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Vascular
http://vas.sagepub.com/content/19/2/111
The online version of this article can be found at:
DOI: 10.1258/vasc.2010.cr0228
2011 19: 111Vascular
Laura Capoccia, Caterina Pelonara, Cesira Imondi, Enrico Sbarigia and Francesco Speziale
plaques
From embolization to remodeling: the need for early carotid endarterectomy in symptomatic carotid
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at Univesita La Sapienza on May 22, 2013vas.sagepub.comDownloaded from
CASE REPORT
From embolization to remodeling: the need for early
carotid endarterectomy in symptomatic carotid plaques
Laura Capoccia*, Caterina Pelonara†, Cesira Imondi†, Enrico Sbarigia*and Francesco Speziale*
Atheromatous plaques are dynamic structures undergoing continuous remodeling. Duplex ultrasound is now an accepted technique
to classify the severity of arterial stenoses. It gives information about the ultrasonic echogenicity of tissue, the plaque surface and
the velocity of blood flowing through vessels with the latest equipment. We report the case of a 59-year-old male patient with left
hemispheric stroke and a 50% left carotid artery stenosis whose remodeling and reabsorption developed throughout three months
from the onset of symptoms. Plaque surface and structural echomorphology assessment and standardization, along with the degree
of carotid stenosis, might be helpful in identifying patients most likely to benefit from carotid endarterectomy.
Key words: carotid artery; duplex ultrasound; plaque embolization
Introduction
Some important trials have derived data about the risk of
neurological ischemic symptoms related to carotid plaque
stenosis mainly based on percentage evaluation.
1,2
Nevertheless, the probability of giving neurological symp-
toms rely not only on that assessment, but also on non-
standardized and underreported characteristic features of
potentially unstable plaque.
3–5
Atheromatous plaques are
dynamic structures undergoing continuous remodeling.
6
Histological studies of excised carotid atherectomy speci-
mens have highlighted morphological features such as
surface ulceration, intraplaque hemorrhage, a large lipid or
necrotic core, thinning and disruption of the fibrous cap,
and infiltration of the cap by a greater number of macro-
phages and T cells, as is more frequent in recently sympto-
matic carotid plaque.
7–10
The natural history of plaque
remodeling after a neurological event, through in-site reab-
sorption or distal embolization, remains unknown.
Case report
A 59-year-old man with pre-existing hypertension, hyperli-
pidemia, obesity and diabetes presented with right hemipar-
esis and expressive aphasia. A diagnosis of parietal left
hemispheric brain infarct in the periventricular area was
established by CT and he was admitted to a rehabilitation
hospital to undergo physical and language therapy. Six
thousand UI per day of low-molecular-weight heparin
(enoxaparin) was administered, along with his scheduled
antiplatelet (ASA 100 mg per day), antihypertensive (enala-
pril 10 mg per day), antidiabetic (metformin 500 mg twice a
day) and statin (atorvastatin 40 mg per day) therapy.
During hospitalization, he underwent transesophageal echo-
cardiography, aortic arch and supra-aortic vessel CT angio-
graphy, and carotid duplex ultrasound to detect the source
of embolization, and a 50% left carotid artery stenosis was
encountered (internal carotid artery peak systolic velocity
[ICA PSV] 113 cm/s, ICA end diastolic velocity [EDV] 43 cm/s,
ICA/common carotid artery [CCA] PSV ratio (1.6).
Echomorphological evaluation showed a mixed echogenic
and echolucent plaque composition, a gray scale median
11
(GSM) score of 47.5 (mean value calculated in two longitudi-
nal images with maximum plaque area, using two reference
Accepted May 27, 2010
*Vascular Surgery Division, Department of Surgery ‘Paride Stefanini’,
Policlinico Umberto I, ‘Sapienza’University of Rome, Rome 00161,
Italy;
†
Rehabilitation Care Unit, Istituto San Raffaele-Tosinvest Sanità,
Cassino 03043, Italy.
Correspondence to: Laura Capoccia, Vascular Surgery Division,
Department of Surgery ‘Paride Stefanini’, Policlinico Umberto I,
‘Sapienza’University of Rome, Rome 00161, Italy; e-mails: lauracapoc-
cia@yahoo.it; laurakp@hotmail.com
Vascular, Vol. 19 No. 2, pp. 111–115, 2011
© 2011 Royal Society of Medicine Press. All rights reserved.
ISSN: 1708-5381.
DOI: 10.1258/vasc.2010.cr0228
111
at Univesita La Sapienza on May 22, 2013vas.sagepub.comDownloaded from
points to set the gray scale from 0 or black = blood to 255 or
white = adventitia) and an ulcerated surface (Figure 1). The
size of the brain infarct was subsequently evaluated by
contrast-enhanced CT and was found to be 10 mm in dia-
meter in the left periventricular middle cerebral artery area.
According to international guidelines for symptomatic carotid
artery stenosis treatment, the patient was counseled for left
carotid endarterectomy, but he chose not to be submitted to
surgery in an urgent setting. He continued his rehabilitation
program with residual dysarthria and partial upper limb
motor impairment (evaluated by National Institutes of Health
Stroke Scale [NIHSS] = 5 and Barthel Index [BI] = 95) for two
months after the first neurological event when he presented a
sudden worsening of upper limb motor deficit (NIHSS = 8,
BI = 65). A new brain CT angiography was performed and no
new ischemic area was detected (Figure 2). The patient was
referred to our institution for carotid endarterectomy, but a
new duplex ultrasound scanning showed a plaque remodeling
with partial reabsorption or disruption of the atheroma,
causing a residual stenosis of less than 30% (ICA PSV 75 cm/s,
ICA EDV 38 cm/s, ICA/CCA PSV ratio 1.1), a mixed echolu-
cent and echogenic composition, and a GSM score of 40.3
(Figure 3). To confirm duplex investigation the patient under-
went supra-aortic vessel CT angiography (Figures 4a and b)
that revealed 30% residual stenosis. Therefore he was again
sent for rehabilitation with no more improvement thereafter.
One month after the second neurological event, duplex ultra-
sound scanning revealed further remodeling of the carotid
plaque with a small residual stenosis and a GSM score of 37
(Figure 5).
Discussion
In the present case, plaque remodeling developed through
in-site reabsorption and/or distal embolization. Because the
patient refused surgery, we were able to witness the various
stages of transformation of the plaque during the fluctuation
of neurological symptoms. Nowadays, duplex ultrasound
allows the assessment of many features of atheromatous
Figure 1 Carotid duplex ultrasound
showing a 50% left carotid artery stenosis
(internal carotid artery peak systolic velo-
city [ICA PSV] 113 cm/sec, ICA end dia-
stolic velocity [EDV] 43 cm/sec, ICA/
common carotid artery [CCA] PSV ratio
1.6), a mixed echogenic and echolucent
plaque composition and an ulcerated
surface
Figure 2 Brain CT angiography performed after the second neurologic
event
112 Capoccia et al.
at Univesita La Sapienza on May 22, 2013vas.sagepub.comDownloaded from
plaque that were not previously reported. Ultrasonic duplex
scanning is a standardized method to classify the severity of
arterial stenoses. It gives information on the ultrasonic
echogenicity of tissue, the plaque surface and the velocity of
blood flowing through vessels, along with the stenosis per-
centage. To date we have some standardization for the
definition/classification of plaques that are still not taken
into account when drawing up guidelines for the treatment
of carotid stenosis.
4,5
Atheromatous plaque can be consid-
ered a living entity that undergoes remodeling, thus becom-
ing more or less dangerous for the risk of stroke. Plaque
remodeling is mainly achieved through the reabsorption of
intraplaque hemorrhage and lipid core and the increase in
fibrous content, thus justifying a more dangerous configura-
tion immediately after an ischemic neurological event and a
more stable configuration with increasing time. The associa-
tion among plaque heterogeneity, intraplaque hemorrhage
and recent neurological symptoms was first described in
1983 by Reilly et al.
12
Since then many studies have focused
on plaque echomorphology and symptoms. Feeley et al.
7
demonstrated a reduction in collagen/fibrous tissue in
plaque, causing symptoms as observed in unstable plaques.
In a study of 270 plaques, the European Carotid Plaque
Study reported a reduction in the ‘soft tissue’content of
Figure 3 After a second ischemic neurolo-
gic event, a new duplex ultrasound scan-
ning showed plaque remodeling with
partial reabsorption of the atheroma and a
mixed echolucent and echogenic composi-
tion, causing a residual stenosis of less
than 30% (ICA PSV 75 cm/sec, ICA EDV
38 cm/sec, ICA/CCA PSV ratio 1.1)
Figure 4 (a) and (b) Supra-aortic vessel
CT-angiography confirmed a residual ste-
nosis of 30%
From embolization to remodeling 113
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plaques examined more than five months after an ischemic
neurological event.
13
In the Oxford plaque study, plaques
causing stroke were reported most unstable immediately
after the neurological event, with the prevalence of plaque
rupture and instability falling to plateau levels at approxi-
mately 90–100 d.
14
The relation between GSM plaque echo-
morphology and ischemic symptoms was analyzed by
Russell et al.,
15
which confirmed the maximal echolucency
of symptomatic plaques before 30 d after a neurological
event and a decrease from then on. Furthermore, plaque
surface irregularity or ulceration has been described as
related to neurological symptoms. The analysis of the
macroscopic appearance of endarterectomy specimens sug-
gested that the effect of plaque irregularity on stroke risk
could be mediated by ulceration and surface thrombus for-
mation.
16
The old classification of carotid plaques, and the
consequent neurological risk estimation, based on assess-
ment of the percentage of stenosis, might be supplemented
by plaque composition and surface evaluation.
17
Data from
the Asymptomatic Carotid Atherosclerosis Study
(ACAS)
1,2,18
suggested the need to consider the more
proper ‘unstable’definition for the plaque at high risk of
producing symptomatic embolization or carotid occlusion,
while not necessarily being more stenotic. The atherosclero-
tic plaque is composed of a core of lipid and necrotic debris
covered with a dense cap of connective tissue embedded
with smooth muscle cells. It contains monocyte-derived
macrophages, smooth muscle cells and T lymphocytes.
Interaction between these cell types and the connective
tissue appears to determine the development and complica-
tions of plaque, including plaque rupture.
19
Because plaque
rupture depends on the balance between surface tension
and the pressure exerted on the surface, rupture can easily
be mediated by a sudden rise in blood pressure and heart
rate or a weakening of the wall structure due to intraplaque
hemorrhage.
20–22
Vasa vasorum in the atherosclerotic
plaque originate from branches of the external carotid
artery or ICA distal to the location of the plaque.
23–25
In
these small vessels, the pressure is lower than in the arterial
lumen and the enhanced velocity and pressure depression
occurring in the stenotic segment could be responsible for a
blood suction effect into the plaque from the vasa vasorum,
as suggested by Texon according to the Bernoulli effect.
26
These findings are confirmed by recent plaque echomor-
phological and immunohistological studies reporting the
symptomatic plaques being associated with an increased
number of small-diameter (20–30 µm) microvessels staining
for vascular endothelial growth factor (VEGF).
27
In their quantitative evaluation of carotid plaque echo-
genicity, Nagano et al.
3
reported a strong association
between plaque echolucency, histological findings (mea-
sured by integrated backscatter analysis [IBS]) and the
occurrence of cerebral infarction, thus justifying the central
role played by duplex ultrasound in the diagnosis and treat-
ment planning of carotid artery stenosis. Some authors
28,29
have demonstrated differences in the B-mode ultrasound
GSM of various tissue components and their association
with specific histological features in carotid plaques. In the
Figure 5 One month after the second neu-
rologic event, duplex ultrasound scanning
revealed further remodeling of the carotid
plaque with a small residual stenosis
114 Capoccia et al.
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Imaging in Carotid Angioplasty and Risk of Stroke
(ICAROS) study, Biasi et al.
30
reported that plaques with a
low GSM (<25) are more likely to have an adverse outcome
from carotid angioplasty and stenting, consistent with an
increased risk of embolization from unstable plaques.
Conclusion
As atheromatous plaques are dynamic structures undergoing
continuous remodeling, duplex ultrasound might be consid-
ered the best method for plaque stenosis, surface and mor-
phology assessment, because it is easy to perform and has low
invasiveness and low cost. Such features used during the eva-
luation of symptomatic plaques are extremely valuable to
identify eventual recurrences of neurological ischemic events.
Acknowledgments
Financial disclosure of authors and reviewers: none reported.
References
1 Beneficial effect of carotid endarterectomy in symptomatic
patients with high-grade carotid stenosis. North American
Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl
J Med 1991;325:445–53
2 Randomised trial of endarterectomy for recently symptomatic
carotid stenosis: final results of the MRC European Carotid
Surgery Trial (ECST). Lancet 1998;351:1379–87
3 Nagano K, Yamagami H, Tsukamoto Y, et al. Quantitative
evaluation of carotid plaque echogenicity by integrated backscatter
analysis: correlation with symptomatic history and histologic
findings. Cerebrovasc Dis 2008;26:578–83
4 Tegos TJ, Sohail M, Sabetai MM, et al. Echomorphologic and
histopathologic characteristics of unstable carotid plaques. AJNR
Am J Neuroradiol 2000;21:1937–44
5 Stary HC, Chandler AB, Dinsmore RE, et al. A definition of
advanced types of atherosclerotic lesions and a histological
classification of atherosclerosis. A report from the Committee on
Vascular Lesions of the Council on Arteriosclerosis, American
Heart Association. Circulation 1995;92:1355–74
6 Chalela JA. Evaluating the carotid plaque: going beyond stenosis.
Cerebrovasc Dis 2009;27(S1):19–24
7 Feeley TM, Leen EJ, Colgan MP, et al. Histologic characteristics of
carotid artery plaque. J Vasc Surg 1991;13:719–24
8 Avril G, Batt M, Guidoin R, et al. Carotid endarterectomy
plaques: correlations of clinical and anatomic findings. Ann Vasc
Surg 1991;5:50–4
9 Park AE, McCarthy WJ, Pearce WH, Matsumura JS, Yao JS.
Carotid plaque morphology correlates with presenting
symptomatology. J Vasc Surg 1998;27:872–8
10 Golledge J, Greenhalgh RM, Davies AH. The symptomatic carotid
plaque. Stroke 2000;31:774–81
11 El-Barghouty NM, Levine T, Ladva S, Flanagan A, Nicolaides A.
Histological verification of computerized carotid plaque
characterization. Eur J Vasc Endovasc Surg 1996;11:414–6
12 Reilly LM, Lusby RJ, Hughes L, Ferrell LD, Stoney RJ, Ehrenfeld
WK. Carotid plaque histology using real-time ultrasonography.
Clinical and therapeutic implications. Am J Surg 1983;146:188–93
13 Carotid artery plaque composition–relationship to clinical
presentation and ultrasound B-mode imaging. European Carotid
Plaque Study Group. Eur J Vasc Endovasc Surg 1995;10:23–30
14 Redgrave JN, Lovett JK, Gallagher PJ, Rothwell PM. Histological
assessment of 526 symptomatic carotid plaques in relation to the
nature and timing of ischemic symptoms: the Oxford plaque
study. Circulation 2006;113:2320–8
15 Russell DA, Wijeyaratne SM, Gough MJ. Changes in carotid
plaque echomorphology with time since a neurologic event.
J Vasc Surg 2007;45:367–72
16 Rothwell PM, Gibson R, Warlow CP. Interrelation between plaque
surface morphology and degree of stenosis on carotid angiograms
and the risk of ischemic stroke in patients with symptomatic
carotid stenosis. On behalf of the European Carotid Surgery
Trialists’Collaborative Group. Stroke 2000;31:615–21
17 Golledge J, Siew D-A. Identifying the carotid ‘high risk’plaque: is
still a riddle wrapped up in an enigma? Eur J Vasc Endovasc Surg
2008;35:2–8
18 Endarterectomy for asymptomatic carotid artery stenosis. Executive
Committee for the Asymptomatic Carotid Atherosclerosis Study.
JAMA 1995;273:1421–8
19 Ross R. The pathogenesis of atherosclerosis: a perspective for the
1990s. Nature 1993;362:801–9
20 Muller JE, Tofler GH, Stone PH. Circadian variation and triggers of
onset of acute cardiovascular disease. Circulation 1989;79:733–43
21 Lin CS, Penha PD, Zak FG, Lin JC. Morphodynamic
interpretation of acute coronary thrombosis, with special
reference to volcano-like eruption of atheromatous plaque caused
by coronary artery spasm. Angiology 1988;39:535–47
22 Barger AC, Beeuwkes III R. Rupture of coronary vasa vasorum as
a trigger of acute myocardial infarction. Am J Cardiol 1990;66:
41G–43G
23 Bo WJ, McKinney WM, Bowden RL. The origin and distribution
of vasa vasorum at the bifurcation of the common carotid artery
with atherosclerosis. Stroke 1989;20:1484–7
24 Williams JK, Orgren KI, Armstrong ML, Heistad DD. Vasa
vasorum in the carotid sinus of atherosclerotic monkeys:
implications for baroreceptor function. Atherosclerosis 1989;78:
25–32
25 Beach KW, Hatsukami T, Detmer PR, et al. Carotid artery
intraplaque hemorrhage and stenotic velocity. Stroke 1993;24:
314–9
26 Texon M. A hemodynamic concept of atherosclerosis, with
particular reference to coronary occlusion. AMA Arch Intern Med
1957;99:418–27
27 Giannoni MF, Vicenzini E, Citone M, et al. Contrast carotid
ultrasound for the detection of unstable plaques with neo-
angiogenesis: a pilot study. Eur J Vasc Endovasc Surg 2009;37:722–7
28 Lal BK, Hobson II RW, Pappas PJ, et al. Pixel distribution
analysis of B-mode ultrasound scan images predicts histologic
features of atherosclerotic plaques. J Vasc Surg 2002;35:1210–7
29 Aly S, Bishop CC. An objective characterization of atherosclerotic
lesion. An alternative method to identify unstable plaque. Stroke
2000;31:1921–4
30 Biasi GM, Froio A, Diethrich EB, et al. Carotid plaque
echolucency increases the risk of stroke in carotid stenting. The
Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS)
study. Circulation 2004;110:756–62
From embolization to remodeling 115
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