Outcome of acute ischemic stroke with absent opacification of the cervical internal carotid artery at CT-angiography after endovascular treatment

Abstract

Purpose: Occlusion of the distal internal carotid artery can simulate a proximal occlusion of its cervical tract on CT angiography in patients with acute ischemic stroke, that is, pseudo-occlusion. As true and false carotid occlusions can present similarly on non-invasive imaging in patients undergoing endovascular treatment for stroke, our study aimed to evaluate clinical and technical differences of these conditions and the possible consequences of a misdiagnosis. Methods: We retrospectively reviewed consecutive patients who underwent mechanical thrombectomy for acute ischemic stroke at a single center between July 2015 and May 2022 and included patients with absent opacification of the cervical carotid artery on CT-angiography. Digital subtraction angiography (DSA) imaging and procedural data were evaluated to define the actual localization of the occlusion. We compared imaging and clinical data between patients with true and false carotid occlusion, including collateral circulation at CTA, revascularization grade, and clinical outcome at 3 months. Results: A total of 116 patients were included, 63 (54%) of whom had true occlusion of cervical internal carotid artery. Compared to the pseudo-occlusion group, collateral circulation at CTA was moderate to good in 75% of cases (vs 32%; p < 0.0001) and the mean ASPECT score at 24 h was 7 versus 2 (p < 0.0001). Modified Rankin scale 0–2 at 90 days was more frequent in patients with true occlusion than those with pseudo-occlusion (48 vs 11%; p = 0.0002). Conclusion: Pseudo-occlusion of the cervical internal carotid artery in patients with acute ischemic stroke appears to be associated with worst prognosis and poorer collateral circulation in comparison with tandem occlusion.

Introduction

Non-invasive neuroimaging modalities can lead to diagnostic misinterpretations in the acute occlusion of internal carotid artery (ICA) in patients presenting with acute ischemic stroke.^1,2 Distal ICA occlusion can simulate a more proximal occlusion at the cervical level, a condition known as pseudo-occlusion. ³ CT angiography is the most accessible method for identifying intracranial large arteries occlusion and evaluating collateral circulation in these patients.^4,5

Endovascular mechanical thrombectomy (MT), with or without systemic thrombolysis, has been shown in several randomized controlled trials to reduce morbidity and mortality in patients with acute ischemic stroke caused by intracranial large-vessel occlusion, compared with systemic thrombolysis alone. ⁶ Current indications for mechanical thrombectomy include occlusion of large intracranial vessels, such as the ICA, M1, and proximal M2 segments, as well as tandem occlusions, that is, the association of extracranial ICA occlusion with downstream intracranial large vessel occlusion.^7,8 These two conditions may present with at least partially overlapping features on non-invasive vascular imaging, such as absent opacification of the cervical ICA. Despite their similar clinical and imaging presentations, these conditions arise from completely different etiologies: proximal true occlusions of the ICA are mostly atheromatous or dissective, while distal occlusions are more frequently embolic. ⁹ Acute ICA occlusion is associated with poor clinical outcomes. ¹⁰ Nevertheless, patients with acute ICA occlusion can present ranging from asymptomatic to affected by acute severe stroke symptoms, depending on occlusion pattern, hemodynamic impairment, and collateral circulation. ¹¹ Our study aimed to compare these conditions in terms of technical and clinical outcomes in patients who are candidates for mechanical thrombectomy.

Methods

Study design

We retrospectively reviewed consecutive patients who underwent mechanical thrombectomy for acute ischemic stroke between July 2015 and May 2022 at a single third-level stroke center (Figure 1).

Figure 1.

Standard for reporting diagnostic accuracy studies (STARD) flow diagram for patients’ selection. CTA = CT angiography; ICA = internal carotid artery.

Selection criteria

We included all consecutive patients with absent opacification of cervical ICA on CT-angiography, except a short proximal segment of 2 cm. Digital subtraction angiography (DSA) imaging and procedural data were used as the gold standard to define the actual localization of the occlusion and hence the mechanism for absent ICA opacification. Pseudo-occlusion was defined as non-opacification at CTA simulating a proximal occlusion but with patency confirmed on a prolonged DSA run or at catheter exploration with actual distal occlusion, as suggested by Grossberg JA et al. ³ Patients with partial opacification of the cervical ICA at CTA or with a contrast gradient along the vessel were excluded, as the diagnosis of false occlusion is obvious. We collected demographic, clinical, and imaging data, including age, sex, baseline Nation Institute of Health Stroke Scale (NIHSS) score, intravenous administration of recombinant tissue plasminogen activator (rtPA), Alberta Stroke Program Early CT (ASPECT) score at presentation and after 24 hours, modified Thrombolysis in Cerebral Infarction (mTICI) score, any intraparenchymal hemorrhage at 24 hours CT, and modified Rankin Score (mRS) after 3 months.

Technique and protocols

All CT imaging was obtained on a 2 × 64 detector rows Dual Source scanner. Non-contrast CT was acquired using the axial technique with 120 kVp, 100–350 auto-mAs, and 5-mm section thickness reconstructions. CTA was acquired using a triple phase technique after 60 mL of 350 mgI/ml iodinated contrast medium injection at a 4 mL/s flow rate. The first phase, from the aortic root to the vertex, was acquired using bolus tracking technique with 5 seconds delay after a 100 HU threshold was reached in the aortic arch, whereas the second and the third phases, limited to the intracranial circle, were acquired with a fixed 8-second delay from the previous ones. In case of unknown stroke onset time or if beyond 6 hours from onset time, CT perfusion was used to select patients according to DAWN and DEFUSE-3 randomized clinical trials criteria, followed by a single-phase CTA from the aortic arch to the intracranial circulation. ⁷

Endovascular treatment

Endovascular procedures were performed on a biplane X-ray system by one out of four radiologists with 5 to 15 years of experience in stroke interventions. All patients underwent a preliminary angiographic examination to confirm and precisely localize the occlusion and to guide the subsequent treatment. Pseudo-occlusion was diagnosed by documenting sluggish, slow, and pulsatile progression of contrast into the ICA. In those cases, a diagnostic 5F catheter or a large-bore aspiration catheter was advanced to look for a terminal occlusion. Our interventional team adopted a shared technical approach to intracranial large vessel occlusion starting with aspiration only, for up to 3 passes, followed by a stent retriever when aspiration failed. ¹² Cervical occlusions were crossed and dilated with the guiding catheter or with balloon angioplasty to prioritize intracranial occlusion and treated with stenting only if necessary (in cases of significant residual stenosis and incomplete circle of Willis).

Image analysis

Qualitative image analysis was performed by two neuroradiologists, with 13 and 10 years of experience in stroke imaging and treatment, respectively, who were blinded to patients’ clinical data, on a dedicated workstation using commercially available software (syngo.via Version VB30, Siemens, Erlangen, Germany). They were asked to assess ASPECTS (0–10) on unenhanced brain CT, both baseline and at 24 hours, and the collateral score (good/intermediate/poor collaterals) on CTA, according to the classification by Tan et al. ⁵ Discrepancies were solved by consensus. Post-procedural DSA imaging was also evaluated to determine revascularization according to the mTICI score.

Statistical analysis

Continuous variables were expressed as mean ± SD or medians with interquartile ranges (IQR), depending on normal distribution. Categorical variables were presented as proportions. Normality was assessed using the D’Agostino–Pearson test. Interobserver agreement was evaluated using Cohen’s kappa statistic. An independent-samples two-tailed t test or the Mann–Whitney U-test was applied, as appropriate, to compare continuous variables, while Fisher’s exact test and the chi-square test were used for categorical variables. Parameters with p-values <0.10 in univariate analyses were included in a binary logistic regression. A p-value <0.05 was considered statistically significant. MedCalc (version 20, MedCalc Software) was used for all statistical analyses.

Results

On a total of 620 endovascular stroke procedures, 116 consecutive patients with absent opacification of the ICA at baseline CTA were included. Of these, 63 (54%) had a true occlusion of the cervical ICA associated with a large intracranial vessel occlusion (51 atheromatic, 8 dissected, and 4 embolic), while 53 (46%) had distal ICA occlusion presenting as pseudo-occlusion (PO), the latter being all embolic.

Cohen’s kappa analysis demonstrated a k = 0.56 (95% CI, 0.47 to 0.64) for ASPECT score assessment between the two radiologists (13 years and 10 years of experience) and a k = 0.59 (95% CI, 0.53 to 0.64) for ASPECT at 24 hours, indicating moderate interobserver agreement. For the assessment of collateral circulation, the kappa value was k = 0.66 (95% CI, 0.58 to 0.75), reflecting substantial agreement.

The ASPECT score on admission and intravenous administration of r-tPA did not significantly differ between the two groups. Compared to the PO group, collateral circulation at CTA was moderate to good in 75% of cases (vs 32%; p < 0.0001) and the mean infarction volume measured as ASPECT score at 24 h control CT was lower: 2 (IQR: 0–6) versus 7 (IQR: 4–8) (p < 0.0001). A good outcome after 3 months, defined as modified Rankin Score 0–2, was more likely in patients with true occlusion (TO) than patients with pseudo-occlusion (48% vs 11%; p = 0.002); furthermore, mortality was almost double in the PO group (p = 0.0014). Notably, there was no significant difference in terms of revascularization (78% in TO vs 70% in PO, p = 0.4) or intracranial parenchymal hemorrhage at the 24 h CT (Table 1).

Table 1.

IQR = interquartile range; NIHSS = National Institutes of Health Stroke Scale; CS = collateral score according to Tan IYL et al. ⁵ ; rt-PA = recombinant tissue-type plasminogen activator; TICI = thrombolysis in cerebral infarction revascularization score; ASPECT = Alberta Stroke Program Early CT score; avg = average; IPH = intracranial parenchymal hemorrhage; mRS = modified Rankin scale.

Variable	True occlusion (n = 63)	Pseudo-occlusion (n = 53)	p-Value
Baseline
Sex, male	45 (71%)	23 (43%)	p = 0.0027
Age, years (median, IQR)	65 (IQR: 58–78)	77 (IQR: 70–84)	p < 0.0001
Age, years (min–max)	30–88	43–93	-
NIHSS on admission	18 (IQR: 15–23)	23 (IQR: 19–24)	p = 0.0003
ASPECT	8 (IQR: 7–9)	8 (IQR: 6–9)	p = 0.106
CS score 2–3	49 (75%)	17 (32%)	p < 0.0001
Etiology (%)
- Atheromatous	81	-
- Embolic	4 (6%)	100
- Dissective	8 (13%)	-
Intervention
Intravenous rt-PA	40 (64%)	27 (51%)	p = 0.2
TICI score 2B-3	49 (78%)	37 (70%)	p = 0.4
Outcome
ASPECT after 24 h, avg	7 (IQR: 4–8)	2 (IQR: 0–6)	p < 0.0001
IPH after 24 h (%)	16 (25%)	15 (28%)	p = 0.83
mRS 0–2 at 90 days	30 (48%)	6 (11%)	p = 0.0002
Mortality at 90 days	12 (19%)	25 (47%)	p = 0.0014

Logistic regression analysis was conducted on a sample of 116 patients (46% cases with pseudo-occlusion and 54% cases with true occlusion). The model demonstrated a strong fit, with a chi-squared value of 51.831 (DF = 5, p < 0.0001), indicating substantial predictive power (Cox & Snell R² = 0.3603, Nagelkerke R² = 0.4817). Significant predictors included mRS (OR = 1.33, 95% CI: 1.01–1.74, p = 0.0437), suggesting an increased odd of a pseudo-occlusion. Female gender was associated with a significantly higher odds of pseudo-occlusion (OR = 3.84, 95% CI: 1.42–10.35, p = 0.0079), as was a higher baseline NIHSS score (OR = 1.12, 95% CI: 1.00–1.25, p = 0.0448). Conversely, good collateral circulation was associated with lower odds of a pseudo-occlusion (OR = 0.39, 95% CI: 0.24–0.65, p = 0.0003). Patient age was not a significant predictor (p = 0.5754). The Hosmer–Lemeshow test (χ² = 5.56, DF = 8, p = 0.6966) indicated good model calibration.

Discussion

Mechanical thrombectomy dramatically changed the outcome of patients with acute ischemic stroke due to anterior circulation intracranial large vessel occlusion. Randomized clinical trials included patients with terminal ICA occlusion and the M1 tract of the middle cerebral artery, also with concomitant cervical tract ICA occlusion or severe stenosis (tandem lesions). ⁶ Prespecified subgroup analysis found a higher treatment effect for patients with stroke due to ICA occlusion in comparison with more distal locations (common Odds Ratio 3.96) as well as for patients with tandem lesions (cOR 2.95), ⁶ but ICA occlusion has also been reported as a negative prognostic factor.^13,14 Terminal carotid occlusion and tandem occlusions were also associated with a higher complication rate during mechanical thrombectomy in the French ETIS registry, being predictors of embolus to new territory. ¹⁵ Similarly, the Italian Registry of Endovascular Stroke Treatment reported a higher risk of subarachnoid hemorrhage/arterial perforation rate and a higher risk of developing symptomatic intracranial hemorrhage in patients treated for distal intracranial carotid occlusion. ¹⁶

ICA occlusions encompass different clinical conditions and can be misinterpreted.^1–3 The ICA can be involved in many different ways in patients undergoing endovascular treatment for acute ischemic stroke: distal occlusion involving the apical tract are usually embolic and frequently caused by the migration of massive thrombi originating from cardiac chambers due to atrial fibrillation, whereas proximal occlusions are usually atheromatous or due to dissection. ⁹ Isolated apex occlusions show different presentations at CT-angiography according to the opacification of the upstream cervical tract, due to presence or absence of outflow vessels: if outflow arteries as the ophthalmic or the posterior communicating branches are absent, there is no progression of contrast medium into the vessel simulating proximal ICA occlusion (pseudo-occlusion). If outflow vessels are thin with a limited downstream capacity, there can be a slow progression of contrast medium that can be documented as a contrast gradient along the ICA or a late opacification at multiphase CTA.^17,18 Although morphology of occlusion at CTA and multiphase CTA has been suggested to improve diagnostic accuracy, pseudo-occlusions remain a significant issue with angiographic microcatheter exploration being often required for an accurate diagnosis.^3,19–21 In this study, we decided to adopt a very strict definition of pseudo-occlusion, excluding patients with a contrast gradient along the ICA since this makes differential diagnosis more obvious, and we did not consider later phase acquisition.

As suggested by multiple studies, pseudo-occlusion is a particularly unfavorable presentation of acute ischemic stroke in patients treated both with intravenous thrombolysis and mechanical thrombectomy.^22–25 These authors consistently reported a lower revascularization rate in patients with pseudo-occlusions after endovascular treatment, in contrast with our experience. We reported unfavorable outcomes for patients with pseudo-occlusions without a significant difference in terms of reperfusion rates. Our technical approach was not different in treat the two conditions in the study period: aspiration first and stent retriever-assisted thrombectomy only if necessary, and in cases of tandem occlusion, intracranial first treatment and carotid stenting only in a limited number of selected cases. ¹²

Collateral status is a well-known prognostic factor in patients undergoing endovascular treatment for acute ischemic stroke.^26–28 For example, the composition of the circle of Willis can determine different outcomes in patients with distal ICA occlusion. ²⁹ Poor collateral circulation is a possible explanation for the unfavorable outcome of patients with pseudo-occlusion, the latter being associated with slow or absent flow through the ICA. ²² There are different possible mechanisms for this association: large clot volume and occlusion of outflow vessels could reduce collateral circulation; higher risk of thrombus fragmentation and distal embolization during endovascular treatment of distal ICA occlusion; and absent flow could prevent intravenously administered r-tPA from reaching the thrombus and could promote platelet aggregation and thrombus expansion. Multiphase CTA seems to be superior to single-phase CTA to evaluate collateral circulation, but due to radiation dose exposure it should be used as an alternative to CT perfusion.^30,31 MCTA could also help in identifying pseudo-occlusion, ²¹ but this only applies to slow-flow cases and not to cases with completely absent inflow. ³ Our study found a relevant difference in terms of clinical outcome and collateral circulation evaluated at single-phase CT-angiography, which was available for both patients who underwent CT perfusion (beyond 6 hours from stroke onset time and unknown onset time) and multiphase CT angiography (within 6 hours from stroke onset time). Interestingly this observation, if confirmed by larger studies, could be widely adopted because of a fast and easy examination. Regarding clinical implications of this finding, it is crucial to correctly differentiate true or false cervical ICA occlusion at baseline imaging, even if both conditions are compatible with endovascular treatment and thus can be angiographically distinguished. Pseudo-occlusion could become a negative prognostic factor to consider in the decision-making process for borderline cases. Moreover, a specific technical approach could be chosen, for example, by using a balloon guiding catheter to prevent distal thrombus migration.

Our study is primarily limited by its retrospective design. Secondly, we adopted a stricter definition of pseudo-occlusions than usual. Moreover, it reports data from a single stroke center and images were not evaluated by an independent core laboratory and the follow-up period was limited to 3 months. A larger multicenter study is needed to confirm our results including more clinical and technical variables which can impact outcome.

Conclusions

Pseudo-occlusion of the cervical internal carotid artery in patients with acute ischemic stroke is likely associated with a worse prognosis and reduced collateral circulation. This imaging feature could serve as an additional factor to consider when selecting stroke patients for endovascular treatment.

Ethical statement

Ethical approval

The retrospective study was approved by the Ethical Committee of the Azienda Sanitaria della Provincia Autonoma di Bolzano (n. 51-2022).

Informed consent

Informed consent to participate was waived by Ethical Committee due to retrospective design.

ORCID iD

Alessio Comai https://orcid.org/0000-0002-0566-395X