Journal of the Neurological Sciences 381 (2017) 74–82

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Journal of the Neurological Sciences

journal homepage: www.elsevier.com/locate/jns

Review Article

Cerebral hyperperfusion syndrome and intracranial hemorrhage after MARK

carotid endarterectomy or carotid stenting: A meta-analysis
George Galyfosa,⁎, Argiri Sianoub, Konstantinos Filisa
a
First Department of Propaedeutic Surgery, University of Athens Medical School, Hippocration Hospital, Athens, Greece
b
Department of Microbiology, University of Athens Medical School, Areteion Hospital, Athens, Greece

A R T I C L E I N F O A B S T R A C T

Keywords: Introduction: Cerebral hyperperfusion syndrome (CHS) and intracranial hemorrhage (ICH) after carotid re-
Cerebral hyperperfusion syndrome vascularization have been associated with significant morbidity and mortality, although pooled data comparing
Intracranial hemorrhage these outcomes between open and endovascular treatment are lacking. Aim of this meta-analysis is to compare
Carotid endarterectomy CHS and ICH risk between carotid endarterectomy (CEA) and carotid angioplasty with stenting (CAS).
Carotid stenting
Methods: A systematic literature review was conducted conforming to established criteria, in order to identify
eligible articles published prior to February 2017. Eligible studies compared CHS and/or ICH between patients
undergoing CEA and CAS. Other outcomes evaluated in this review included stroke and death due to ICH.
Outcome risks are presented as odds ratios (OR) and 95% confidence intervals (CI).
Results: Overall, 6 studies (5 studies reporting on CHS and 4 studies reporting on ICH) included 236,537 pro-
cedures (218,144 CEA; 18,393 CAS) in total. CEA was associated with a higher risk for CHS compared to CAS
(pooled OR = 1.432 [95% CI = 1.078–1901]; P = 0.015), although this difference was generated mainly from
older studies (prior to 2012). However, no difference was found regarding ICH risk between the two methods
(pooled OR = 0.544 [95% CI = 0.111–2.658]; P = 0.452). Regarding stroke incidence, no difference was found
between the two methods as well, although this resulted mainly from studies with a higher volume of CAS
procedures (pooled OR = 0.964 [95% CI = 0.741–1.252]; P = 0.833). Finally, death rate was significantly
higher among patients with ICH compared to patients without ICH (pooled OR = 386.977 [95%
CI = 246.746–606.906]; P < 0.0001). Pooled data were not adequate to calculate potential risk factors for
CHS/ICH after CEA compared to CAS.
Conclusions: CEA seems to be associated with a higher risk for CHS compared to CAS, although this difference
was generated mainly from older studies. However, there seems to be no difference regarding ICH risk between
the two methods, with ICH being associated with a significantly higher risk for death.

1. Introduction
Cerebral hyperperfusion syndrome (CHS) has been described as a
primary complication after carotid artery revascularization procedures
by many authors [1,2]. It seems to be associated with inadequate ar-
terial blood pressure control and increased blood flow through the
cerebral arteries postoperatively, leading to increased morbidity [3].
Although this phenomenon has been initially described after carotid
endarterectomy (CEA) [4], many authors have evaluated its prevalence
after carotid angioplasty and stenting (CAS) as well [5]. Main diag-
nostic criteria include typical neurologic symptoms such as seizures or
headache as well as imaging criteria such as increased cerebral artery
flow or exclusion of cerebral ischemia [6].
Furthermore, intracranial hemorrhage (ICH) has also been
associated with CHS after carotid interventions [7]. Several risk factors
have been found to predispose to ICH, including preoperative hy-
pertension, bilateral carotid disease or contralateral carotid occlusion
as well as impaired cerebrovascular reserve [7,8]. Morbidity and
mortality rates are high in such patients, either treated with open or
endovascular repair, thus necessitating an offensive prevention strategy
postoperatively [9].
However, data comparing postoperative CHS and ICH incidence
between open and endovascular treatment of internal carotid artery
(ICA) disease are limited, and no pooled data have been evaluated to
date. Therefore, aim of this review is to collect and analyze all available
comparative data, in order to produce useful conclusions for everyday
clinical practice.

⁎
Corresponding author at: 6 Melinas Merkouri Street, Neon Iraklion, 14122 Athens, Greece.
E-mail address: georgegalyfos@hotmail.com (G. Galyfos).

http://dx.doi.org/10.1016/j.jns.2017.08.020
Received 1 June 2017; Received in revised form 3 August 2017; Accepted 15 August 2017
Available online 18 August 2017
0022-510X/ © 2017 Elsevier B.V. All rights reserved.
G. Galyfos et al.
Fig. 1. Study selection - flow chart of study selection (CEA, carotid endarterectomy; CAS,
carotid angioplasty and stenting; CHS, cerebral hyperperfusion syndrome; ICH, in-
tracranial hemorrhage).
2. Materials and methods
2.1. Data sources and search
We systematically searched Pubmed, Embase, Scopus and Cochrane
Library (for the period January–February 2017) for studies published
online prior to February 2017 comparing CEA and CAS as far as CHS
and/or ICH rates are concerned. This review was conducted according
to established methods for systematic reviews in cardiovascular medi-
cine (PRISMA criteria) [10]. The following medical subject terms were
utilized for the online search: ‘carotid endarterectomy’ or ‘carotid an-
gioplasty ± stenting’ and ‘cerebral hyperperfusion syndrome’ and/or
‘intracranial hemorrhage’. In addition to searching databases, reference
lists of all included studies, meta-analyses and reviews were manually
evaluated, including unpublished data. There was no language restric-
tion for the online search. References from eligible articles or textbooks
were also reviewed to identify further potential sources.
2.2. Data extraction
Three authors independently completed data collection after fol-
lowing search criteria and quality assessment. Data were obtained from
tables, graphs and text. When data were presented in percentage, the
75
Journal of the Neurological Sciences 381 (2017) 74–82
absolute values were calculated. Disagreements were resolved by con-
sensus after review by the senior author of the study. For each study,
the following data were collected: first author, year of publication,
country of publication, type of study, number of patients, basic demo-
graphics/comorbidities and rate of clinical events, including CHS, ICH,
stroke and death due to ICH.
2.3. Quality assessment
Three authors independently reviewed study eligibility and quality.
Disagreements were resolved by consensus. The quality of each study
was assessed using well established criteria [11] for non-randomized
studies, specifically evaluating: collection of data, aim of the studies,
incomplete outcome data, statistical analysis and other sources of bias.
Quality of each study was evaluated and reported as high, medium or
low, based on design and methodology of study according to the
aforementioned criteria [11].
2.4. Selection criteria
Studies included in this meta-analysis met the following criteria:
studies comparing CHS and/or ICH incidence as primary endpoints
between patients undergoing CEA and patients undergoing CAS. All
kind of clinical studies were eligible (prospective, retrospective, ran-
domized).
Exclusion criteria included: (i) studies evaluating the incidence of
CHS or ICH in patients undergoing either CEA or CAS without com-
paring outcomes between the two methods, (ii) types of publication
other than clinical studies such as reviews, letters, meta-analyses, case
reports/series (< 10 patients) or editorials, (iii) studies not referring to
humans, and (iv) overlapping patient populations, identified either by
studies developed over the same period of time in common study
centers or by data collected from overlapping patients' databases. In the
latter case, only the study with a greater number of patients was in-
cluded.
2.5. Study selection and outcomes - definitions
After applying the inclusion/exclusion criteria, 6 clinical studies
[12–17] were identified as appropriate for analysis and overall 740
studies were excluded (Fig. 1). All included studies were published
between 2007 and 2014.
Primary outcomes of all studies should include one of the two fol-
lowing:
• CHS, defined as: (1) severe headache, seizure, deterioration of
consciousness level, and/or development of focal neurological signs;
2) absence of any additional ischemic lesion on brain imaging; and/
or 3) postoperative increases in cerebral blood flow in the ipsilateral
hemisphere, exceeding the flow in the contralateral hemisphere, or
postoperative increases in middle cerebral artery blood flow velocity
of > 100% of the preoperative values.
• ICH, defined as: punctate or confluent hyperdensities consistent
with blood within the parenchyma of the cerebral hemispheres or
within the subarachnoid space as demonstrated on computed to-
mography (CT) imaging.
Secondary outcomes evaluated in this study were:
• Stroke, defined as episode of neurological dysfunction caused by
focal cerebral, spinal, or retinal infarction, based on Pathological,
Imaging, Other Objective Evidence, and/or Clinical Evidence [18].
Only cerebral infarctions reported ipsilateral to the carotid artery
G. Galyfos et al. Journal of the Neurological Sciences 381 (2017) 74–82

Table 1
Characteristics of included studies.

Study Year of publication/location Type of study Total number of procedures CEA/CAS (number of procedures) Quality of study

Ogasawara et al. [12] 2007/Japan Retrospective 4494 1596/2898 High

Posacioglu et al. [13] 2008/Turkey Retrospective 115 59/56 Medium
Mcdonald et al [14] 2011/USA Retrospective 228,896 215,012/13,884 High
Buczek et al. [15] 2013/Poland Prospective observational 61 28/33 Medium
Altinbas et al. [16] 2014/UK, Netherlands RCT 1713 819/766 High
Ziaja et al. [17] 2014/Poland Retrospective 1386 625/761 High

Study Primary endpoints Criteria for CHS used in each study

Ogasawara et al. CHS, ICH, stroke, Death, MI, nerve palsy, 1) severe headache, seizure, deterioration of consciousness level, and/or development of focal
[12] gastrointestinal bleeding neurological signs such as motor weakness; 2) absence of any additional ischemic lesion on magnetic
resonance imaging performed on the 1st postoperative day; and 3) postoperative increases in CBF in
the ipsilateral hemisphere exceeding the flow in the contralateral hemisphere, as measured using
perfusion single photon emission CT or cold xenon-enhanced CT, or postoperative increases in middle
cerebral artery blood flow velocity of > 100% of the preoperative values on transcranial Doppler
ultrasonography
Posacioglu et al. Death, stroke, CHS, ICH, nerve palsy Clinical signs (seizures/headaches/focal neurologic deficit), and typical MRI findings
[13]
McDonald et al. ICH, in-hospital mortality, unfavorable discharges N/A
[14] (discharges requiring skilled care [short-term
hospitalization, skilled nursing facility, home health
care])
Buczek et al. Stroke, CHS, ICH Clinical signs (severe headache, ocular or facial pain, confusion, visual disturbances, epileptic
[15] seizuresand new focal deficits), exclusion of cerebral ischemia, transcranial Doppler examination
(> 100% increase in MCA blood velocity)
Altinbas et al. Stroke, death, MI, hemodynamic depression, CHS Clinical signs: epilepsy, headache, or confusion, exclusion of ischemic event
[16]
Ziaja et al. [17] Neurological symptoms (including CHS), stroke, Neurological signs not attributed to cerebral ischemia, in a patient with a new onset of headache
death ipsilateral to the carotid revascularization

RCT, randomized trial; CEA, carotid endarterectomy; CAS, carotid angioplasty and stenting.
CHS, cerebral hyperperfusion syndrome; ICH, intracranial hemorrhage; CBF, cerebral blood flow; CT, computed tomography; MRI, magnetic resonance imaging; N/A, not reported; MI,
myocardial infarction.

treated in the included studies were evaluated in this review, as this
would be of greater clinical interest.
• Death due to ICH, defined as 30-day mortality in patients presenting
ICH.
2.6. Statistical analysis
Meta-analysis was carried out utilizing the StatsDirect Statistical
software (Version 2.8.0, StatsDirect Ltd). Odds ratios (OR) were used to
determine effect size, along with 95% confidence interval (CI). Inter-
study variations and heterogeneities were estimated using Q-statistic
with P < 0.05 indicating a statistically significant heterogeneity. The
present meta-analysis also quantified the effect of heterogeneity by
using the I2 index (range, 0–100%), which represents the proportion of
inter-study variability attributed to heterogeneity, rather than to
chance. When heterogeneity was not observed, the effect size was cal-
culated based on a fixed effect model. However, random effects were
also calculated for sensitivity analysis. Chi-square test with Yate's cor-
rection was utilized for comparing categorical variables between the
two groups of patients. The P values were two-sided, and P < 0.05 was
considered to indicate a statistically significant difference. All statistical
analyses were conducted using the absolute values and not percentages.
Percentages are presented rounded up at the first decimal. Risk of bias
was also assessed applying Egger test, and generating funnel plots.
3. Results
In this meta-analysis, overall 236,537 procedures (218,144 CEA
procedures and 18,393 CAS procedures) were included. Overall, 6
studies [12–17] were included, out of which 5 studies [12,13,15–17]
reported on CHS rate and 4 studies [12–15] reported on ICH rate. The
majority of the studies were retrospective, with only one study being a
prospective observational study [15], and one study being a rando-
mized trial [16]. However, no study was found to be of low quality.
(Table 1) Moreover, Table 1 lists all major outcomes reported in the
included studies as well as the CHS criteria utilized for each study.
Mean age of all patients was 69.8 years (CEA = 69.7; CAS = 70.4)
and the rate of male patients reached 43.3% (pooled rate). Basic de-
mographics and comorbidities of all patients are presented in Table 2.
The epidemiologic factors did not differ between CEA and CAS patients,
except for the presence of prior symptoms (CEA = 5.7%; C-
AS = 23.8%; P < 0.05).
Regarding overall outcomes, 105 CEA patients (3.4%) presented
CHS compared to 100 CAS patients (2.2%) (pooled OR = 1.432 [95%
CI = 1.078–1901]; P = 0.015). However, no difference was found re-
garding ICH incidence between the two groups (CEA = 224 patients
(0.1%); CAS = 137 patients (0.8%); pooled OR = 0.544 [95%
CI = 0.111–2.658]; P = 0.452), although this result was generated
mostly by one study with the largest number of patients [14]. Con-
cerning other outcomes, 4 studies [5,12,13,17] reported on stroke rate
and 4 studies [12–15] reported on death due to ICH. Regarding stroke
incidence, no difference was found between the two methods

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G. Galyfos et al. Journal of the Neurological Sciences 381 (2017) 74–82

(CEA = 93 patients (4.1%); CAS = 160 patients (4.3%); pooled

12433/4379 (6%/24%; p < 0.05)

149980/12174 (69%/66%; NS)
OR = 0.964 [95% CI = 0.741–1.252]; P = 0.833). Finally, death rate

93358/8414 (43%/48%; NS)

55314/5026 (25%/27%; NS)

36564/2391 (17%/17%; NS)

90058/7228 (42%/52%; NS)

was significantly higher among patients with ICH (60/361) compared

277/193 (18%/12%; NS)

8743/1233 (4%/8%; NS)
613/582 (70%/71%; NS)
4308/922 (2%/6%; NS)
to patients without ICH (97/233,205) (pooled OR = 386.977 [95%

41/50 (5%/6%; NS)

CI = 246.746–606.906]; P < 0.0001). (Table 3; Figs. 2–5) However,
(218144/18393)

there were no adequate data to compare the ICH incidence between

69.7/70.4 (NS)

patients with and without CHS. Finally, bias assessment plots were
generated for each comparison, and all Egger tests were calculated to
Overall

be > 0.05, indicating low bias rate for this meta-analysis.

Regarding potential risk factors for CHS or ICH, only two studies
[12,14] evaluated potential predictors, and therefore, no pooled mul-
tivariable analysis could be conducted to calculate potential overall
70(57-82)/73(62-83)

predictors. Ogasawara et al. [12] found that strict blood pressure con-
Ziaja et al. [17]

trol was associated with ICH (OR = 0.035; 95% CI [0.002–0542];

P = 0.017). Additionally, McDonald et al. [14] found the following
(625/761)

489/395

176/145
375/449
70/123

137/59

predictors for ICH: symptomatic stenosis (OR = 6.81; 95% CI

68/57
N/A

N/A

N/A
N/A
N/A

[5.28–8.74]; P < 0.0001); female gender (OR = 1.49; 95% CI

[1.19–1.87]; P < 0.001); age (OR = 0.99; 95% CI [0.99–0.98];
P < 0.05); Charlson score (per unit increase) (OR = 1.94; 95% CI
Altinbas et al. [16]

[1.85–2.13]; P < 0.0001); hyperlipidemia (OR = 0.64; 95% CI

[0.50–0.83]; P < 0.01); diabetes mellitus (OR = 0.51; 95% CI
(819/766)

[0.38–0.68]; P < 0.0001); myocardial infarction (OR = 0.51; 95% CI

533/570

525/562
179/167
819/766
220/213

130/122

587/548

CAD, coronary disease; TIA, transient ischemic attack; PAD, peripheral artery disease; CRD, chronic renal disease; ICA, internal carotid artery; N/A, not reported.

[0.28–0.87]; P < 0.001); chronic heart failure (OR = 0.23; 95% CI

70/70

33/47

CEA, carotid endarterectomy; CAS, carotid angioplasty and stenting; NS, non-significant; DM, diabetes mellitus; COPD, chronic obstructive pulmonary disease.
N/A

N/A

N/A

[0.15–0.36]; P < 0.0001); chronic obstructive pulmonary disease

(OR = 0.48; 95% CI [0.34–0.65]; P < 0.0001); chronic renal failure
(OR = 0.55; 95% CI [0.30–0.94]; P < 0.05) [14].
70.2 ± 9.4/67.1 ± 8.2

When the analysis was stratified according to year of publication,

CEA was found to be associated with a higher CHS risk (OR = 1.79;
Buczek etal. [15]

95% CI [1.088–2.957]; P = 0.022) compared to CAS in studies pub-

lished prior to 2012 (10 to 5 years ago). However, for studies published
within the last 5 years (after 2012), there was no difference between the
(33/28)
23/28

22/33

27/38

two methods as far as CHS risk is concerned (OR = 1.29; 95% CI

N/A
N/A
N/A
N/A
N/A

N/A
8/6

4/2

[0.915–1.821]; P = 0.147). Regarding the ICH risk, only one study out
of the four included was published within the last 5 years, so no stra-
McDonald et al. [14]

72(65-78)/71(64-79)

tification based on the year was conducted.

(215012/13884)

147628/8904

4. Discussion
91334/5538

54352/3599
10049/1251

36554/2379

90033/7212
8675/1176
3687/226

The present study confirmed that CEA is associated with a higher

N/A

N/A
N/A

CHS risk compared to CAS although this result was observed mainly in
the older studies. However, there seems to be no difference regarding
the ICH risk, with ICH being strongly associated with a higher death
Posacio glu et al. [13]

65.8 ± 9/66.3 ± 9

risk postoperatively.
CEA was associated with a higher CHS risk in this review, although
the included studies did not provide adequate data to conduct multi-
regression analysis for potential risk factors. However, hypertension
(59/56)
32/35

39/44
15/10
32/29
26/34
10/12
10/12

26/34

25/16

and inadequate control of arterial blood pressure have been associated

N/A

4/1

with postoperative CHS by many authors [19,20]. The incidence of CHS

Basic epidemiologic data of patients undergoing CEA versus CAS.

post CEA reaches up to 3% in studies evaluating CHS using cerebral

flow measurements [21]. However, systematic reviews referring to CHS
69.3 ± 8.2/69.8 ± 6.3
Ogasawara et al. [12]

after CAS only report up to 1.1% incidence, concurring with our pooled
results [7]. A possible mechanism explaining the higher risk post CEA is
the intraoperative ischemia caused during clamping of ICA [22]. Due to
(1596/2898)
1436/2243

1277/2236

1330/2150

ischemia/reperfusion injury, reactive oxygen species are produced and

690/1121

cerebral tissue edema is generated, promoting the presentation of CHS

N/A
N/A
N/A
N/A
N/A
N/A
N/A

[23]. However, literature data suggest an earlier onset of CHS post CAS,
possibly due to the prolonged baroreceptor stimulation by the stent that
may induce bradycardia, hypotension and ischemic damage [24,25].
Prior Stroke/TIA/amaurosis

Contralateral ICA occlusion

Therefore, hemodynamic instability after carotid intervention necessi-

tates an offensive strategy of early management with intravenous an-
History of Smoking

tihypertensive medication, in order to prevent adverse sequelae [26].

Mean age (years)

Hyperlipidemia

Finally, it should be underlined that the association between CHS and

Hypertension
Male gender
(CEA/CAS)

CEA was observed mainly in older studies, indicating that improvement

of endovascular techniques during the last years may have improved
Studies

COPD
Table 2

CAD

CRD
PAD

outcomes as well.
DM

Regarding ICH risk, no difference was found between open and

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G. Galyfos et al. Journal of the Neurological Sciences 381 (2017) 74–82

Table 3
Primary and secondary outcomes evaluated in this meta-analysis.

Studies (n) CHS (CEA/CAS) ICH (CEA/CAS) Stroke (CEA/CAS) Death (ICH/no ICH)

Ogasawara et al. [12] (n = 4494) 30/31 6/21 68/137 7/1

Posacioglu et al. [13] (n = 115) 1/0 2/0 0/3 0/1
Mcdonald et al. [14] (n = 228,896) N/A 215/116 N/A 52/95
Buczek et al. [15] (61) 5/4 1/0 3/2 1/0
Altinbas et al. [16] (n = 1713) 3/4 N/A N/A N/A
Ziaja et al. [17] (n = 1386) 66/61 N/A 22/18 N/A
Overall 105/100 (3132/4509) 224/137 (216,700/16866) 93/160 (2313/3743) 60/97 (361/233205)

CHS, cerebral hyperperfusion syndrome; CEA, carotid endarterectomy; CAS, carotid angioplasty and stenting; ICH, intracranial hemorrhage; N/A, not reported; n, number of procedures.
In the Overall row, the total number of CEA/CAS or ICH/no ICH (last column) from studies reporting the above outcomes is given in parenthesis.

Fig. 2. Comparison of CHS risk between patients undergoing CEA and CAS. (CHS, cerebral hyperperfusion syndrome; CEA, carotid endarterectomy; CAS, carotid angioplasty and
stenting).

endovascular repair. Although ICH has been strongly associated with artery velocity or pulsatility index were not found to predict a higher
CHS syndrome [27], the assumption that impaired cerebral auto- risk for ICH [28]. As aforementioned, both open surgery and stenting
regulation accounts for the development of ICH may not be accurate. In could promote cerebral tissue damage either through oxidative stress
a large study by Newman et al., significant increases in middle cerebral induced by ICA clamping or through baroreceptor dysfunction by stent

78
G. Galyfos et al.
Fig. 3. Comparison of ICH risk between patients undergoing CEA and CAS. (ICH, intracranial hemorrhage; CEA, carotid endarterectomy; CAS, carotid angioplasty and stenting).
forces, respectively [14,27]. Moreover, because CAS is usually followed
by dual antiplatelet therapy, one could also expect a higher risk for
cerebral bleeding [29]. However, Lee et al. have shown in a large meta-
analysis that dual antiplatelet therapy did not differ from aspirin
monotherapy as far as ICH risk is concerned [30]. Finally, recent data
indicate that bleeding risk does not differ, regardless of the existence of
preoperative symptoms, although more symptomatic patients under-
went endovascular repair in our review [31].
Additionally, we found no difference concerning the stroke risk
between CEA and CAS. This finding does not concur with recently
published pooled data where CAS has been associated with a higher
stroke risk compared to CEA [32,33]. Even when only imaging criteria
are applied, pooled data indicate that CAS is associated with a higher
risk for postoperative diffusion weighted imaging lesions observed with
magnetic resonance scanning [34]. This could indicate that en-
dovascular repair may be associated with a higher ischemic burden
reflecting a higher stroke risk. Furthermore, this difference could be
explained as most of the published meta-analyses evaluate large ran-
domized trials comparing major outcomes including stroke, between
CEA and CAS. However, in our review, most of the studies were
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Journal of the Neurological Sciences 381 (2017) 74–82
retrospective and half of them were conducted in institutions with large
volumes of endovascular procedures. This could indicate that the op-
erating experience is probably higher, and the incidence of periopera-
tive cerebrovascular events is lower. Finally, as some authors underline,
distinguishing CHS from stroke or transient ischemic attack (TIA) could
be difficult even when strict diagnostic criteria are applied [35].
Moreover, death rate was found to be significantly higher in patients
with ICH. Regarding the pathophysiology, the edema associated with
CHS is initially reversible. However, if CHS progresses to ICH, the
prognosis is not favorable as up to 30% of patients remain at least
partially disabled, and mortality rates could reach up to 50% [36].
Coutts et al. were the first to stratify ICH into different forms as far as
timing is concerned [37]. Specifically, acute ICH usually appears post
CAS and it is strongly associated with high mortality. However, delayed
ICH is a more ‘classic’ form and it is usually observed post CEA [37]. In
a large series by Timaran et al., almost one third of patients that de-
veloped acute ICH and underwent CAS died during the same hospita-
lization, whereas no deaths occurred among patients that developed
ICH post CEA [38]. This could be attributed to late occurrence and
misdiagnosing of CHS and ICH events post CEA.
G. Galyfos et al.
Fig. 4. Comparison of Stroke risk between patients undergoing CEA and CAS. (CEA, carotid endarterectomy; CAS, carotid angioplasty and stenting).
Concerning potential predictors for CHS or ICH, only two studies in
this review evaluated any risk factors [12,14]. Strict control of blood
pressure was found to be protective by Ogasawara et al. [12], whereas
McDonald et al. [14] found that several comorbidities such as hy-
perlipidemia, history of myocardial infarction or chronic renal failure
are also protective. However, in the latter study, symptomatic carotid
disease, CAS, female gender and an increased Charlson comorbidities
score were found to promote ICH [14]. Other authors have identified
timing of procedure, increasing age, critical ICA stenosis, recent stroke
or TIA and severe contralateral carotid disease as risk factors for CHS
[1,7,39]. Therefore, a well-designed prevention/management strategy
should include close monitoring and strict control of arterial blood
pressure, avoidance of vasodilating drugs such as calcium channel
blockers, treatment of ICA stenosis within two weeks of symptoms,
careful selection of anesthetics and addition of hypertonic saline/
mannitol to decrease cerebral edema [36,40].
Finally, there are certain limitations in this study. First, this meta-
analysis includes a small number of mainly retrospective studies. This
may limit the value of the analysis slightly although the total number of
patients is adequate and the quality of individual studies is of medium
to high level. Second, there is heterogeneity of studies, mainly due to
the inclusion of one large study that holds most of the effect weight in
the analysis, especially considering the ICH analysis. However, random
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Journal of the Neurological Sciences 381 (2017) 74–82
effects have been calculated as well in order to improve the strength of
the analysis. Additionally, data were insufficient in the individual stu-
dies in order to conduct pooled multivariable analysis and evaluate
potential predictors for CHS or ICH, although conclusions regarding
main outcomes could be extracted. Finally, there were insufficient data
in the included studies to compare long-term outcomes.
5. Conclusions
CEA seems to be associated with a higher risk for CHS compared to
CAS although this difference seems to be generated mainly from older
studies. However, there seems to be no difference regarding ICH risk
between the two methods, with ICH being associated with a sig-
nificantly higher risk for death. Stroke risk was also found to be no
different between the two methods in the included studies.
Declaration of conflict of interest
On behalf of all authors, the corresponding author states that there
is no conflict of interest.
G. Galyfos et al.
Fig. 5. Comparison of Death risk between patients with ICH and without ICH after carotid revascularization. (ICH, intracranial hemorrhage).
Acknowledgments
There are no acknowledgments.
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