Abstract
Background: Although carotid artery web (CaW) was initially described in 1973 as a potential etiology of ischemic stroke, it still remains underrecognized. Because CaW is a membrane affixed perpendicularly from the carotid wall that projects out into the lumen above the bifurcation, it typically is not stenotic, and hence, utilizing only 1 vessel imaging modality during conventional stroke workup may instead lead to a diagnosis of ESUS: embolic stroke of undetermined source. The term ESUS was created in 2014 by researchers to define a subset of cryptogenic, nonlacunar (embolic-appearing) strokes without clear cardiac or vascular cause. Purpose: In this review, we describe how, after multiple evaluations of vessels, CaW was diagnosed in relatively young patients (age 39-47 years old, without significant vascular risk factors) in whom otherwise were considered embolic stroke of undetermined source. This observation dovetails with the accompanying Neurohospitalist article entitled, “Delayed Thrombus Formation on Carotid Web and Its Medical and Endovascular Management for Secondary Stroke Prevention.” Research Design: Not applicable. Case review. Results/Conclusion: This report demonstrates the futility of antiplatelet therapy for a young patient with CaW-related stroke. Based on these collective experiences and review of the literature, we postulate that: (1) multiple vascular imaging modalities during stroke workup may result in a CaW diagnosis instead of ESUS; (2) young stroke patients without traditional vascular risk factors are candidates for this “web browsing” of extended imaging of vessels; and (3) carotid artery stenting (CAS) or carotid endarterectomy (CEA) may be preferred as first-line over medical therapy alone (ie, antiplatelet or anticoagulation) because CEA/CAS addresses the stroke etiology, CaW, definitively.
Keywords: internal carotid artery, carotid web, ischemic stroke, endovascular intervention, endarterectomy
Introduction
An internal carotid artery web (CaW) is an underestimated cause of ischemic stroke. 1 Initially described in 1973 as a “web formation,” CaW has subsequently been reported as a web-like septum, diaphragm, spur, pseudovalvular fold, or atypical fibromuscular dysplasia (FMD). 2 This shelf-like protrusion juts out perpendicularly from the arterial wall into the lumen from the posterior proximal internal carotid artery (ICA) bulb.1,3,4 On vascular imaging, CaW characteristically has a non-stenotic appearance, and hence on imaging reports may be considered “within normal limits” or “nonspecific vasculopathy” or “mild atherosclerosis” or dissection.1-4 Embryonically, CaW is developmental in origin, non-atherosclerotic, non-inflammatory, and without tissue regression, essentially “an intimal variant of FMD”1,2,3,5
At a minimum, the workup for an embolic-appearing, non-lacunar ischemic stroke includes vessel studies, blood work, and cardiac tests, however if these are reported as “unremarkable,” then the discharge diagnosis may point towards “cryptogenic stroke” or “embolic stroke of undetermined source” (ESUS). However, in a certain subset of ESUS patients, CaW – a treatable condition – may be overlooked. 6 This “anchoring bias” whereby clinicians fixate upon ESUS instead of diving deeper for alternate etiologies such as CaW may explain why CaW is underestimated. Such a diagnostic omission parallels arrhythmia undermonitoring for occult atrial fibrillation in elderly ESUS patients. 7 However, CaW is at the other end of the age spectrum: more common in young, African American women and Afro-Caribbean populations1,8 without significant vascular risk factors. 5
Carotid artery web can present as non-calcified atherosclerosis without hemodynamically significant stenosis. 6 Hence, solely 1 image modality of the carotids may be insufficient in young ESUS patients with features of “non-calcified” or “non-significant” vascular abnormalities ipsilateral to their stroke. Once identified, CaW may benefit from surgical carotid endarterectomy (CEA) or carotid artery stenting (CAS) over medical treatment alone with antiplatelets or anticoagulants. We therefore read with interest the accompanying Neurohospitalist article entitled, “Delayed Thrombus Formation on Carotid Web and Its Medical and Endovascular Management for Secondary Stroke Prevention” which showed the futility of antiplatelet therapy for a young patient with CaW and stroke. Similarly, at our institution, a few recent ESUS patients received CEA or CAS with excellent outcomes after their etiology was identified by repeated/follow-up vessel imaging confirming CaW instead of a “mild carotid irregularity.”
Based on these cumulative experiences, including this report in Neurohospitalist and other literature, we postulate that: (1) multiple vascular imaging modalities during stroke workup may result in a CaW diagnosis instead of ESUS; (2) young stroke patients without traditional vascular risk factors are candidates for this “web browsing” of extended imaging of vessels; and (3) neuroendovascular intervention with CAS or neurosurgical treatment with CEA, may be preferred as first-line over medical therapy alone (ie, antiplatelet or anticoagulation) because CEA/CAS addresses the stroke etiology, CaW, definitively.
Case 1
A 47-year-old, right-handed African American man without significant past medical history presented with right arm and face weakness, mild expressive aphasia, and right-left confusion. Magnetic Resonance Imaging (MRI) brain revealed a non-lacunar ischemic stroke in the left lentiform nucleus. Computed tomographic angiography (CTA) revealed a shelf-like abnormality, reported as “a possible dissection” above the bifurcation of the left ICA (Figure 1). Neck Magnetic Resonance Angiography (MRA) and Digital Subtraction Angiography (DSA) confirmed this to be a CaW (Figure 2). Electrocardiogram (EKG)/telemetry monitoring, transthoracic and trans-esophageal echocardiograms, and hypercoagulable studies were all unremarkable. The patient received CAS without complication and was discharged home on dual antiplatelets (aspirin and clopidogrel daily) and atorvastatin. At follow up clinic visit, carotid ultrasound was stable, he reported no new symptoms, and antiplatelet regimen was reduced to aspirin monotherapy.
Figure 1.
CT angiography with axial (A) and sagittal views (B) of each CaW. In Case 1, a shelf-like abnormality is seen in the left internal carotid artery (ICA) bifurcation (1A;1B). In Case 2, a similar abnormality is seen in the right ICA (2A;2B). In Case 3, there is posterior wall outpouching at the left ICA bifurcation (3A;3B).
Figure 2.
Digital Subtraction Angiography (DSA) anteroposterior and lateral views. In Case 1, contrast stagnation/embolic material is seen between a web fold and the posterior wall of left ICA pre-stent (A, B), which improved post-stent (C, D). In Case 2, the right ICA web (E, F) was treated with CEA. In Case 3, the left ICA posterior wall outpouching is seen pre-stent (G, H) and also improved post-stent (J, K).
Case 2
A 48 year-old, right-handed African American woman with medical history significant for mild hypertension and diet-controlled hyperlipidemia presented with acute-onset right gaze deviation, left sided dense hemiplegia, sensory loss and neglect. She received alteplase and underwent thrombectomy for a right middle cerebral artery (MCA) occlusion, with improvement in symptoms. MRI revealed acute infarction in the right MCA territory involving the basal ganglia and sylvian cortex. Computed tomographic angiography and DSA revealed a right CaW (Figures 1 and 2). 3 days post-stroke, patient underwent CEA without complication. She was started on aspirin and atorvastatin daily. At 4 months follow up, patient reported no new or residual deficits.
Case 3
A 39-year-old, right-handed, African American woman without significant past medical history noticed painless vision loss in the right eye and left hemiparesis for 30 minutes. Neuroimaging was unremarkable and CTA revealed a small right ICA dissection vs CaW. She received dual antiplatelet therapy for 14 days and then clopidogrel monotherapy. She remained asymptomatic for 6 months but then presented to our emergency department with intermittent left hemiparesis and right amaurosis fugax. Another MRI also did not reveal an ischemic stroke, so she was diagnosed with a transient ischemic attack (TIA), which based on symptomatology, may have been an embolic clot that lysed. Repeat CTA followed by DSA demonstrated a posterior wall outpouching into the lumen at the level of the carotid bifurcation consistent with CaW (Figures 1 and 2). Therefore, she received CAS and dual antiplatelet therapy was restarted. Workup was otherwise unremarkable aside from a contralateral (asymptomatic) CaW, which was managed medically. The dual antiplatelet regimen was transitioned to aspirin monotherapy at her 3-month follow-up clinic visit, and she reported no new or recurrent neurological deficits.
Discussion
As reports such as ours and our colleagues in Neurohospitalist emerge describing CaW-related stroke outcomes benefiting from multiple vessel imaging modalities and treatment with CAS or CEA instead of medication alone, providers may become more inclined to pursue carotid “web-browsing” in young ESUS patients. Given that women are more likely to have CaW than men, are typically younger with a mean age range of 38-50 years, and lack significant vascular risk factors,1,3 CaW browsing should be considered early, with high-speed in this ESUS subgroup, and utilizing >1 modality to examine vessels before ruling it out. The rationale behind this approach is that CaW is not uncommon, just underdiagnosed: 1 study suggests that as many as 1 in 13 patients with cryptogenic ischemic stroke may actually have CaW as the occult etiology 3 . Moreover, diagnosing CaW will change management: when CaW is identified as the etiology, optimal treatment may be CEA or CAS – unlike antiplatelet or anticoagulant alone, which has been associated with recurrent cerebrovascular events 2 .
Diagnosing CaW
Upon close inspection of CTA and/or MRA, a CaW may appear as an intraluminal filling defect that protrudes into the lumen. Morphologically, a CaW is typically small with a thickness of only 1-2 mm.9,10,11 Histological evaluation may reveal intimal fibro-elastic thickening, fibromuscular proliferation with fibrosis and/or myxoid degeneration without significant atheromatous changes or cholesterol-rich core.3,12 Radiographically, CaW is differentiated from atherosclerotic plaques and dissection by their location and characteristic diaphragmatic appearance. 12 Clinically, risk factors are different as well, atherosclerosis tends to stem from uncontrolled hypertension, diabetes, hyperlipidemia and/or tobacco abuse.
Any combination of imaging modalities – CTA, MRA, DSA, or even carotid ultrasound (CUS) – can together confirm or exclude CaW; 1 modality alone may be insufficient. The real-time visualization during DSA may identify thrombus and stasis of blood flow in the CaW pocket. 1 CTA has a high correlation when compared to DSA in diagnosing CaW. 1 Benefits of MRA, if obtained with gadolinium, include its ability to provide morphology, wall composition, biomechanics and flow dynamics. 10 Lastly, a CaW in a CUS may reveal a wedge-shaped band protruding into the arterial lumen, but is less accurate than CTA or DSA and so may require a highly experienced sonographer to confirm CaW.1,13
General unawareness of CaW, coupled with the overwhelming prevalence of large-vessel intra- and extra-cranial atherosclerosis in western society, make CaW a diagnostic challenge. Employing only 1 vessel imaging modality may not differentiate CaW from atherosclerotic plaque or dissection. 3 Pattern recognition of the shelf-like protrusion emanating from the posterior wall of the ICA bulb should prompt further evaluation with additional modalities to increase diagnostic yield.
Typically, the degree of stenosis seen in CaW is minimal (under 50%) or nonexistent; some experts feel NASCET does not even apply to CaW lesions.5,6,9 In a series of patients with symptomatic CaW, the average degree of stenosis per NASCET criteria was 0% (range 0-11). 2 Nevertheless, larger-sized CaW lesions do exist and could increase likelihood of stroke. 6 Asymptomatic CaW usually have a more benign course. 6 The absence of an obvious luminal stenosis is likely the main reason CaW remains underappreciated and perhaps has resulted in a global overdiagnosis of ESUS and/or cryptogenic strokes and an underdiagnosis of CaW.
Clinical Presentation of CaW
Similar to carotid atherosclerosis, CaW can lead to stroke by artery-to-artery emboli (clot sitting on the CaW shelf dislodges and moves to the brain), or in the setting of a partially stenotic CaW vessel, via hemodynamic forces. To-date, literature on CaW includes case series, case reports and small studies, which have included brain images of “cryptogenic” non-lacunar lesions (Table 1).6,12,14,15 Most strokes were hemispheric, occurring in the ipsilateral middle cerebral artery distribution. Patients predominantly had unilateral CaW in a single carotid artery, but a sizeable minority (17%) were bilateral. Based on these reports, and including our observations, we postulate that younger patients with non-lacunar ischemic strokes already categorized as ESUS (or cryptogenic TIA) may actually instead have CaW as their etiology. Moreover, the criteria for ESUS, established in 2014, and subsequently in the literature requested for revision or disposal, can simply be modified to exclude CaW prior to diagnosis. 16 This could benefit clinical practice as well as future research on ESUS, with the mnemonic HEAD: Head imaging confirming non-lacunar stroke, Echocardiogram and EKG/Extended cardiac monitoring excluding cardioembolic source, Arterial studies excluding ipsilateral vessel pathology such as stenosis, vasculitis, or CaW, and Differential diagnosis for hypercoaguable state and rare causes.
Table 1.
Location of Strokes, Thrombi, and CaW.
| No. | Stroke location | Thrombus location | CaW location | |
|---|---|---|---|---|
| Mc Grory B, et al 17 | 1 | Right frontal lobe | M2 | Right |
| Compagne KCG, et al 18 | 1 | Right hemisphere | M1 | Right |
| 2 | Right hemisphere | M1 | Right | |
| 3 | Right hemisphere | M1 | Right | |
| 4 | Left hemisphere | ICA | Left | |
| 5 | Right hemisphere | ICA | Right | |
| 6 | Right hemisphere | M2 | Right | |
| 7 | Right hemisphere | ICA | Right | |
| 8 | Left hemisphere | ICA | Left | |
| 9 | Right hemisphere | M1 | Right | |
| 10 | Right hemisphere | M1 | Right | |
| 11 | Right hemisphere | M1 | Right | |
| Wojcik K, et al 11 | 1 | Right MCA territory | M2 | Right |
| 2 | Right lentiform nucleus | ICA | Right | |
| 3 | Left insula and posterior temporal lobe | N/A | Left | |
| 4 | TIA | N/A | Left | |
| 5 | Left insular cortex | MCA | Bilateral | |
| Sajedi. P, et al 12 | 1 | Right MCA territory | M1 | Bilateral |
| 2 | Right MCA territory | M1 | Right | |
| 3 | Right basal ganglia and temporal lobe | M1-M2 | Right | |
| 4 | Left MCA territory | M1-M2 | Bilateral | |
| 5 | Left MCA territory | left M1 | Bilateral | |
| 6 | Left basal ganglia and insular cortex | left M2 | Left | |
| 7 | Left basal ganglia and insular cortex | left M2 | Left |
Abbreviation: MCA, of Middle Cerebral Artery; M1, Sphenoidal or Horizontal Segment of Middle Cerebral Artery; M2, Insular Segment of Middle Cerebral Artery; ICA, Internal Carotid Artery.
Without a through, multi-modality evaluation of vessels, our cases (and countless others) may have received inaccurate diagnoses of ESUS or cryptogenic TIA. Conceivably, these young ESUS patients may have consequently received insufficient treatment (medical therapy alone instead of CEA or CAS) that may have resulted in further strokes and avoidable disability.
Management of CaW
In terms of treatment choice, there are no clear guidelines for optimal management of CaW. Suggested therapies include antiplatelets, anticoagulation, CAS and CEA. Treating only with antiplatelet therapy without CEA or CAS may pose an increased risk for recurrence of ischemic stroke secondary to a CaW: a series of Afro-Caribbean women found a 30% recurrence rate without CAS or CEA. 8 The rationale for anticoagulation is because of the CaW-associated thrombogenic milieu generated by the flow stagnation and superimposed thrombosis; while anticoagulation may resolve thrombus upon the CaW shelf itself, it is not an optimal long-term solution. 11 Anticoagulation poses short-term risks of hemorrhagic transformation of the infarct, and long-term cumulative risks of bleeding both within and outside the cranial vault.
In a series of 24 CaW patients who received CAS and dual antiplatelet therapy, the only peri-procedural events were 2 cases of asymptomatic hypotension and bradycardia. 2 Clinical follow-up after stent placement recorded no new cerebrovascular events, with functional independence of 91% at 90 days. As demonstrated in this case series and in our patients, CAS or CEA may be superior to medical treatment alone, as it provides a definitive remedy and does not require lifelong medication.2,14,15 Although there has not been (and may never be) a randomized controlled trial for CaW therapies, the literature favors CEA or CAS given their excellent outcomes, which are not uniformly seen with medical therapy alone.2,3,14,15
Conclusion
Likely underrecognized and overlooked, CaW is a plausible etiology for ESUS and cryptogenic TIA, and should be considered in young patients without significant vascular risk factors. Stroke Neurologists, Neurohospitalists and any clinicians who care for stroke patients may be susceptible to “anchoring bias” 9 and forgo further evaluation or closer review to look for CaW. This may lead to a “premature closure” of the case 9 after the “standard evaluation” is unrevealing – a scenario that occurs in about a third of all stroke patients who are labeled “cryptogenic” or ESUS. Obtaining multiple vessel studies such as MRA, CTA, CUS and/or DSA may identify more CaW in patients with ESUS. This approach may reduce heterogeneity in ESUS clinical trials, and avoid diagnostic uncertainty in these vulnerable patients for which CAS or CEA is effective. Due to the possibility of publication bias and/or reporting bias, our opinions and this review should be interpreted with care.
Footnotes
Authors’ Note: The patients provided informed consent for publication of this report.
Declaration of Conflicting Interests: DZR has received research support from BMS/Pfizer and honoraria from Boston Scientific, FirstKind, Ltd., Medtronic, CSL-Behring, Boehringer-Ingelheim, and Chiesi. SR has received honoraria from FirstKind, Ltd. Other authors report no disclosures.
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
ORCID iDs
Swetha Renati https://orcid.org/0000-0001-6479-3634
David Z. Rose https://orcid.org/0000-0002-9449-6494
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