of this retrospective analysis was to demonstrate the safety and perioperative risks associated with
revascularization in theoretically high-risk patients in
whom medical management has failed and who showed
definitive impaired cerebrovascular reserve. Here we dem-

onstrate that when done at a high-volume cerebrovascular
center with specified neuroanesthesia, this procedure can
be done with a reasonable level of morbidity and may represent an effective salvage procedure in certain patients.
In this series perioperative ischemic events occurred in
9% of patients (3/35), with only 1 patient developing an
irreversible neurological deficit.
The original 1985 extracranial-intracranial bypass trial randomized 137 patients with symptomatic carotid or
intracranial steno-occlusive disease but failed to stratify
patients by risk prior to randomization.7 Ultimately, no
benefit was found with surgical intervention at an average
follow-up of 55.8 months, with stroke rates in the medical
arm of 29% versus 31% in the surgical arm. Following
the publication of these results, validated criteria for cerebral hemodynamic impairment were developed via the
STLCOS.3,5 At that time, studies on bypass hemodynamics demonstrated that revascularization was able to correct
impaired hemodynamics in patients.11 That being said, the
increased OEF used to randomize patients in the COSS
may not have been an adequate predictor of hemodynamic
impairment.2
The STLCOS established that PET OEF was able to
predict stroke risk in patients with symptomatic cerebrovascular steno-occlusive disease and stage II hemodynamic impairment. In patients with misery perfusion
and increased OEF, the stroke risk approached 26.5% at
2 years, compared to 5.6% in patients without impaired
perfusion, which led to a predicted benefit of 40% when
developing the COSS and determined patient number to
power the study.3,5,7 However, in the medical arm of the
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COSS the stroke risk amounted to 22% over the 2-year
study period, with the medical arm faring far better than
predicted.10 Given that the predicted stroke risk used for
the COSS was based on studies done in the 1990s, further studies have investigated whether, with newer medical therapy, misery perfusion still predicts stroke risk.12
More recently, Yamauchi et al. demonstrated that misery
perfusion on PET OEF still predicts increased stroke risk
in patients with symptomatic cerebrovascular steno-occlusive disease.13 The authors established that even with the
most recent optimal medical management, increased OEF
alone (as used in STLCOS and COSS) leaves patients at
increased risk of stroke. Therefore, stricter management
of these patients is required, and there may still be a role
for revascularization in these highest-risk patients. In this
study we mainly used SPECT imaging combined with a
Diamox challenge in order to perform risk stratification in
patients with hypoperfusion and to determine which patients have decreased cerebrovascular reserve.
Ultimately, it was not the goal of this series to validate
diagnostic criteria. However, all patients were selected to
be possible candidates for bypass based on their clinical
presentation combined with hemodynamic imaging in the
form of SPECT with and without Diamox, QMRA NOVA,
MR perfusion, or CT perfusion. Therefore, further studies
would be justified to define the optimal modality to determine impaired cerebral hemodynamics and define misery
perfusion.
The outcomes of the COSS were driven by two main
factors: the impressively good outcomes of the medically
managed patients and the perioperative morbidity of revascularization surgery. Perioperative stroke risk in the
COSS was 14%, which was similar to that of the original
extracranial-intracranial bypass trial, and these perioperative ischemic events made up the majority of stroke risk
in this study group.10 Once past the initial perioperative
period the surgical patients maintained a significantly
lower stroke risk than those in the medical arm. Therefore,
decreasing perioperative morbidity and ensuring operative
safety is important going forward. In this series we demonstrate that at a high-volume center with specialized neuroanesthesia, perioperative risk in high-risk patients was
maintained at less than 10%. Analysis of the COSS data
predicted that to show benefit, surgical risk would need to
be roughly 50% of what it was. That being said, this patient population should be considered somewhat separate
from the COSS population because, for reasons that have
been previously discussed, optimal medical therapy had
failed.
Indeed, although the indications for cerebral revascularization for patients with symptomatic steno-occlusive
cerebrovascular disease have waned after the publication
of the COSS, they have not gone away altogether. However, literature addressing the individual patient populations that may benefit the most has waned as well. This
series represents a unique assessment of perioperative risk
in high-risk patients not clearly addressed by the COSS.
Clearly, further research into this patient group is warranted in order to assess the risk of further stroke after
initial therapy as well as to determine optimal treatment
modalities.
6

Conclusions

Cerebral revascularization for nonmoyamoya symptomatic steno-occlusive cerebrovascular disease has not been
shown to provide clinical benefit, but remains an effective and safe option as rescue therapy in patients in whom
conventional medical therapy alone has failed. However,
this should only be practiced at high-volume centers with
specialized staff and experienced surgeons.

References

1. Barnett HJM, Peerless SJ, Fox AJ, Valberg B, Peacock J, Sackett DL, et al: Failure of extracranial-intracranial arterial bypass
to reduce the risk of ischemic stroke. Results of an international randomized trial. N Engl J Med 313:1191–1200, 1985
2. Carlson AP, Yonas H, Chang YF, Nemoto EM: Failure of
cerebral hemodynamic selection in general or of specific
positron emission tomography methodology?: Carotid Occlusion Surgery Study (COSS). Stroke 42:3637–3639, 2011
3. Derdeyn CP, Yundt KD, Videen TO, Carpenter DA, Grubb
RL Jr, Powers WJ: Increased oxygen extraction fraction is
associated with prior ischemic events in patients with carotid
occlusion. Stroke 29:754–758, 1998
4. Esposito G, Amin-Hanjani S, Regli L: Role of and indications for bypass surgery after Carotid Occlusion Surgery
Study (COSS)? Stroke 47:282–290, 2016
5. Grubb RL Jr, Derdeyn CP, Fritsch SM, Carpenter DA, Yundt
KD, Videen TO, et al: Importance of hemodynamic factors
in the prognosis of symptomatic carotid occlusion. JAMA
280:1055–1060, 1998
6. Grubb RL Jr, Powers WJ, Clarke WR, Videen TO, Adams
HP Jr, Derdeyn CP: Surgical results of the Carotid Occlusion
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WR: The Carotid Occlusion Surgery Study. Neurosurg Focus 14(3):e9, 2003
8. Kataoka H, Miyamoto S, Ogasawara K, Iihara K, Takahashi
JC, Nakagawara J, et al: Results of prospective cohort study
on symptomatic cerebrovascular occlusive disease showing
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(Tokyo) 55:460–468, 2015
9. Miyamoto S, Yoshimoto T, Hashimoto N, Okada Y, Tsuji I,
Tominaga T, et al: Effects of extracranial-intracranial bypass
for patients with hemorrhagic moyamoya disease: results of
the Japan Adult Moyamoya Trial. Stroke 45:1415–1421, 2014
10. Powers WJ, Clarke WR, Grubb RL Jr, Videen TO, Adams
HP Jr, Derdeyn CP: Extracranial-intracranial bypass surgery
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306:1983–1992, 2011 (Erratum in JAMA 306:2672, 2011)
11. Reynolds MR, Derdeyn CP, Grubb RL Jr, Powers WJ, Zipfel
GJ: Extracranial-intracranial bypass for ischemic cerebrovascular disease: what have we learned from the Carotid Occlusion Surgery Study? Neurosurg Focus 36(1):E9, 2014
12. Yamauchi H, Fukuyama H, Nagahama Y, Nabatame H, Nakamura K, Yamamoto Y, et al: Evidence of misery perfusion
and risk for recurrent stroke in major cerebral arterial occlusive diseases from PET. J Neurol Neurosurg Psychiatry
61:18–25, 1996
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Disclosures

The authors report no conflict of interest concerning the materi-

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White et al.

als or methods used in this study or the findings specified in this
paper.

Author Contributions

Conception and design: all authors. Acquisition of data: White,
Abou-Al-Shaar, Park. Analysis and interpretation of data: White.
Drafting the article: White. Critically revising the article: White,
Dehdashti. Reviewed submitted version of manuscript: White,
Langer, Dehdashti. Approved the final version of the manuscript on behalf of all authors: White. Statistical analysis: White.
Administrative/technical/material support: Abou-Al-Shaar. Study
supervision: Katz, Langer, Dehdashti.

Correspondence

Timothy G. White: North Shore University Hospital, Barbara and
Donald Zucker School of Medicine at Hofstra Northwell, Manhasset, NY. twhite7@northwell.edu.

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