Predictors of Aneurysm Obliteration in Patients Treated with the WEB Device: Results of a Multicenter Retrospective Study.

BACKGROUND AND PURPOSE: Despite the numerous studies evaluating the occlusion rates of aneurysms following WEB embolization, there are limited studies identifying predictors of occlusion. Our purpose was to identify predictors of aneurysm occlusion and the need for retreatment. MATERIALS AND METHODS: This is a review of a prospectively maintained database across 30 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB who had available intraprocedural data and long-term follow-up. RESULTS: We studied 763 patients with a mean age of 59.9 (SD, 11.7) years. Complete aneurysm occlusion was observed in 212/726 (29.2%) cases, and contrast stasis was observed in 485/537 (90.3%) of nonoccluded aneurysms. At the final follow-up, complete occlusion was achieved in 497/763 (65.1%) patients, and retreatment was required for 56/763 (7.3%) patients. On multivariable analysis, history of smoking, maximal aneurysm diameter, and the presence of an aneurysm wall branch were negative predictors of complete occlusion (OR, 0.5, 0.8, and 0.4, respectively). Maximal aneurysm diameter, the presence of an aneurysm wall branch, posterior circulation location, and male sex increase the chances of retreatment (OR, 1.2, 3.8, 3.0, and 2.3 respectively). Intraprocedural occlusion resulted in a 3-fold increase in the long-term occlusion rate and a 5-fold decrease in the retreatment rate (P < .001), offering a specificity of 87% and a positive predictive value of 85% for long-term occlusion. CONCLUSIONS: Intraprocedural occlusion can be used to predict the chance of long-term aneurysm occlusion and the need for retreatment after embolization with a WEB device. Smoking, aneurysm size, and the presence of an aneurysm wall branch are associated with decreased chances of successful treatment.

Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

OBJECTIVE: This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS: A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS: The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). CONCLUSIONS: The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.

The impact of postoperative aspirin in patients undergoing Woven EndoBridge: a multicenter, institutional, propensity score-matched analysis.

BACKGROUND: The Woven EndoBridge (WEB) device is frequently used for the treatment of intracranial aneurysms. Postoperative management, including the use of aspirin, varies among clinicians and institutions, but its impact on the outcomes of the WEB has not been thoroughly investigated. METHODS: This was a retrospective, multicenter study involving 30 academic institutions in North America, South America, and Europe. Data from 1492 patients treated with the WEB device were included. Patients were categorized into two groups based on their postoperative use of aspirin (aspirin group: n=1124, non-aspirin group: n=368). Data points included patient demographics, aneurysm characteristics, procedural details, complications, and angiographic and functional outcomes. Propensity score matching (PSM) was applied to balance variables between the two groups. RESULTS: Prior to PSM, the aspirin group exhibited significantly higher rates of modified Rankin scale (mRS) mRS 0-1 and mRS 0-2 (89.8% vs 73.4% and 94.1% vs 79.8%, p<0.001), lower rates of mortality (1.6% vs 8.6%, p<0.001), and higher major compaction rates (13.4% vs 7%, p<0.001). Post-PSM, the aspirin group showed significantly higher rates of retreatment (p=0.026) and major compaction (p=0.037) while maintaining its higher rates of good functional outcomes and lower mortality rates. In the multivariable regression, aspirin was associated with higher rates of mRS 0-1 (OR 2.166; 95% CI 1.16 to 4, p=0.016) and mRS 0-2 (OR 2.817; 95% CI 1.36 to 5.88, p=0.005) and lower rates of mortality (OR 0.228; 95% CI 0.06 to 0.83, p=0.025). However, it was associated with higher rates of retreatment (OR 2.471; 95% CI 1.11 to 5.51, p=0.027). CONCLUSIONS: Aspirin use post-WEB treatment may lead to better functional outcomes and lower mortality but with higher retreatment rates. These insights are crucial for postoperative management after WEB procedures, but further studies are necessary for validation.

Stent-assisted Woven EndoBridge device for the treatment of intracranial aneurysms: an international multicenter study.

OBJECTIVE: The Woven EndoBridge (WEB) device is an intrasaccular flow disruptor designed for wide-necked bifurcation aneurysms. These aneurysms may require the use of a concomitant stent. The objective of this study was to determine the clinical and radiological outcomes of patients undergoing stent-assisted WEB treatment. In addition, the authors also sought to determine the predictors of a concomitant stent in aneurysms treated with the WEB device. METHODS: The data for this study were taken from the WorldWideWEB Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups based on treatment: stent-assisted WEB and WEB device alone. The authors compared clinical and radiological outcomes of both groups. Univariable and multivariable binary logistic regression analyses were performed to determine factors that predispose to stent use. RESULTS: The study included 691 intracranial aneurysms (31 with stents and 660 without stents) treated with the WEB device. The adequate occlusion status did not differ between the two groups at the latest follow-up (83.3% vs 85.6%, p = 0.915). Patients who underwent stenting had more thromboembolic (32.3% vs 6.5%, p < 0.001) and procedural (16.1% vs 3.0%, p < 0.001) complications. Aneurysms treated with a concomitant stent had wider necks, greater heights, and lower dome-to-neck ratios. Increasing neck size was the only significant predictor for stent use. CONCLUSIONS: This study demonstrates that there is no difference in the degree of aneurysm occlusion between the two groups; however, complications were more frequent in the stent group. In addition, a wider aneurysm neck predisposes to stent assistance in WEB-treated aneurysms.

Longitudinal radiological follow-up of individual level non-ischemic cerebral enhancing lesions following endovascular aneurysm treatment.

BACKGROUND: Non-ischemic cerebral enhancing (NICE) lesions following aneurysm endovascular therapy are exceptionally rare, with unknown longitudinal evolution. OBJECTIVE: To evaluate the radiological behavior of individual NICE lesions over time. METHODS: Patients included in a retrospective national multicentric inception cohort were analyzed. NICE lesions were defined, using MRI, as delayed onset punctate, nodular, or annular foci enhancements with peri-lesion edema, distributed in the vascular territory of the aneurysm treatment, with no other confounding disease. Lesion burden and the longitudinal behavior of individual lesions were assessed. RESULTS: Twenty-two patients were included, with a median initial lesion burden of 36 (IQR 17-54) on the first MRI scan. Of the 22 patients with at least one follow-up MRI scan, 16 (73%) had new lesions occurring mainly within the first 200 weeks after the date of the procedure. The median number of new lesions per MRI was 6 (IQR 2-16). Among the same 22 patients, 7 (32%) had recurrent lesions. The median persistent enhancement of a NICE lesion was 13 weeks (IQR 6-30). No factor was predictive of early regression of enhancement activity with lesion regression kinetics mainly being patient-dependent. CONCLUSIONS: The behavior of individual NICE lesions was found to be highly variable with an overall patient-dependent regression velocity.

Hemodynamic nature of black-blood enhancement in long-term coiled cerebral aneurysms.

PURPOSE: Vessel wall imaging (VWI) with black-blood (BB) technique can demonstrate aneurysmal enhancement preluding to growth/rupture in treatment-naive cerebral aneurysms. Interestingly, recent works showed that BB enhancement may also occur in endovascularly treated aneurysms, though its meaning is controversial. Hypothesizing a flow-related mechanism of BB enhancement, we explored its relationship with incomplete occlusion status and coil packing density at DSA. METHODS: We analyzed the subjects undergoing 3T MRI between January 2017 and October 2020 for a previous aneurysmal coiling. All the MRI studies included pre- and post-contrast 3D BB sequences. The presence of intra-aneurysmal pre-contrast BB signal was assessed. BB enhancement (when present) was classified as follows: (1) enhancement at the neck, (2) intrasaccular/intra-coil enhancement, and (3) peripheral enhancement. Coil packing density and aneurysmal occlusion status (according to the modified Raymond-Roy classification, MRRC) were determined on post-treatment DSA and compared with BB findings using generalized linear mixed-effect model and ANOVA. Significant p values were <0.05. RESULTS: Forty-eight aneurysms from 44 patients were eligible for analysis. Pre-contrast BB signal was observed in 50% of the aneurysms and showed a relationship with baseline aneurysmal size. BB enhancement was detectable in 31 aneurysms (65%), being significantly associated with incomplete aneurysmal occlusion and reduced coil packing density at DSA. CONCLUSION: BB enhancement of coiled aneurysms is related with increasing degrees of post-coiling aneurysmal remnants and with loose coil packing density at DSA. This supports a hemodynamic interpretation of BB enhancement in long-term coiled aneurysms.

Long-Term Follow-Up of Cerebral Aneurysms Completely Occluded at 6 Months After Intervention with the Woven EndoBridge (WEB) Device: a Retrospective Multicenter Observational Study.

The Woven EndoBridge (WEB) device has been widely used to treat intracranial wide neck bifurcation aneurysms. Initial studies have demonstrated that approximately 90% of patients have same or improved long-term aneurysm occlusion after the initial 6-month follow up. The aim of this study is to assess the long-term follow-up in aneurysms that have achieved complete occlusion at 6 months. We also compared the predictive value of different imaging modalities used. This is an analysis of a prospectively maintained database across 13 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB device who achieved complete occlusion at first follow-up and had available long-term follow-up. A total of 95 patients with a mean age of 61.6 ± 11.9 years were studied. The mean neck diameter and height were 3.9 ± 1.3 mm and 6.0 ± 1.8 mm, respectively. The mean time to first and last follow-up was 5.4 ± 1.8 and 14.1 ± 12.9 months, respectively. Out of all the aneurysms that were completely occluded at 6 months, 84 (90.3%) showed complete occlusion at the final follow-up, and 11(11.5%) patients did not achieve complete occlusion. The positive predictive value (PPV) of complete occlusion at first follow was 88.4%. Importantly, this did not differ between digital subtraction angiography (DSA), magnetic resonance angiography (MRA), or computed tomography angiography (CTA). This study underlines the importance of repeat imaging in patients treated with the WEB device even if complete occlusion is achieved short term. Follow-up can be performed using DSA, MRA or CTA with no difference in positive predictive value.

Comparing treatment outcomes of various intracranial bifurcation aneurysms locations using the Woven EndoBridge (WEB) device.

BACKGROUND: The Woven EndoBridge (WEB) device has Food and Drug Administration approval for treatment of wide-necked intracranial bifurcation aneurysms. The WEB device has been shown to result in adequate occlusion in bifurcation aneurysms overall, but its usefulness in the individual bifurcation locations has been evaluated separately only in few case series, which were limited by small sample sizes. OBJECTIVE: To compare angiographic and clinical outcomes after treatment of bifurcation aneurysms at various locations, including anterior communicating artery (AComA), anterior cerebral artery (ACA) bifurcation distal to AComA, basilar tip, internal carotid artery (ICA) bifurcation, and middle cerebral artery (MCA) bifurcation aneurysms using the WEB device. METHODS: A retrospective cohort analysis was conducted at 22 academic institutions worldwide to compare treatment outcomes of patients with intracranial bifurcation aneurysms using the WEB device. Data include patient and aneurysm characteristics, procedural details, angiographic and functional outcomes, and complications. RESULTS: A total of 572 aneurysms were included. MCA (36%), AComA (35.7%), and basilar tip (18.9%) aneurysms were most common. The rate of adequate aneurysm occlusion was significantly higher for basilar tip (91.6%) and ICA bifurcation (96.7%) aneurysms and lower for ACA bifurcation (71.4%) and AComA (80.6%) aneurysms (p=0.04). CONCLUSION: To our knowledge, this is the most extensive study to date that compares the treatment of different intracranial bifurcation aneurysms using the WEB device. Basilar tip and ICA bifurcation aneurysms showed significantly higher rates of aneurysm occlusion than other locations.

The Woven EndoBridge (WEB) Device for the Treatment of Intracranial Aneurysms: Ten Years of Lessons Learned and Adjustments in Practice from the WorldWideWEB Consortium.

Several studies have shown promising outcomes of the Woven EndoBridge (WEB) device for the treatment of wide-necked intracranial bifurcation aneurysms. This is a multicenter study attempts to explore the changes in trends and treatment outcomes over time for WEB embolization of intracranial aneurysms. The WorldWideWEB consortium is a retrospective multicenter collaboration of data from international centers spanning from January 2011 and June 2021, with no limitations on aneurysm location or rupture status. Both bifurcation and sidewall aneurysms were included. These patients were stratified based on treatment year into five treatment intervals: 2011-2015 (N = 66), 2016-2017 (N = 77), 2018 (N = 66), 2019 (N = 300), and 2020-2021 (N = 173). Patient characteristics and angiographic and clinical outcomes were compared between these time intervals. This study comprised 671 patients (median age 61.4 years; 71.2% female) with 682 intracranial aneurysms. Over time, we observed an increasing tendency to treat patients presenting with ruptured aneurysms and aneurysms with smaller neck, diameter, and dome widths. Furthermore, we observed a trend towards more off-label use of the WEB for sidewall aneurysms and increased adoption of transradial access for WEB deployment. Moreover, the proportion of patients with adequate WEB occlusion immediately and at last follow-up was significantly higher in more recent year cohorts, as well as lower rates of compaction and retreatment. Mortality and complications did not differ over time. This learning curve study suggests improved experience using the WEB for the treatment of intracranial aneurysms and has yielded higher rates of adequate occlusion over time.

Intrasaccular flow disruption for ruptured aneurysms: an international multicenter study.

BACKGROUND: The Woven EndoBridge (WEB) device is a novel intrasaccular flow disruptor tailored for bifurcation aneurysms. We aim to describe the degree of aneurysm occlusion at the latest follow-up, and the rate of complications of aneurysms treated with the WEB device stratified according to rupture status. METHODS: Our data were taken from the WorldWideWeb Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups: ruptured and unruptured. We compared clinical and radiologic outcomes of both groups. Propensity score matching (PSM) was done to match according to age, gender, bifurcation, location, prior treatment, neck, height, dome width, daughter sac, incorporated branch, pretreatment antiplatelets, and last imaging follow-up. RESULTS: The study included 676 patients with 691 intracranial aneurysms (529 unruptured and 162 ruptured) treated with the WEB device. The PSM analysis had 55 pairs. In both the unmatched (85.8% vs 84.3%, p=0.692) and matched (94.4% vs 83.3%, p=0.066) cohorts there was no significant difference in the adequate occlusion rate at the last follow-up. Likewise, there were no significant differences in both ischemic and hemorrhagic complications between the two groups. There was no documented aneurysm rebleeding after WEB device implantation. CONCLUSION: There was no significant difference in both the radiologic outcomes and complications between unruptured and ruptured aneurysms. Our findings support the feasibility of treatment of ruptured aneurysms with the WEB device.

Silk Vista Baby flow diverter stent for ruptured intracranial aneurysms: a retrospective observational study.

PURPOSE: Flow diversion changed the approach to complex intracranial aneurysms, leading to a widespread use and a rapid technological evolution. Indeed, indications continued to expand, including ruptured intracranial aneurysms in selected cases. Recently, new devices have been designed specifically to target smaller vessels. Therefore, we conducted a multicenter study to evaluate clinical outcome, complications, and occlusion rate of patients with ruptured aneurysms treated with new generation low profile Silk Vista Baby (SVB) flow diverter stent (FD). METHODS: We performed a retrospective observational study on consecutive patients who underwent treatment with SVB for ruptured aneurysms at 12 Italian centers. Primary end point was favorable clinical outcome rate, defined as modified ranking score (mRS) of 0-2 at the 3 months. Secondary outcomes were complication rate, aneurysm re-rupture, and complete aneurysm occlusion at last radiological follow-up. RESULTS: Twenty-five patients were included; at 3 months' follow-up, 19 patients (79.1%) had favorable clinical outcome (mRS 0-2). Three patients (12.5%) died during follow-up. In-stent thrombosis occurred in two cases (8.3%), managed with glycoprotein IIb/IIIA and intra-stent angioplasty, without clinical consequences. In 18 (85.7%) patients, complete occlusion at 3 months was demonstrated. No rebleeding occurred during follow-up. Presentation with unfavorable World Federation of Neurosurgical Societies grading system (WFNS) and posterior circulation location were both significantly correlated with unfavorable clinical outcome (p = 0.005 and p = 0.02). CONCLUSIONS: Our data suggests that low profile FD treatment of ruptured intracranial aneurysms located distally of the circle of Willis is feasible. New generation low profile FD may represent an alternative option in carefully selected cases.

Multicenter Study for the Treatment of Sidewall versus Bifurcation Intracranial Aneurysms with Use of Woven EndoBridge (WEB).

Background The Woven EndoBridge (WEB) device was explicitly designed for wide-neck intracranial bifurcation aneurysms. Small-scale reports have evaluated the off-label use of WEB devices for the treatment of sidewall aneurysms, with promising outcomes. Purpose To compare the angiographic and clinical outcomes of the WEB device for the treatment of sidewall aneurysms compared with the treatment of bifurcation aneurysms. Materials and Methods A retrospective review of the WorldWideWEB Consortium, a synthesis of retrospective databases spanning from January 2011 to June 2021 at 22 academic institutions in North America, South America, and Europe, was performed to identify patients with intracranial aneurysms treated with the WEB device. Characteristics and outcomes were compared between bifurcation and sidewall aneurysms. Propensity score matching (PSM) was used to match by age, pretreatment ordinal modified Rankin Scale score, ruptured aneurysms, location of aneurysm, multiple aneurysms, prior treatment, neck, height, dome width, daughter sac, and incorporated branch. Results A total of 683 intracranial aneurysms were treated using the WEB device in 671 patients (median age, 61 years [IQR, 53-68 years]; male-to-female ratio, 1:2.5). Of those, 572 were bifurcation aneurysms and 111 were sidewall aneurysms. PSM was performed, resulting in 91 bifurcation and sidewall aneurysms pairs. No significant difference was observed in occlusion status at last follow-up, deployment success, or complication rates between the two groups. Conclusion No significantly different outcomes were observed following the off-label use of the Woven EndoBridge, or WEB, device for treatment of sidewall aneurysms compared with bifurcation aneurysms. The correct characterization of the sidewall aneurysm location, neck angle, and size is crucial for successful treatment and lower retreatment rate. © RSNA, 2022 See also the editorial by Hetts in this issue.

Transradial versus transfemoral access for embolization of intracranial aneurysms with the Woven EndoBridge device: a propensity score-matched study.

OBJECTIVE: Transradial access (TRA) is commonly utilized in neurointerventional procedures. This study compared the technical and clinical outcomes of the use of TRA versus those of transfemoral access (TFA) for intracranial aneurysm embolization with the Woven EndoBridge (WEB) device. METHODS: This is a secondary analysis of the Worldwide WEB Consortium, which comprises multicenter data related to adult patients with intracranial aneurysms who were managed with the WEB device. These aneurysms were categorized into two groups: those who were treated with TRA or TFA. Patient and aneurysm characteristics and technical and clinical outcomes were compared between groups. Propensity score matching (PSM) was used to match groups according to the following baseline characteristics: age, sex, subarachnoid hemorrhage, aneurysm location, bifurcation aneurysm, aneurysm with incorporated branch, neck width, aspect ratio, dome width, and elapsed time since the last follow-up imaging evaluation. RESULTS: This study included 682 intracranial aneurysms (median [interquartile range] age 61.3 [53.0-68.0] years), of which 561 were treated with TFA and 121 with TRA. PSM resulted in 65 matched pairs. After PSM, both groups had similar characteristics, angiographic and functional outcomes, and rates of retreatment, thromboembolic and hemorrhagic complications, and death. TFA was associated with longer procedure length (median 96.5 minutes vs 72.0 minutes, p = 0.006) and fluoroscopy time (28.2 minutes vs 24.8 minutes, p = 0.037) as compared with TRA. On the other hand, deployment issues were more common in those treated with TRA, but none resulted in permanent complications. CONCLUSIONS: TRA has comparable outcomes, with shorter procedure and fluoroscopy time, to TFA for aneurysm embolization with the WEB device.

Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients.

Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thrombotic events. Ischemic stroke in COVID-19 patients entails high severity and mortality rates. Here we aimed to analyze cerebral thrombi of COVID-19 patients with large vessel occlusion (LVO) acute ischemic stroke to expose molecular evidence for SARS-CoV-2 in the thrombus and to unravel any peculiar immune-thrombotic features. We conducted a systematic pathological analysis of cerebral thrombi retrieved by endovascular thrombectomy in patients with LVO stroke infected with COVID-19 (n = 7 patients) and non-covid LVO controls (n = 23). In thrombi of COVID-19 patients, the SARS-CoV-2 docking receptor ACE2 was mainly expressed in monocytes/macrophages and showed higher expression levels compared to controls. Using polymerase chain reaction and sequencing, we detected SARS-CoV-2 Clade20A, in the thrombus of one COVID-19 patient. Comparing thrombus composition of COVID-19 and control patients, we noted no overt differences in terms of red blood cells, fibrin, neutrophil extracellular traps (NETs), von Willebrand Factor (vWF), platelets and complement complex C5b-9. However, thrombi of COVID-19 patients showed increased neutrophil density (MPO+ cells) and a three-fold higher Neutrophil-to-Lymphocyte Ratio (tNLR). In the ROC analysis both neutrophils and tNLR had a good discriminative ability to differentiate thrombi of COVID-19 patients from controls. In summary, cerebral thrombi of COVID-19 patients can harbor SARS-CoV2 and are characterized by an increased neutrophil number and tNLR and higher ACE2 expression. These findings suggest neutrophils as the possible culprit in COVID-19-related thrombosis.

Non-ischemic cerebral enhancing lesions after intracranial aneurysm endovascular repair: a retrospective French national registry.

BACKGROUND: Non-ischemic cerebral enhancing (NICE) lesions are exceptionally rare following aneurysm endovascular therapy (EVT). OBJECTIVE: To investigate the presenting features and longitudinal follow-up of patients with NICE lesions following aneurysm EVT. METHODS: Patients included in a retrospective national multicentre inception cohort were analysed. NICE lesions were defined, using MRI, as delayed onset punctate, nodular or annular foci enhancements with peri-lesion edema, distributed in the vascular territory of the aneurysm EVT, with no other confounding disease. RESULTS: From a pool of 58 815 aneurysm endovascular treatment procedures during the study sampling period (2006-2019), 21/37 centres identified 31 patients with 32 aneurysms of the anterior circulation who developed NICE lesions (mean age 45±10 years). Mean delay to diagnosis was 5±9 months, with onset occurring a month or less after the index EVT procedure in 10 out of 31 patients (32%). NICE lesions were symptomatic at time of onset in 23 of 31 patients (74%). After a mean follow-up of 25±26 months, 25 patients (81%) were asymptomatic or minimally symptomatic without disability (modified Rankin Scale (mRS) score 0-1) at last follow-up while 4 (13%) presented with mild disability (mRS score 2). Clinical follow-up data were unavailable for two patients. Follow-up MRI (available in 27 patients; mean time interval after onset of 22±22 months) demonstrated persistent enhancement in 71% of cases. CONCLUSIONS: The clinical spectrum of NICE lesions following aneurysm EVT therapy spans a wide range of neurological symptoms. Clinical course is most commonly benign, although persistent long-term enhancement is frequent.

Cerebral thrombi of cardioembolic etiology have an increased content of neutrophil extracellular traps.

BACKGROUND: Inflammation is emerging as an essential trigger for thrombosis. In the interplay between innate immunity and coagulation cascade, neutrophils and neutrophil extracellular traps (NETs) can promote thrombus formation and stabilization. In ischemic stroke, it is uncertain whether the involvement of the inflammatory component may differ in thrombi of diverse etiology. We here aimed to evaluate the presence of neutrophils and NETs in cerebral thrombi of diverse etiology retrieved by endovascular thrombectomy (EVT). METHODS: We performed a systematic histological analysis on 80 human cerebral thrombi retrieved through EVT in acute ischemic stroke patients. Thrombus composition was investigated in terms of neutrophils (MPO+ cells) and NET content (citH3+ area), employing specific immunostainings. NET plasma content was determined and compared to NET density in the thrombus. RESULTS: Neutrophils and NETs were heterogeneously represented within all cerebral thrombi. Thrombi of diverse etiology did not display a statistically significant difference in the number of neutrophils (p = 0.51). However, NET content was significantly increased in cardioembolic compared to large artery atherosclerosis thrombi (p = 0.04), and the association between NET content and stroke etiology remained significant after adjusted analysis (beta coefficient = -6.19, 95%CI = -11.69 to -1.34, p = 0.01). Moreover, NET content in the thrombus was found to correlate with NET content in the plasma (p ≤ 0.001, r = 0.62). CONCLUSION: Our study highlights how the analysis of the immune component within the cerebral thrombus, and specifically the NET burden, might provide additional insight for differentiating stroke from diverse etiologies.

Absence of susceptibility vessel sign is associated with aspiration-resistant fibrin/platelet-rich thrombi.

BACKGROUND: The composition of the thrombus influences its retrievability by mechanical thrombectomy. PURPOSE: Our study aimed to report on thrombi resistant to aspiration, regarding susceptibility vessel sign and histologic composition. METHODS: This observational study was based on a prospective database of acute anterior circulation ischemic strokes treated by mechanical thrombectomy. Endovascular first-line strategy was aspiration and in case of failure, combined therapy-rescue was performed. The positivity of susceptibility vessel sign (SVS+) or its negativity (SVS-) was assessed on T2* sequences. The thrombus composition was analyzed with hematoxylin eosin staining. RESULTS: Histological analysis was performed on 102 clots. Thrombi with SVS- were significantly richer in fibrin/platelets, p = 0.04. Out of 210 mechanical thrombectomy, aspiration first pass strategy was performed in 131/210 (62%) patients. Combined therapy-rescue was needed in 37% of aspiration first pass strategy cases (n = 131). Clots retrieved combined therapy-rescue were richer in fibrin/platelets 63.9% versus 50.8% for aspiration first pass strategy, p = 0.03. Logistic regression analysis showed that fibrin/platelet-poor clots (<60%) were significantly more likely to be recanalized by aspiration first pass strategy compared to fibrin/platelet-rich clots (>60%) that were more likely recanalized by combined therapy-rescue after aspiration first pass strategy failure (OR = 3.5; 95% CI = 1.2-10.8; p = 0.0054). CONCLUSIONS: Our results confirm that SVS- clots are rich in fibrin/platelets and suggest that these "white clots" are less likely to be retrieved by aspiration alone and more often require the use of combined therapy.