The role of non-stenosing carotid artery plaques in embolic stroke of undetermined source, is it a silent offender? A review of literature

9 Pages·2022·4.425 MB·English

Review Article
InterventionalNeuroradiology
The role of non-stenosing carotid artery plaques 1–9
©TheAuthor(s)2022
in embolic stroke of undetermined source, Articlereuseguidelines:
sagepub.com/journals-permissions
is it a silent offender? A review of literature DOI:10.1177/15910199221143172
journals.sagepub.com/home/ine
Ammar Jumah1 , Hassan Aboul Nour2 , Michael Fana1 ,
Omar Choudhury1, Lara Eltous3, Sohaib Zoghoul4, Fareed Jumah5,
Owais K Alsrouji1, Hisham Alhajala6, Osama Intikhab7, Horia Marin8 ,
Alex Chebl1 and Daniel Miller1
Abstract
Purpose:Atheroscleroticcervicalinternalcarotidarterydiseaseisoneofthemajorcausesofischemicstrokeandtransientischemic
attacks.Theriskofstrokefrommildtomoderatestenoses(i.e.<50%stenosis)mightbeunderestimated.Thereisincreasingevi-
dence that plaque morphological features reflect plaque instability that may harbor high risk for embolization. In this narrative
review,wewillreviewtheliteratureonplaquefeaturesthatpredictvulnerabilitybeyondthedegreeofstenosis,discusstheclinical
associationwithstroke,andevaluatetheevidencethattheselesionsserveasasourceforembolicstrokeofunknownsource(ESUS).
Methods:WeperformedaliteraturesearchusingPubMed,EMBASE,andWebofScience.Theterms“embolicstrokeofundeter-
minedsource”and“plaquemorphology”wereusedeitheraloneorincombinationwith“non-flowlimitingstenosis,”“non-sten-
osingplaques,”“high-riskplaquefeatures”or“internalcarotidarteryplaque.”DataonplaquemorphologyandESUSweremainly
takenfromreviewarticles,observationalstudiesincludingretrospectivecohortandcross-sectionalstudies,meta-analyses,andsys-
tematic reviews.
Conclusion:Nonstenosingcarotidarteryplaqueswithhigh-riskfeaturescarryaremarkableriskforstrokeoccurrenceandrandomized
clinicaltrialsarewarrantedforfurtherevaluationofusingcarotidarterystentingorcarotidendarterectomytomitigatetheriskofstroke.
Keywords
Embolic stroke of undetermined source, non-stenosing carotid plaques, high-risk plaque features, carotid artery stenting
Received25October2022;accepted17November2022
Introduction superficial/cortical brain lesion) with no evidence of an
obvious source of emboli. ESUS accounts for 9%–25%
Acuteischemicstroke(AIS)isoneoftheleadingcausesof of all ischemic strokes.5–7 Cryptogenic strokes pose a
disabilityanddeathworldwide.Thesecondarypreventionof
remarkable treatment dilemma, as secondary prevention
strokevariesbasedontherootcauseoftheinitialevent;thus, of stroke depends heavily on the identified cause, and
determining the cause of an individual AIS is critical for
these strokes have no apparent cause. For patients with
implementing effective care.1 The well-described TOAST
ESUS, secondary stroke prevention strategies are
classificationisusedtoclassifystrokeetiologyandassigns
strokecausestooneoffivemajorcategories:largearteryath-
erosclerosis (LAA), cardioembolism, small vessel disease, 1DepartmentofNeurology,HenryFordHospital,Detroit,MI,USA
stroke of other determined cause, or stroke of an undeter- 2DepartmentofVascularNeurology,EmoryUniversityHospital,Atlanta,
mined cause.2 According to this paradigm, the presence of GA,USA
large vessel disease is considered high risk for subsequent 3JordanUniversityofScienceandTechnology,Irbid,Jordan
4DepartmentofRadiology,HamadMedicalCorporation,Doha,Qatar
strokeonlyif>50%carotidarterystenosisispresent.
5DepartmentofNeurosurgery,UniversityofMissouriHospital,Columbia,
Cryptogenic strokes represent around 30% of all AIS
MO,USA
and are further classified as follows: stroke with no 6DepartmentofVascularNeurology,UniversityofToledo,Toledo,OH,USA
causedespitecompleteworkup,strokewithmultiplepos- 7DepartmentofInterventionalNeuroradiology,JohnsHopkinsHospital,
sible underlying causes, and stroke with incomplete Baltimore,MD,USA
workup.3,4 Embolic stroke of unknown source (ESUS) 8DepartmentofNeuroradiology,HenryFordHospital,Detroit,MI,USA
is a subcategory of the first cryptogenic stroke classifica- Correspondingauthor:
AmmarJumah,DepartmentofNeurology-K11,HenryFordHospital,2799
tion and is characterized as a non-lacunar ischemic
WGrandBlvd,Detroit,MI48202,USA.
stroke presumed to be of an embolic origin (i.e. Email:[email protected]
2 Interventional Neuroradiology
primarilynonspecific,typicallyconsistingofantithrombo- plaque’ssusceptibilitytoruptureandisaproposeddetermin-
tic treatment with aspirin.7 ant of high risk for superimposed thrombosis.24 From this
The most widely accepted predictor for AIS is the concept, researchers have been investigating possible
degree of carotid arterial stenosis, and rupture of the plaquefeaturesthatwoulddesignateplaquesas“vulnerable”
plaque itself is the main etiologic factor of embolic cere- inthehopesofaidingsecondarypreventionprotocolstoavert
brovascular events.8 But several studies have indicated futurecerebrovascularevents.4,25–27
that measuring plaque stenosis alone underestimates the According to a meta-analysis conducted by Kamtchum-
true plaque burden since certain physical plaque features Tatueneetal.thatanalyzed64studies,high-riskplaquefea-
aresuggestedtoplayasignificantroleintheplaque’scon- tureswerethreetimesmoreprevalentinpatientswithsymp-
tribution to stroke risk (i.e. high-risk plaques), even in tomatic versus asymptomatic carotid stenosis (Odds Ratio
non-stenotic internal carotid artery (ICA) plaques.9–11 It [OR]=3.4).25 Another study showed that high-risk plaque
has been well reported that ipsilateral non-stenotic ICA signs were more common in symptomatic patients with
plaques occur in approximately 40% of ESUS patients.6 mild-to-moderatecarotidstenosisthaninpatientswithasymp-
Despite the clear association between plaque composition tomaticstenosis—namely,thinorrupturedfibrouscap(100%
andvulnerabilitytostroke development,currentalgorithms vs.36%,);IPH(86%vs.33%);andthepresenceofalipid-rich
and guidelines still mainly use degree of stenosis and not necroticcore(100%vs.39%).17
plaque morphology as a decision-making criterion for sec- IPH, defined as high-intensity signals seen on fat-
ondary prevention strategies.12 Also, the reporting of suppressedT1-weightedsequencesbymagneticresonance
plaque features in radiological reports usually lacks a imaging(MRI),hasbeenidentifiedasapotentialtriggerof
description of the plaque and tends to focus solely on the plaque instability (Figure 1).28 This phenomenon is based
degree of carotid stenosis.13 Therefore, our aim was to onhistologicexaminationsthathaveshownfreehemoglo-
conductareviewoftheliteraturetoassesswhatiscurrently bin and erythrocytes within thin-walled microvessels,
knownabouthownon-stenosingcarotidarteryplaquescon- which may be prone to disruption.29 Gupta et al. reported
tributetotheoccurrenceofstrokeandTIA,andwhetherpar- a significant association between IPH and cryptogenic
ticularplaquefeaturesmightbeusedasatoolforpredicting strokes.30 And three separate meta-analyses have also
patients’riskofrecurrentstrokeandTIAevents. foundthatsymptomatic patientswithcarotid IPH have an
annual stroke risk of 15%–45%, despite optimization of
medical therapy.21,31,32 This study illustrated the higher
High-risk features indicating plaque riskforrecurrentstrokeinpatientswithESUSwithaniden-
vulnerability tifiableIPH(16.7%vs.2.4%forpatientswithoutIPH).33
Maximumsoftplaquethicknessand“rimsign”(thinadven-
Researchers have described the following high-risk fea- titial calcifications) are usually identified through computed
turesofplaquesthatmayleadtostroke:presenceofintra-
tomography angiography (CTA), and these signs in combin-
plaque hemorrhage (IPH), lipid-rich necrotic core, large
ation are likely to predict the presence of IPH that can be
plaquevolume,significantplaquethickness,echolucency, seen by magnetic resonance angiography (MRA).13,34,35
thin/ruptured fibrous cap, plaque irregularity (0.3–0.9mm
Additionally, identifying a rim sign, maximum soft plaque
fluctuation of plaque surface), plaque ulceration (depression
thickness(foreachmmincreaseinthickness),andintraluminal
of>1mminplaquesurface),andplaqueinflammation/hyper-
thrombus was more predictive of stroke than measuring the
metabolism.4,14–23 Plaque vulnerability, in other words, is a
degreeofstenosisalone.AsystematicreviewbySinghetal.
showed that the risk of recurrent stroke/transient ischemic
attack in patients who have non-stenosing carotid plaques
was 2.6 per 100 patient-years, and this increased to 4.9 per
100patient-yearsifIPHwasidentified.36
Higherplaquethicknessinnon-stenosingICAplaques
is also shown to be associated with a higher risk for an
ipsilateralAIS.Coutinhoetal.reportedthatplaquethick-
nessof≥3mmwassignificantlymorecommonlylocated
ipsilateraltothesideofthestroke(35%)thanincontralat-
eral carotid arteries (15%) (Figure 2).37 Similar to
Coutinho’s results, they found that plaques thicker than
3mm were significantly associated with a higher risk for
an ipsilateral (29.2%) rather than contralateral (18.7%)
AIS. Inthesame study,however,theydidnot findasig-
nificant association between plaque features (plaque
Figure1. MRAwithcontrastshowinganon-stenosingplaque(A). irregularity, ulceration, density, plaque calcification) and
MPRAGE MRA showshyperintensityon T1-signalonthe left
occurrence of ipsilateral AIS, likely because the analysis
carotidartery suggestive ofintraplaque hemorrhage (B).
may have been underpowered. Interestingly, Siegler
MPRAGE,magnetization-preparedrapidacquisitionwithgradient
echo;CCA,commoncarotidartery; ECA,external carotidartery; et al. also showed similar findings in 2019, and they
ICA,internalcarotidartery(FromLarsonetal.33withpermission). found that 35% of patients with ESUS had ≥ 3mm of
Jumah et al. 3
carotidarteryplaqueipsilateraltothestrokeversus15%of studyanalyzedplaqueareasthatwerecausing12%–99%sten-
patients with the problem in the contralateral artery.38 osis as assessed by ultrasonography in patients with carotid
Not only plaque thickness, but also plaque length disease and found that higher plaque areas (>0.8 cm2) were
wasinvestigated;Jumahetal.reportedsignificantassoci- associated with an increased risk for ipsilateral stroke.41 A
ation between Plaques with >1 cm length and ulcerated study by Elhfnawy et al. evaluated internal carotid artery
plaques on CTA with ipsilateral ESUS (Figure 3).26 plaques with 20%–40% stenosis in both symptomatic and
Aretrospectivecohortstudydiscussedanovelparadigm asymptomatic patients. Interestingly, plaques with a cross-
forpredictingwhichpatientswereathighestriskfordevel- sectionalarea≥0.36cm2had71%sensitivityand76%speci-
oping a new stroke due to carotid artery disease.39 Their ficityforpredictingsymptomaticipsilateralICA-stenosis.27
model included patients 75 years of age or above, with a Somestudiesshowedthatvulnerableandcomplexplaques
maximal carotid wall thickness of >4mm, and the pre- hadhigherfluorodeoxyglucoseuptakeasseenonPETscans
scribedantihypertensivemedicationregimenwasincluded in which this metabolic activity is thought to be due to
inthemodel.Themodel’sreceiveroperatingcharacteristic increased inflammatory cell content (e.g. activated macro-
curve (ROC) analysis showed an area under the curve of phages) within the location of complicated plaques, which
0.706 for prediction of new stroke, identifying 10 out of leads to the high risk for embolism (Figure 4).15,42 Watase
14 patients who had a new carotid stroke. A lower cutoff etal.usedMRItostudyplaquefeatures,theplaquelocation
value for plaque thickness (≥ 1.5mm) was also found to relative to stroke laterality, and the presence of high-risk
be more often seen ipsilaterally rather than contralaterally plaquefeaturesinthecarotidarteryipsilateraltoarecentische-
tothesideofthestroke(59%vs.42%).40 mic stroke of the anterior circulation.39 They categorized
Plaquesizehasalsobeenhighlightedintheliteratureto patients’ internal carotid arteries into four groups based on
be associated with an increased risk for AIS. The ACSRS the presence of significant stenosis (50% vs. <50%) and/or
the presence of a high-risk plaques. The group that had
high-risk plaques, but no significant stenosis had greater
wallthicknessandeccentricityindicesthanthosewhohadsig-
nificant stenosis but no high-risk plaques, suggesting a high
risk for rupture and embolism despite a lack of significant
stenosis.
Current evidence on the relationship between
ESUS and non-stenosing carotid artery plaques
Laterality of carotid plaques and stroke
Figure2. Right(A) and left (B) distal carotidarteriesshowing a
softplaque of5mmand amixedplaque of4.1mmthickness, Multiple studies have observed a higher prevalence of
respectively. high-risk plaques being ipsilateral to the stroke side,
Figure3. Left-sidedinternalcarotidarteryshowinganulceratedplaqueonsagittal(A)andaxial(B)sections.(C)and(D)showleft-sided
carotidarteries harboring calcifiedplaques of >1cminlength.
4 Interventional Neuroradiology
Figure4. CarotidPET/CT(fromlefttoright,axialCTA,fusedPET/CTandPETimage)showinginflamedleftcarotidarteryplaqueinapatient
who hada stroke inthesame vascular territory.(From Marnane et al.42 with permission).
substantiating the idea of a direct relationship waiting to however,lackeddetailedimagingofhigh-riskplaquefea-
beconfirmed.26,43,44 tures and instead used ultrasonographic assessments of
TheCAPIAStrialwasanobservationalstudythatana- luminal stenosis.51 Evidently, multiple questions and
lyzed patients older than 49 years of age who were diag- ambiguities still exist, suggesting that more research is
nosed with AIS with unilateral or bilateral carotid artery needed to establish causation between non-stenosing
plaques causing <70% stenosis.45 Patients with compli- carotid plaques and ESUS and to quantify the risk for
cateddiseasemorefrequentlyhadipsilateralinfarcts;spe- ESUS and rates of recurrence.
cifically, patients with 50%–69% stenosis had a higher
prevalence of complicated plaques, which most com-
Arterial stiffness index in ESUS
monly featured IPH.
Ameta-analysis thatassessed323patientswithESUS Blood pressure variability has been shown to be asso-
showed that mild carotid stenosis with unstable or high- ciated with an increased incidence of cerebrovascular
riskplaquefeatures(i.e.rupturedfibrouscap)wassignifi- events, as greater variability means greater mechanical
cantly more commonly located ipsilateral to the stroke stress applied on arterial walls.52 This was thought to be
sideinpatientswithESUS(32.5%)versusbeingcontral- duetothepressureleadingtohigherriskforcarotidarter-
aterally located (4.6%).46 This was similarly shown by ial stiffness and arterial remodeling, thus resulting in
Kamel et al., who studied 579 patients enrolled in the rupture of atheroscleroticplaques.
Cornell Acute Stroke Academic Registry (CAESAR).47 Arterial compliance is the linear regression slope of
This study, which used MRI with contrast enhancement, diastolic bloodpressure onsystolicbloodpressure calcu-
showedthattheprevalenceofcomplicatedatherosclerotic latedthroughplottingbloodpressuremeasurementsmon-
plaques ipsilateral to the infarct were more than twice as itored continuously. Its complement (1 minus the Slope)
prevalent as those that were found contralaterally; 31% indicates arterial stiffness index (ASI) which is a
and 12%, respectively. Similar to the CAPIAS trial, the measure of arterial stiffness and plaque burden.53 With
most frequent characteristic of an ipsilateral complicated thatsaid,arterialstiffnessisaconceptthoughttobeasso-
plaque in the CAESAR studywas IPH.45 ciated with higher atherosclerotic disease burden, and
Knight-Greenfield et al. evaluated plaque features by higher arterial stiffness index (ASI) values have been
CTAinpatientswithAISwhodidnothavehemodynamic observed in patients who have had ischemic and hemor-
stenosis.TheyfoundthatpatientswithESUShadahigher rhagic strokes, which would suggest a prognostic value
total plaque thickness ipsilateral to the stroke side.48 of ASI for predicting ESUS.54,55 A study by Acampa
Inflammationplaysaninterestingroleinthestabilityof et al. showed that patients with ESUS and non-stenosing
carotid plaques as shown in previous studies.49 A very carotid plaques had high ASI values (>0.7), indicating
recentstudybyHuetal.,analyzedtheprevalenceofperi- thatthesepatientshadasimilarcardiovascularcomplica-
carotid fat density, measured by Hounsfield units on tion risk as patients with stroke due to atherosclerosis.53
CTAs. The authors showed that it significantly increased
ipsilateral to ESUS when compared with strokes on the
Ultrasonography and ESUS
contralateral side. This was suggestive for the presence
of inflammation that extends beyond the vessel lumen, Ultrasonography is a safe diagnostic tool that has almost
putting patients at a higher risk for plaque rupture.50 On no contraindications, which makes it a useful approach
thecontrary,Lietal.arguedagainstoccultatherosclerotic for determining stroke risk in patients with carotid
disease as a cause of cryptogenic stroke. This study, disease. Transcranial doppler is a validated tool used to
Jumah et al. 5
detect microembolic signals by using a probe that is Fitzgeraldetal.showedthathigherplateletcountinthe
placed next to the ipsilateral middle cerebral artery.56 It thrombus was indicative of LAA as a cause of stroke,
is mainly used for the detection of embolism in patients which supports treatment algorithms for cryptogenic
with carotid stenosis, and severe degrees of stenosis are strokes that include usingantiplatelet agents.
significantly associated with higher microembolic signal
detection.57 Reportedly, researchers have shown that
Carotid endarterectomy for non-stenotic carotid
ESUS was detected more often by microembolic signals
plaques
(50%) than by LAA (40%), cardioembolism (33%), TIA
(17%), and small vessel disease (14%).58 This supports Indeed, current guidelines do not support using CAS or
the nature of embolic phenomena in patients with CEA for addressing non-stenosing carotid plaques.
ESUS, irrespective of the origin of the embolus. However, as mentioned earlier, a growing body of evi-
Nonetheless, echolucency via ultrasonography can dence suggests that not all symptomatic plaques result in
revealhighlipidcontent,macrophagedensity,andhemor- clinically significant stenosis. In a study by Tonetti
rhage, which reflect a higher tendency for the plaque to et al., the number of patients with carotid stenosis ≥50%
rupture (Figure 5).59–61 Plaque burden was also assessed was overestimated based on non-invasive carotid
bymeasuringplaquelength,thickness,volume,andecho- imagingresults,andtheuseofdigitalsubtractionangiog-
lucency, all quantified through carotid ultrasonography. raphyshowedthatmanyofthesepatientsactuallyhadan
This suggested that a greater carotid plaque burden is insignificant (<50%) stenosis.66 Also, most patients were
potentially associated with a higher risk for emboliza- found to have ulcerations and higher plaque thickness,
tion.62 A meta-analysis that was conducted by Brinjikji correlating with a higher risk of stroke risk despite the
et al. reported that high-risk plaque features (including mild stenosis.
plaqueneovascularity,echolucency,ulceration,andintra- A systematic review performed by Larson et al. ana-
plaque motion) seen by ultrasonography were associated lyzed 6 studies on the treatment of non-stenosing carotid
with a higher risk for anischemic process.63 plaques. Prior to the CEA, 55.8% of the patients had a
recurrent ipsilateral ischemic event despite optimal
medical therapy; after CEA, none of the 138 patients
Clot composition and stroke etiology
who had an available follow-up (mean 36.1 months) had
Thedevelopmentofstentretrievers andadvancements in a recurrent ipsilateral ischemic event.67 This opens the
endovascular reperfusion via mechanical thrombectomy consideration for CEA as a beneficial treatment for
inclinicalpracticehaveresultedinthepossibilityofana- patients with non-stenosing carotid plaques and supports
lyzing retrieved blood clots. Understanding thrombus thehypothesisthatCEAmightbeaplausibleintervention
characteristics to determine the causes of a stroke has asasecondarystrokepreventionstrategyinpatientswith
the potential to improve the treatment of stroke, and this symptomatic mild carotid stenosis harboring high-risk
hasgainedsignificantattentionintherecentliterature.64,65 features. In a study by Coutinho et al., the authors have
Figure5. CarotidUSshowingecholucentplaques(arrowsinA).ContrastenhancedcarotidUSshowingintraplaqueneovascularization(B).
Microbubblesseenwithin atheromatousplaque(Green arrowheads).Whitearrowindicates aregionof theplaque notperfusedby
microbubblecontrast (A;from Skagen et al.60with permission), (B; FromShalhoub et al.61;with permission).
6 Interventional Neuroradiology
alsosuggestedthatpatientswhohavehadmultiplestrokes have revealed that the metabolic activity within the
stemming from problems in the same territory of a high- plaque’s milieu may be correlated with its vulnerability.15
risk non-stenosing plaque and who were not treated suc- Nonetheless, with the development of sophisticated
cessfully with optimal current treatments may benefit imagingtechniques,wearenowabletobettercharacterize
from investigation into alternative causes and treatment ICAplaquesandidentifythecommonlyseenfeaturesthat
with CEA.37 reflectahigh-riskforembolism(Table1).
Some studies have focused on plaque features other
than the degree of stenosis. In defining LAA, the
Discussion
Chinese Ischemic Stroke Subclassification (CISS)
Studies using data from retrospective and prospective system incorporates plaque vulnerability into the classifi-
registries have revealed a remarkably higher risk of cationscheme,whichoffersdetailsonstrokepathophysi-
ESUS within the context of ipsilateral non-stenotic ICA ology.69 The Subtype of Ischemic Stroke Classification
plaques, suggesting a possible association between these System (SPARKLE) focuses on plaque burden for defin-
two clinical phenomena.30,68 As detailed in this review, ing LAA, and the authors suggest a total plaque area of
multiple adequately powered studies looking at the pos- ≥1.19 cm2 as a definition for LAA.70 This helped the
sible characteristics and features that cause a highrisk of authors identify more cases of LAA than when the
ESUS, such as stroke location compared to plaque loca- degreeofstenosisalonewasused(33%vs.21%,respect-
tion, plaque morphology, arterial stiffness, and others, ively). The validation of these classification systems was
havebeendone,andtheycumulativelysuggestanassoci- studied by Zhang et al., showing a substantial agreement
ationbetweenthepresenceofnon-stenosingICAplaques among the 3 main stroke classification schemes: TOAST,
andESUS.However,fewofthesestudieshavebeenrepli- CISS, and SPARKLE. In the same analysis, the CISS
cated to reinforce the aforementioned relationship. This system showed excellent inter-rater reliability (k=
association hasbeenshown notonlyinstudies used CTA 0.857).71TheassociationbetweenESUSandnon-stenotic
and MRA for identifying non-stenosing ICA plaques, but ICAplaquesisplausible,andfromthereviewers’perspec-
also in studies that looked at PET scan results, which tive, a routine description of asymptomatic carotid artery
Table1. High-Risk Carotid Plaque Features.
Imaging
Feature Description modalityused Author Year
Intraplaquehemorrhage32 PlaquehyperintensityonfatsuppressedT1WI MRA Larsonetal. 2021
Plaqueirregularity4 0.3–0.9mmfluctuationofplaquesurface MRA Kamtchum-Tatuene 2021
etal.
Plaqueulceration4 >1mmdepressioninplaquesurface MRA Kamtchum-Tatuene 2021
etal.
Thin/rupturedfibrous Hypointensebandsurroundingahyperintenselumenon MRA Kamtchum-Tatuene 2020
cap25 TOFMRA etal.
Muralthrombus4 Fillingdefectwithinthelumen MRA/CTA Kamtchum-Tatuene 2021
etal.
Plaquelength26 lengthofplaque>1cm CTA Jumahetal. 2022
Plaquethickness36 ≥3mmthicknessperpendiculartothelongaxisofthe CTA Coutinhoetal. 2016
artery,atthelocationofgreatestplaquethickness
Pericarotidfatdensity49 Densityofthefatsurroundingthecarotidarterymeasured CTA Huetal. 2021
byHounsfieldUnit
Plaqueneovascularity60 Visualizedvesselsinsidetheplaque US Brinjikjietal. 2015
Intraplaquemotion60 Asynchronousmovementofcarotidatheromatousplaque US Brinjikjietal. 2015
Echolucency59 Hypoechoicareawithintheplaque US Buonetal. 2018
Plaquecross-sectional Outliningplaquebordersattheprojectionshowingthe US Elhfnawyetal. 2019
area27 largestcross-sectionalareasandthencalculatingitsarea
(cm2)
Microembolicsignal Randomaudibleincreasesindopplersignals TCDs Higuchietal. 2020
detection57
Plaquehypermetabolism/ Higherfluorodeoxyglucoseuptake PETscan Hyafiletal. 2016
inflammation15
Plaquecomposition63 Proportionoffibrinandbloodformedelements NA Fitzgeraldetal. 2019
Arterialstiffnessindex52 AmeasurementofArterialstiffness NA Acampaetal. 2020
Commonfeaturesstudiedthroughouttheliterature,thatdeclareplaquesasbeingvulnerableandatriskforembolization,althoughhavinganunremarkable
stenosisperNASCETcriteria.ASI,arterialstiffnessindex;CTA,computedtomographyangiography;ESUS,Embolicstrokeofundeterminedsource;MRI,
magnetic resonance imaging; MES, microembolic signals; NA, not available; OR, odds ratio; PET, positron emission tomography; TCDs, transcranial
dopplers;TOF,time-of-flight;US,ultrasonography;WI,weightedimage.
Jumah et al. 7
plaques in radiology reports is warranted to be used as a Code availability
future reference in clinical trials to help answer whether
Notapplicable.
interventions for such plaques by either CEA or CAS for
the prevention of future strokes is justifiable. Finally,
Disclosures
caution must be taken while interpreting the association
Authorshavenorelationshipstodisclose.
between high-risk plaque features and ESUS, as there are
noclinicaltrialstosuggestabsolutebenefitfrominterven-
Declaration of conflicting interests
tion. Predictive models and scoring systems incorporating
multiple plaque features for the assessment of recurrence The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
riskofstrokeandTIA events are of utmostimportancein
article.
guidingtreatmentinthefuture.
Ethics approval
Conclusion
Noinstitutionalapprovalrequiredforreviewarticles.
Despite the evidence that high-risk plaque features can
Informed consent
predict a recurrent stroke, adoption of this principle and
its integration into the medical guidelines have not yet Consentisnotapplicableforreviewarticles.
been established. This reflects a lack of clinical trials
that have utilized detailed plaque characterization for Funding
assessing risk of stroke. Thus, randomized controlled The author(s) received no financial support for the research,
trials are warranted to evaluate the utility of using CEA authorship,and/orpublicationofthisarticle.
andCASversusoptimizedmedicalcarefortreatinghigh-
risk,non-stenosingICAplaques,asthismayclarifyfuture ORCID iDs
stroke risk stratification and may guide development of
AmmarJumah https://orcid.org/0000-0001-5316-2415
improved treatment strategies.
HassanAboulNour https://orcid.org/0000-0002-6698-5848
MichaelFana https://orcid.org/0000-0003-4256-6961
Abbreviations and Acronyms HoriaMarin https://orcid.org/0000-0003-1567-959X
ACSRS AsymptomaticCarotidStenosisandRiskof
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Acknowledgements AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/
SNIS/SVM/SVS guideline on the management of patients
The authors thank Karla D Passalacqua, PhD, at Henry Ford
with extracranial carotid and vertebral artery disease:
Hospitalforeditorialservices.
Executive summary: A report of the American College of
Cardiology Foundation/American Heart Association Task
Availability of data and material
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