Abstract
Background
The optimal management of patients with acute ischemic stroke (AIS) due to tandem occlusion (TO) and underlying carotid dissection (CD) remains unclear.
Objective
We present our multicenter-experience of endovascular treatment (EVT) approach used and outcomes for AIS patients with CD-related TO (CD-TO).
Methods
Consecutive AIS patients underwent EVT for CD-TO at five Italian Neuro-interventional Tertiary Stroke Centers were retrospectively identified. TO from atherosclerosis and other causes of, were excluded from the final analysis. Primary outcome was successful (mTICI 2b-3) and complete reperfusion (mTICI 3); secondary outcome was patients’ 3-months functional independence (mRS≤2).
Results
Among 214 AIS patients with TO, 45 presented CD-TO. Median age was 54 years (range 29–86), 82.2% were male. Age <65 years (p < 0.0001), lower baseline NIHSS score (p = 0.0002), and complete circle of Willis (p = 0.0422) were associated with mRS ≤ 2 at the multivariate analysis. Comparisons between antegrade and retrograde approaches resulted in differences for baseline NIHSS scores (p = 0.001) and number of EVT attempts per-procedure (p = 0.001). No differences in terms of recanalization rates were observed between antegrade and retrograde EVT approaches (p = 0.811) but higher rates of mTICI3 revascularization was observed with the retrograde compared to the antegrade approach (78.6% vs 73.3%), anyway not statistically significant. CD management technique (angioplasty vs aspiration vs emergent stenting) did not correlate with 3-months mRS≤2.
Conclusion
AIS patients with CD-TO were mostly treated with the retrograde approach with lower number of attempts per-procedure but it offered similar recanalization rates compared with the antegrade approach. Emergent carotid artery stenting (CAS) proved to be safe for CD management but it does not influence 3-months patients’ clinical outcomes.
Keywords: Endovascular, Internal carotid artery dissection, Interventional, Ischemic stroke, Stroke, Tandem occlusion, Thrombectomy
Introduction
The optimal endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) and tandem occlusion (TO) has yet to be established.1,2 TO mostly derive from atherosclerosis or cervical carotid dissection (CD). These two etiologies relate with distinct demographic and clinical characteristics of affected patients and show differences in recurrence rates and outcomes, which may influence the decision among available endovascular approaches.3,4
CD is a common cause of stroke in young adults, accounting for approximately 20% of all cerebral ischemic events in patients aged less than 45 years 5 Clinical data on the management of carotid dissection-related tandem occlusions (CD-TO) are still sparse. 6 In contrast to the increasing scientific evidence for atheromatous-related TOs, the need for emergent carotid artery stenting (CAS) in CD-TO remains controversial and current evidence is limited to few studies with small sample sizes.5,7–10
In this work, we present our multicenter experience with AIS patients due to CD-TO, analyzing the safety and efficacy of different EVT approaches, including the management of extracranial CD and outcomes.
Methods
Study Design
Consecutive patients with AIS treated with EVT at five Italian Neuro-interventional Tertiary Stroke Centers from January 2018 to January 2020 were retrospectively identified. Patients were included if they presented with: 1) anterior circulation TO from internal CD; 2) CT-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) >5; 3) premorbid modified Rankin Scale (mRS) score <2.
CD was diagnosed based on the angiogram. Patients with unclear or different carotid disease etiologies at imaging evaluation were excluded.
No ethics committee approval was required for this retrospective observational study.
The following study was devised in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (Supplementary File 1). 11
Outcomes
The primary objective of this study was to analyze and compare the role of different EVT recanalization approaches in CD-TO and techniques in the management of extracranial CD.
The primary outcome included successful reperfusion (i.e. modified Thrombolysis in Cerebrovascular Infarction (mTICI) scores of 2b or 3), complete reperfusion (i.e. mTICI score of 3), all-cause 3-months mortality, any procedural-related complications (including symptomatic intracerebral hemorrhage (sICH) and thromboembolism).
Secondary outcome measure was 90-days functional independence defined as mRS score ≤2.
Clinical and Imaging Data collection
The following variables were collected: demographics (i.e. age, gender), cardiovascular risk factors (i.e. smoking, atrial fibrillation, arterial hypertension, diabetes mellitus, hypercholesterolemia, previous cardio-cerebrovascular accidents), clinical and radiologic assessments (i.e. baseline mRS score, National Institute of Health Stroke Scale (NIHSS) score, ASPECTS score), stroke laterality, completeness of the circle of Willis, hemorrhagic transformation, antegrade or retrograde recanalization approach, procedural time (i.e. onset-to-groin time, onset-to-recanalization time), number of EVT attempts (including both intracranial and cervical extracranial procedures) and extracranial CD treatment strategies.
Extracranial CD treatments included: carotid angioplasty, aspiration via a large-bore catheter to pass the lesion, or emergent carotid artery stenting (CAS).
Clinical data were prospectively collected at pre-procedural, procedural, 24–48-h post-procedural, discharge, and 3-months follow-up.
All CT scans were obtained with 64 slices using a helicoid acquisition (LightSpeed VCT 64, GE Healthcare, Chicago, IL). At each institution, two neuro-interventional radiologists independently analyzed preprocedural CT scans. Any disagreement was resolved by consensus with a third neuroradiologist. CT angiography was used also to assess completeness of the Circle of Willis, defined as the presence of both the anterior and posterior communicating arteries and carotid patency, and the presence of significant stenosis (≥70%) of contralateral carotid according to NASCET criteria. 12 All stroke cases presented in this series were diagnosed using CT angiography as the routine practice of the centers involved in the study and the perfusion study has been performed in patients with “wake up stroke” or with neurological symptoms onset beyond 6 h. No urgent MRI was performed. CD was identified on angiograms by the presence of a tapered or flame-shaped stenosis or occlusion occurring >2 cm from the internal carotid origin, extending or distant from the skull base. 13
Follow-up CT or MR imaging were performed 24 h after the acute therapy to assess infarction size and hemorrhagic status. As per the European Cooperative Acute Stroke Study (ECASS), sICH was defined as a documented hemorrhage associated with a decline of ≥4 points in the NIHSS score. 14
Embolic complication was defined as an angiographic occlusion in a previously unaffected vascular territory observed at angiography after clot removal and associated with new ischemic changes at 24-h CT or MR imaging.
Intravenous Thrombolysis
Eligibility for intravenous thrombolysis (IVT) and EVT was evaluated at each center according to the American Heart Association/American Stroke Association guidelines. 15
Mechanical Thrombectomy Approach and Carotid Dissection Management
Each center independently decided on the type of approach (i.e. antegrade or retrograde), the CD treatment (i.e. angioplasty, aspiration, emergent CAS), and the EVT treatment for the MCA occlusion (i.e. aspiration and/or stent retriever) according to individual experiences.
In the antegrade approach, the CD that could not be initially crossed was primarily treated and then intracranial EVT was performed to relieve the MCA occlusion, divided according to the site of occlusion in M1-MCA and M2-MCA.
In the retrograde approach, after achieving the intracranial reperfusion, the CD was eventually managed with angioplasty, aspiration, or emergent CAS.
In our experience, once crossed the dissection, the use of an exchange guidewire left intracranially was used to “keep the way up” to the intracranial vessels during the retrograde approach.
In both antegrade and retrograde approaches, the choice of emergent CAS placement was decided on a case-by-case basis. But, emergent CAS was always placed in case of a flow-limiting lesion, defined as an intracranial ipsilateral venous drainage delay >2 s compared with the contralateral carotid injection or if a re-occlusion occurred within minutes following intracranial treatment. 16
The choice of the stent-type was at the discretion of the operator. After EVT, all patients were managed with medical therapy. The choice of antiplatelet medication was also at the discretion of the operators, including a single-antiplatelet drug, such as a regular dose aspirin (up to 300 mg) or a dose of 500 mg of intravenous lysine acetylsalicylate, administered before carotid stenting. Continuation of antiplatelet therapy was discussed based on the presence/absence of hemorrhagic transformation detected on the 24-h CT imaging. If no sICH occurred, dual antiplatelet therapy was administered for 3 months. If a major hemorrhagic transformation (sICH) occurred, the antiplatelet therapy was stopped in the acute phase. At the postoperative follow-up, the antiplatelet therapy was further discussed by the medical team and restarted if CT or MR imaging showed resolution of prior hemorrhages.
Statistical Analysis
Statistical analyses were conducted using SPSS V.27 (IBM Corp, Armonk, NY). Continuous variables are reported as mean ± SD or median with range, while categorical variables as number and percentage. Contingency analyses for categorical variables were performed using the Chi-square test. Cohen’s kappa was used to measure interobserver agreement in differentiating patients with carotid dissection-related tandem occlusion versus patients with atherosclerosis-related tandem occlusion. Bivariate analyses were used for testing hypotheses of association. Student’s t-test group comparisons and univariate logistic regression analyses were performed to test differences among the study groups and identify factors influencing clinical outcomes. Multivariate logistic regression analyses were conducted including all the variables deemed of potential relevance (corresponding to a cut-off of p < 0.10 at the univariate analysis) and retained in the multivariate model with a statistically significant power (p < 0.05). A two-sided p-value <0.05 was considered to indicate statistical significance for all analyses.
Results
Study Population
Between January 2018 and January 2020, 1080 patients with AIS underwent mechanical thrombectomy. Out of 214 patients who presented with TO, 45 patients had CD-TO and were included in the current analysis (Table 1).
Table 1.
Overall characteristics and outcomes of the study population.
| Characteristics | All patients with tandem occlusion | Patients with carotid dissection-related tandem occlusion |
|---|---|---|
| Cohort size (no.) | 214 | 45 |
| Demographics | ||
| Median age (range) (years) | 68 (29–95) | 54 (29–86) |
| Male, no. (%) | 147 (68.7%) | 37 (82.2%) |
| Left hemisphere stroke | 112 (52.3%) | 20 (44.4%) |
| Cardiovascular risk factors | No. (%) | No. (%) |
| Atrial fibrillation, no. (%) | 29 (13.9%) | 4 (8.8%) |
| Diabetes mellitus, no. (%) | 24 (11.5%) | 1 (2.2%) |
| Prior transient ischemic attack, no. (%) | 13 (6.2%) | 2 (4.4%) |
| Smoking, no. (%) | 55 (26.4%) | 10 (22.2%) |
| Baseline assessment | ||
| NIHSS Score, median (±SD) | 17 ( ± 5.4) | 16 ( ± 5.9) |
| ASPECTS score, median (±SD) | 8 ( ± 1.7) | 9 ( ± 1.8) |
| Treatment characteristics | ||
| Onset-to-groin time (minutes), median (±SD) | 230 ( ± 157.7) | 225 ( ± 206.1) |
| Onset-to-recanalization time (minutes), median (±SD) | 300 ( ± 161.6) | 313 ( ± 203.7) |
| Procedural time (minutes), median (±SD) | 63 ( ± 55.9) | 73 ( ± 52.6) |
| EVT attempts per-procedure, median (±SD) | 2 ( ± 2.2) | 2 ( ± 1.9) |
| Antegrade approach, no. (%) | 109 (51.6%) | 15 (33.3%) |
| Retrograde approach, no. (%) | 102 (48.4%) | 30 (66.7%) |
| Internal carotid artery angioplasty, no. (%) | 37 (17.3%) | 7 (15.5%) |
| Internal carotid artery aspiration, no. (%) | 82 (38.3%) | 21 (46.7%) |
| Internal carotid artery emergent stenting, no. (%) | 95 (44.4%) | 17 (37.7%) |
| Medical treatment | No. (%) | No. (%) |
| Preprocedural antiplatelet therapy, no. (%) | 39 (18.2%) | 6 (13.3%) |
| Intraprocedural antiplatelet therapy, no. (%) | 63 (29%) | 13 (28.9%) |
| Preprocedural anticoagulation therapy, no. (%) | 10 (4.7%) | 1 (2.2%) |
| Intraprocedural anticoagulation therapy, no. (%) | 50 (23.4%) | 9 (20%) |
| Intravenous thrombolysis | 101 (52.6%) | 25 (65.8%) |
| Intraoperative angiographic findings | No. (%) | No. (%) |
| Complete circle of willis | 115 (65.7%) | 25 (75.7%) |
| Contralateral significant internal carotid artery stenosis | 33 (18.1%) | 1 (3%) |
| Treatment outcomes | ||
| mTICI ≥2b, no. (%) | 162 (78.3%) | 40/43 (93%) |
| mTICI ≥3, no. (%) | 108 (51.9%) | 33/43 (76.7%) |
| Intracerebral hemorrhage, no. (%) | 75 (35%) | 17 (37.8%) |
| Symptomatic intracerebral hemorrhage, no. (%) | 23 (10.7%) | 7 (15.6%) |
| 90-days mRS, median (±SD) | 3 ( ± 2.2) | 1.5 ( ± 2.2) |
| 90-days mRS ≤2, no. (%) | 86 (44.8%) | 25/42 (59.5%) |
| 90-days mRS ≤3, no. (%) | 106 (55.2%) | 28/42 (66.7%) |
| 90-days death, no. (%) | 42 (21.9%) | 5 (11.9%) |
Interobserver agreement in radiological diagnosis was excellent (k = 0.78).
The median age was 54 (range 29–86) years and 37 patients (82.2%) were males.
Median baseline ASPECTS was nine and baseline NIHSS was 16; 65.8% of patients (25/38) received IVT in conjunction with EVT. The median onset-to-groin time was 225 ± 206.1 min, the median onset-to-recanalization time was 313 ± 203.7 min, and the median procedural time was 73 ± 52.6 min.
Intracranial occlusions were diagnosed on M1-MCA site in 33 patients (73.3%) and on M2-MCA site in 12 patients (26.7%). The presence of the anterior communicating artery (AcomA) and both posterior communicating arteries (PcomA) was angiographically demonstrated in 25/45 patients (55.5%). In the remaining 20/45 cases (44.4%) the absence of cross-flow was documented. From the direct injection from the controlater internal cerebral artery and homolateral vertebral artery 25/45 (55.5%) patients had the anterior communicating artery (AcomA) and both posterior communicating arteries (PcomA), and in the remaining 20/45 (44.4%) cases was documented the absence of cross-flow from the AcomA. An antegrade approach was used in 15 of 45 patients (33.3%), and 30 patients (66.7%) were treated with a retrograde approach.
The occlusion of internal carotid artery (ICA) was treated with angioplasty in 7/45 patients (15.5%), with extracranial ICA aspiration in 21/45 (46.7%), and with emergent CAS in 17/45 (37.7%). In 29 patients (64.4%), not receiving previous antiplatelet medication, a dose of 500 mg of intravenous lysine acetylsalicylate administered before deployment of carotid stent placement was considered a regular single dosage. Dual antiplatelet therapy was defined as a treatment with combined medications (e.g. aspirin with clopidogrel) or a double regular dose of a single drug (e.g. lysine acetylsalicylate, 1000 mg). In 16 patients (35.5%) already receiving antiplatelet medications, a single antiplatelet therapy was defined as a regular dosage of aspirin (i.e. up to 300 mg) or clopidogrel 75 mg.
Clinical and Angiographic Outcomes
At 3-months post-stroke follow-up, 25 of 42 patients (59.5%) were functionally independent (mRS 0–2) and 28 of 42 (66.7%) achieved an outcome on mRS between 0–3; the mortality rate was 11.9%. A successful intracranial recanalization (mTICI = 2b-3) was achieved in 40 of 43 patients (93%) and mTICI = 3 in 33 patients (76.7%); the rate of unsuccessful recanalization was 7%.
In 21 of 45 cases (46.7%) treated only with aspiration there was no significant delay after recanalization of the intracranial occlusion and these patients did not require further treatment.
The overall rate of post-procedural intracerebral hemorrhage was 37.8%, and sICH occurred in seven out of 45 patients (15.6%). Of note, no patients experienced a new stroke nor re-occlusion after EVT, regardless of the technique used.
Factors Influencing Clinical Outcomes
At the univariate analyses, several clinical factors resulted significantly associated to functional independence (mRS ≤ 2) at 3-months follow-up including age >65 (p < 0.0001), gender (p = 0.0176), baseline NIHSS score (p < 0.0001), baseline ASPECTS score (p = 0.0453), atrial fibrillation (p = 0.0032), diabetes mellitus (p = 0.0160), complete circle of Willis (p = 0.0056), and preprocedural anticoagulation therapy (p = 0.0185) (Table 2). At the multivariate analysis, age >65 (p < 0.0001), baseline NIHSS score (p = 0.0002), and complete circle of Willis (p = 0.0422) resulted in significant prognostic factors of functional independence. We found no statistical association between endovascular technique and functional independence (mRS ≤ 2): angioplasty (p = 0.930); aspiration (p = 0.119); emergent CAS (p = 0.730).
Table 2.
Univariate and multivariate logistic regression analysis predicting patients’ functional independence (mRS ≤2).
| Characteristics | Univariate analysis OR (95%CI) | p Value a | Multivariate analysis OR (95%CI) | p Value b |
|---|---|---|---|---|
| Age >65 | 0.138 (0.071–0.271) | <0.0001 | 0.152 (0.065–0.356) | <0.0001 |
| Gender | 0.904 (0.509–1.603) | 0.0176 | ||
| Left hemisphere stroke | 0.474 (0.256–0.878) | 0.729 | ||
| Baseline NIHSS score | 0.860 (0.803–0.023) | <0.0001 | 0.844 (0.772–0.923) | 0.0002 |
| Baseline ASPECTS score | 1.201 (1.00–1.437) | 0.0453 | ||
| Atrial fibrillation | 0.247 (0.098–0.626) | 0.0032 | ||
| Diabetes mellitus | 0.311 (0.120–0.804) | 0.0160 | ||
| Smoking | 1.076 (0.559–2.072) | 0.8264 | ||
| Prior transient ischemic attack | 1.075 (0.328–3.518) | 0.9052 | ||
| Complete circle of willis | 2.609 (1.324–5.139) | 0.0056 | 2.165 (0.961–4.875) | 0.0422 |
| Type of EVT treatment | 0.862 (0.369–2.011) | 0.7305 | ||
| Preprocedural anticoagulation therapy | 0.081 (0.010–0.657) | 0.0185 | ||
| Antegrade/Retrograde approach | 1.716 (0.962–3.061) | 0.0673 | ||
| Angioplasty | 1.034 (0.490–2.180) | 0.9306 | ||
| Aspiration | 0.625 (0.346–1.129) | 0.1192 | ||
| Emergent carotid stenting | 1.005 (0.472–2.139) | 0.7305 |
ap-value < 0.10 was considered statistically significant for the univariate analyses, then included in the multivariate analyses.
bp-value < 0.05 was considered statistically significant for the multivariate analysis.
Table 3 shows comparisons in treatment outcomes between the antegrade and retrograde approaches. We found statistical differences for baseline NIHSS scores (p = 0.001; means 19.0 in antegrade vs 13.8 in retrograde) and number of EVT attempts per-procedure (p = 0.001; means 3.9 in antegrade vs 1.8 in retrograde). Despite seeming counterintuitive performing the antegrade approach in those patients presented with a higher baseline NIHSS, we interpreted our result as the consequence of the not infrequent difficulty to obtain direct intracranial access through the dissected carotid artery before reaching the intracranial occlusion. Although we noted higher rates of complete revascularization (mTICI 3) in patients treated with the retrograde approach compared with patients treated with the antegrade approach (78.6% vs 73.3%, respectively), no significant differences were found (p = 0.811).
Table 3.
Characteristics of patients and outcomes according to antegrade versus retrograde approach.
| Characteristics | Antegrade approach | Retrograde approach | p-value |
|---|---|---|---|
| Cohort size (no.) | 15 | 30 | |
| Demographics | |||
| Median age (range) (years) | 55 (29–96) | 53 (38–83) | 0.275 a |
| Male, no. (%) | 13 (86.7%) | 24 (80%) | 0.890^ |
| Left hemisphere stroke | 6/15 (40%) | 19/30 (63.3%) | 0.847^ |
| Cardiovascular risk factors | No. (%) | No. (%) | |
| Atrial fibrillation, no. (%) | 1/14 (7.1%) | 3/29 (10.3%) | 0.798^ |
| Diabetes mellitus, no. (%) | 0/14 (0%) | 1/29 (3.4%) | 0.706^ |
| Prior transient ischemic attack, no. (%) | 1/14 (7.1%) | 1/29 (3.4%) | 0.815^ |
| Smoking, no. (%) | 4/14 (28.6%) | 6/29 (20.7%) | 0.851^ |
| Baseline assessment | |||
| NIHSS Score, mean (±SD) | 19.0 ( ± 4.0) | 13.8 ( ± 6.0) | 0.001 a |
| ASPECTS score, mean (±SD) | 9.3 ( ± 1.0) | 8.3 ( ± 1.9) | 0.064 a |
| Treatment characteristics | |||
| Onset-to-groin time (minutes), mean (±SD) | 313 ( ± 232) | 300 ( ± 196) | 0.845 a |
| Onset-to-recanalization time (minutes), mean (±SD) | 397 ( ± 236) | 366 ( ± 189) | 0.636 a |
| Procedural time (minutes), mean (±SD) | 92 ( ± 53) | 75 ( ± 53) | 0.345 a |
| EVT attempts per-procedure, mean (±SD) | 3.9 ( ± 2.6) | 1.8 ( ± 1.2) | 0.001 a |
| Internal carotid artery angioplasty, no. (%) | 3/15 (20%) | 4/30 (13.3%) | 0.884^ |
| Internal carotid artery aspiration, no. (%) | 6/15 (40%) | 15/30 (50%) | 0.751^ |
| Internal carotid artery emergent stenting, no. (%) | 6/15 (40%) | 11/30 (36.7%) | 0.913^ |
| Medical treatment | No. (%) | No. (%) | |
| Preprocedural antiplatelet therapy, no. (%) | 2/15 (13.3%) | 4/30 (13.3%) | 0.642^ |
| Intraprocedural antiplatelet therapy, no. (%) | 3/15 (20%) | 10/30 (33.3%) | 0.561^ |
| Preprocedural anticoagulation therapy, no. (%) | 0/15 (0%) | 1/30 (3.3%) | 0.721^ |
| Intraprocedural anticoagulation therapy, no. (%) | 3/15 (20%) | 5/30 (16.7%) | 0.890^ |
| Intravenous thrombolysis | 9/11 (81.8%) | 16/27 (59.2%) | 0.341^ |
| Intraoperative angiographic findings | No. (%) | No. (%) | |
| Complete circle of willis | 6/8 (75%) | 19/24 (79.2%) | 0.805^ |
| Contralateral significant internal carotid artery stenosis | 0/8 (0%) | 1/25 (4%) | 0.542^ |
| Treatment outcomes | |||
| mTICI ≥2b, no. (%) | 13/15 (86.7%) | 27/28 (96.4%) | 0.569^ |
| mTICI ≥3, no. (%) | 11/15 (73.3%) | 22/28 (78.6%) | 0.811^ |
| Intracerebral hemorrhage, no. (%) | 9/15 (60%) | 8/30 (26.7%) | 0.065^ |
| Symptomatic intracerebral hemorrhage, no. (%) | 3/15 (20%) | 4/30 (13.3%) | 0.884^ |
| NIHSS Score at discharge, mean (±SD) | 10.0 ( ± 8.0) | 5.8 ( ± 7.8) | 0.168 a |
| Variation in NIHSS score, mean (±SD) | −5.2 ( ± 4.7) | −3.9 ( ± 7.6) | 0.548 a |
| 90-days mRS, mean (±SD) | 2.6 ( ± 2.2) | 2.1 ( ± 2.2) | 0.476 a |
| 90-days mRS ≤2, no. (%) | 7/14 (50%) | 18/28 (64.3%) | 0.578^ |
| 90-days mRS ≤3, no. (%) | 8/14 (57.1%) | 20/28 (71.4%) | 0.563^ |
| 90-days death, no. (%) | 1/14 (7.1%) | 4/28 (14.3%) | 0.866^ |
aT-test; ^chi-square test. p value <0.05 was considered statistically significant for all tests.
Discussion
There is several evidence in favor of the EVT approach for CD-TO, also reporting stenting as safe treatment, but clear guidelines on the usefulness of different types of EVT approach for CD-TO and acute extracranial CD management are still lacking.
In this multicenter retrospective study, the retrograde approach was overall preferred over the antegrade. The high rate of complete intracranial vessel recanalization in this subgroup of tandem lesion may be explained by the easier chance to remove the erythrocyte-rich clots underlying the carotid CD-TO as compared to the atheromatous intracranial emboli, which are variable in composition.17,18 Furthermore, we explained the higher number of EVT attempts with the antegrade approach to be related with the need of performing at least two EVT attempts (one intracranial and one extracranial) with this approach compared with the retrograde approach which may requires more often only one EVT attempt. Although the retrograde approach was the overall preferred approach and associated with lower number of passages and higher rates of complete mTICI three recanalization, these results must be interpreted with caution. Indeed, the difficulties encountered crossing long segments of CD and the limited ability to access the intracranial vessels before treating the carotid lesion, as observed in almost one third of our patients, make it difficult to define the superiority of one approach over the other.
Increasing scientific evidence suggests the safety and efficacy of emergent CAS for TOs, but most of current studies focus on atherosclerotic-related lesions ,7–10,19 and only few considered TOs solely from CD.5,9,20 However, CD-TO is a distinct nosological entity in comparison to TO-related stroke from atheromatous carotid lesions. Thus, the potential drawbacks associated to emergent CAS in CD-TO should be carefully considered alongside with the limited benefit of this extracranial carotid management observed in our multicenter experience.21,22 We confirmed that emergent CAS is a safe procedure with low risks of post-operative sICH rates in patients with CD-TO, despite in our series it is slightly higher than other authors .9,10 Comparing our case-series with other even larger ones, such as the TITAN-ETIS, a difference in terms of onset-to-recanalization time, which is longer in our case-series, is evident and mainly related with the patient’s arrival to the angio suite which should be definitely implemented. We also found that CAS was not significantly related (p = 0.730) with superior functional independence (mRS ≤ 2) at 3-months when compared with other EVT techniques. CAS Indeed, we found that 24/33 (72.7%) of patients with post-treatment mTICI ≥ 3 and mRS ≤ 2 underwent carotid angioplasty or thrombus aspiration, further suggesting that all three EVT techniques proved effective and that other clinical characteristics may play more important prognostic roles. As per our multivariate analysis, the main features influencing favorable patient outcomes (i.e. mRS ≤ 3) were patients’ younger age, lower NIHSS at onset, and complete circle of Willis. Hence, baseline clinical and functional status of affected patients still represent the most important prognostic factors needed to be evaluated when planning the most appropriate tailored treatments strategies. 23 Of interest, the stand-alone aspiration of the carotid thrombus was successful to restore carotid vessel patency in 61.9% of the treated patients. In these patients, the angiographic findings after direct thrombus aspiration better revealed the presence of the dissection flap but after crossing and dilating the dissected ICA sequentially with a microcatheter and then with the aspiration catheter followed by advancement of a six French sheath allowed the restoration of a regular vessel size which did not require further treatment.
However, it should also be considered that the stented cases could probably be the more complicated ones and a biased lack of superior functional independence at 3-months for these cases may be present. Moreover, the small sample size of our series precluded the drawing of definitive conclusions also because the decision of stenting mostly depended on the specific case-scenario.
Based on the present experience, the decision of stenting depends mainly on the specific case-scenario. Based on our results we may advise for emergent CAS in CD-TO only in case of persistent brain hypoperfusion or high risk of intracranial vessel re-occlusion, including high-grade residual stenosis, early carotid re-occlusion after intracranial recanalization or to the presence of thrombus at the level of the dissection. However, since the stented cases of our series were more probably the more complicated ones, a potential bias regarding lack of superior functional independence at 3-months observed in our stented patients may be present and this precludes drawing a definitive conclusion. The major challenges of stenting comprise the routine requirement for post-operative antiplatelet therapy and the not infrequent hardships in CAS deployment due to the frequent cervical carotid loops present in the dissected carotid segment or the extended dissection length. The ongoing Thrombectomy in Tandem Lesion randomized trial will provide further and more robust evidence on this topic. 24
Limitations
Our study has several limitations. First, its retrospective and non-controlled design may have determined a selection bias. Second, the choice among available EVT approaches, the endovascular strategies, the stenting protocols, and the antiplatelet regimens were not standardized, and then were different at each involved institution. However, we note that these biases may be intrinsic in every multicenter observational study, but also reflect the possible variability in decision making processes that may be found in routine emergent clinical practice. Third, three patients were lost at follow-up and/or some data were missing. Fourth, the rarity of carotid dissection-related tandem occlusions and the relatively small sample size of our cohort may have reduced the power of our statistical analyses. Finally, due to the limited number of patients included, we failed to demonstrate any absolute significant difference in comparing the antegrade versus retrograde approaches; but it should be noted that our study was not designed to answer this question. Despite these limitations, our study has several strengths including its multicenter design, the use of contemporary technology in a real-world practice and the description of one the largest series of patients undergoing EVT for carotid dissection-related tandem occlusions.
Conclusions
In our retrospective multi-center experience on AIS patients with CD-TO underwent EVT, the retrograde approach was overall preferred over the antegrade approach, with a significantly lower number of EVT attempts per-procedure but, remained difficult to define from our series the superiority of one approach over the other. On the other hand, the baseline clinical and functional status (i.e. younger age, lower NIHSS at onset, and complete circle of Willis) still represented the most important prognostic factors needed to be evaluated when planning the most appropriate and tailored EVT strategy. Moreover, emergent CAS for CD management proved to be safe in this series but, differently from the recent literature regarding TO due to atheromatous cause, it does not influence 3-months patients’ clinical outcomes. This latter result seems to point out how carotid lesion etiology underlies TO should be carefully considered when planning emergent stenting in AIS patients and the decision of stenting mainly depends on the specific case-scenario.
Further robust evidence is needed to confirm our results concerning this specific subgroup of AIS patients.
Highlights
• Retrograde approach, first passage intracranial vessel recanalization and complete intracranial recanalization determines favorable clinical outcome in tandem occlusion due to carotid dissection.
• Emergent carotid stenting of the carotid dissection in tandem occlusion is safe.
• Emergent carotid stenting of the carotid dissection in tandem occlusion is not determinant for 3-months good clinical outcome.
Supplemental Material
Supplemental Material for Endovascular treatment of patients with acute ischemic stroke and tandem occlusion due to internal carotid artery dissection: A multicenter experience by Valerio Da Ros, Federica Pusceddu, Simona Lattanzi, Jacopo Scaggiante, Fabrizio Sallustio, Federico Marrama, Monica Bandettini di Poggio, Gianpaolo Toscano, Francesca Di Giuliano, Claudia Rolla-Bigliani, Maria Ruggiero, Niccolo Haznedari, Alessandro Sgreccia, Giuseppina Sanfilippo, Cinzia Finocchi, Marina Diomedi, Santino O Tomasi, Paolo Palmisciano, Giuseppe E Umana, Lidia Strigari, Christoph J Griessenauer, Francesca Pitocchi, Francesco Garaci, Roberto Floris in The Neuroradiology Journal
Author’s Contribution: Valerio Da Ros: Conceptualization, methodology, validation, formal analysis, investigation, writing—original draft preparation, visualization; Federica Pusceddu: Resources, writing—reviewing and editing; Simona Lattanzi: Resources, writing—reviewing and editing; Jacopo Scaggiante: Resources, writing—reviewing and editing; Fabrizio Sallustio: Resources, writing—reviewing and editing; Federico Maramma: Resources, writing—reviewing and editing; Monica Bandettini di Poggio: Resources, writing—reviewing and editing; Gianpaolo Toscano: Resources, writing—reviewing and editing; Francesca Di Giuliano: Resources, writing—reviewing and editing; Claudia Rolla-Bigliani: Resources, writing—reviewing and editing; Maria Ruggiero: Resources, writing—reviewing and editing; Niccolo Haznedari: Resources, writing—reviewing and editing; Alessandro Sgreccia: Resources, writing—reviewing and editing; Giuseppina Sanfilippo: Resources, writing—reviewing and editing; Cinzia Finocchi: Resources, writing—reviewing and editing; Marina Diomedi: Resources, writing—reviewing and editing; Santino O. Tomasi: Resources, writing—reviewing and editing; Paolo Palmisciano: Resources, writing—reviewing and editing; Giuseppe E. Umana: Resources, writing—reviewing and editing; Lidia Strigari: Statistical analysis, writing—reviewing and editing; Christoph J. Griessenauer: Resources, writing—reviewing and editing; Francesca Pitocchi: Resources, writing—reviewing and editing; Francecsco Garaci and Roberto Floris: Conceptualization, methodology, formal analysis, writing—reviewing and editing, supervision.
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Christoph J. Griessenauer: consulting honoraria from MicroVention and Stryker, research support from Medtronic and Penumbra. Neither are related to the content of this publication.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
Supplemental Material: Supplemental material for this article is available online.
ORCID iDs
Valerio Da Ros https://orcid.org/0000-0001-7167-7594
Federica Pusceddu https://orcid.org/0000-0001-8388-0178
Jacopo Scaggiante https://orcid.org/0000-0002-9531-9131
Alessandro Sgreccia https://orcid.org/0000-0002-0834-644X
Christoph J Griessenauer https://orcid.org/0000-0002-2952-3812
Francesca Pitocchi https://orcid.org/0000-0003-3428-6660
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Supplementary Materials
Supplemental Material for Endovascular treatment of patients with acute ischemic stroke and tandem occlusion due to internal carotid artery dissection: A multicenter experience by Valerio Da Ros, Federica Pusceddu, Simona Lattanzi, Jacopo Scaggiante, Fabrizio Sallustio, Federico Marrama, Monica Bandettini di Poggio, Gianpaolo Toscano, Francesca Di Giuliano, Claudia Rolla-Bigliani, Maria Ruggiero, Niccolo Haznedari, Alessandro Sgreccia, Giuseppina Sanfilippo, Cinzia Finocchi, Marina Diomedi, Santino O Tomasi, Paolo Palmisciano, Giuseppe E Umana, Lidia Strigari, Christoph J Griessenauer, Francesca Pitocchi, Francesco Garaci, Roberto Floris in The Neuroradiology Journal