Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial.

OBJECTIVE: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. METHODS: The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed). RESULTS: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. INTERPRETATION: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024.

Collateral Circulation in Thrombectomy for Stroke After 6 to 24 Hours in the DAWN Trial.

BACKGROUND AND PURPOSE: Collaterals govern the pace and severity of cerebral ischemia, distinguishing fast or slow progressors and corresponding therapeutic opportunities. The fate of sustained collateral perfusion or collateral failure is poorly characterized. We evaluated the nature and impact of collaterals on outcomes in the late time window DAWN trial (Diffusion-Weighted Imaging or Computed Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo). METHODS: The DAWN Imaging Core Lab prospectively scored collateral grade on baseline computed tomography angiography (CTA; endovascular and control arms) and digital subtraction angiography (DSA; endovascular arm only), blinded to all other data. CTA collaterals were graded with the Tan scale and DSA collaterals were scored by ASITN grade (American Society of Interventional and Therapeutic Neuroradiology collateral score). Descriptive statistics characterized CTA collateral grade in all DAWN subjects and DSA collaterals in the endovascular arm. The relationship between collateral grade and day 90 outcomes were separately analyzed for each treatment arm. RESULTS: Collateral circulation to the ischemic territory was evaluated on CTA (n=144; median 2, 0-3) and DSA (n=57; median 2, 1-4) before thrombectomy in 161 DAWN subjects (mean age 69.8±13.6 years; 55.3% women; 91 endovascular therapy, 70 control). CTA revealed a broad range of collaterals (Tan grade 3, n=64 [44%]; 2, n=45 [31%]; 1, n=31 [22%]; 0, n=4 [3%]). DSA also showed a diverse range of collateral grades (ASITN grade 4, n=4; 3, n=22; 2, n=27; 1, n=4). Across treatment arms, baseline demographics, clinical variables except atrial fibrillation (41.6% endovascular versus 25.0% controls, P=0.04), and CTA collateral grades were balanced. Differences were seen across the 3 levels of collateral flow (good, fair, poor) for baseline National Institutes of Health Stroke Scale, blood glucose <150, diabetes, previous ischemic stroke, baseline and 24-hour core infarct volume, baseline and 24-hour Alberta Stroke Program Early CT Score, dramatic infarct progression, final Thrombolysis in Cerebral Infarction 2b+, and death. Collateral flow was a significant predictor of 90-day modified Rankin Scale score of 0 to 2 in the endovascular arm, with 43.7% (31/71) of subjects with good collaterals, 30.8% (16/52) of subjects with fair collaterals, and 17.7% (6/34) of subjects with poor collaterals reaching modified Rankin Scale score of 0 to 2 at 90 days (P=0.026). CONCLUSIONS: DAWN subjects enrolled at 6 to 24 hours after onset with limited infarct cores had a wide range of collateral grades on both CTA and DSA. Even in this late time window, better collaterals lead to slower stroke progression and better functional outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02142283.

FLAIR vascular hyperintensities predict functional outcome after endovascular thrombectomy in patients with large ischemic cores.

OBJECTIVES: To establish whether collateral circulation was associated with functional outcome in stroke patients with large infarct size (Alberta Stroke Program Early CT Score [ASPECTS] ≤ 5) undergoing endovascular thrombectomy (EVT) METHODS: Consecutive patients with acute ischemic stroke due to large-vessel occlusion in the anterior circulation and an ASPECTS of ≤ 5 were analyzed. Quantification of collateral circulation was performed using a fluid-attenuated inversion recovery vascular hyperintensity (FVH)-ASPECTS rating system (score ranging from 0 [no FVH] to 7 [FVHs abutting all ASPECTS cortical areas]) by two independent neuroradiologists. Good functional outcome was defined by modified Rankin Scale (mRS) score of 0 to 3 at 3 months. We determined the association between FVH score and clinical outcome using multivariable regression analyses. RESULTS: A total of 139 patients (age, 63.1 ± 20.8 years; men, 51.8%) admitted between March 2012 and December 2017 were included. Good functional outcome (mRS 0-3) was observed in 65 (46.8%) patients, functional independence (mRS 0-2) was achieved in 43 (30.9%) patients, and 33 (23.7%) patients died at 90 days. The median FVH score was 4 (IQR, 3-5). FVH score was independently correlated with good outcome (adjusted OR = 1.41 [95% CI, 1.03-1.92]; p = 0.03 per 1-point increase). CONCLUSIONS: In stroke patients with large-volume infarcts, good collaterals as measured by the FVH-ASPECTS rating system are associated with improved outcomes and may help select patients for reperfusion therapy. KEY POINTS: • Endovascular thrombectomy can allow almost 1 in 2 patients with large infarct cores to achieve good functional outcome (modified Rankin Scale [mRS] of 0-3) and 1 in 3 patients to regain functional independence (mRS 0-2) at 3 months. • The extent of FVH score (as reflected by FLAIR vascular hyperintensity [FVH]-Alberta Stroke Program Early CT Score [ASPECTS] values) is associated with functional outcome at 3 months in this patient group.

White Matter Hyperintensity Burden and Collateral Circulation in Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: White matter hyperintensity (WMH), a marker of chronic cerebral small vessel disease, might impact the recruitment of leptomeningeal collaterals. We aimed to assess whether the WMH burden is associated with collateral circulation in patients treated by endovascular thrombectomy for anterior circulation acute ischemic stroke. METHODS: Consecutive acute ischemic stroke due to anterior circulation large vessel occlusion and treated with endovascular thrombectomy from January 2015 to December 2017 were included. WMH volumes (periventricular, deep, and total) were assessed by a semiautomated volumetric analysis on fluid-attenuated inversion recovery-magnetic resonance imaging. Collateral status was graded on baseline catheter angiography using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system (good when ≥3). We investigated associations of WMH burden with collateral status. RESULTS: A total of 302 patients were included (mean age, 69.1±19.4 years; women, 55.6%). Poor collaterals were observed in 49.3% of patients. Median total WMH volume was 3.76 cm3 (interquartile range, 1.09-11.81 cm3). The regression analyses showed no apparent relationship between WMH burden and the collateral status measured at baseline angiography (adjusted odds ratio, 0.987 [95% CI, 0.971-1.003]; P=0.12). CONCLUSIONS: WMH burden exhibits no overt association with collaterals in large vessel occlusive stroke.

Stroke Imaging Selection Modality and Endovascular Therapy Outcomes in the Early and Extended Time Windows.

BACKGROUND AND PURPOSE: Advanced imaging has been increasingly used for patient selection in endovascular stroke therapy. The impact of imaging selection modality on endovascular stroke therapy clinical outcomes in extended time window remains to be defined. We aimed to study this relationship and compare it to that noted in early-treated patients. METHODS: Patients from a prospective multicentric registry (n=2008) with occlusions involving the intracranial internal carotid or the M1- or M2-segments of the middle cerebral arteries, premorbid modified Rankin Scale score 0 to 2 and time to treatment 0 to 24 hours were categorized according to treatment times within the early (0-6 hour) or extended (6-24 hour) window as well as imaging modality with noncontrast computed tomography (NCCT)±CT angiography (CTA) or NCCT±CTA and CT perfusion (CTP). The association between imaging modality and 90-day modified Rankin Scale, analyzed in ordinal (modified Rankin Scale shift) and dichotomized (functional independence, modified Rankin Scale score 0-2) manner, was evaluated and compared within and across the extended and early windows. RESULTS: In the early window, 332 patients were selected with NCCT±CTA alone while 373 also underwent CTP. After adjusting for identifiable confounders, there were no significant differences in terms of 90-day functional disability (ordinal shift: adjusted odd ratio [aOR], 0.936 [95% CI, 0.709-1.238], P=0.644) or independence (aOR, 1.178 [95% CI, 0.833-1.666], P=0.355) across the CTP and NCCT±CTA groups. In the extended window, 67 patients were selected with NCCT±CTA alone while 180 also underwent CTP. No significant differences in 90-day functional disability (aOR, 0.983 [95% CI, 0.81-1.662], P=0.949) or independence (aOR, 0.640 [95% CI, 0.318-1.289], P=0.212) were seen across the CTP and NCCT±CTA groups. There was no interaction between the treatment time window (0-6 versus 6-24 hours) and CT selection modality (CTP versus NCCT±CTA) in terms of functional disability at 90 days (P=0.45). CONCLUSIONS: CTP acquisition was not associated with better outcomes in patients treated in the early or extended time windows. While confirmatory data is needed, our data suggests that extended window endovascular stroke therapy may remain beneficial even in the absence of advanced imaging.

Serial ASPECTS in the DAWN Trial: Infarct Evolution and Clinical Impact.

Background and Purpose: The impact of baseline ischemia on Alberta Stroke Program Early CT Score (ASPECTS) and evolution over 24 hours may be distinct in late thrombectomy. We analyzed predictors of serial ASPECTS and clinical outcomes in the DAWN trial (Diffusion-Weighted Imaging or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo). Methods: The DAWN Imaging Core Laboratory independently scored ASPECTS at baseline and 24 hours. Descriptive statistics characterized ASPECTS on computed tomography/magnetic resonance imaging at baseline and 24 hours, delineating ASPECTS change over 24 hours. Results: 206 subjects (mean age 70.0±13.7 years; 54.9% (n=113) female; baseline National Institutes of Health Stroke Scale median (interquartile range) 17 (13, 21) were included. Baseline ASPECTS was median (interquartile range) 8.0 (7­8), with 92/205 (44.9%) between 0 and 7 and 113/205 (55.1%) 8 and 10. 24-hour ASPECTS was median 6.0 (4­8), with ASPECTS change or infarct evolution having median −1, ranging from −8 to +2. Multivariable logistic regression showed older age (odds ratio [OR] for 10-year interval, 1.26 [95% CI, 1.02­1.55], P=0.030) and dyslipidemia (OR, 1.84 [95% CI, 1.06­3.19], P=0.031) were independently associated with higher baseline ASPECTS. Higher 24-hour ASPECTS was predicted by endovascular treatment (OR, 2.76 [95% CI, 1.58­4.81], P=0.0004), baseline glucose <150 mg/dL (OR, 2.86 [95% CI, 1.50­5.46], P=0.001), lower baseline National Institutes of Health Stroke Scale (OR, 0.93 [95% CI, 0.89­0.98], P=0.010), and older age (OR for 10-year interval, 1.25 [95% CI, 1.01­1.55], P=0.041). Internal carotid artery lesion location (OR, 0.47 [95% CI, 0.24­0.89], P=0.021) was inversely related to 24-hour ASPECTS. Good clinical outcome (day 90 modified Rankin Scale score 0­2) was predicted by 24-hour ASPECTS (OR, 1.46 [95% CI, 1.08­1.96], P=0.014). Extensive infarct evolution (ASPECTS decrease ≥6) occurred in 14/201 (7.0%). Elevated baseline serum glucose ≥150 mg/dL was a predictor of ASPECTS decrease of ≥4 points (OR, 2.78 [95% CI, 1.21­6.35] P=0.016) as was internal carotid artery occlusion (OR, 2.49 [95% CI, 1.05­5.88]; P=0.038). ASPECTS change was influenced by treatment arm (P=0.001 by Wilcoxon), including 0 ASPECTS change in 42/105 (40.0%) of the endovascular arm and only 20/96 (20.8%) of the medical arm. Conclusions: DAWN subjects enrolled with small infarct cores had a broad range of baseline ASPECTS. Twenty-four-hour ASPECTS, strikingly influenced by endovascular therapy, predicted good clinical outcomes. Registration: https://www.clinicaltrials.gov; Unique identifier: NCT02142283.

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct.

BACKGROUND: The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. METHODS: We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days. RESULTS: A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00). CONCLUSIONS: Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .).

FLAIR vascular hyperintensities and functional outcome in nonagenarians with anterior circulation large-vessel ischemic stroke treated with endovascular thrombectomy.

OBJECTIVES: To establish whether imaging assessments of irreversibly injured ischemic core and potentially salvageable penumbral volumes and collateral circulation were associated with functional outcome in nonagenarians (90 years or older) undergoing endovascular thrombectomy (EVT). METHODS: Data from a prospectively maintained institutional registry of consecutive stroke patients treated with EVT from January 2012 to December 2018 were retrospectively analyzed. Functional outcome was evaluated with the modified Rankin scale (mRS) at 3 months. mRS score of 0-3 was defined as a good clinical outcome. Ischemic core and penumbral volumes were calculated using the RAPID software. Quantification of collateral circulation was performed using a fluid-attenuated inversion recovery vascular hyperintensity (FVH)-Alberta Stroke Program Early CT Score (ASPECTS) rating system. RESULTS: Among 85 patients (age, 92.4 ± 2.6 years; men, 30.6%) treated with EVT, good outcome (mRS 0-3) was achieved in 29 (34.1%) patients and 31 (36.5%) patients died at 90 days. The median estimated ischemic core volume was 15 mL (IQR, 7-27 mL). The median mismatch volume was 83 mL (IQR, 43-120 mL). The median FVH score was 4 (IQR, 3-4). FVH score was independently associated with good functional outcome (adjusted OR = 1.96 [95% CI, 1.16-3.32]; p = 0.01 per 1-point increase) and mortality (adjusted OR = 0.54 [95% CI, 0.34-0.85]; p = 0.007 per 1-point increase). Ischemic core and mismatch volumes were associated with neither good outcome nor mortality. CONCLUSIONS: In nonagenarians with anterior circulation large-vessel ischemic stroke, good collaterals as measured by the FVH-ASPECTS rating system are independently associated with improved outcomes and may help select patients for reperfusion therapy in this frail population. KEY POINTS: • Endovascular thrombectomy can allow at least 1 in 3 patients older than 90 years of age to achieve good functional outcome (modified Rankin scale of 0-3) at 3 months. • Functional outcome at 3 months is associated with pre-stroke status (number and severity of patients' comorbidities). • A higher FVH score (as reflected by higher FLAIR vascular hyperintensity [FVH]-Alberta Stroke Program Early CT Score [ASPECTS] values) is independently associated with better 3-month functional outcome and mortality in nonagenarians with anterior circulation ischemic stroke.

Impact of endovascular reperfusion therapy in nonagenarians with anterior circulation large-vessel ischaemic stroke.

BACKGROUND AND PURPOSE: The benefit of endovascular thrombectomy (EVT) among nonagenarians (90 years or older) is poorly documented. We aimed to investigate the clinical and imaging factors associated with good outcomes and mortality at 90 days in nonagenarians undergoing EVT for acute ischemic stroke (AIS). METHODS: Data from a prospectively maintained institutional registry of consecutive AIS patients treated with EVT from January 2012 to December 2018 were retrospectively analysed. Comorbid conditions were classified with a modified version of the Charlson Comorbidity Index (CCI). The degree of disability was assessed by the modified Rankin Scale (mRS). Outcomes included good functional outcome (mRS scores of 0-3) and mortality at 90 days. RESULTS: Among 110 patients (age, 92.3 ± 2.5 years; men, 28.2%) treated with EVT, good outcome was achieved in 39 (35.5%) patients, successful reperfusion (modified Thrombolysis in Cerebral Infarction grades of 2b-3) was achieved in 78 (70.9%) patients and 38 (34.5%) patients died at 90 days. The functional outcome at 3 months was associated with pre-stroke status (CCI and pre-stroke mRS score). Successful reperfusion (adjusted odds ratio [OR], 11.6; 95% CI, 1.3-104.2; P = 0.03) and early neurologic improvement at 24 h (adjusted OR, 16.4; 95% CI, 5.2-51.5; P < 0.001) were independent predictors of a good outcome. Early neurological improvement (adjusted OR, 0.06; 95% CI, 0.02-0.23; P < 0.001) was an independent predictor of 90-day mortality. CONCLUSIONS: Successful reperfusion therapy improves the functional outcome of nonagenarians who should not be excluded from EVT. The presence and severity of comorbidities should be considered in the procedural management of this vulnerable population.

Optimal intracranial pressure in patients with aneurysmal subarachnoid hemorrhage treated with coiling and requiring external ventricular drainage.

Optimal management of intracranial pressure (ICP) among aneurysmal subarachnoid hemorrhage (aSAH) patients requiring external ventricular drainage (EVD) is controversial. To analyze predictors of delayed cerebral ischemia (DCI)-related cerebral infarction after aSAH and the influence of ICP values on DCI, we prospectively collected consecutive patients with aSAH receiving coiling and requiring EVD. Predictors of DCI-related cerebral infarction (new CT hypodensities developed within the first 3 weeks not related to other causes) were studied. Vasospasm and brain hypoperfusion were studied with CT angiography and CT perfusion (RAPID-software). Among 50 aSAH patients requiring EVD, 21 (42%) developed DCI-related cerebral infarction, while 27 (54%) presented vasospasm. Mean ICP ranged between 2 and 19 mmHg. On the multivariate analysis, the mean ICP (OR = 2, 95%CI = 1.01-3.9, p = 0.042) and the mean hypoperfusion volume on Tmax delay > 6 (OR = 1.2, 95%CI = 1.01-1.3, p = 0.025) were independent predictors of DCI. To predict DCI-related cerebral infarction, Tmax delay > 6 s presented the highest AUC (0.956, SE = 0.025), with a cutoff value of 18 ml showing sensitivity, specificity, PPV, NPV, and accuracy of 90.5% (95%CI = 69-98.8%), 86.2% (95%CI = 68.4-96%), 82.6% (95%CI = 65.4-92%), 92.5% (95%CI = 77-98%), and 88% (95%CI = 75-95%), respectively. The AUC of the mean ICP was 0.825 (SE = 0.057), and the best cutoff value was 6.7 mmHg providing sensitivity, specificity, PPV, NPV, and accuracy of 71.4% (95%CI = 48-89%), 62% (95%CI = 42-79%), 58% (95%CI = 44-70%), 75% (95%CI = 59-86%), and 66% (95%CI = 51-79%) for the prediction of DCI-related cerebral infarction, respectively. Among aSAH patients receiving coiling and EVD, lower ICP (< 6.7 mmHg in our study) could potentially be beneficial in decreasing DCI-related cerebral infarction. Brain hypoperfusion with a volume > 18 ml at Tmax delay > 6 s presents a high sensibility and specificity in prediction of DCI-related cerebral infarction.

Anterior cranial fossa dural arteriovenous fistula: Transarterial embolization from the ophthalmic artery as first-line treatment.

OBJECTIVE: To retrospectively review the outcome of patients with dural arteriovenous fistula of the anterior cranial fossa (afDAVF) treated by transarterial embolization. MATERIAL AND METHODS: Six consecutive patients were referred to our hospital for afDAVF treatment. After a multidisciplinary discussion, they underwent endovascular embolization with Onyx injection through the ophthalmic artery. Their clinical presentation, management and outcomes were retrospectively assessed. RESULTS: All interventions were performed with the liquid embolic agent Onyx through the transarterial route from the ophthalmic artery to access the fistulous point. All patients showed a good outcome with complete afDAVF obliteration. CONCLUSION: This study demonstrates that afDAVFs can be safely and completely obliterated by transarterial embolization via the ophthalmic artery.

Safety and efficacy of the Silk flow diverter: Insight from the DIVERSION prospective cohort study.

BACKGROUND AND PURPOSE: Flow diverters are considered as an essential tool in the stent-based treatment of complex intracranial aneurysms. We report here a subgroup analysis of the nationwide prospective DIVERSION study to investigate the safety and efficacy of the Silk flow diverter at 12 months follow-up. METHODS: We performed a subgroup analysis of patients included in the DIVERSION, a national prospective cohort study including all flow diverters placement between 2012 and 2014 in France, and treated with the Silk. The primary outcome was the morbi-mortality at 12 months, including death, morbidity event and aneurysm retreatment within 12 months post-treatment. All reported serious events were adjudicated by an independent Data Safety and Monitoring Board. Satisfactory occlusion was defined as 3 or 4 on Kamran's scale by an independent imaging core laboratory during follow-up. RESULTS: A total of 102 procedures involving 101 patients (mean age±standard deviation, 54.3±13.5 years) harbouring 118 aneurysms (113/118 located in the anterior circulation; mean size 8.2±7.1mm) were included. During the 12-month follow-up, 34 (33.3%) procedures experienced at least one morbi-mortality event: 3 deaths, 27 morbidity events and 4 retreatments. Overall, 1/3 deaths and 10/27 morbidity events were related to the device and/or the procedure, leading to a specific survival rate and a specific free-morbidity survival rate at 12 months of 98.98% [95% confidence interval, 92.98%-99.86%] and 89.73% [95%CI, 81.71%-94.36%], respectively. The rate of permanent-related neurological deficit was 5.9% within 12 months. One year follow-up imaging showed satisfactory occlusion in 82.2% of cases. CONCLUSION: Flow diversion with the Silk device has a reasonable safety and effectiveness profile for the endovascular treatment of intracranial aneurysms.

Impact of Periprocedural and Technical Factors and Patient Characteristics on Revascularization and Outcome in the DAWN Trial.

Background and Purpose- Because of unique attributes of mechanical thrombectomy performed between 6 and 24 hours after symptom onset in acute ischemic stroke patients, it is not known if predictors of angiographic recanalization and favorable outcome in patients treated with thrombectomy in the late (6-24 hour) time window are similar to those treated in the early time window. Methods- We analyzed data from the DAWN trial (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) which enrolled patients with symptom onset 6 to 24hours after last known well and occlusion of the intracranial internal carotid artery or proximal middle cerebral artery with a mismatch between severity of clinical deficit and infarct core volume as identified by computed tomography-perfusion or diffusion magnetic resonance imaging. We evaluated the effect of tandem occlusions, periprocedural heparin use, procedural speed (from puncture to procedure completion), general anesthesia, balloon-guide catheters, thrombectomy device size, and number of passes on substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b/3) and on likelihood of obtaining a modified Rankin Scale at 3 months indicating functional independence. Results- Of 107 patients who underwent MT in the interventional arm of DAWN, substantial reperfusion and modified Rankin Scale score 0 to 2 at 3 months was seen in 90 (84%) and 52 (49%), respectively. In univariate analysis, general anesthesia (odds ratio [OR] 0.27; P=0.042) and ≥3 passes with stent retriever (OR, 0.17; P=0.002) were inversely associated with substantial reperfusion. In multivariate analyses, only ≥3 passes were associated with lack of revascularization (OR, 0.17; P=0.002). in univariate analysis ≥3 passes (OR, 0.24; P =0.003) and baseline National Institutes of Health Stroke Scale score >17 (OR, 0.19; P<0.001) were inversely associated with functional independence at 3 months. In multivariate analyses, ≥3 passes (OR, 0.24; P=0.003) and National Institutes of Health Stroke Scale score >17 (OR, 0.19; P<0.001) remained inversely associated with favorable outcome at 3 months. Conclusions- Patients requiring ≥3 thrombectomy passes had reduced substantial reperfusion and favorable outcome at 3 months in DAWN. Whether or not additional thrombectomy techniques beyond ≥3 thrombectomy passes with the Trevo stent retriever are beneficial for patient outcomes in this patient population remains to be clarified by future studies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02142283.

Complications During Inter-Hospital Transfer of Patients with Acute Ischemic Stroke for Endovascular Therapy.

Purpose: Few data are available on complications occurring during inter-hospital transfer from a primary stroke center (PSC) to a comprehensive stroke center (CSC) for endovascular treatment (EVT) after large vessel occlusion (LVO). Therefore, we prospectively studied data from consecutive patients transferred from our PSC to the next CSC during 4 years to determine the incidence and risk factors of complications during transfer. Methods: This observational, single-center study included consecutive patients transferred from January 1, 2015 to December 31, 2018. During inter-hospital transfer, all medical incidents were systematically recorded. A new complete clinical examination was performed on arrival at the CSC. Results: Among the 253 patients transferred to the CSC during the study period, 68 (26.9%) had one or more complications. In 11 patients (4.3%) these were life-threatening and required emergency intervention by a physician. Baseline characteristics were not different between patients with and without complications, except for the LVO location. Specifically, basilar artery (BA) occlusion was strongly associated with complications during the transport (p < 0.0005). Conclusion: Complications occurred in 26.9% of patients during transfer. Only BA occlusion could predict complication during transfer. Future studies should identify variables to help stratifying patients at high and low risk of complications during transportation.

WEB-assisted microwire navigation for the treatment of complex wide-neck intracranial aneurysms: Technical note.

BACKGROUND: Unfavorable aneurysm anatomy can make microwire navigation challenging, increasing the risk of complications. We present our experience of WEB-assisted microcatheterization in complex aneurysms. CLINICAL PRESENTATION: Flow diversion was performed for three wide-neck large/giant intracranial aneurysms. A WEB was placed inside the sac, blocking the aneurysm neck and providing a contact surface to redirect the microwire across the aneurysm. CONCLUSION: WEB-assisted microcatheterization appears an alternative strategy for the treatment of complex aneurysms.

Chronic occlusion of the internal carotid artery: Endovascular revascularization technique of long occlusive lesions.

BACKGROUND: Despite series of endovascular recanalization of chronically occluded ICA (COICA) have been already reported, technical aspects of this strategy were not described. We discussed technical details and feasibility of this strategy. CLINICAL PRESENTATION: Five COICA (C1-cavernous ICA) patients presenting symptomatic hypoperfusion were recanalized with multiple coronary and carotid stents. All patients experienced long-term reperfusion with resolution of the clinical symptoms. CONCLUSION: Endovascular revascularization of COICA appears feasible and associated with improvement of the hypoperfusion.

Flow Diverters for Intracranial Aneurysms: The DIVERSION National Prospective Cohort Study.

Background and Purpose- Flow diverters are used for endovascular therapy of intracranial aneurysms. We did a nationwide prospective study to investigate the safety and effectiveness of flow diversion at 12 months. Methods- DIVERSION was a national prospective cohort study including all flow diverters placement between October 2012 and February 2014 in France. The primary end point was the event-free survival rate at 12 months, defined as the occurrence of morbidity (intracranial hemorrhage, ischemic stroke, noncerebral hemorrhage, or neurological deficit due to mass effect), retreatment, or death within 12 months post-treatment. A quality control was carried out on 100% of the collected data and of at least 10% of the included patients in each center, chosen at random. All reported serious events were adjudicated by an independent Data Safety and Monitoring Board. Satisfactory occlusion was defined as 3 or 4 on Kamran scale by an independent imaging core laboratory at 12 months. Results- We enrolled 398 patients harboring 477 intracranial aneurysms. At least 1 morbidity-mortality event was noted in 95 of 408 interventions representing an event-free survival rate of 75.7% (95% CI, 71.1-79.7). The rate of permanent-related serious events and mortality was 5.9% and 1.2% at 12 months, respectively. Multivariate analysis showed that high baseline blood pressure (hazard ratio, 2.54; 95% CI, 1.35-4.79; P=0.039), diabetes mellitus (hazard ratio, 3.70; 95% CI, 1.60-8.6; P=0.0022), and larger aneurysms (hazard ratio, 1.07; 95% CI, 1.04-1.11; P<0.0001) were associated with the occurrence of a neurological deficit. The satisfactory occlusion rate at 12 months was 79.9%, and the absence of high baseline blood pressure (odds ratio, 2.01; 95% CI, 1.12-3.71; P=0.0193) and postprocedural satisfactory occlusion (odds ratio, 2.75; 95% CI, 1.49-5.09; P=0.0012) were associated with a 12-month satisfactory occlusion. Conclusions- A satisfactory occlusion was achieved in almost 80% of cases after flow diverter treatment with a permanent-related serious event and mortality rates of 5.9% and 1.2% at 12 months, respectively.

Outcome in Direct Versus Transfer Patients in the DAWN Controlled Trial.

Background and Purpose- The impact of transfer status on clinical outcomes in the DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) population is unknown. We analyzed workflow and clinical outcome differences between direct versus transfer patients in the DAWN population. Methods- The following time metrics were analyzed for each group: (1) last known well to hospital arrival, (2) hospital arrival to eligibility imaging, (3) hospital arrival to arterial puncture, (4) qualifying imaging to arterial puncture, (5) last known well to arterial puncture, (6) last known well to reperfusion. The primary end point was the rate of functional independence (90-day modified Rankin Scale [mRS] score, 0-2). Using univariate unconditional logistic regression, we calculated odds ratios and 95% CIs for the association between clinically relevant time metrics, transfer status, and functional independence (mRS 0-2). Results- A total of 206 patients were enrolled. Among these, 121 (59%) patients were transferred, and 85 (41%) patients presented directly to a thrombectomy capable center. Median time last seen well to hospital arrival time was similar between the 2 groups (678 versus 696 minutes). The time from hospital arrival to groin puncture was significantly longer in direct patients compared with transferred patients 140 minutes (interquartile range, 105.5-177.5 minutes) and 88 minutes (interquartile range, 55-125 minutes), respectively (P<0.001). Differences in treatment effect or differences in rates of mRS 0-2 in the thrombectomy treated patients were not statistically significant in direct versus transfer patients (odds ratios for mRS 0-2, thrombectomy versus control, were 5.62 in direct and 6.63 in transfer patients, respectively, Breslow-Day P=0.817). Conclusions- Although transfer patients had a faster door to puncture time, benefits of thrombectomy, and rates of mRS 0 to 2 in the treatment group were similar between direct and transferred patients in the DAWN population. These results may inform prehospital and primary stroke centers triage protocols in patients presenting in the late time window. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02142283.

Noncontrast Computed Tomography Alberta Stroke Program Early CT Score May Modify Intra-Arterial Treatment Effect in DAWN.

Background and Purpose- It is unknown whether noncontrast computed tomography (NCCT) can identify patients who will benefit from intra-arterial treatment (IAT) in the extended time window. We sought to characterize baseline Alberta Stroke Program Early CT Score (ASPECTS) in DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and to assess whether ASPECTS modified IAT effect. Methods- Core lab adjudicated ASPECTS scores were analyzed. The trial cohort was divided into 2 groups by qualifying imaging (computed tomography versus magnetic resonance imaging). ASPECTS-by-treatment interaction was tested for the trial coprimary end points (90-day utility-weighted modified Rankin Scale (mRS) score and mRS, 0-2), mRS 0 to 3, and ordinal mRS. ASPECTS was evaluated separately as an ordinal and a dichotomized (0-6 versus 7-10) variable. Results- Of 205 DAWN subjects, 123 (60%) had NCCT ASPECTS, and 82 (40%) had diffusion weighted imaging ASPECTS. There was a significant ordinal NCCT ASPECTS-by-treatment interaction for 90-day utility-weighted mRS (interaction P=0.04) and mRS 0 to 2 (interaction P=0.02). For both end points, IAT effect was more pronounced at higher NCCT ASPECTS. The dichotomized NCCT ASPECTS-by-treatment interaction was significant only for mRS 0 to 2 (interaction P=0.04), where greater treatment benefit was seen in the ASPECTS 7 to 10 group (odds ratio, 7.50 [2.71-20.77] versus odds ratio, 0.48 [0.04-5.40]). A bidirectional treatment effect was observed in the NCCT ASPECTS 0 to 6 group, with treatment associated with not only more mRS 0 to 3 outcomes (50% versus 25%) but also more mRS 5 to 6 outcomes (40% versus 25%). There was no significant modification of IAT effect by diffusion weighted imaging ASPECTS. Conclusions- Baseline NCCT ASPECTS appears to modify IAT effect in DAWN. Higher NCCT ASPECTS was associated with greater benefit from IAT. No treatment interaction was observed for diffusion weighted imaging ASPECTS.

Benefit of Endovascular Thrombectomy by Mode of Onset: Secondary Analysis of the DAWN Trial.

Background and Purpose- It is unknown whether the benefit of thrombectomy in late presenting acute stroke patients with imaging evidence of clinical-infarct mismatch is different in patients presenting with wake-up stroke compared with those presenting with witnessed onset or unwitnessed onset. Methods- Prespecified secondary analysis was performed from DAWN (Diffusion Weighted Imaging [DWI] or Computerized Tomography Perfusion [CTP] Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention), a multicenter, prospective, randomized clinical trial with blinded end point assessment comparing thrombectomy with the Trevo device against standard medical therapy in patients with acute stroke and clinical-infarct mismatch presenting 6 to 24 hour after the time last seen well. For the purposes of this study, the primary outcome was the proportion of modified Rankin Scale score 0 to 2 at 90 days. Univariable analysis and multivariable logistic regression was used to assess the relationship between outcome and mode of onset. Results- All 206 enrolled patients were included in the study. Mode of onset was: wake-up stroke (55.3%, n=114), witnessed onset (12.1%, n=25), and unwitnessed onset (32.5%, n=67) with median time last seen well to randomization (13.4±3.7, 10.0±3.7, 14.1±4.9 hours) respectively. Rates of 90-day modified Rankin Scale score of 0 to 2 and symptomatic intracerebral hemorrhage in the thrombectomy arm were not statistically different across patient onset subtypes (P=0.79 and P=0.40, respectively). The benefit of thrombectomy compared with best medical therapy was maintained across all 3 onset modes (rates of 90-day modified Rankin Scale score of 0 to 2 in patients allocated to thrombectomy versus control: wake-up stroke-49.3% versus 10.6%, witnessed onset-63.6% versus 21.4%, UW-41.4% versus 13.2%; P×interaction=0.79). In univariable and multivariable analyses, mode of onset was not identified as a significant predictor of modified Rankin Scale score 0 to 2 at 90 days. Conclusions- In patients with acute ischemic stroke presenting between 6 and 24 hours from time last seen well and harboring clinical-infarct mismatch, the benefit of thrombectomy was similar regardless of the wake-up, unwitnessed, or witnessed mode of onset.