Comparison of Three Scores of Collateral Status for Their Association With Clinical Outcome: The HERMES Collaboration.

BACKGROUND: Leptomeningeal collateral status on baseline computed tomographic angiography (CTA) is associated with clinical outcome after acute ischemic stroke treatment. However, assessment of collateral status is not uniform. To compare 3 different CTA collateral scores (CS) and imaging techniques about their association with clinical outcome. METHODS: Pooled analysis of patient-level data from the Highly Effective Reperfusion Using Multiple Endovascular Devices collaboration. Patients with large vessel occlusion from 7 randomized controlled trials that compared endovascular thrombectomy with standard medical care were included. Three different CS (Tan CS, regional CS [rCS], and regional Alberta Stroke Program Early CT Score CS) and 2 imaging techniques (single-phase [sCTA] and multiphase/dynamic CTA) were evaluated. Functional independence (modified Rankin Scale score 0-2) at 3 months poststroke was the primary outcome. Furthermore, we assessed the effect of sCTA image acquisition time on collateral status assessment using an adjusted ordinal logistic regression model to obtain predicted values for the trichotomized rCS. RESULTS: Among 1147 pooled patients, 948 (82.7%) had sCTA and 199 (17.3%) multiphase/dynamic CTA as baseline angiography. With all 3 collateral scales, better CSs were associated with better 3-month functional outcome. With sCTA images, the rCS (area under the curve [AUC] 0.63) and regional Alberta Stroke Program Early CT Score CS (AUC 0.62) better predicted functional outcome than the Tan CS (AUC 0.60, respectively; P<0.001 and P=0.02). With multiphase/dynamic CTA images, all collateral scales performed similarly in predicting functional outcome (rCS [AUC 0.61]; regional Alberta Stroke Program Early CT Score CS [AUC 0.61] versus Tan CS [AUC 0.61], respectively; P=0.93 and P=0.91). Overall, no endovascular thrombectomy treatment effect modification by collateral status (rCS) was demonstrated (P=0.41). sCTA timing independently influenced CS assessment. On earlier timed sCTA, the predicted proportions of scans with poor collaterals was higher and vice versa. CONCLUSIONS: In this data set of highly selected patients with stroke, using a regional CS on sCTA likely allows for the most accurate prediction of functional outcome while on time-resolved CTA, the type of CS did not matter. Patients across all collateral grades benefit from endovascular thrombectomy. sCTA timing independently influenced CS assessment.

Correlation Between Computed Tomography-Based Tissue Net Water Uptake and Volumetric Measures of Cerebral Edema After Reperfusion Therapy.

BACKGROUND: Cerebral edema after large hemispheric infarction is associated with poor functional outcome and mortality. Net water uptake (NWU) quantifies the degree of hypoattenuation on unenhanced-computed tomography (CT) and is increasingly used to measure cerebral edema in stroke research. Hemorrhagic transformation and parenchymal contrast staining after thrombectomy may confound NWU measurements. We investigated the correlation of NWU measured postthrombectomy with volumetric markers of cerebral edema and association with functional outcomes. METHODS: In a pooled individual patient level analysis of patients presenting with anterior circulation large hemispheric infarction (core 80-300 mL or Alberta Stroke Program Early CT Score ≤5) in the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set, cerebral edema was defined as the volumetric expansion of the ischemic hemisphere expressed as a ratio to the contralateral hemisphere(rHV). NWU and midline-shift were compared with rHV as the reference standard on 24-hour follow-up CT, adjusted for hemorrhagic transformation and the use of thrombectomy. Association between edema markers and day 90 functional outcomes (modified Rankin Scale) was assessed using ordinal logistic regression. RESULTS: Overall (n=144), there was no correlation between NWU and rHV (rs=0.055, P=0.51). In sub-group analyses, a weak correlation between NWU with rHV was observed after excluding patients with any degree of hemorrhagic transformation (rs=0.211, P=0.015), which further improved after excluding thrombectomy patients (rs=0.453, P=0.001). Midline-shift correlated strongly with rHV in all sub-group analyses (rs>0.753, P=0.001). Functional outcome at 90 days was negatively associated with rHV (adjusted common odds ratio, 0.46 [95% CI, 0.32-0.65]; P<0.001) and midline-shift (adjusted common odds ratio, 0.85 [95% CI, 0.78-0.92]; P<0.001) but not NWU (adjusted common odds ratio, 1.00 [95% CI, 0.97-1.03]; P=0.84), adjusted for age, baseline National Institutes of Health Stroke Scale, and thrombectomy. Prognostic performance of NWU improved after excluding patients with hemorrhagic transformation and thrombectomy (adjusted odds ratio, 0.90 [95% CI, 0.80-1.02]; P=0.10). CONCLUSIONS: NWU correlated poorly with conventional markers of cerebral edema and was not associated with clinical outcome in the presence of hemorrhagic transformation and thrombectomy. Measuring NWU postthrombectomy requires validation before implementation into clinical research. At present, the use of NWU should be limited to baseline CT, or follow-up CT only in patients without hemorrhagic transformation or treatment with thrombectomy.

Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial.

Importance: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits. Objective: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion. Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3. Interventions: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52). Main Outcomes and Measures: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death. Results: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication. Trial Registration: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40.

Cerebral Edema in Patients With Large Hemispheric Infarct Undergoing Reperfusion Treatment: A HERMES Meta-Analysis.

Background and Purpose: Whether reperfusion into infarcted tissue exacerbates cerebral edema has treatment implications in patients presenting with extensive irreversible injury. We investigated the effects of endovascular thrombectomy and reperfusion on cerebral edema in patients presenting with radiological evidence of large hemispheric infarction at baseline. Methods: In a systematic review and individual patient-level meta-analysis of 7 randomized controlled trials comparing thrombectomy versus medical therapy in anterior circulation ischemic stroke published between January 1, 2010, and May 31, 2017 (Highly Effective Reperfusion Using Multiple Endovascular Devices collaboration), we analyzed the association between thrombectomy and reperfusion with maximal midline shift (MLS) on follow-up imaging as a measure of the space-occupying effect of cerebral edema in patients with large hemispheric infarction on pretreatment imaging, defined as diffusion-magnetic resonance imaging or computed tomography (CT)-perfusion ischemic core 80 to 300 mL or noncontrast CT-Alberta Stroke Program Early CT Score ≤5. Risk of bias was assessed using the Cochrane tool. Results: Among 1764 patients, 177 presented with large hemispheric infarction. Thrombectomy and reperfusion were associated with functional improvement (thrombectomy common odds ratio =2.30 [95% CI, 1.32­4.00]; reperfusion common odds ratio =4.73 [95% CI, 1.66­13.52]) but not MLS (thrombectomy ß=−0.27 [95% CI, −1.52 to 0.98]; reperfusion ß=−0.78 [95% CI, −3.07 to 1.50]) when adjusting for age, National Institutes of Health Stroke Score, glucose, and time-to-follow-up imaging. In an exploratory analysis of patients presenting with core volume >130 mL or CT-Alberta Stroke Program Early CT Score ≤3 (n=76), thrombectomy was associated with greater MLS after adjusting for age and National Institutes of Health Stroke Score (ß=2.76 [95% CI, 0.33­5.20]) but not functional improvement (odds ratio, 1.71 [95% CI, 0.24­12.08]). Conclusions: In patients presenting with large hemispheric infarction, thrombectomy and reperfusion were not associated with MLS, except in the subgroup with very large core volume (>130 mL) in whom thrombectomy was associated with increased MLS due to space-occupying ischemic edema. Mitigating cerebral edema-mediated secondary injury in patients with very large infarcts may further improve outcomes after reperfusion therapies.

Thrombectomy within 8 hours after symptom onset in ischemic stroke.

BACKGROUND: We aimed to assess the safety and efficacy of thrombectomy for the treatment of stroke in a trial embedded within a population-based stroke reperfusion registry. METHODS: During a 2-year period at four centers in Catalonia, Spain, we randomly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy (including intravenous alteplase when eligible) and endovascular therapy with the Solitaire stent retriever (thrombectomy group) or medical therapy alone (control group). All patients had confirmed proximal anterior circulation occlusion and the absence of a large infarct on neuroimaging. In all study patients, the use of alteplase either did not achieve revascularization or was contraindicated. The primary outcome was the severity of global disability at 90 days, as measured on the modified Rankin scale (ranging from 0 [no symptoms] to 6 [death]). Although the maximum planned sample size was 690, enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials. RESULTS: Thrombectomy reduced the severity of disability over the range of the modified Rankin scale (adjusted odds ratio for improvement of 1 point, 1.7; 95% confidence interval [CI], 1.05 to 2.8) and led to higher rates of functional independence (a score of 0 to 2) at 90 days (43.7% vs. 28.2%; adjusted odds ratio, 2.1; 95% CI, 1.1 to 4.0). At 90 days, the rates of symptomatic intracranial hemorrhage were 1.9% in both the thrombectomy group and the control group (P=1.00), and rates of death were 18.4% and 15.5%, respectively (P=0.60). Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals. CONCLUSIONS: Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset, stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence. (Funded by Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others; REVASCAT ClinicalTrials.gov number, NCT01692379.).

A Novel and Freely Available Interactive 3d Model of the Internal Carotid Artery.

We describe a new and freely available 3D interactive model of the intracranial internal carotid artery (ICA) and the skull base that also allows to display and compare its main segment classifications. High-resolution 3D human angiography (isometric voxel's size 0.36 mm) and Computed Tomography angiography images were exported to Virtual Reality Modeling Language (VRML) format for processing in a 3D software platform and embedding in a 3D Portable Document Format (PDF) document that can be freely downloaded at http://diposit.ub.edu/dspace/handle/2445/112442 and runs under Acrobat Reader on Mac and Windows computers and Windows 10 tablets. The 3D-PDF allows for visualisation and interaction through JavaScript-based functions (including zoom, rotation, selective visualization and transparentation of structures or a predefined sequence view of the main segment classifications if desired). The ICA and its main branches and loops, the Gasserian ganglion, the petrolingual ligament and the proximal and distal dural rings within the skull base environment (anterior and posterior clinoid processes, silla turcica, ethmoid and sphenoid bones, orbital fossae) may be visualized from different perspectives. This interactive 3D-PDF provides virtual views of the ICA and becomes an innovative tool to improve the understanding of the neuroanatomy of the ICA and surrounding structures.

Vessel Wall Enhancement and Blood-Cerebrospinal Fluid Barrier Disruption After Mechanical Thrombectomy in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Less than half of acute ischemic stroke patients treated with mechanical thrombectomy obtain permanent clinical benefits. Consequently, there is an urgent need to identify mechanisms implicated in the limited efficacy of early reperfusion. We evaluated the predictors and prognostic significance of vessel wall permeability impairment and its association with blood-cerebrospinal fluid barrier (BCSFB) disruption after acute stroke treated with thrombectomy. METHODS: A prospective cohort of acute stroke patients treated with stent retrievers was analyzed. Vessel wall permeability impairment was identified as gadolinium vessel wall enhancement (GVE) in a 24- to 48-hour follow-up contrast-enhanced magnetic resonance imaging, and severe BCSFB disruption was defined as subarachnoid hemorrhage or gadolinium sulcal enhancement (present across >10 slices). Infarct volume was evaluated in follow-up magnetic resonance imaging, and clinical outcome was evaluated with the modified Rankin Scale at day 90. RESULTS: A total of 60 patients (median National Institutes of Health Stroke Scale score, 18) were analyzed, of whom 28 (47%) received intravenous alteplase before mechanical thrombectomy. Overall, 34 (57%) patients had GVE and 27 (45%) had severe BCSFB disruption. GVE was significantly associated with alteplase use before thrombectomy and with more stent retriever passes, along with the presence of severe BCSFB disruption. GVE was associated with poor clinical outcome, and both GVE and severe BCSFB disruption were associated with increased final infarct volume. CONCLUSIONS: These findings may support the clinical relevance of direct vessel damage and BCSFB disruption after acute stroke and reinforce the need for further improvements in reperfusion strategies. Further validation in larger cohorts of patients is warranted.

Risk factors for the development of chronic back pain after percutaneous vertebroplasty versus conservative treatment.

In a recent randomized controlled trial comparing vertebroplasty (VP) versus conservative treatment (CT) in patients with symptomatic vertebral fractures (VF), we observed the development of chronic back pain (CBP) in nearly one-quarter of patients. The aim of this study was to identify the risk factors related to the development of severe CBP in these subjects. We evaluated risk factors including visual analog scale (VAS) at baseline and during the 1-year follow-up, age, gender, symptom onset time, number, type and severity of VF at baseline, number of vertebral bodies treated, incident VF, and antiosteoporotic treatment, among others. CBP was considered in patients with VAS ≥ 7 at 12 months. 91/125 patients completed the 12-months follow-up. CBP was observed in 23% of VP-treated patients versus 23% receiving CT. Patients developing CBP after VP showed a longer symptom onset time (82% ≥ 4 months in VP vs. 40% in CT, P = 0.03). On univariate analysis, female gender (OR 1.52; 95% CI 1.47-1.57, P < 0.0001), multiple acute VF (OR 1.79; 95% CI 1.71-1.87, P < 0.0001), VAS ≥ 7 two months after treatment (OR 11.04; 95% CI 6.71-18.17, P < 0.0001), and type of antiosteoporotic drug (teriparatide) (OR 0.12; 95% CI 0.03-0.60, P = 0.0236) were risk factors of CBP development in both groups. In the multivariate analysis, the main risk factors were baseline and post-treatment VAS ≥ 7, longer symptom onset time, and type of antiosteoporotic treatment. In conclusion, 23% of patients with symptomatic osteoporotic VF developed severe CBP independently of the type of treatment. Symptom onset time before VP and persistence of severe CBP after treatment were the main factors related to CBP with teriparatide treatment decreasing the risk of this complication.

Medical and endovascular treatment of patients with large vessel occlusion presenting with mild symptoms: an observational multicenter study.

BACKGROUND: A significant proportion of stroke patients presenting with mild symptoms does not have a successful recovery, especially when a large vessel is occluded. IV thrombolysis is safe and may benefit patients presenting with mild symptoms. In this study, we tested whether endovascular therapy (ET) is superior to medical therapy in these patients. METHODS: Observational, prospectively collected, multicenter study of 78 consecutive patients admitted from 2009 to 2012 within 6 h of stroke, with NIHSS≤5 at presentation or during initial diagnostic work-up and large vessel occlusion. Data for patients undergoing ET and/or IV thrombolysis were taken from the SONIIA registry of reperfusion therapies in Catalonia, or from our local stroke registry if no reperfusion therapy was delivered. We compared risk factors, clinical course, collateral circulation, revascularization rates, hemorrhagic complications, infarct volume, and the functional outcome at 3 months of patients treated with ET and those not receiving ET. Ordinal regression was used to assess the independent effect of ET on functional outcome. RESULTS: Baseline characteristics were similar for ET (n=34) and medically (n=44) treated patients, except for older age in the latter. The occlusions were located in the terminal internal carotid artery (1%), M1 segment of the middle cerebral artery (33%), M2 segment (30%), posterior circulation (31%), and 5% of the patients had tandem lesions, with no significant differences between groups. Most patients in both treatment groups had good collateral flow. The rate of successful revascularization (91.2 vs. 63.4%; p=0.006) and the risk of symptomatic intracranial hemorrhage (11.8 vs. 0%; p=0.033) were higher in the ET group. The NIHSS scores were similar at hospital arrival, after initial neuroimaging, and at 24 h in both treatment groups and there were no significant differences in the infarct volume in a follow-up MRI. At 3 months, 35.9% of the patients had some disability. The functional outcome was similar in both treatment groups in univariate analysis and also in models adjusted for age and initial NIHSS or for variables associated to functional outcome on univariate comparison. Conversely, IV thrombolysis was associated with significantly greater chances of full recovery after adjusting for baseline differences (OR 3.70, p=0.015). CONCLUSIONS: One third of stroke patients with mild symptoms and large vessel occlusions do not have a successful recovery. ET is effective to recanalize the occluded vessel but increases the risk of serious bleeding significantly without improving the functional outcome, and is therefore not justified routinely in these patients.

Collaterals at angiography guide clinical outcomes after endovascular stroke therapy in HERMES.

BACKGROUND: Robust collateral circulation has been linked with better reperfusion and clinical outcomes. It remains unclear how individual assessments of collateral circulation may be translated into clinical practice. METHODS: The pooled Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) angiography dataset was analyzed by a centralized, independent imaging core blinded to other clinical data. Conventional angiography was acquired immediately prior to endovascular therapy. Collaterals were graded with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) system and associated with baseline patient characteristics, reperfusion, and day 90 modified Rankin Score (mRS). Both 90-day all-cause mortality and day 90 mRS were modeled via multivariable logistic regression. RESULTS: Angiography was available in 376/605 (62%) patients. Baseline ASPECTS (Alberta Stroke Program Early CT Score) (p=0.043), history of diabetes mellitus (p=0.048), site of occlusion (p<0.001), and degree of subsequent Thrombolysis in Cerebral Infarction (TICI) reperfusion (p<0.001) were associated with collateral grades. ASITN collateral grade was strongly associated with ordinal mRS from baseline to 90 days in an unadjusted analysis (p<0.001). Multivariable regression demonstrated that collateral status is a strong determinant of mRS outcome in the presence of other predictors (OR=1.37 per grade, 95% CI [1.05 to 1.74], p=0.018). By comparing ORs, 1 unit of ASITN was determined to be approximately equivalent to 4.5 points of NIHSS, 11 years of age, 1.5 points of ASPECTS, or 100 min less delay from onset to puncture, in terms of impact on mRS. CONCLUSIONS: Individual collateral physiology may contribute significantly to reperfusion success and clinical outcomes after acute ischemic stroke. Building a consensus for the role of angiographic collateral assessment in the allocation of adjuvant reperfusion therapies may help galvanize a precision medicine approach in stroke.

Derivo embolization device for intracranial aneurysms: a Spanish multicenter retrospective study.

BACKGROUND: Flow diverters have emerged in recent years as a safe and effective treatment for intracranial aneurysms, with expanding indications. The Derivo embolization device (DED) is a second-generation flow diverter with a surface finish that may reduce thrombogenicity. We report our multicenter experience evaluating its safety and efficacy. METHODS: We retrospectively analyzed all patients treated with the DED in eight centers in Spain between 2016 and 2020. Demographics, clinical data, procedural complications, morbidity and aneurysm occlusion rates were collected. RESULTS: A total of 209 patients with 250 aneurysms were treated (77.5% women). The majority of aneurysms were located in the internal carotid artery (86.8%) and most (69.2%) were small (<10 mm) with a median maximum diameter of 5.85 mm and median neck size of 4 mm. DED deployment was successful in all cases, despite two malfunctioning devices (1%). Major complications occurred in nine patients (4.3%), while mild neurologic clinical events were registered in 23 (11%); four patients died (1.9%). A total of 194 aneurysms had an angiographic follow-up at 6 months and showed complete aneurysm occlusion in 75% of cases. Twelve-month follow-up was available for 112 of the treated aneurysms, with a total occlusion rate of 83%. CONCLUSION: The DED is a second-generation surface-modified flow diverter that presents an option for treatment of intracranial aneurysms with comparable safety and efficacy to other available flow diverter devices. Nonetheless, risks are not negligible, and must be balanced against the natural history risk of cerebral aneurysms, considering the tendency to widen indications for treatment of smaller and less complex lesions in day-to-day use.

Single-center experience of cerebral artery thrombectomy using the TREVO device in 60 patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: We sought to explore the safety and efficacy of the new TREVO stent-like retriever in consecutive patients with acute stroke. METHODS: We conducted a prospective, single-center study of 60 patients (mean age, 71.3 years; male 47%) with stroke lasting <8 hours in the anterior circulation (n=54) or <12 hours in the vertebrobasilar circulation (n=6) treated if CT perfusion/CT angiography confirmed a large artery occlusion, ruled out a malignant profile, or showed target mismatch if symptoms >4.5 hours. Successful recanalization (Thrombolysis In Cerebral Infarction 2b-3), good outcome (modified Rankin Scale score 0-2) and mortality at Day 90, device-related complications, and symptomatic hemorrhage (parenchymal hematoma Type 1 or parenchymal hematoma Type 2 and National Institutes of Health Stroke Scale score increment ≥ 4 points) were prospectively assessed. RESULTS: Median (interquartile range) National Institutes of Health Stroke Scale score on admission was 18 (12-22). The median (interquartile range) time from stroke onset to groin puncture was 210 (173-296) minutes. Successful revascularization was obtained in 44 (73.3%) of the cases when only the TREVO device was used and in 52 (86.7%) when other devices or additional intra-arterial tissue-type plasminogen activator were also required. The median time (interquartile range) of the procedure was 80 (45-114) minutes. Good outcome was achieved in 27 (45%) of the patients and the mortality rate was 28.3%. Seven patients (11.7%) presented a symptomatic intracranial hemorrhage. No other major complications were detected. CONCLUSIONS: The TREVO device was reasonably safe and effective in patients with severe stroke. These results support further investigation of the TREVO device in multicentric registries and randomized clinical trials.

Combined Approach to Stroke Thrombectomy Using a Novel Short Flexible Aspiration Catheter with a Stent Retriever : Preliminary Clinical Experience.

BACKGROUND: Large-bore aspiration catheters enabling greater flow rates and suction force for mechanical thrombectomy might improve outcomes in patients with stroke secondary to large-vessel occlusion. Complete or near-complete reperfusion after a single thrombectomy pass (first-pass effect) is associated with improved clinical outcomes. We assessed the efficacy and safety of novel MIVI Q™ aspiration catheters in combination with stent-retriever devices. METHODS: We retrospectively analyzed demographics, procedure characteristics, and clinical data from consecutive patients with acute anterior large-vessel occlusion treated with a combined approach using MIVI Q™ aspiration catheters and stent retrievers. Reperfusion was defined according to the modified thrombolysis in cerebral infarction (mTICI) score. Clinical outcomes were measured by the National Institute of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores. RESULTS: We included 52 patients (median age, 75 y IQR: 64-83); 31 (59.6%) women; 14 (26.9%) with terminal internal carotid artery occlusions, 26 (50%) middle cerebral artery (MCA) segment M1 occlusions, and 12 (23.1%) MCA segment M2 occlusions; median NIHSS score at admission was 19 (IQR: 13-22). After the first pass, 25 (48%) patients had mTICI ≥ 2c. At the end of the procedure, 47 (90.4%) had mTICI ≥ 2b and 35 (67.3%) had mTICI ≥ 2c. No serious device-related adverse events were observed. Symptomatic intracranial hemorrhage developed in 1 patient. Mean NIHSS score was 13 at 24 h and 5 at discharge. At 90 days, 24 (46.2%) patients were functionally independent (mRS 0-2). CONCLUSION: This preliminary study found good efficacy and safety for MIVI Q™ aspiration catheters used in combination with stent-retriever devices.

Venous tortuosity as a novel biomarker of rupture risk in arteriovenous malformations: ARI score.

BACKGROUND: Risk of rupture in arteriovenous malformations (AVMs) varies considerably among series. Hemodynamic factors, especially within the venous side of the circuit, seem to be responsible but are not yet well defined. We analyzed tortuosity in the draining vein as a potential new marker of rupture in AVMs, and propose a simple index to predict AVM bleeding. METHODS: A retrospective analysis of the venous angioarchitecture of brain AVMs was carried out at our center from 2013 to 2021, with special attention to venous tortuosity. After univariate analysis, the features of interest were combined to construct several predictive models using multivariate logistic regression. The best model proposed was the new AVM rupture index (ARI), which was then validated in an independent cohort. RESULTS: 68 AVMs were included in the first step and 32 in the validation cohort. Venous tortuosity, expressed as at least one curve >180°, was a significant predictor of rupture (p=0.023). The proposed bleeding index consisted of: venous tortuosity (any curve of >180°), single draining vein, and paraventricular/infratentorial location. It seems to be a robust evaluation tool, with an area under the receiver operating characteristic (AUROC) curve of 0.806 (95% CI 0.714 to 0.899), consistently replicated in the independent sample (AUROC 0.759 (95% CI 0.607 to 0.911)), and with an inter-rater kappa coefficient of 0.81 . CONCLUSIONS: Venous tortuosity may serve as a predictor of bleeding in AVMs that warrants further investigation. This likely new marker was one of the three elements of the proposed ARI. ARI outperformed the predictive accuracy of previous scores, and remained consistent in an independent cohort.

Addition of intracranial aspiration to balloon guide catheter does not improve outcomes in large vessel occlusion anterior circulation stent retriever based thrombectomy for acute stroke.

BACKGROUND: Balloon guide catheter (BGC) in stent retriever based thrombectomy (BGC+SR) for patients with large vessel occlusion strokes (LVOS) improves outcomes. It is conceivable that the addition of a large bore distal access catheter (DAC) to BGC+SR leads to higher efficacy. We aimed to investigate whether the combined BGC+DAC+SR approach improves angiographic and clinical outcomes compared with BGC+SR alone for thrombectomy in anterior circulation LVOS. METHODS: Consecutive patients with anterior circulation LVOS from June 2019 to November 2020 were recruited from the ROSSETTI registry. Demographic, clinical, angiographic, and outcome data were compared between patients treated with BGC+SR alone versus BGC+DAC+SR. The primary outcome was first pass effect (FPE) rate, defined as near complete/complete revascularization (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) after single device pass. RESULTS: We included 401 patients (BGC+SR alone, 273 (66.6%) patients). Patients treated with BGC+SR alone were older (median age 79 (IQR 68-85) vs 73.5 (65-82) years; p=0.033) and had shorter procedural times (puncture to revascularization 24 (14-46) vs 37 (24.5-63.5) min, p<0.001) than the BGC+DAC+SR group. Both approaches had a similar FPE rate (52% in BGC+SR alone vs 46.9% in BGC+DAC+SR, p=0.337). Although the BGC+SR alone group showed higher rates for final successful reperfusion (mTICI ≥2b (86.8% vs 74.2%, p=0.002) and excellent reperfusion, mTICI ≥2 c (76.2% vs 55.5%, p<0.001)), there were no significant differences in 24 hour National Institutes of Health Stroke Scale score or rates of good functional outcome (modified Rankin Scale score of 0-2) at 3 months across these techniques. CONCLUSIONS: Our data showed that addition of distal intracranial aspiration catheters to BGC+SR based thrombectomy in patients with acute anterior circulation LVO did not provide higher rates of FPE or improved clinical outcomes.

Stent-retriever alone versus combined use of stent-retriever and contact aspiration technique for middle cerebral artery M2 occlusions: a propensity score analysis.

BACKGROUND: The optimal endovascular treatment (EVT) technique for middle cerebral artery (MCA) M2 segment occlusions remains unknown. We aim to analyze whether reperfusion rate, procedure times, procedure-related complications, and clinical outcome differed between patients with isolated M2 occlusions who underwent stent-retriever (SR) alone versus combined SR and contact aspiration (CA) as a front-line EVT. METHODS: Patients who underwent EVT for isolated MCA-M2 occlusion were recruited from the prospectively ongoing ROSSETTI registry. Patients were divided regarding the EVT approach into SR alone versus SR+CA and propensity score matching was used to achieve baseline balance. Demographic, procedural, safety, and clinical outcomes were compared between groups. Multivariable logistic regression analysis was performed to identify independent predictors of first-pass effect (FPE) and 90-day modified Rankin scale (mRS) 0-2. RESULTS: 214 patients underwent EVT for M2 occlusion, 125 treated with SR alone and 89 with SR+CA. Propensity score matchnig analysis selected 134 matched patients. The rates of FPE (42% vs 40%, p=1.000) and 90-day mRS 0-2 (60% vs 51%, p=0.281) were comparable between groups. Patients treated with SR alone had lower need of rescue therapy (p=0.006), faster times to reperfusion (p<0.001), and lower procedure-related complications (p=0.031). Higher initial Alberta Stroke Program Early CT Score was an independent predictor of FPE. Age, baseline National Institutes of Health Stroke Scale score, and procedure duration were significant predictors of good clinical outcome at 3 months. CONCLUSIONS: As front-line modality in M2 occlusions, the SR alone approach results in similar rates of reperfusion and good clinical outcomes to combined SR+CA and might be advantageous due to faster reperfusion times and fewer adverse events.

Multimodal CT-assisted thrombolysis in patients with acute stroke: a cohort study.

BACKGROUND AND PURPOSE: The value of multimodal CT to assist thrombolysis has received little attention in stroke. METHODS: We assessed prospectively the impact derived from the routine application of CT perfusion and CTA in patients with acute stroke treated consecutively with alteplase. The safety and efficacy of thrombolytic therapy were compared in 106 patients assisted with CT/CTA/CT perfusion (multimodal CT group) and 262 patients assisted without full multimodal brain imaging (control group) during a 5-year period (2005-2009). RESULTS: Good outcome (modified Rankin scale score ≤2) at 3 months was increased in the multimodal group compared with controls (adjusted OR, 2.88; 95% CI, 1.50-5.52). Multimodal-assisted thrombolysis yielded superior benefits in patients treated beyond 3 hours (adjusted OR, 4.48; 95% CI, 1.68-11.98) than treated within 3 hours (adjusted OR, 1.31; 95% CI, 0.80-2.16; interaction test P=0.043). Mortality (14% and 15%) and symptomatic hemorrhage (5% and 7%) were similar in both groups. CONCLUSIONS: Multimodal CT use in routine clinical practice may heighten the overall efficacy of thrombolytic therapy in acute ischemic stroke. The benefits seem greater in patients treated >3 hours after stroke onset, but further randomized clinical trials are needed to confirm these findings.

Three-dimensional morphological analysis of intracranial aneurysms: a fully automated method for aneurysm sac isolation and quantification.

PURPOSE: Morphological descriptors are practical and essential biomarkers for diagnosis and treatment selection for intracranial aneurysm management according to the current guidelines in use. Nevertheless, relatively little work has been dedicated to improve the three-dimensional quantification of aneurysmal morphology, to automate the analysis, and hence to reduce the inherent intra and interobserver variability of manual analysis. In this paper we propose a methodology for the automated isolation and morphological quantification of saccular intracranial aneurysms based on a 3D representation of the vascular anatomy. METHOD: This methodology is based on the analysis of the vasculature skeleton's topology and the subsequent application of concepts from deformable cylinders. These are expanded inside the parent vessel to identify different regions and discriminate the aneurysm sac from the parent vessel wall. The method renders as output the surface representation of the isolated aneurysm sac, which can then be quantified automatically. The proposed method provides the means for identifying the aneurysm neck in a deterministic way. The results obtained by the method were assessed in two ways: they were compared to manual measurements obtained by three independent clinicians as normally done during diagnosis and to automated measurements from manually isolated aneurysms by three independent operators, nonclinicians, experts in vascular image analysis. All the measurements were obtained using in-house tools. The results were qualitatively and quantitatively compared for a set of the saccular intracranial aneurysms (n = 26). RESULTS: Measurements performed on a synthetic phantom showed that the automated measurements obtained from manually isolated aneurysms where the most accurate. The differences between the measurements obtained by the clinicians and the manually isolated sacs were statistically significant (neck width: p <0.001, sac height: p = 0.002). When comparing clinicians' measurements to automatically isolated sacs, only the differences for the neck width were significant (neck width: p <0.001, sac height: p = 0.95). However, the correlation and agreement between the measurements obtained from manually and automatically isolated aneurysms for the neck width: p = 0.43 and sac height: p = 0.95 where found. CONCLUSIONS: The proposed method allows the automated isolation of intracranial aneurysms, eliminating the interobserver variability. In average, the computational cost of the automated method (2 min 36 s) was similar to the time required by a manual operator (measurement by clinicians: 2 min 51 s, manual isolation: 2 min 21 s) but eliminating human interaction. The automated measurements are irrespective of the viewing angle, eliminating any bias or difference between the observer criteria. Finally, the qualitative assessment of the results showed acceptable agreement between manually and automatically isolated aneurysms.

Intraoperative magnetic resonance imaging for cerebral cavernous malformations: When is it maybe worth it?

OBJECTIVE: Intraoperative magnetic resonance imaging (iMRI) can be useful for cerebral cavernous malformations (CCM) surgery. However, literature on this topic is scarce. We aim to investigate its clinical utility and propose criteria for the selection of patients who may benefit the most from iMRI. METHODS: From 2017 to 2019, all patients with CCMs who required surgery assisted with iMRI were included in the study. Clinical and radiological features were analyzed. Outcome measures included the need for an immediate second-look resection and clinical course in early post-surgery -Timepoint 1- (Tp1) and at the 6-to-12-month follow-up -Timepoint2- (Tp2). RESULTS: Out of 19 patients with 20 CCMs, 89% had bleeding in the past, and in 75% the CCM affected an eloquent area. According to the iMRI results, an immediate second-look resection was needed in 16% of them. In one patient, a remnant was not seen on iMRI. The mRS worsened in the immediate post-surgical exam (median, 1; IQR, 1) with improvements on the 6-month visit (median, 1; IQR, 2), (p = 0.018). When comparing the outcome of patients with and without symptoms at baseline, the latter fared better at Tp2 (p = 0.005). CONCLUSIONS: iMRI is an intraoperative imaging tool that seems safe for CCM surgery and might reduce the risk of lesion remnants. In our series, it allowed additional revision for further resection in 16% of the patients. In our experience, iMRI may be especially useful for lesions in eloquent areas, those with a significant risk of brain shift and for large CCMs.

Edema Resolution and Clinical Assessment in Poor-Grade Subarachnoid Hemorrhage: Useful Indicators to Predict Delayed Cerebral Infarctions?

BACKGROUND: The level of consciousness and cerebral edema are among the indicators that best define the intensity of early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). Although these indicators are usually altered in patients with a poor neurological status, their usefulness for selecting patients at risk of cerebral infarction (CI) is not well established. Furthermore, little is known about the evolution of these indicators during the first week of post-ictal events. Our study focused on describing the association of the longitudinal course of these predictors with CI occurrence in patients with severe aSAH. METHODS: Out of 265 aSAH patients admitted consecutively to the same institution, 80 patients with initial poor neurological status (WFNS 4-5) were retrospectively identified. After excluding 25 patients with early mortality, a total of 47 patients who underwent early CT (<3 days) and late CT (<7 days) acquisitions were included in the study. Early cerebral edema and delayed cerebral edema were calculated using the SEBES score, and the level of consciousness was recorded daily during the first week using the Glasgow Coma Scale (GCS). RESULTS: There was a significant improvement in the SEBES (Early-SEBES median (IQR) = 3 (2-4) versus Delayed-SEBES = 2 (1-3); p = 0.001) and in GCS scores (B = 0.32; 95% CI 0.15-0.49; p = 0.001) during the first week. When comparing the ROC curves of Delayed-SEBES vs Early-SEBES as predictors of CI, no significant differences were found (Early-SEBES Area Under the Curve: 0.65; Delayed-SEBES: 0.62; p = 0.17). Additionally, no differences were observed in the relationship between the improvement in the GCS across the first week and the occurrence of CI (p = 0.536). CONCLUSIONS: Edema and consciousness level improvement did not seem to be associated with the occurrence of CI in a surviving cohort of patients with severe aSAH. Our results suggest that intensive monitoring should not be reduced in patients with a poor neurological status regardless of an improvement in cerebral edema and level of consciousness during the first week after bleeding.