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;96:356-364.

Large vessel occlusion prediction scale thresholds that are sensitive for DAWN Trial patients.

BACKGROUND: Large vessel occlusion (LVO) prediction scales are used to triage prehospital suspected stroke patients with a high probability of LVO stroke to endovascular therapy centers. The sensitivities of these scales in the 6-to-24-h time window are unknown. Higher scale score thresholds are typically less sensitive and more specific. Knowing the highest scale score thresholds that remain sensitive could inform threshold selection for clinical use. Sensitivities may also vary between left and right-sided LVOs. METHODS: LVO prediction scale scores were retrospectively calculated using the National Institutes of Health Stroke Scale (NIHSS) scores of patients enrolled in the DAWN Trial. All patients had last known well times between 6 and 24 h, NIHSS scores ≥ 10, intracranial internal carotid artery or proximal middle cerebral artery occlusions, and mismatches between their clinical severities and infarct core volumes. Scale thresholds with sensitivities ≥ 85% were identified, along with scores ≥ 5% more sensitive for left or right-sided LVOs. Specificities could not be calculated because all patients had LVOs. RESULTS: A total of 201 out of 206 patients had the required NIHSS subitem scores. CPSS = 3, C-STAT ≥ 2, FAST-ED ≥ 4, G-FAST ≥ 3, RACE ≥ 5, and SAVE ≥ 3 were the highest thresholds that were still 85% sensitive for DAWN Trial LVO stroke patients. RACE ≥ 5 was the only typically used score threshold more sensitive for right-sided LVOs, though similar small differences were seen for other scales at higher thresholds. CONCLUSIONS: Our findings likely represent the maximum sensitivities of the LVO prediction scales tested for ideal thrombectomy candidates in the 6-to-24-h time window because NIHSS scores were documented in hospitals during a clinical trial rather than in the prehospital setting. Patients with NIHSS scores < 10 or more distal LVOs would lower sensitivities further. Selecting even higher scale thresholds for LVO triage would lead to many missed LVO strokes.

Admission systolic blood pressure and effect of endovascular treatment in patients with ischaemic stroke: an individual patient data meta-analysis.

BACKGROUND: Current guidelines for ischaemic stroke treatment recommend a strict, but arbitrary, upper threshold of 185/110 mm Hg for blood pressure before endovascular thrombectomy. Nevertheless, whether admission blood pressure influences the effect of endovascular thrombectomy on outcome remains unknown. Our aim was to study the influence of admission systolic blood pressure (SBP) on functional outcome and on the effect of endovascular thrombectomy. METHODS: We used individual patient data from seven randomised controlled trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, PISTE, and THRACE) that randomly assigned patients with anterior circulation ischaemic stroke to endovascular thrombectomy (predominantly using stent retrievers) or standard medical therapy (control) between June 1, 2010, and April 30, 2015. We included all patients for whom SBP data were available at hospital admission. The primary outcome was functional outcome (modified Rankin Scale) at 90 days. We assessed the association of SBP with outcome in both the endovascular thrombectomy group and the control group using multilevel regression analysis and tested for non-linearity and for interaction between SBP and effect of endovascular thrombectomy, taking into account treatment with intravenous thrombolysis. FINDINGS: We included 1753 patients (867 assigned to endovascular thrombectomy, 886 assigned to control) after excluding 11 patients for whom SBP data were missing. We found a non-linear association between SBP and functional outcome with an inflection point at 140 mm Hg (732 [42%] of 1753 patients had SBP <140 mm Hg and 1021 [58%] had SBP ≥140 mm Hg). Among patients with SBP of 140 mm Hg or higher, admission SBP was associated with worse functional outcome (adjusted common odds ratio [acOR] 0·86 per 10 mm Hg SBP increase; 95% CI 0·81-0·91). We found no association between SBP and functional outcome in patients with SBP less than 140 mm Hg (acOR 0·97 per 10 mm Hg SBP decrease, 95% CI 0·88-1·05). There was no significant interaction between SBP and effect of endovascular thrombectomy on functional outcome (p=0·96). INTERPRETATION: In our meta-analysis, high admission SBP was associated with worse functional outcome after stroke, but SBP did not seem to negate the effect of endovascular thrombectomy. This finding suggests that admission SBP should not form the basis for decisions to withhold or delay endovascular thrombectomy for ischaemic stroke, but randomised trials are needed to further investigate this possibility. FUNDING: Medtronic.

Effects of the flow diversion technique on nucleotide levels in intra-cranial aneurysms: A feasibility study providing new research perspectives.

Introduction: The flow diverter stent (FDS) has become a first-line treatment for numerous intra-cranial aneurysms (IAs) by promoting aneurysm thrombosis. However, the biological phenomena underlying its efficacy remain unknown. We proposed a method to collect in situ blood samples to explore the flow diversion effect within the aneurysm sac. In this feasibility study, we assessed the plasma levels of nucleotides within the aneurysm sac before and after flow diversion treatment. Materials and methods: In total, 14 patients with unruptured IAs who were selected for FDS implantation were prospectively recruited from February 2015 to November 2015. Two catheters dedicated to (1) FDS deployment and (2) the aneurysm sac were used to collect blood samples within the parent artery (P1) and the aneurysm sac before (P2) and after (P3) flow diversion treatment. The plasma levels of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) at each collection point were quantified with liquid chromatography and tandem mass spectrometry. Results: The aneurysms were extradural in nine (64.3%) patients and intra-dural in five (35.7%) patients. They presented an average diameter of 15.5 ± 7.1 mm, height of 15.8 ± 4.6 mm, and volume of 2,549 ± 2,794 ml. In all patients (100%), 16 FDS implantations and 42 in situ blood collections were performed successfully without any complications associated with the procedure. The ATP, ADP, and AMP concentrations within the aneurysm sac were decreased after flow diversion (p = 0.005, p = 0.03, and p = 0.12, respectively). Only the ATP levels within the aneurysm sac after flow diversion were significantly correlated with aneurysm volume (adjusted R 2 = 0.43; p = 0.01). Conclusion: In situ blood collection within unruptured IAs during a flow diversion procedure is feasible and safe. Our results suggest that the flow diversion technique is associated with changes in the nucleotide plasma levels within the aneurysm sac.

Endovascular Treatment of Complex Intracranial Aneurysms With LEO+ Stents: The LEO II Cohort Study.

Introduction: Stent-assisted coiling is an established treatment option for intracranial aneurysms, particularly, wide neck aneurysms with complex anatomy. The purpose of the present study was to assess the safety and efficacy of LEO+ stents in the treatment of intracranial aneurysms. Materials and Methods: A prospective, observational, multicenter study including 12 centers was performed on patients with ruptured, unruptured, and recanalized intracranial aneurysms treated with LEO+ stents. The primary efficacy endpoint was the rate of complete aneurysmal occlusion at 18 months post-procedure, and the primary safety endpoint was the morbidity and mortality at 18 months post-procedure. Results: From March 2015 to June 2017, 176 patients were enrolled (mean age of 54.8 ± 11.5 years; 65.9% women). The aneurysms were located mainly in the anterior communicating artery (29.2%) and the middle cerebral artery (28.6%). They were mostly saccular (94%), with a mean dome size of 5.3 ± 2.6 mm and a mean aspect ratio of 1.2 ± 1.0. In total, 3% of the aneurysms were treated in the acute phase of rupture. Complete/nearly complete aneurysmal occlusion and major recanalization were observed in 89% (n = 146/164) and 1.8% (n = 3/164) of patients at 18-month follow-up, respectively. The LEO+ related mortality rate was 0.6% (n = 1/170), the morbidity rate was 4.1% (n = 7/170), and these patients were mRS 0-2 at 18 months. Conclusion: Our results reflecting the use of LEO+ stents in real-world conditions confirm the efficacy and safety of LEO+ stents in the management of complex intracranial aneurysms.

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.

Diversion-p64: results from an international, prospective, multicenter, single-arm post-market study to assess the safety and effectiveness of the p64 flow modulation device.

BACKGROUND: The use of flow diversion to treat intracranial aneurysms has increased in recent years. OBJECTIVE: To assess the safety and angiographic efficacy of the p64 flow modulation device. METHODS: Diversion-p64 is an international, prospective, multicenter, single-arm, study conducted at 26 centers. The p64 flow modulation device was used to treat anterior circulation aneurysms between December 2015 and January 2019. The primary safety endpoint was the incidence of major stroke or neurologic death at 3-6 months, with the primary efficacy endpoint being complete aneurysm occlusion (Raymond-Roy Occlusion Classification 1) on follow-up angiography. RESULTS: A total of 420 patients met the eligibility criteria and underwent treatment with the p64 flow modulation device (mean age 55±12.0 years, 86.2% female). Mean aneurysm dome width was 6.99±5.28 mm and neck width 4.47±2.28 mm. Mean number of devices implanted per patient was 1.06±0.47, with adjunctive coiling performed in 14.0% of the cases. At the second angiographic follow-up (mean 375±73 days), available for 343 patients (81.7%), complete aneurysm occlusion was seen in 287 (83.7%) patients. Safety data were available for 413 patients (98.3%) at the first follow-up (mean 145±43 days) with a composite morbidity/mortality rate of 2.42% (n=10). CONCLUSIONS: Diversion-p64 is the largest prospective study using the p64 flow modulation device. The results of this study demonstrate that the device has a high efficacy and carries a low rate of mortality and permanent morbidity.

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.

Influence of time to endovascular stroke treatment on outcomes in the early versus extended window paradigms.

BACKGROUND: The effect of time from stroke onset to thrombectomy in the extended time window remains poorly characterized. AIM: We aimed to analyze the relationship between time to treatment and clinical outcomes in the early versus extended time windows. METHODS: Proximal anterior circulation occlusion patients from a multicentric prospective registry were categorized into early (≤6 h) or extended (>6-24 h) treatment window. Patients with baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 10 and intracranial internal carotid artery or middle cerebral artery-M1-segment occlusion and pre-morbid modified Rankin scale (mRS) 0-1 ("DAWN-like" cohort) served as the population for the primary analysis. The relationship between time to treatment and 90-day mRS, analyzed in ordinal (mRS shift) and dichotomized (good outcome, mRS 0-2) fashion, was compared within and across the extended and early windows. RESULTS: A total of 1603 out of 2008 patients qualified. Despite longer time to treatment (9[7-13.9] vs. 3.4[2.5-4.3] h, p < 0.001), extended-window patients (n = 257) had similar rates of symptomatic intracranial hemorrhage (sICH; 0.8% vs. 1.7%, p = 0.293) and 90-day-mortality (10.5% vs. 9.6%, p = 0.714) with only slightly lower rates of 90-day good outcomes (50.4% vs. 57.6%, p = 0.047) versus early-window patients (n = 709). Time to treatment was associated with 90-day disability in both ordinal (adjusted odd ratio (aOR), ≥ 1-point mRS shift: 0.75; 95%CI [0.66-0.86], p < 0.001) and dichotomized (aOR, mRS 0-2: 0.73; 95%CI [0.62-0.86], p < 0.001) analyses in the early- but not in the extended-window (aOR, mRS shift: 0.96; 95%CI [0.90-1.02], p = 0.15; aOR, mRS0-2: 0.97; 95%CI [0.90-1.04], p = 0.41). Early-window patients had significantly lower 90-day functional disability (aOR, mRS shift: 1.533; 95%CI [1.138-2.065], p = 0.005) and a trend towards higher rates of good outcomes (aOR, mRS 0-2: 1.391; 95%CI [0.972-1.990], p = 0.071). CONCLUSIONS: The impact of time to thrombectomy on outcomes appears to be time dependent with a steep influence in the early followed by a less significant plateau in the extended window. However, every effort should be made to shorten treatment times regardless of ischemia duration.

Clinical effectiveness of endovascular stroke treatment in the early and extended time windows.

BACKGROUND: The clinical efficacy of mechanical thrombectomy has been unequivocally demonstrated in multiple randomized clinical trials. However, these studies were performed in carefully selected centers and utilized strict inclusion criteria. AIM: We aimed to assess the clinical effectiveness of mechanical thrombectomy in a prospective registry. METHODS: A total of 2008 patients from 76 sites across 12 countries were enrolled in a prospective open-label mechanical thrombectomy registry. Patients were categorized into the corresponding cohorts of the SWIFT-Prime, DAWN, and DEFUSE 3 trials according to the basic demographic and clinical criteria without considering specific parenchymal imaging findings. Baseline and outcome variables were compared across the corresponding groups. RESULTS: As compared to the treated patients in the actual trials, registry-derived patients tended to be younger and had lower baseline ASPECTS. In addition, time to treatment was earlier and the use of intravenous tissue plasminogen activator (IV-tPA) and general anesthesia were higher in DAWN- and DEFUSE-3 registry derived patients versus their corresponding trials. Reperfusion rates were higher in the registry patients. The rates of 90-day good outcome (mRS0-2) in registry-derived patients were comparable to those of the patients treated in the corresponding randomized clinical trials (SWIFT-Prime, 64.5% vs. 60.2%; DAWN, 50.4% vs. 48.6%; Beyond-DAWN: 52.4% vs. 48.6%; DEFUSE 3, 52% vs. 44.6%, respectively; all P > 0.05). Registry-derived patients had significant less disability than the corresponding randomized clinical trial controls (ordinal modified Rankin Scale (mRS) shift odds ratio (OR), P < 0.05 for all). CONCLUSION: Our study provides favorable generalizability data for the safety and efficacy of thrombectomy in the "real-world" setting and supports that patients may be safely treated outside the constraints of randomized clinical trials.

Multi-centric European post-market follow-up study of the Neuroform Atlas Stent System: primary results.

BACKGROUND: Few prospective series have described the safety and effectiveness of the Neuroform Atlas Stent System. We aimed to investigate the efficacy and safety of the device in patients treated for unruptured aneurysm. METHODS: ATLAS EU PMCF is a consecutive, prospective, multicentric study that included patients with unruptured saccular aneurysm of all sizes. Follow-up visits were scheduled at 3-6 months and 12-16 months with digital subtraction angiography (DSA) or MRI imaging follow-up as per the site standard of care. The primary efficacy endpoint was adequate aneurysm occlusion (Raymond Roy occlusion grade I and II) on 12 month angiography. The primary safety endpoint was any major stroke or ipsilateral stroke or neurological death within 12 months. RESULTS: Of the 106 patients consented, 105 were treated with at least one Neuroform Atlas stent. There was a failed implantation attempt in 1 patient, 85 patients received lateral stenting, and 19 patients received Y-stenting. Mean aneurysm neck size was 4.2 mm (range 1.9-33 mm). Adequate occlusion was observed in 95.1% immediately after the procedure and in 98.9% of cases at 1 year DSA follow-up. Overall, 1.0% (1/102; 95% CI 0.0% to 5.3%) of patients experienced a primary safety endpoint of major stroke. Three minor strokes resulted in a modified Rankin Scale score of 2. CONCLUSIONS: In this multicentric, prospective study, stent-assisted coiling of medium size unruptured aneurysms with the Neuroform Atlas stent resulted in a favorable rate of satisfactory occlusion. In our findings, the use of the Y-stenting technique was associated with increased rates of procedural complications. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02783339.

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.

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.

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.

Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Endovascular Thrombectomy.

OBJECTIVE: To determine whether pretreatment cerebral microbleeds (CMBs) presence and burden are correlated with an increased risk of intracranial hemorrhage (ICH) or poor functional outcome following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). METHODS: Consecutive patients treated by EVT for anterior circulation AIS were retrospectively analyzed. Experienced neuroradiologists blinded to functional outcomes rated CMBs on T2*-MRI using a validated scale. We investigated associations of CMB presence and burden with ICH and poor clinical outcome at 3 months (modified Rankin Scale score >2). RESULTS: Among 513 patients, 281 (54.8%) had a poor outcome and 89 (17.3%) had ≥1 CMBs. A total of 190 (37%) patients experienced ICH; 66 (12.9%) were symptomatic. CMB burden was associated with poor outcome in a univariable analysis (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.03-1.36 per 1-CMB increase; p = 0.02), but significance was lost after adjustment for sex, age, stroke severity, hypertension, diabetes mellitus, atrial fibrillation, prior antithrombotic medication, IV thrombolysis, and reperfusion status (OR, 1.05; 95% CI, 0.92-1.20 per 1-CMB increase; p = 0.50). Results remained nonsignificant when taking into account CMB location or presumed underlying pathogenesis. CMB presence, burden, location, or presumed pathogenesis were not independently correlated with ICH. CONCLUSIONS: Poor functional outcome or ICH were not correlated with CMB presence or burden on pre-EVT MRI after adjustment for confounding factors. Excluding such patients from reperfusion therapies is unwarranted. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with AIS undergoing EVT, after adjustment for confounding factors, the presence of CMBs is not significantly associated with clinical outcome or the risk of ICH.

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.

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.

Neurological manifestations of patients infected with the SARS-CoV-2: a systematic review of the literature.

OBJECTIVE: To perform an updated review of the literature on the neurological manifestations of COVID-19-infected patients METHODS: A PRISMA-guideline-based systematic review was conducted on PubMed, EMBASE, and SCOPUS. Series reporting neurological manifestations of COVID-19 patients were studied. RESULTS: 39 studies and 68,361 laboratory-confirmed COVID-19 patients were included. Up to 21.3% of COVID-19 patients presented neurological symptoms. Headache (5.4%), skeletal muscle injury (5.1%), psychiatric disorders (4.6%), impaired consciousness (2.8%), gustatory/olfactory dysfunction (2.3%), acute cerebrovascular events (1.4%), and dizziness (1.3%), were the most frequently reported neurological manifestations. Ischemic stroke occurred among 1.3% of COVID-19 patients. Other less common neurological manifestations were cranial nerve impairment (0.6%), nerve root and plexus disorders (0.4%), epilepsy (0.7%), and hemorrhagic stroke (0.15%). Impaired consciousness and acute cerebrovascular events were reported in 14% and 4% of patients with a severe disease, respectively, and they were significantly higher compared to non-severe patients (p < 0.05). Individual patient data from 129 COVID-19 patients with acute ischemic stroke (AIS) were extracted: mean age was 64.4 (SD ± 6.2), 78.5% had anterior circulation occlusions, the mean NIHSS was 15 (SD ± 7), and the intra-hospital mortality rate was 22.8%. Admission to the intensive care unit (ICU) was required among 63% of patients. CONCLUSION: This updated review of literature, shows that headache, skeletal muscle injury, psychiatric disorders, impaired consciousness, and gustatory/olfactory dysfunction were the most common neurological symptoms of COVID-19 patients. Impaired consciousness and acute cerebrovascular events were significantly higher among patients with a severe infection. AIS patients required ICU admission in 63% of cases, while intra-hospital mortality rate was close to 23%.

Usefulness of a single-parameter tool for the prediction of large vessel occlusion in acute stroke.

BACKGROUND: In acute stroke, large vessel occlusion (LVO) should be promptly identified to guide patient's transportation directly to comprehensive stroke centers (CSC) for mechanical thrombectomy (MT). In many cases, prehospital multi-parameter scores are used by trained emergency teams to identify patients with high probability of LVO. However, in several countries, the first aid organization without intervention of skilled staff precludes the on-site use of such scores. Here, we assessed the accuracy of LVO prediction using a single parameter (i.e. complete hemiplegia) obtained by bystander's telephone-based witnessing. PATIENTS AND METHODS: This observational, single-center study included consecutive patients who underwent intravenous thrombolysis at the primary stroke center and/or were directly transferred to a CSC for MT, from January 1, 2015 to March 1, 2020. We defined two groups: patients with initial hemiplegia (no movement in one arm and leg and facial palsy) and patients without initial hemiplegia, on the basis of a bystander's witnessing. RESULTS: During the study time, 874 patients were included [mean age 73 years (SD 13.8), 56.7% men], 320 with initial hemiplegia and 554 without. The specificity of the hemiplegia criterion to predict LVO was 0.88, but its sensitivity was only 0.53. CONCLUSION: Our results suggest that the presence of hemiplegia as witnessed by a bystander can predict LVO with high specificity. This single criterion could be used for decision-making about direct transfer to CSC for MT when the absence of emergency skilled staff precludes the patient's on-site assessment, especially in regions distant from a CSC.

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.