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Interventional compared with medical management of symptomatic carotid web: A systematic review

Open AccessPublished:August 20, 2022DOI:https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106682

      Abstract

      Background

      Carotid web (CaW) is non-atheromatous, shelf-like intraluminal projection, generally affecting the posterolateral wall of the proximal internal carotid artery, and associated with embolic stroke, particularly in younger patients without traditional stroke risk factors. Treatment options for symptomatic CaWs include interventional therapy with carotid endarterectomy or carotid stenting versus medical therapy with antiplatelet or anticoagulants. As safety and efficacy of these approaches have been incompletely delineated in small-to-moderate case series, we performed a systematic review of outcomes with interventional and medical management.

      Methods

      Systematic literature search was conducted and data analyzed per PRISMA guidelines (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) from January 2000 to October 2021 using the search strategy: "Carotid web" OR "Carotid shelf" OR “Web vessels” OR "Intraluminal web". Patient-level demographics, stroke risk factors, technical procedure details, medical and interventional management strategies were abstracted across 15 series. All data were analyzed using descriptive statistics.

      Results

      Among a total of symptomatic 282 CaW patients across 14 series, age was 49.5 (44–55.7) years, 61.7% were women, and 76.6% were black. Traditional stroke risk factors were less frequent than the other stroke causes, including hypertension in 28.6%, hyperlipidemia 14.6%, DM 7.0%, and smoking 19.8%. Thrombus adherent to CaW was detected on initial imaging in 16.2%. Among 289 symptomatic CaWs across 15 series, interventional management was pursued in 151 (52.2%), carotid artery stenting in 87, and carotid endarterectomy in 64; medical management was pursued in 138 (47.8%), including antiplatelet therapy in 80.4% and anticoagulants in 11.6%. Interventional and medical patients were similar in baseline characteristics. The reported time from index stroke to carotid revascularization was median 14 days (IQR 9.5–44). In the interventional group, no periprocedural mortality was noted, major periprocedural complications occurred in 1/151 (0.5%), and no recurrent ischemic events were observed over follow-up range of 3–60 months. In the medical group, over a follow-up of 2–55 months, the recurrence cerebral ischemia rate was 26.8%.

      Conclusion

      Cumulative evidence from multiple series suggests that carotid revascularization is a safe and effective option for preventing recurrent ischemic events in patients with symptomatic carotid webs.

      Keywords

      Introduction

      A carotid web (CaW) is a non-atherosclerotic and non-inflammatory shelf-like intraluminal membrane within the carotid bulb. By causing stenosis of the carotid artery lumen, CaWs can produce turbulence that catalyzes a pro-aggregatory platelet response and/or stasis that provokes coagulation, leading to thromboembolism and cerebral infarction.
      • Mac Grory B.
      • Emmer B.J.
      • Roosendaal S.D.
      • Zagzag D.
      • Yaghi S.
      • Nossek E.
      Carotid web: an occult mechanism of embolic stroke.
      Radiographically, a CaW appears as an intraluminal filling defect, typically along the posterolateral wall of the proximal cervical internal carotid artery.
      • Mac Grory B.
      • Emmer B.J.
      • Roosendaal S.D.
      • Zagzag D.
      • Yaghi S.
      • Nossek E.
      Carotid web: an occult mechanism of embolic stroke.
      Leading considerations for the pathogenesis of CaWs include: (1) they are an intimal variant of fibromuscular dysplasia (FMD), or (2) they are a congenital anomaly arising from aberrant embryologic development of the carotid bifurcation and internal carotid artery from the third aortic arch.
      • Guglielmi V.
      • Compagne K.C.J.
      • Sarrami A.H.
      • et al.
      Assessment of recurrent stroke risk in patients with a carotid web.
      With advances in neuroimaging, CaWs are being increasingly recognized as a cause of first and recurrent strokes.
      • Mac Grory B.
      • Emmer B.J.
      • Roosendaal S.D.
      • Zagzag D.
      • Yaghi S.
      • Nossek E.
      Carotid web: an occult mechanism of embolic stroke.
      ,
      • Zhang A.J.
      • Dhruv P.
      • Choi P.
      • et al.
      A systematic literature review of patients with carotid web and acute ischemic stroke.
      However, the optimal treatment approach for secondary prevention in patients with symptomatic carotid webs is uncertain. Some studies have reported a low risk of recurrent strokes with medical antithrombotic management alone,
      • Joux J.
      • Chausson N.
      • Jeannin S.
      • et al.
      Carotid-bulb atypical fibromuscular dysplasia in young Afro-Caribbean patients with stroke.
      • Semerano A.
      • Mamadou Z.
      • Desilles J.P.
      • et al.
      Carotid webs in large vessel occlusion stroke: clinical, radiological and thrombus histopathological findings.
      • Olindo S.
      • Chausson N.
      • Signate A.
      • et al.
      Stroke recurrence in first-ever symptomatic carotid web: a cohort study.
      and other case series have suggested positive long-term outcomes following carotid revascularization procedures.
      • Borghese O.
      • Pisani A.
      • Di Centa I.
      Surgical treatment of carotid webs in symptomatic young adults.
      • Brinjikji W.
      • Agid R.
      • Pereira V.M.
      Carotid stenting for treatment of symptomatic carotid webs: a single-center case series.
      • Haussen D.C.
      • Grossberg J.A.
      • Bouslama M.
      • et al.
      Carotid web (Intimal Fibromuscular Dysplasia) has high stroke recurrence risk and is amenable to stenting.
      • Haussen D.C.
      • Grossberg J.A.
      • Koch S.
      • et al.
      Multicenter experience with stenting for symptomatic carotid web.
      We undertook a systematic review to identify all reports in the published literature to marshall the available evidence to inform management strategies and technical details on interventional therapy.

      Methods

      The authors declare that all supporting data are available within the article (and it's in the online-only Data Supplement) and the cited published case series. As a study of publicly available data, the investigation was deemed exempt from detailed review and from the need for patient informed consent by the Institutional Review Board at the University of Los Angeles (UCLA).
      This systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews) guidelines.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      • The P.G.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      We searched Embase, PubMed, and Web of Science from January 2000 to October 2021 using the search strategy: "Carotid web" OR "Carotid shelf" OR “Web vessels” OR "Intraluminal web." We also reviewed the references from extracted studies to identify any additional salient reports. Studies were included if they met the following criteria: (1) reported cases of symptomatic ischemic stroke or transient ischemic attack (TIA) ipsilateral to CaW, (2) described the type of medical management and/or interventional management pursued secondary prevention; (3) had a follow-up period of at least two months, (4) study population age ≥ 18 years, and (5) sample size ≥ four patients. Two neurologists (SP and KT) independently performed a review of retrieved articles to determine study eligibility. The same two neurologists also independently abstracted data from qualifying reports. Disagreements were resolved by consensus discussion.
      Data abstracted from each eligible study included: author-name; year published; sample size; patient age; sex; race-ethnicity; treatment with medical management only or treatment with carotid revascularization procedure; if medical management, type of agent (antiplatelets (AP) or anticoagulants (AC)); if revascularization, type of intervention (carotid endarterectomy (CEA) or carotid artery stenting (CAS)); perioperative complications peri-procedural ischemic stroke, intracerebral hemorrhage, or mortality; occurrence of recurrent ischemic stroke during the follow-up period; occurrence of in-stent stenosis or thrombosis during the follow-up period. We also abstracted data regarding baseline comorbidities data including hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), patent foramen ovale (PFO), smoking status, oral contraceptive (OC) use, migraine, micro embolic signal (MES) detection on transcranial doppler (TCD), and thrombus on carotid web detected on initial imaging.
      All data were analyzed using descriptive statistics. Pooled weighted means were calculated as the total number of events divided by the total sample size. Patients’ characteristics in the medical management and the revascularization intervention groups were compared using t-tests for parametric data, Wilcoxon rank-sum for nonparametric data, and chi-square tests for dichotomous data. A Microsoft excel-sheet was used to tabulate or visually display results of individual studies and syntheses.

      Results

      The flow chart for article selection is shown in Fig. 1 and CaW cases are presented in Fig. 2. The search yielded 344 candidate articles: Embase (143), PubMed (83), and Web of Science (117). A total of 15 studies met inclusion criteria for symptomatic CaWs. Out of 289, 151 (52.2%) underwent carotid intervention and 138 (47.8%) were managed with medical therapy alone.
      Fig 1
      Fig. 1PRISMA flow chart for study selection.
      Baseline characteristics were reported for 97.6% (282/289) of patients, including separately for interventional patients in 9 studies reporting 90 patients, separately for medical management patients in 3 studies reporting 73 patients, and among intermingled patients in 5 studies reporting 54 interventional and 65 medical management patients. Patient characteristics within individual studies are shown in Table 1; aggregate patient characteristics across studies by treatment group are shown in Table 2.
      Table 1Baseline characteristics in individual studies of interventional vs. medical management of carotid webs (N = 282).
      Interventional management studies (N = 90)
      Study nameNSex (Female)

      n (%)
      Age (years)Race (Black)

      n
      HTNHLDAFiBDMPFOSmokingOC useMigraineMES on TCDThrombus on Carotid Web
      Multon et al., 2021115

      (45.5%)
      Median 42

      (IQR: 39-51)
      9 Black

      2 Other
      9.1%36.4%.0.0%.27.3%.18.2%..
      Mathew et al., 2021107

      (70.0%)
      Mean 55.7

      (Range 37–64)
      7 Black

      3 Other
      90.0%20.0%.20.0%.20.0%....
      Haynes et al., 202165

      (83.3%)
      Mean±SD

      55 ± 12.6
      4 Black

      2 Other
      16.7%16.7%...16.7%....
      Borghese et al., 202053

      (60.0%)
      Median 48.4 (range: 44-53)4 White

      1 Other
      60.0%....20.0%....
      Brinjikji et al., 201843

      (75.0%)
      Mean±SD

      44 ± 9.5
      ..........25.0%
      Choi et al., 201542

      (50.0%)
      Mean 52.3 (range 41-59)3 White

      1 Other
      ....25.0%-.25.0%-50.0%
      Olindo et al., 20212312 (52.2%)Mean±SD

      46.2±9.7
      23 Black8.7%4.4%.-13.0%....
      Haussen et al., 20172414 (58.3%)Median 47 (IQR, 41–61)17 Black37.0%16.0%0.0%16.0%.4.0%...21.0%
      Wojcik et al., 201832

      (66.7%)
      Mean 46.7 (range 44-51)..33.3%........
      Medical management studies (N=73)
      Study nameNSex (Female)

      n (%)
      Age (years)Race (Black)

      n
      HTNHLDAFiBDMPFOSmokingOC useMigraineMES on TCDThrombus on Carotid Web
      Olindo et al., 2021

      6940 (57.9%)Mean±SD

      51.1±9.9
      69 Black24.6%11.6%.4.4%.23.2%....
      Choi et al., 201533

      (100%)
      Mean 48.3 (range 44-52)1 White

      2 Other
      .....33.3%..33.3%.
      Wojcik et al., 20181047..100%........
      Interventional and medical management studies (N=119)
      Study nameNFemale

      n (%)
      Age (years)Race

      n
      HTNHLDAFiBDMPFOSmokingOC useMigraineMES on TCDThrombus on Carotid Web
      Joux et al., 20142516 (64.0%)Mean±SD 45.7±6.525 Black.....-...12.0%
      Semerano et al., 2021116

      (55.0%)
      Median 47

      (IQR: 38–50)
      10 Black

      1 Other
      0.0%..9.0%18.0%9.0%9.0%..18.0%
      Guglielmi et al., 20213022 (73.0%)Median* 57

      (IQR: 46-66)
      .33.0%17.0%20.0%7.0%.18.0%....
      Brinster et al., 20203222 (68.8%)Mean 4823 Black

      9 Other
      .........50.0%
      Turpinat et al., 20212111 (52.4%)Mean±SD 50.6±9.216 White

      5 Other
      38.1%9.5%.9.5%14.3%42.9%...28.6%
      Table 2Aggregate, cross-study baseline characteristics of interventional vs. medical management of carotid webs.
      Interventional Management

      (n = 90)
      Medical Management

      (n = 73)
      Mixed Interventional + Medical Management

      (n = 119)
      Age, mean (range)49.5 [44-55.7]50.9 [47.0-51.1]48.1 [45.7-50.6]
      Sex, female, n/N (%)53/90 (58.9%)43/73 (58.9%)77/119 (64.7%)
      Race
      Black, n/N (%)60/83 (72.3%)69/72 (95.8%)58/89 (65.2%)
      White, n/N (%)11/83 (13.3%)1/72 (1.4%)17/89 (19.1%)
      Asian, n/N (%)2/83 (2.4%)2/72 (2.8%)1/89 (1.1%)
      Others, n/N (%)10/83 (12.0%)0/0 (0.0%)13/89 (14.6%)
      HTN, n/N (%)25/79 (31.6%)17/69 (24.6%)18/62 (29.0%)
      HLD, n/N (%)13/77 (16.8%)9/70 (12.9%)7/51 (13.7%)
      AFIB, n/N (%)0/0 (0.0%)0/0 (0.0%)6/30 (20.0%)
      DM, n/N (%)6/45 (13.3%)3/69 (4.3%)5/62 (8.0%)
      Smoking, n/N (%)11/79 (13.9%)17/72 (23.6%)15/62 (24.2%)
      PFO, n/N (%)1/4 (25.0%)0/0 (0.0%)5/32 (15.6%)
      Migraine, PFO, n/N (%)3/15 (20.0%)0/0 (0.0%)0/0 (0.0%)
      OC use, n/N (%)0/0 (0.0%)0/0 (0.0%)1/11 (9.0%)
      MES on TCD, n/N (%)0/0 (0.0%)1/3 (33.3%)0/0 (0.0%)
      Thrombus on CaW, n/N (%)8/32 (25.0%)0/0 (0.0%)27/89 (30.3%)
      Overall, among all 282 patients, the weighted mean age was 49.5 (range 44–55.7) years, 61.7% were women, and 76.6% were Black. The overall pooled weighted prevalence of hypertension (HTN) was 28.6%, hyperlipidemia (HLD) 14.6%, diabetes mellitus (DM) 7.0%, and smoking 19.8%. Among the 7 studies reporting imaging findings among a total of 35 patients, the proportion of carotid webs detected with thrombus attached to CaW was 16.2%.
      Considering patients with known treatment approaches, there was no difference between interventional and medical patients in age, sex, race-ethnicity, history of hypertension or hyperlipidemia (Table 2). Differences not reaching statistical significance were noted for DM was 13.0% vs. 4.4% (p = 0.08), and history of smoking was 13.9% vs. 23.6% (p = 0.13) for the interventional and medical groups, respectively (Table 2).

      Interventionally treated group

      Across 15 studies, 42.4% (64/151) of patients underwent CEA and 57.6% (87/151) CAS in the intervention group. Across the 9 studies (83 patients) reporting median or mean time from index ischemic events to intervention, the interval median time was 14 days (IQR 9.5–44, range 7–225). (Table I in the online-only Data Supplement).
      Across the 15 studies (151 patients) reporting follow-up duration separately for interventionally treated patients, 4 studies (55) patients reported median duration of follow-up with overall interval median follow-up time was 25.9 months (IQR 9-40.9, range 6–42). Another 9 studies (89 patients) reported mean follow-up time with overall mean 18.4 months (range 5.5–60). There were zero recurrent events in the interventional group during the study follow-up periods (Table 3).
      Table 3Ischemic events in individual studies of interventional vs. medical management of carotid webs (n = 289).
      Study nameIntervention groupMedical group
      Patients

      n
      Ischemic events

      n
      Patients

      n
      Ischemic events

      n
      Follow-up (months)
      1Choi et al., 20154031Range 3-7
      2Joux et al., 201470186Mean 25.3
      3Olindo et al., 20212306919Intervention: Median 39.8

      Medical: Median 36
      4Semerano et al., 20216050Median 42
      5Guglielmi et al., 202120284Median 6
      6Brinster et al., 202025077Intervention: Average 19

      Medical: Average 28
      7Turpinat et al., 202114070Intervention: Mean 10.6

      Medical: Range 7-55
      8Wojcik et al., 20183010Intervention: Range 4-12

      Medical: Average 2
      9Haussen et al., 2018240--Intervention: Median 12
      10Multon et al., 2021110--Mean 12
      11Mathew et al., 2021100--Mean 5.5
      12Haynes et al., 202160--Mean 6.1
      13Borghese et al., 202050--Mean 18
      14Brinjikji et al., 201840--Mean 9
      15Pereira et al., 201770--Average 60
      Total151

      (CAS 87 (57.6%), CEA 64 (42.4%))
      013837Intervention: Range 3 - 60

      Medical: Range 2 - 55
      For patients undergoing CAS, procedural aspects varied across studies providing detailed data. Balloon angioplasty was used in all patients in 1 series of 14 patients,
      • Turpinat C.
      • Collemiche F.L.
      • Arquizan C.
      • et al.
      Prevalence of carotid web in a French cohort of cryptogenic stroke.
      used only when regression of web tissue after stent deployment was incomplete in 1 series of 7 patients,
      • Pereira B.J.A.
      • Batista U.C.
      • Tosello R.T.
      • Ströher I.N.
      • Baeta A.M.
      • Piske R.L.
      Web vessels: literature review and neurointerventional management.
      and not used in 2 series of 28 patients.
      • Brinjikji W.
      • Agid R.
      • Pereira V.M.
      Carotid stenting for treatment of symptomatic carotid webs: a single-center case series.
      ,
      • Haussen D.C.
      • Grossberg J.A.
      • Bouslama M.
      • et al.
      Carotid web (Intimal Fibromuscular Dysplasia) has high stroke recurrence risk and is amenable to stenting.
      Among 5 studies reporting use of embolic protection devices (EPDs), EPDs were used in 87% (41/47) of patients.
      • Brinjikji W.
      • Agid R.
      • Pereira V.M.
      Carotid stenting for treatment of symptomatic carotid webs: a single-center case series.
      ,
      • Haussen D.C.
      • Grossberg J.A.
      • Koch S.
      • et al.
      Multicenter experience with stenting for symptomatic carotid web.
      ,
      • Pereira B.J.A.
      • Batista U.C.
      • Tosello R.T.
      • Ströher I.N.
      • Baeta A.M.
      • Piske R.L.
      Web vessels: literature review and neurointerventional management.
      • Multon S.
      • Denier C.
      • Charbonneau P.
      • et al.
      Carotid webs management in symptomatic patients.
      • Mathew S.
      • Davidson D.D.
      • Tejada J.
      • Martinez M.
      • Kovoor J.
      Safety and feasibility of carotid revascularization in patients with cerebral embolic strokes associated with carotid webs and histopathology revisited.
      A majority of CAS series described discharging patients on a dual AP regimen for 1 to 6 months.
      • Haussen D.C.
      • Grossberg J.A.
      • Koch S.
      • et al.
      Multicenter experience with stenting for symptomatic carotid web.
      ,
      • Pereira B.J.A.
      • Batista U.C.
      • Tosello R.T.
      • Ströher I.N.
      • Baeta A.M.
      • Piske R.L.
      Web vessels: literature review and neurointerventional management.
      ,
      • Mathew S.
      • Davidson D.D.
      • Tejada J.
      • Martinez M.
      • Kovoor J.
      Safety and feasibility of carotid revascularization in patients with cerebral embolic strokes associated with carotid webs and histopathology revisited.
      ,
      • Wojcik K.
      • Milburn J.
      • Vidal G.
      • Steven A.
      Carotid webs: radiographic appearance and significance.
      (Table I in the online-only Data Supplement)
      For patients undergoing CEA, surgical procedures also varied across studies supplying information. Among 26 patients across 5 studies
      • Borghese O.
      • Pisani A.
      • Di Centa I.
      Surgical treatment of carotid webs in symptomatic young adults.
      ,
      • Multon S.
      • Denier C.
      • Charbonneau P.
      • et al.
      Carotid webs management in symptomatic patients.
      • Mathew S.
      • Davidson D.D.
      • Tejada J.
      • Martinez M.
      • Kovoor J.
      Safety and feasibility of carotid revascularization in patients with cerebral embolic strokes associated with carotid webs and histopathology revisited.
      • Wojcik K.
      • Milburn J.
      • Vidal G.
      • Steven A.
      Carotid webs: radiographic appearance and significance.
      • Haynes J.
      • Raz E.
      • Tanweer O.
      • et al.
      Endarterectomy for symptomatic internal carotid artery web.
      reporting surgical approaches, resection followed by end-to-end anastomosis was used in 54%, resection with primary arteriotomy closure in 23%, and patch angioplasty in 23%. (Table I in the online-only Data Supplement)
      Out of 15 intervention case series, none reported any significant intra- or post-procedural mortality, ischemic and/or hemorrhagic strokes, or substantial in-stent thrombosis or restenosis on a short to mid-term follow-up. Among CAS patients, one patient had asymptomatic 10% proximal stenosis of a stent on follow-up images
      • Wojcik K.
      • Milburn J.
      • Vidal G.
      • Steven A.
      Carotid webs: radiographic appearance and significance.
      and one case of external iliac artery rupture requiring implantation of a covered stent without residual stenosis on follow-up.
      • Multon S.
      • Denier C.
      • Charbonneau P.
      • et al.
      Carotid webs management in symptomatic patients.
      (Table I in the online-only Data Supplement)

      Medically treated group

      Across the 8 series reporting 138 medically-treated patients, the medication regimen was antiplatelet agents (AP) in 80.4% (111), anticoagulants (AC) in 11.6% (16), no antithrombotic in 6.5% (9), and 1.5% (2) were on AP and AC.
      Across the 3 studies (102 patients) reporting follow-up time separately for medically treated patients, the interval was median 36 months (range 6–42).
      The overall rate of recurrent ischemic stroke or transient ischemic attack was 26.8% (37/138) (Table 3). Rates of recurrent cerebral ischemia did not statistically differ between AP vs. AC patients, 28.8% (32/111) vs. 18.8% (3/16); p = 0.39. Also, rates of recurrent ischemic did not statistically differ between patients receiving any antithrombotic (AP or AC) vs. no antithrombotic, 27.9% (36/129) vs. 11.1% (1/9); p = 0.27. (Table II in the online-only Data Supplement)
      The difference in rate of recurrent ischemic stroke and TIA between interventionally-treated vs medically-treated patients was highly statistically significant, 0% (0/151) vs 26.8% (37/138), p < 0.0001.

      Discussion

      In this systematic review of 289 patients with symptomatic carotid webs across 15 series, half were treated with carotid revascularization procedures and half with medical therapy. In both groups, patients typically presented in late midlife, were more often female, and were more often Black. Among the 151 patients treated with intervention, carotid procedures showed a favorable efficacy and safety profile, with no recurrent stroke events and only 1 major procedural complication without enduring adverse effects. In contrast, among the 138 patients treated with medical therapy, about almost 3 of every 10 experienced a recurrent ischemic cerebral event.
      The findings from this study accord with, and importantly extend, prior investigations. Compared with the previously meta-analysis and Zhang and colleagues, this current study aggregates baseline data for more than twice the numbers of symptomatic CaW patients (282 vs 135) and follow-up data for more three times the number of CaW patients (282 vs 87). At baseline, most atherosclerotic risk factors were found present at similar frequencies, but rates of hypertension were higher in this updated meta-analysis. The current meta-analysis uniquely characterized the frequency of thrombus on carotid webs, documenting a high-rate present in one-sixth of patients. The current study also uniquely compared baseline characteristics in among the treatment groups, finding interventional patients had nominally higher rates of hypertension, hyperlipidemia, and diabetes, often had thrombi on CaW, and had a lower rate of smoking. These findings suggest that confounding by indication was not a major factor in the differences in recurrent stroke rates.
      With respect to interventions, the current study provides data on technical procedural aspects not previously aggregated. With regard to follow-up, among interventionally treated patients, the current meta-analysis aggregates not only more patients (151 vs 42) but also longer follow-up periods 1.5-2-fold longer. The current study accordingly provides substantially more support for the findings of high rates of recurrent stroke in medically treated patients and no reported recurrent strokes in interventionally treated patients.
      The characteristics of patients in this updated meta-analysis accord with prior studies with regard to presenting and diagnostic characteristics, including a higher proportion of women, a higher proportion of Black patients, and a lower prevalence of traditional vascular risk factors.
      • Mac Grory B.
      • Emmer B.J.
      • Roosendaal S.D.
      • Zagzag D.
      • Yaghi S.
      • Nossek E.
      Carotid web: an occult mechanism of embolic stroke.
      ,
      • Zhang A.J.
      • Dhruv P.
      • Choi P.
      • et al.
      A systematic literature review of patients with carotid web and acute ischemic stroke.
      The demographic profile of patients with carotid webs has commonalities and differences compared with patients with classic fibromuscular dysplasia, of which CaWs may be an intimal variant. There is a female predominance in both conditions, consistent with the higher prevalence of collagen vascular disorders generally in women, potentially related to X-chromosome carried genes or hormonal effects.
      • Angum F.
      • Khan T.
      • Kaler J.
      • Siddiqui L.
      • Hussain A.
      The prevalence of autoimmune disorders in women: a narrative review.
      However, while patients of the white race have predominated in a series of classic FMD,
      • Rana M.N.
      • Al-Kindi S.G.
      Prevalence and manifestations of diagnosed fibromuscular dysplasia by sex and race: Analysis of >4500 FMD cases in the United States.
      patients of the black race predominate in a series of CaWs. The reason for this disparity has not yet to our knowledge been well described.
      Study findings regarding therapeutic strategies should be considered taking into account the current understanding of the pathophysiology of ischemic stroke in patients with CaWs. CaW is a focal shelf-like lesion from fibrotic dysplasia/hyperplasia and protrudes into the main vessel lumen rather than involving a long vertical segment of the vessel wall seen in atheromatous plaques. In addition, CaWs usually cause lumen narrowing of under 50%, in contrast to atheromatous plaques which cannot infrequently produce severe stenoses or occlusions.
      • Zhang A.J.
      • Dhruv P.
      • Choi P.
      • et al.
      A systematic literature review of patients with carotid web and acute ischemic stroke.
      As a result, CaWs usually do not produce hemodynamic impairment. Instead, it is postulated that the presence of the CaW causes alterations in laminar flow and the creation of recirculation zones below and above the projecting stenosis. Thrombi may then arise either from platelet activation due to fast-moving but dyslaminar flow streams or from coagulation cascade activation by blood stasis in slow-moving eddy regions. The thrombi then produce artery-to-artery embolism to recipient brain arteries or local severe stenosis or occlusion at the site of the CaW. Several of the series here analyzed reported cases of visualized thrombus upon CaWs, sometimes reaching one-quarter of the series.
      For medical therapy, this pathophysiology provides support for either antiplatelet therapy for platelet over-activation or anticoagulant therapy to avert stasis clotting. For interventional procedures, this pathophysiology indicates that anatomic removal (via endarterectomy) or reduction (via angioplasty/stenting) of the carotid web will ameliorate the thrombotic propensity. It also suggests that procedural complications may be less with CaWs than with atherosclerotic plaques as the lesion to be addressed is less extensive in length and often less severe in a degree of lumen compromise.
      The aggregate data across the series in the current analysis provide evidence for the efficacy and safety of a strategy of carotid revascularization to prevent recurrent ischemic stroke in patients with CaWs and suggest that a strategy of medical therapy may be less advantageous. No recurrent strokes were reported among interventionally treated patients, while 26.8% of medically treated patients had recurrent cerebral ischemia. The event rate in the medical group over the follow-up range of 2–55 months is notably high. It contrasts with a recurrent stroke rate in patients with symptomatic moderate (50–69%) atherosclerotic carotid disease under medical therapy of 22.2% over 60 months.
      • Barnett H.J.M.
      • Taylor D.W.
      • Eliasziw M.
      • et al.
      Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis.
      The peri-procedural safety of CaW in this study compared favorably with the 6.8–7.2% rate of complications of carotid endarterectomy and carotid stenting for symptomatic atherosclerotic carotid disease.
      • Brott T.G.
      • Hobson R.W.
      • Howard G.
      • et al.
      Stenting versus endarterectomy for treatment of carotid-artery stenosis.
      The low rate of procedural complication reflects the younger patient's age, absence of extended and irregularly surfaced atheromatous plaques, absence of intraplaque hemorrhage, and non-inflammatory nature of CaW. For carotid stenting, the procedure is technically less complex than for atherosclerotic stenosis as a substantial luminal opening is typically preserved, and pre-and post-stent angioplasty is not needed as there is no flow-limiting stenosis.
      • Haussen D.C.
      • Grossberg J.A.
      • Koch S.
      • et al.
      Multicenter experience with stenting for symptomatic carotid web.
      Caution must be exercised regarding drawing conclusions about the relative efficacy of surgical versus medical management for symptomatic CaWs from the current study. Even after aggregation of patients across series, the treatment groups had a modest sample size. While interventional and medical patients did not differ greatly in reported baseline characteristics, they may have differed in unreported ways with selecting healthier patients for intervention. In addition, it is possible that some patients who planned for interventional therapy had a stroke before treatment and were included in medically treated groups, introducing ascertainment bias. Non-publication of interventional series with unfavorable outcomes may have caused publication bias.
      In the current study, both CEA and CAS appeared safe and effective in reducing the future risk of recurrent strokes. This finding suggests that intervention modality selection should be based on a multidisciplinary team approach from vascular neurologists, neuroendovascular interventionalists, and performers of open surgery, taking into account each individual patient's comorbidities, carotid angioarchitecture, and presence of intraluminal thrombus attached to the CaW. CEA may be preferable over CAS for patients with extremely challenging tortuous vascular anatomy, the origin of web tissue involving the ostium of external carotid artery, or a history of coagulopathy where dual antiplatelet therapy for stent protection may not be feasible. CAS may be advantageous in patients with higher carotid bifurcations making surgical access to the CaW challenging, a prior history of neck surgery or radiotherapy, or multiple comorbidities likely to be high-risk surgical candidates.
      This study has limitations. First, the systematic review is identified evidence only from non-randomized, observational data, making a patient selection and publication biases probable. Second, procedure-related complications were self-reported and not adjudicated by independent neurologic examiners. Third, no consistent information is available about the number of recurrent strokes with/without medical therapy before pursuing revascularization over medical management. Fourth, information was not reported or only intermittently reported on whether the morphology of CaW differed in interventional compared with medical patients, including a degree of stenosis, evidence of contrast stasis on conventional angiography, and presence of supervening thrombus, and severity of index stroke. Fourth, baseline characteristics were inconsistently reported across the 14 studies, leading to reduced data regarding some traditional stroke risk factors. Fifth, case studies were excluded because they often focus upon unusual presentations and events. Including them would bias the analysis away from delineating patient typical course and outcomes.

      Conclusion

      This series suggests that for symptomatic CaW disease, carotid revascularization with either stenting or endarterectomy may be a safe and effective option in addition to standard medical therapy. Establishing long-term data registries for patients with CaW disease might be helpful to further improve the quality of evidence.

      Sources of funding

      This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors received no financial support for this article's research, authorship, and/or publication.

      Disclosures

      None.

      CRediT authorship contribution statement

      Smit D. Patel: Conceptualization, Funding acquisition, Formal analysis, Writing – original draft, Writing – review & editing, Project administration, Resources, Software. Fadar Oliver Otite: Funding acquisition, Formal analysis, Writing – review & editing, Project administration, Resources, Software. Karan Topiwala: Funding acquisition, Formal analysis, Writing – review & editing, Project administration, Resources, Software. Hamidreza Saber: Funding acquisition, Formal analysis, Writing – review & editing, Project administration, Resources, Software. Naoki Kaneko: Funding acquisition, Formal analysis, Writing – review & editing, Project administration, Resources, Software. Eric Sussman: Funding acquisition, Formal analysis, Writing – review & editing, Project administration, Resources, Software. Tapan V. Mehta: Funding acquisition, Formal analysis, Writing – review & editing, Project administration, Resources, Software. Ramachandra Tummala: Funding acquisition, Formal analysis, Writing – review & editing, Project administration, Resources, Software. Jason Hinman: Funding acquisition, Formal analysis, Writing – review & editing, Project administration, Resources, Software. Raul Nogueira: Funding acquisition, Formal analysis, Writing – review & editing, Project administration, Resources, Software. Diogo C. Haussen: Funding acquisition, Formal analysis, Writing – review & editing, Project administration, Resources, Software. David S. Liebeskind: Conceptualization, Funding acquisition, Formal analysis, Writing – review & editing, Supervision, Project administration, Resources, Software. Jeffrey L. Saver: Conceptualization, Funding acquisition, Formal analysis, Writing – original draft, Writing – review & editing, Supervision, Project administration, Resources, Software.

      Acknowledgments

      None.

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