1DepartmeCopernicus Ho

2Cranio-MUniversity in L

3Plastic, RUniversity in L

4DepartmeUniversity of W

CorrespondSurgery, Medi62 Pabianickavp.pl

Ann Vasc SurDOI: 10.1016/� Annals of V

786

Intracranial Occlusions and Internal CarotidArtery Stenoses: Clinical Implications

Mirosław Stelagowski,1 Katarzyna Bogusiak,2 Anna Kasielska,3 Marek Łysakowski,1

Piotr Ka�zmierski,1 and Małgorzata Szostek,4 Lodz and Warsaw, Poland

Background: The aim of this research was to investigate the influence of intracranial stenosesor occlusions on the outcome of carotid endarterectomy (CEA) in patients with internal carotidartery stenosis. The authors also searched for internal carotid artery plaque’s morphology influ-ence on the atherosclerotic process in intracranial arteries.Methods: The study included 154 patients who underwent angiography and CEA. Intracraniallesions (stenosis or occlusion) were stated in 28 (18.2%) patients.Results: Perioperative stroke - death rate was 3.9%. Statistical analysis revealed that perioper-ative stroke after CEA appeared significantly more often in patients with intracranial stenoses orocclusions ( p ¼ 0.0104). Late death-stroke rate was 13.6%. Log-rank test revealed that aftera 1-year follow-up period, there were significantly more survivals in patients without intracraniallesions than in those with intracranial lesions ( p ¼ 0.048).Conclusions: Intracranial stenosis or occlusion predicts poor perioperative neurologicaloutcome. Patients with intracranial lesions benefit less from endarterectomy in a 1-year follow-up period. On the basis of internal carotid artery plaque’s morphology, no conclusions onadvancement of intracranial arteries’ atherosclerosis can be made.

INTRODUCTION

Intracranial stenoses and occlusions most often are

a consequence of atherosclerosis and embolia

derived from extracranial vessels and cardiac cham-

bers, especially during atrial fibrillation.1-3 Stenoses

and occlusions of intracranial arteries are of great

importance in cerebral stroke pathogenesis. They

are diagnosed in 8-10% patients with cerebral

nt of Vascular, General and Oncologic Surgery, Memorialspital, Lodz, Poland.

axillo-Facial and Oncologic Surgery Clinic, Medicalodz, Lodz, Poland.

econstructive and Aesthetic Surgery Clinic, Medicalodz, Lodz, Poland.

nt of General Surgery and Thoracic Diseases, Medicalarsaw, Warsaw, Poland.

ence to: Mirosław Stelagowski, Department of Vascularcal University in Lodz, Memorial Copernicus Hospital,

Street, 93-513 Lodz, Poland, E-mail: mstelagowski@

g 2010; 24: 786-793j.avsg.2010.02.033ascular Surgery Inc.

ischemic symptoms.4,5 It was assessed that the risk

of cerebral stroke in case of intracranial occlusions

is higher, and ranges from 10 to 24%.6,7 Moreover,

patients with intracranial carotid stenosis or occlu-

sion are characterized by a higher rate of a recurrent

stroke than patients with extracranial carotid occlu-

sion, middle cerebral artery stenosis, or occlusion.

The rate of any of the results, such as recurrent

strokes, vascular deaths, and the composite

endpoint of recurrent stroke and vascular death,

increases by approximately 9% for every 10%

increase in patients with intracranial internal

carotid artery (ICA) stenosis or occlusion.8,9 Some

authors indicate that in patients showing the symp-

toms of acute brain ischemia, intracranial large-

vessel occlusion independently predicts poor

neurological outcome at hospital discharge.10 NAS-

CET study proved that in patients with symptoms of

ICA stenosis, concomitant intracranial stenoses and

occlusions are independent risk factors for cerebral

strokes.11 This research proved that patients with

minimum 70% ICA stenoses unquestionably

benefit from surgical patency restoring, whereas

patients with mild stenoses (50e69%) benefit

Vol. 24, No. 6, August 2010 Intracranial lesions and internal carotid artery stenoses 787

more from the operation; however, the advantage is

not so clear.12-15 Rothwell obtained data from the

European Carotid Surgery Trial, North American

Symptomatic Carotid Endarterectomy Trial (NAS-

CET), and Veterans Affairs trial 309 and reassessed

carotid angiograms. Re-analyzing the trials using

the same measurements and definitions yielded

that surgery is of some benefit for patients with

50-69% symptomatic stenosis, and highly beneficial

for those with 70% symptomatic stenosis or greater

but without near-occlusion.16

Some authors suggested that endarterectomy

appears to be more beneficial in patients with mild

and high stenoses with accompanying intracranial

lesions than in patients with isolated ICA stenosis.

Therefore, diagnosing intracranial stenoses concom-

itant with mild ICA stenoses may lead to a decision

to perform endarterectomy in these cases.17,18 It

was also discussed that indications for operative

procedures could be established on the basis of accu-

rate intracranial circulation diagnostics and taking

other risk factors connected with surgical treatment

into consideration.14,17,19-21

Lack of clear results in the available references and

the ongoing controversies about the influence of

intracranial lesions on the outcome of ICA endarter-

ectomy encouraged the authors to investigate this

issue. The aim of this prospective study was to inves-

tigate whether there is any influence of concomitant

intracranial stenoses or occlusions on the outcome of

surgical treatment of patients with ICA stenosis e we

searched for perioperative and late general complica-

tions (stroke or death) in patients after endarterec-

tomy. Additionally, we evaluated the association of

ICA plaque’s morphology and the advancement of

atherosclerotic process in intracranial arteries.

MATERIALS AND METHODS

All the patients with neurological symptoms sug-

gesting ICA stenosis are routinely diagnosed with

bilateral ultrasound Doppler (USG Doppler). Those

with stenoses 70-99% assessed with the USG

have additionally some other imaging performed.

In the analyzed period angiography was the most

available method of arteries’ imaging, and so it

was performed to assess intracranial stenoses or

occlusions on the side with a higher ICA stenosis.

In patients who had one-sided high-grade ICA

stenosis >70% and contralateral ICA stenosis

<50% (assessed with USG Doppler), only left-

sided or right-sided angiography was performed

(ipsilateral to higher stenosis). It is in accordance

with evidence-based medicine recommending

invasive techniques as the standard of care only

for high grade (70-99%) recently symptomatic

stenoses in patients with reasonable surgical risk,

to provide significant protection against subsequent

ipsilateral stroke.22 According to the aforemen-

tioned presented algorithm, we collected 154 one-

sided angiograms.

Participants

Of the total number of patients hospitalized in the

Vascular Surgery Department in 2000-2005, 154

were included in the study. The study material

comprised 103 men and 51 women. Their age

ranged from 45-83, with mean age of 64 ± 9.5

years. All of them were symptomatic; suffered

from a transient ischemic attack, amaurosis fugax,

or cerebral stroke (confirmed with computed

tomography imaging). These were patients with

one-sided high-grade ICA stenosis (70-99%) and

contralateral stenosis <50% (assessed with USG

Doppler) planned for endarterectomy. The partici-

pants did not have diabetes and atrial fibrillation,

but at the same time all suffered from ischemic heart

disease. Routinely, all the patients with ischemic

heart disease and/or carotid atherosclerosis were

treated with acetylsalicylic acid, statins, and beta-

blockers. Demographic features and cardiovascular

risk factors of the examined group were collected

from medical documentation, which was prepared

in accordance with the aim of this research. Demo-

graphic characteristics were presented in Table I.

Procedure

Digital subtraction angiography was performed

through femoral artery approach and illustrated

common carotid artery and internal carotid artery

in its extra- and intracranial part with the main

branches: ophthalmic artery, choroid artery, middle

cerebral artery, anterior cerebral artery, and also

communicating cerebral artery anterior. The degree

of ICA stenosis was measured with NASCET

method.11 Intracranial arteries were assessed angio-

graphically. Angiograms were analyzed for intra-

cranial vessel stenoses >50% or occlusions.

Intracranial stenoses were measured with a jeweler’s

eyepiece with the stenosis as the numerator and

adjacent normal vessel as the denominator. Pres-

ence of at least one stenosis >50% or occlusion in

the mentioned intracranial arteries was a criterion

for intracranial lesion diagnosis. The angiograms

were objectively assessed by a radiologist before

the patient was qualified for surgery. No systemic

adverse events caused by angiography were

Table I. Demographic characteristic of the examined group

Sex

Females Males Total

Number 51 103 154

Mean age ± SD 68.3 ± 4.8 61.9 ± 11.2 64 ± 9.5

Caucasian race (n) 51 103 154

City >100,000 inhabitants (n) 48 101 149

Town <100,000 inhabitants (n) 3 2 5

788 Stelagowski et al. Annals of Vascular Surgery

observed. Five patients were diagnosed with

uncomplicated groin hematoma.

All the examined patients underwent classical

endarterectomy with primary closure under local

anesthesia. The mean of closure of the artery was

dependent on the diameter of the internal carotid

artery. If the diameter of the internal carotid artery

was >4e5 mm, then it was sealed using a simple

sewing up technique. No carotid shunts were used

during carotid endarterectomy in this group of

patients. When ischemic cerebral symptoms

appeared after common carotid artery clamping

a patient was disqualified from open carotid surgery

and after 7 days he underwent carotid artery

stenting.

During the surgical procedure, an overall superfi-

cial assessment of the atherosclerotic plaque was

performed by one person unaware of the aim of

this research, a vascular surgeon specialist (M.q.,

one of the authors of the paper). During the assess-

ment procedure, all the plaques were cut open. On

the basis of the American Heart Association (AHA)

plaques’ classification, the authors divided the

examined plaques into two groups: type VI by

(AHA) or other types by AHA.23,24 Type VI athero-

sclerotic plaque is characterized by plaque rupture,

intraplaque hemorrhage, thrombus on the plaque’s

surface, large lipid core, and less fibrous

tissue.23,25,26 Plaques without the aforementioned

features were classified as ‘‘other types by AHA.’’

All of the patients since the second day after

surgery continued their previous pharmacotherapy

(statins, acetylsalicylic acid, and beta-blockers).

None of the patients received clopidogrel or any anti-

platelet agent other than an acetylsalicylic acid, as

neither of the patients had a contra-indication to ace-

tylsalicylic acid, which is a medicine of choice for

these patients. The pharmacotherapy was continued

through the follow-up period. Within 30 days after

the surgery the patients were observed for early

general complications (stroke or death). Mean

follow-up was 31 days (range 29-34 days).

Throughout the next 11 months, they were

examined in the aspect of late follow-up endpoints:

death or stroke. Mean follow-up was 11.9 months.

Routinely, all the patients after endarterectomy

underwent a follow-up examination after 3, 6, and

12 months since the surgery, during which a physical

examination and carotid USG were performed and

medical history was completed.

Statistical Analysis

Statistical comparison included plaque’s

morphology in relation to the presence of intracra-

nial occlusions. As a measure of this correlation,

a chi-square test was applied. Fisher’s exact test

was used to evaluate the correlation between the

presence of intracranial lesions and perioperative

complications. To assess primary outcome (stroke

or death) adjusted for baseline risk factors, an

adjusted logistical regression (uninominal and

multi-nominal logistic regression) was performed.

To compare a late stroke/death rate among those

with and without intracranial lesions a chi-square2

test was used. As a level of importance p < 0.05

was accepted. Time to late stroke/death after endar-

terectomy in groups with and without intracranial

lesions was compared by means of Kaplan-Mayer

analysis (log-rank test). We used a two-sided test

at 0.05 significance level. Statistical analysis was

conducted using a STATA 9 statistical package.

RESULTS

Of 154 patients, 28 were diagnosed with intracranial

lesions (stenosis or occlusion).

Cardiovascular risk factors in the examined group

were divided into those with versus without intra-

cranial lesions as shown in Table II.

In this study perioperative stroke-death rate was

3.9% (n ¼ 6). Statistical analysis with Fisher’s exact

test revealed that perioperative stroke after endar-

terectomy appeared significantly more often in

patients with intracranial stenoses or occlusions

( p ¼ 0.0104). The stroke after the surgery appeared

Table II. Cardiovascular risk factors in the examined group divided into those with versus without

intracranial lesions

Cardiovascular risk factorsWith intracraniallesions (n ¼ 28)

Without intracraniallesions (n ¼ 126) Total (n ¼ 154)

Sex

Females 8 (28.6%) 43 (34.1%) 51 (33.1%)

Males 20 (71.4%) 83 (65.9%) 103 (66.9%)

Mean age ± SD 67.2 63.3

Blood pressure

Normal (<130/85 mm Hg) 12 (42.9%) 61 (48.4%) 73 (47.4%)

High normal (130-139/85-89 mm Hg) 16 (57.1%) 65 (51.6%) 81 (52.6%)

Hypertensiona 0 0 0

Body mass index, kg/m2

Normal weight 18.5-24.9 kg/m2 18 (64.3%) 61 (48.4%) 79 (51.3%)

Overweight 25-29 kg/m2 7 (25.0%) 58 (46.0%) 65 (42.2%)

Obesity >30.0 kg/m2 3 (10.7%) 7 (5.6%) 10 (6.5%)

Cigarette use 11 (39.3%) 48 (38.1%) 59 (38.3%)

Diabetes mellitus I/ II 0 0 0

TC, mg/dL

<200 2 (7.1%) 9 (7.1%) 11 (7.1%)

200-239 19 (67.9%) 97 (77.0%) 116 (75.3%)

>240 7 (25.9%) 20 (15.9%) 27 (17.5%)

HDL-C, mg/dL

>50 for women and >40 for men 18 (64.3%) 94 (74.6%) 112 (72.7%)

<50 for women and <40 for men 10 (35.7%) 32 (25.4%) 42 (27.3)

LDL-C, mg/dL

<130 6 (21.4%) 30 (23.8%) 36 (23.4%)

130-159 14 (50.0%) 68 (54.0%) 82 (53.2%)

>160 8 (28.6%) 28 (22.2%) 36 (23.4%)

aBased on 3 separate blood pressure analyses.

Table III. Correlation between the presence of intracranial stenoses or occlusions and perioperative and

late strokes

Perioperative stroke Late stroke

Present Not presentFisher’sexact test Present Not present c2

ICA stenosis with intracranial lesions 4 24p ¼ 0.0104a 7 21 3.77

p ¼ 0.0527ICA stenosis without intracranial lesions 2 124 14 112

ap < 0.05.

Vol. 24, No. 6, August 2010 Intracranial lesions and internal carotid artery stenoses 789

in four patients with intracranial stenoses (14.3%)

and in two among those without intracranial

lesions (1.6%) (Table III). From all of the analyzed

baseline risk factors the adjusted logistical regres-

sion could be computed for intracranial lesions,

sex, age, body mass index, cigarette use, and

high-density lipoprotein cholesterol. Odds ratios

were significant for two of the variables: intracra-

nial lesions (odds ratio ¼ 14.10, 95% confidence

interval 1.80-110.28) and cigarette use (odds ratio

¼ 12.86, 95% confidence interval 1.19-139.05)

(Table IV).

Late death-stroke rate was 13.6% (n ¼ 21).

Stroke appeared in seven (25%) patients with

intracranial lesions and in 14 (11.1%) of those

without intracranial lesions. No statistical signifi-

cance assessed with chi-square test was found for

these values ( p ¼ 0.0527) (Table III). Log-rank

test revealed that after 1-year follow-up there

were significantly more survivals in patients

without intracranial lesions than in those with

intracranial lesions ( p ¼ 0.048). In most patients

without intracranial lesions strokes/deaths

appeared after 287 days since endarterectomy. In

Table IV. Adjusted logistical regression assessing perioperative outcome (stroke or death) adjusted for

baseline risk factors

Uninominal logistic regression Multinominal logistic regression

Cardiovascular risk factors/intracranial lesions OR 95% CI OR 95% CI

Intracranial lesions

Not present 1.00 e 1.00 ePresent 10.70 1.82-62.73a 14.10 1.80-110.28a

Sex

Male 1.00 e 1.00 eFemale 2.04 0.39-10.64 3.13 0.43-23.05

Age 1.02 0.92-1.14 1.01 0.86-1.18

BMI

Normal weight 1.00 e 1.00 eOverweight and obesity 0.51 0.09-2.93 0.40 0.05-2.97

Cigarette use

No 1.00 e 1.00 eYes 8.77 0.98-78.47

p ¼ 0.05202

12.86 1.19-139.05a

HDL

>50 for women and >40 for men 1.00 e 1.00 e<50 for women and <40 for men 1.28 0.22-7.36 1.33 0.17-10.48

a, statistically significant p < 0.05.

Fig. 1. Survival rate without ischaemic cerebral stroke in

the analyzed groups of patients , assessed with Kaplan-

Mayer analysis.

790 Stelagowski et al. Annals of Vascular Surgery

patients with intracranial lesions most of

the endpoints were observed after 320 days of

follow-up (Fig. 1).

From 154 atherosclerotic plaques analyzed after

endarterectomy, majority (n ¼ 112) was classified

as type VI by AHA. Intracranial lesions (stenosis

>50% or occlusions) were accompanied by 16.1%

of plaques classified as type VI by AHA and 23.8%

of plaques classified as other types by AHA. Statis-

tical analysis with chi-square test did not reveal

a significant correlation between the plaque’s type

and the presence of intracranial stenoses or occlu-

sions ( p ¼ 0.2680) (Table V).

DISCUSSION

Intracranial stenoses and occlusions most often are

caused by atherosclerosis and embolia derived

from heart and extracranial vessels.1,2 Some authors

indicate that more than one-third of the intracranial

occlusions are connected with thrombus formed

in cardiac chambers.3 Heart-derived embolia are

most commonly produced as a course of atrial

fibrillation.27,28 However, it is relatively difficult

to differentiate the pathogenesis of intracranial

lesions e whether they are evoked by local athero-

sclerosis or embolia.3 There are some features

enabling recognition of the possible pathogenetic

process. Embolia are connected with peracute

course and extensive cerebral strokes.29 Moreover,

embolia formed from clots, in most cases, are recan-

alized within a few days since their appearance.30-32

In this research, angiograms were performed 4-6

weeks after the occurrence of cerebral ischemic

symptoms, so it can be assumed that the examined

intracranial occlusions were caused by local athero-

sclerosis, not embolia. Moreover, we excluded atrial

fibrillation as a possible reason for intracranial

occlusions.

Table V. Correlation between the plaques’ type and the presence of intracranial occlusions

Plaques’ type by AHA No. plaques n (%)

No. of unilateral intracranialstenoses >50% orocclusions n (%) c2 test

Type VI 112 (72.7%) 18 (16.1%) 1.227

p ¼ 0.2680Other types 42 (27.3%) 10 (23.8%)

Vol. 24, No. 6, August 2010 Intracranial lesions and internal carotid artery stenoses 791

Based on 853 patients with ICA stenosis analysis

Rouleau et al. found that intracranial lesions accom-

panied 13.5% carotid stenoses. The authors indi-

cated that in these cases it is unknown which

lesion, intracranial or carotid, served symptoms.18

Sacco et al. revealed that intracranial occlusions

are connected with the degree of ICA stenosis,

however, they did not establish a statistical signifi-

cance.5 In our research percentage of intracranial

lesions accompanying high degree ICA stenoses

(70-99%) was 18.2%. It is believed that higher

degree of ICA stenosis more frequently is accompa-

nied by intracranial stenosis or occlusion. It may

result from general and severe atherosclerotic

process and may indicate that carotid arteries can

serve as a detector of advanced atherosclerosis.

High degree of stenosis and concomitant neurolog-

ical symptoms should incline a vascular surgeon to

search intracranial lesions as a possible reason for

cerebral incidents.

Sacco et al. also analyzed correlation between

ICA stenosis accompanied by intracranial occlusion

and presence of ulcerated plaque in internal carotid

artery, but their results did not present a statistical

value.5 This is in accordance with our research.

We did not prove that ulcerated plaque (plaque

type VI by AHA) in carotid artery is correlated posi-

tively with higher frequency of intracranial stenoses

or occlusions. However, these results do not deny

the idea of embolic character of plaque type VI by

AHA, since, as it was stated previously, we per-

formed angiograms after a long period from neuro-

logical symptoms’ appearance. Certainly, some of

the thrombotic lesions could regress within this

time. To establish the frequency of intracranial

occlusion, caused by thrombosis formed in common

carotid artery bifurcation and internal carotid

artery, angiography should be performed shortly

after occurrence of cerebral ischemic symptoms.

Perioperative stroke-death rate after endarterec-

tomy ranges from 2.1 to 5.9%.11,33-36 In the

previous study we evaluated it to be 3.7%.23 In

this research perioperative stroke-death rate is

similar and was measured at 3.9%. However, in

patients with intracranial lesions it was significantly

higher. Patients with intracranial lesions as well as

those smoking cigarettes appeared to be more likely

to have perioperative stroke or death. Long-term

results after endarterectomy assessed by large,

randomized trials in the aspect of general complica-

tions (stroke or death) range from 12.6% after a year

(SAPPHIRE TEA) to 15.8% after 2 years (NAS-

CET).11,23 Results obtained by Klijna et al. showed

that patients with intracranial ICA stenosis or occlu-

sion, regardless of treatment method, have a higher

rate of a recurrent stroke than patients with extra-

cranial ICA or middle cerebral artery lesions.37 In

our research in general population late stroke-

death rate was similar to the mentioned studies

(13.6%). In patients with intracranial stenoses or

occlusions the rate of the endpoints was higher

than in those without, but not significantly.

However, the groups differed significantly in the

aspect of time when late stroke/death appeared.

After a 1-year follow-up there were more survivals

in patients without intracranial lesions, however,

the biggest reduction in survivability in this group

was earlier than in those with intracranial lesions.

The study, however, carries several limitations

including material selection. Our material

comprised patients with only one-sided high-grade

ICA stenosis and though the results may differ in

group of patients with bilateral high-grade stenoses.

Second, we did not asses the contralateral intracra-

nial lesions as there were no reasons to perform

angiography imaging at the side with ICA stenosis

<50%. In addition, other conditions such as poor

cerebral collateral flow (assessed by magnetic reso-

nance angiography, computed tomographic angiog-

raphy or transcranial Doppler ultrasound), impaired

cerebrovascular vasomotor reserve, and detection of

cerebral micorembolic signals (transcranial Doppler

ultrasound) may also be important factors affecting

poor results after carotid endarterectomy.

CONCLUSIONS

In conclusion, on the basis of internal carotid artery

plaque’s morphology no conclusions can be made

on the advancement of intracranial arteries’ athero-

sclerosis. In patients presenting previous ischemic

792 Stelagowski et al. Annals of Vascular Surgery

stroke and treated with endarterectomy, intracra-

nial stenosis or occlusion predicts poor perioperative

neurological outcome. In these patients periopera-

tive strokes or vascular deaths appear more

frequently when compared with those without

intracranial lesions. Intracranial lesions and ciga-

rette usage were found to be the risk factors for peri-

operative stroke. In the aspect of 1-year follow-up,

patients with intracranial lesions benefit less from

endarterectomy than those without intracranial

lesions. Performing routine intracranial vascular

imaging on symptomatic patients with internal

carotid stenosis may allow a more accurate determi-

nation of prognosis and may also guide therapy.

The higher number of perioperative complica-

tions among patients with itracranial lesions might

be the result of the minute embolus material

released during endarterectomy that causes clini-

cally apparent strokes in patients with damaged

intracranial circulation. If the intracranial occlu-

sions are non-existent and the collateral circulation

is efficient, the microembolisms remain asymptom-

atic. Despite worse perioperative and remote esti-

mates we believe that patients with diagnosed

intracranial lesions are a choice for endarterectomy

because the procedure removes the embolism ecausing plaque and thus may cause a reduction in

stroke e causing embolisms in this particular patient

group. What is more, improving the circulation in

the internal cephalic artery also improves the cere-

bral circulation, and therefore reduces the risk of

thrombosis in atherosclerosis - altered intracranial

vessels. The authors are convinced that despite an

increased risk, the patients should be operated on

to increase the blood flow in their internal carotid

arteries.

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