Acute Clinical Events Identified as Relapses With Stable Magnetic Resonance Imaging in Multiple Sclerosis.

Importance: Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development. Objective: To investigate clinical events identified as relapses but not associated with new T2 lesions or gadolinium-enhanced T1 lesions on brain and spinal cord magnetic resonance imaging (MRI). Design, Setting, and Participants: This multicenter observational cohort study was conducted between January 2015 and June 2023. Data were extracted on June 8, 2023, from the French MS registry. All clinical events reported as relapses in patients with relapsing-remitting MS were included if brain and spinal cord MRI was performed within 12 and 24 months before the event, respectively, and 50 days thereafter with gadolinium injection. Exposures: Events were classified as relapses with active MRI (RAM) if a new T2 lesion or gadolinium-enhanced T1 lesion appeared on brain or spinal cord MRI or as acute clinical events with stable MRI (ACES) otherwise. Main Outcomes and Measures: Factors associated with ACES were investigated; patients with ACES and RAM were compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and transition to secondary progressive (SP) MS, and ACES and RAM rates under each disease-modifying therapy (DMT) were estimated. Results: Among 31 885 clinical events, 637 in 608 patients (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) were included. ACES accounted for 166 (26.1%) events and were more likely in patients receiving highly effective DMTs, those with longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), or those presenting with fatigue (OR, 2.14; 95% CI, 1.15-3.96). ACES were associated with significant EDSS score increases, lower than those found for RAM. Before the index event, patients with ACES experienced significantly higher rates of relapse (relative rate [RR], 1.21; 95% CI, 1.01-1.46), CDA (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11), and RAW (HR, 1.72; 95% CI, 1.20-2.45). Patients with ACES were at significantly greater risk of SP transition (HR, 2.58; 95% CI, 1.02-6.51). Although RAM rate decreased with DMTs according to their expected efficacy, ACES rate was stable across DMTs. Conclusions and Relevance: The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.

Safety and efficacy of stent retrievers plus contact aspiration in patients with acute ischaemic anterior circulation stroke and positive susceptibility vessel sign in France (VECTOR): a randomised, single-blind trial.

BACKGROUND: Positive susceptibility vessel sign (SVS) in patients with acute ischaemic stroke has been associated with friable red blood cell-rich clots and more effective recanalisation using stent retrievers versus contact aspiration. We compared the safety and efficacy of stent retrievers plus contact aspiration (combined technique) versus contact aspiration alone as the first-line thrombectomy technique in patients with acute ischaemic anterior circulation stroke and SVS-positive occlusions. METHODS: Adaptive Endovascular Strategy to the Clot MRI in Large Intracranial Vessel Occlusion (VECTOR) was a prospective, randomised, open-label study with blinded evaluation. Patients with SVS-positive anterior circulation occlusions on pretreatment MRI and arterial puncture within 24 h of symptom onset were enrolled from 22 centres in France. A centralised web-based method was used by interventional neuroradiologists for dynamic randomisation by minimisation. Patients were randomly assigned 1:1 to the combined technique or contact aspiration alone. The primary outcome was expanded Thrombolysis in Cerebral Infarction (eTICI) grade 2c or 3 reperfusion after three or fewer passes on post-treatment angiogram, adjudicated by a blinded independent central imaging core laboratory. The intention-to-treat population was used to assess the primary and secondary outcomes. This trial is registered with ClinicalTrials.gov (NCT04139486) and is complete. FINDINGS: Between Nov 26, 2019, and Feb 14, 2022, 526 patients were enrolled, of whom 521 constituted the intention-to-treat population (combined technique, n=263; contact aspiration alone, n=258). The median age of participants was 74·9 years (IQR 64·4-83·3); 284 (55%) were female and 237 (45%) male. The primary outcome did not differ significantly between groups (152 [58%] of 263 patients for the combined technique vs 135 [52%] of 258 for contact aspiration; odds ratio [OR] 1·27; 95% CI 0·88-1·83; p=0·19). Procedure-related adverse events occurred in 32 (12%) of 263 patients in the combined technique group and 27 (11%) of 257 in the contact aspiration group (OR 1·14; 0·65-2·00; p=0·65). The most common adverse event was intracerebral haemorrhage (146 [56%] of 259 patients for the combined technique vs 123 [49%] of 251 for contact aspiration; OR 1·32; 0·91-1·90; p=0·13). All-cause mortality at 3 months occurred in 57 (23%) of 251 patients in the combined technique group and 48 (19%) of 247 in the contact aspiration group (OR 1·19; 0·76-1·86; p=0·45), none of which was treatment-related. INTERPRETATION: The results of the VECTOR trial do not show superiority of the combined stent retriever plus contact aspiration technique over contact aspiration alone in patients with SVS-positive occlusion with respect to achieving eTICI 2c-3 within three passes. These findings support the use of either the combined technique or contact aspiration alone as the initial thrombectomy strategy in patients with acute anterior circulation stroke with SVS on pretreatment MRI. FUNDING: Cerenovus.

Clinical and safety outcomes of acute stenting plus thrombectomy for carotid tandem lesions with large ischemic core.

BACKGROUND: We evaluated the clinical and safety outcomes of emergent carotid artery stenting (eCAS) plus endovascular thrombectomy (EVT) among patients with anterior tandem lesion (TL) and large ischemic core (LIC). METHODS: This retrospective study included consecutive stroke patients enrolled in the Endovascular Treatment in Ischemic Stroke Registry in France between January 2015 and June 2023. We compared the outcomes of carotid stenting vs no stenting in tandem lesion with pre-treatment LIC (Alberta Stroke Program Early CT Score (ASPECTS) 3-5) and stenting in tandem lesion vs thrombectomy alone for isolated intracranial occlusions with pre-treatment LIC. Primary outcome was a score of 0 to 3 on the modified Rankin scale (mRS) at 90 days. Multivariable mixed-effects logistic regression was performed. RESULTS: Among 218 tandem patients with LIC, 55 were treated with eCAS plus EVT. The eCAS group had higher odds of 90-day mRS 0-3 (adjusted Odds Ratio (aOR) 2.40, 95% confidence interval (CI) 1.10 to 5.21; p=0.027). There were no differences in the risk of any intracerebral hemorrhage (OR 1.41, 95% CI 0.69 to 2.86; p=0.346), parenchymal hematoma (aOR 1.216, 95% CI 0.49 to 3.02; p=0.675), symptomatic intracerebral hemorrhage (aOR 1.45, 95% CI 0.60 to 3.48; p=0.409), or 90-day mortality (aOR 0.74, 95% CI 0.33 to 1.68; p=0.472). eCAS was associated with a higher rate of carotid patency at day 1 (aOR 3.54, 95% CI 1.14 to 11.01; p=0.028). Safety outcomes were similar between EVT+eCAS group in TL-LIC and EVT alone group in isolated intracranial occlusions with LIC. CONCLUSION: eCAS appears to be a safe and effective strategy in patients with TL and LIC volume.

Functional Outcome and Hemorrhage Rates After Bridging Therapy With Tenecteplase or Alteplase in Patients With Large Ischemic Core.

BACKGROUND AND OBJECTIVES: IV tenecteplase is an alternative to alteplase before mechanical thrombectomy (MT) in patients with large-vessel occlusion (LVO) ischemic stroke. Little data are available on its use in patients with large ischemic core. We aimed to compare the efficacy and safety of both thrombolytics in this population. METHODS: We conducted a retrospective analysis of patients with anterior circulation LVO strokes and diffusion-weighed imaging Alberta Stroke Program Early CT Score (DWI-ASPECTS) ≤5 treated with tenecteplase or alteplase before MT from the TETRIS (tenecteplase) and ETIS (alteplase) French multicenter registries. Primary outcome was reduced disability at 3 months (ordinal analysis of the modified Rankin scale [mRS]). Safety outcomes were 3-month mortality, parenchymal hematoma (PH), and symptomatic intracranial hemorrhage (sICH). We used propensity score overlap weighting to reduce baseline differences between treatment groups. RESULTS: We analyzed 647 patients (tenecteplase: n = 194; alteplase: n = 453; inclusion period 2015-2022). Median (interquartile range) age was 71 (57-81) years, with NIH Stroke Scale score 19 (16-22), DWI-ASPECTS 4 (3-5), and last seen well-to-IV thrombolysis and puncture times 165 minutes (130-226) and 260 minutes (203-349), respectively. After MT, the successful reperfusion rate was 83.1%. After propensity score overlap weighting, all baseline variables were well balanced between both treatment groups. Compared with patients treated with alteplase, patients treated with tenecteplase had better 3-month mRS (common odds ratio [OR] for reduced disability: 1.37, 1.01-1.87, p = 0.046) and lower 3-month mortality (OR 0.52, 0.33-0.81, p < 0.01). There were no significant differences between thrombolytics for PH (OR 0.84, 0.55-1.30, p = 0.44) and sICH incidence (OR 0.70, 0.42-1.18, p = 0.18). DISCUSSION: Our data are encouraging regarding the efficacy and reassuring regarding the safety of tenecteplase compared with that of alteplase in bridging therapy for patients with LVO strokes and a large ischemic core in routine clinical care. These results support its consideration as an alternative to alteplase in bridging therapy for patients with large ischemic cores. TRIALS REGISTRATION INFORMATION: NCT03776877 (ETIS registry) and NCT05534360 (TETRIS registry). CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with anterior circulation LVO stroke and DWI-ASPECTS ≤5 treated with tenecteplase vs alteplase before MT experienced better functional outcomes and lower mortality at 3 months.

Dynamic Evolution of Infarct Volumes at MRI in Ischemic Stroke Due to Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: The typical infarct volume trajectories in stroke patients, categorized as slow or fast progressors, remain largely unknown. This study aimed to reveal the characteristic spatiotemporal evolutions of infarct volumes caused by large vessel occlusion (LVO) and show that such growth charts help anticipate clinical outcomes. METHODS: We conducted a secondary analysis from prospectively collected databases (FRAME, 2017-2019; ETIS, 2015-2022). We selected acute MRI data from anterior LVO stroke patients with witnessed onset, which were divided into training and independent validation datasets. In the training dataset, using Gaussian mixture analysis, we classified the patients into 3 growth groups based on their rate of infarct growth (diffusion volume/time-to-imaging). Subsequently, we extrapolated pseudo-longitudinal models of infarct growth for each group and generated sequential frequency maps to highlight the spatial distribution of infarct growth. We used these charts to attribute a growth group to the independent patients from the validation dataset. We compared their 3-month modified Rankin scale (mRS) with the predicted values based on a multivariable regression model from the training dataset that used growth group as an independent variable. RESULTS: We included 804 patients (median age 73.0 years [interquartile range 61.2-82.0 years]; 409 men). The training dataset revealed nonsupervised clustering into 11% (74/703) slow, 62% (437/703) intermediate, and 27% (192/703) fast progressors. Infarct volume evolutions were best fitted with a linear (r = 0.809; p < 0.001), cubic (r = 0.471; p < 0.001), and power (r = 0.63; p < 0.001) function for the slow, intermediate, and fast progressors, respectively. Notably, the deep nuclei and insular cortex were rapidly affected in the intermediate and fast groups with further cortical involvement in the fast group. The variable growth group significantly predicted the 3-month mRS (multivariate odds ratio 0.51; 95% CI 0.37-0.72, p < 0.0001) in the training dataset, yielding a mean area under the receiver operating characteristic curve of 0.78 (95% CI 0.66-0.88) in the independent validation dataset. DISCUSSION: We revealed spatiotemporal archetype dynamic evolutions following LVO stroke according to 3 growth phenotypes called slow, intermediate, and fast progressors, providing insight into anticipating clinical outcome. We expect this could help in designing neuroprotective trials aiming at modulating infarct growth before EVT.

Number of passes and outcome of endovascular treatment of anterior circulation large core ischemic stroke: insights from the Endovascular Treatment in Ischemic Stroke (ETIS) registry.

BACKGROUND: The effect of multiple attempts on the outcome of endovascular treatment (EVT) of anterior circulation large ischemic core (LIC) stroke has not been fully explored. METHODS: We analyzed data from the Endovascular Treatment in Ischemic Stroke (ETIS) registry, a prospective, observational, multicenter study of acute ischemic stroke patients treated with EVT at 21 centers in France between January 1, 2015 and June 31, 2023. We included patients with proximal intracranial occlusion and LIC defined as Alberta Stroke Program Early CT Score (ASPECTS) of 0-5 up to 24 hours after last being seen well. We divided patients according to the number of passes with successful reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b) into seven groups, according to the corresponding number of passes. We compared them to the group of patients with unsuccessful reperfusion. RESULTS: A total of 1235 patients with LIC constituted the study cohort. The rate of a modified Rankin Scale (mRS) score of 0 to 3 at 90 days was significantly higher for the one-pass successful recanalization category compared to no recanalization (48.1% vs 17.2%; adjusted OR (aOR) 7.99, 95% CI 4.30 to 14.8, P<0.001) and remained so even after six or more attempts (27.7% vs 17.2%; aOR 3.59, 95% CI 1.37 to 9.39, P=0.009). The rate of symptomatic intracranial hemorrhage was lower for successful recanalization up to two passes (11.1% vs 18.8%; aOR 0.36, 95% CI 0.18 to 0.69, P=0.002) without any significant differences for a higher number of passes. CONCLUSION: In anterior circulation LIC patients, successful reperfusion, even after six passes, is associated with favorable clinical outcomes with no increased hemorrhagic risk when compared to unsuccessful reperfusion.

Tenecteplase versus Alteplase before thrombectomy: A comprehensive evaluation of clinical and angiographic impact: Insights from the ETIS registry.

INTRODUCTION: Data on prior use of Tenecteplase versus Alteplase in acute stroke management by mechanical thrombectomy are controversial. Our primary objective was to make a comprehensive comparative assessment of clinical and angiographic efficacy and safety outcomes in a large prospective observational study. METHODS: We included stroke patients who were eligible for intravenous thrombolysis and endovascular thrombectomy between 2019 and 2021, from an ongoing registry in twenty comprehensive stroke centers in France. We divided patients into two groups based on the thrombolytic agent used (Alteplase vs Tenecteplase). We then compared their treatment times, and their angiographic (TICI scale), clinical (mRS at three months and sICH) and safety outcomes after controlling for potential confounders using propensity score methods. RESULTS: We evaluated 1131 patients having undergone thrombectomy for the final analysis, 250 received Tenecteplase and 881 Alteplase. Both groups were of the same median age (75 vs 74 respectively), and had the same baseline NIHSS score (16) and ASPECTS (8). There was no significant difference for First Pass Effect (OR 0.93, 95 % CI 0.76-1.14, p = 0.75), time required for reperfusion (OR 0.03, 95 % CI 0.09-0.16, p = 0.49), or for final reperfusion status. Clinically, functional independence at 90 days was similar in both groups (OR 0.82, 95 % CI 0.61-1.10, p = 0.18) with the same risk of sICH (OR 1.36, 95 % CI 0.77-2.41, p = 0.28). However, Tenecteplase patients had shorter imaging-to-groin puncture times (99 vs 142 min, p < 0.05). CONCLUSIONS: Tenecteplase showed no better clinical or angiographic impact on thrombectomy compared to Alteplase. Nevertheless, it appeared associated with a shorter thrombolysis-to-groin puncture time.

Inter-hospital transfer for thrombectomy: transfer time is brain.

BACKGROUND AND PURPOSE: Patients with acute ischaemic stroke and a large vessel occlusion who present to a non-endovascular-capable centre often require inter-hospital transfer for thrombectomy. Whether the inter-hospital transfer time is associated with 3-month functional outcome is poorly known. METHODS: Acute stroke patients enrolled between January 2015 and December 2022 in the prospective French multicentre Endovascular Treatment of Ischaemic Stroke registry were retrospectively analysed. Patients with an anterior circulation large vessel occlusion transferred from a non-endovascular to a comprehensive stroke centre for thrombectomy were eligible. Inter-hospital transfer time was defined as the time between imaging in the referring hospital and groin puncture for thrombectomy. The relationship between transfer time and favourable 3-month functional outcome (modified Rankin Scale 0-2) was assessed through a mixed logistic regression model adjusting for centre and symptom-onset-to-referring-hospital imaging time, age, sex, diabetes, referring hospital National Institutes of Health Stroke Scale score, Alberta Stroke Programme Early Computed Tomography Score, occlusion site and intravenous thrombolysis use. RESULTS: Overall, 3769 patients were included (median inter-hospital transfer time 161 min, interquartile range 128-195; 46% with favourable outcome). A longer transfer time was independently associated with lower rates of favourable outcome (p < 0.001). Compared to patients with transfer time below 120 min, there was a 15% reduction in the odds of achieving favourable outcome for transfer times between 120 and 180 min (adjusted odds ratio 0.85; 95% confidence interval 0.67-1.07), and a 36% reduction for transfer times beyond 180 min (adjusted odds ratio 0.64; 95% confidence interval 0.50-0.81). CONCLUSIONS: A shorter inter-hospital transfer time is strongly associated with favourable 3-month functional outcome. A speedier inter-hospital transfer is of critical importance to improve outcome.

Comparison of rescue intracranial stenting versus best medical treatment alone in acute refractory large vessel occlusion: study protocol for the PISTAR multicenter randomized trial.

BACKGROUND: Mechanical thrombectomy (MT) has become a standard treatment for acute ischemic strokes (AIS). However, MT failure occurs in approximately 10-30% of cases, leading to severe repercussions (with mortality rates up to 40% according to observational data). Among the available rescue techniques, rescue intracranial stenting (RIS) appears as a promising option. OBJECTIVE: This trial is poised to demonstrate the superiority of RIS in addition to the best medical treatment (BMT) in comparison with BMT alone, in improving the functional outcomes at 3 months for patients experiencing an AIS due to a large vessel occlusion refractory to MT (rLVO). METHODS: Permanent Intracranial STenting for Acute Refractory large vessel occlusions (PISTAR) is a multicenter prospective randomized open, blinded endpoint trial conducted across 11 French University hospitals. Adult patients (≥18 years) with an acute intracranial occlusion refractory to standard MT techniques will be randomized 1:1 during the procedure to receive either RIS+BMT (intervention arm) or BMT alone (control arm). RESULTS: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin Scale score ≤2 and evaluated by an independent assessor blinded to the randomization arm. Secondary outcomes include hemorrhagic complications, all adverse events, and death. The number of patients to be included is 346. Two interim analyses are planned with predefined stopping rules. CONCLUSION: The PISTAR trial is the first randomized controlled trial focusing on the benefit of RIS in rLVOs. If positive, this study will open new insights into the management of AIS. TRIAL REGISTRATION NUMBER: NCT06071091.

Mechanical thrombectomy in basilar artery occlusions: impact of first-line strategy as a function of the occlusion level.

BACKGROUND: Retrospective studies suggest the superiority of first-line contact aspiration (CA) thrombectomy over stent-retriever (SR) in basilar artery occlusions (BAO). We aimed to investigate the impact of first-line mechanical thrombectomy per the occlusion level, considering differences in stroke etiology prevalence between proximal and distal BAO. METHODS: A retrospective, multicentric analysis of the Endovascular Treatment in Ischemic Stroke Registry (ETIS) included consecutive BAO patients treated from January 2016 to May 2022. Patients were categorized into SR (±aspiration) and CA alone groups. Occlusion levels were determined through digital subtraction angiography. Favorable clinical outcome was defined as 90-day modified Rankin Scale (mRS) 0-3. RESULTS: A total of 380 patients were analyzed (251 CA alone, 129 SR±aspiration). Globally, first-line SR showed lower recanalization rates (89.1% vs 94.8%, OR=0.29, 95% CI 0.16 to 0.53; p<0.001) and worse clinical outcomes (mRS 0-3: 46.0% vs 52.2%, OR=0.62, 95% CI 0.44 to 0.87; p=0.006) compared with CA. In proximal occlusions, SR was significantly associated with poorer clinical outcomes (mRS 0-3: 20.9% vs 37.1%; OR=0.40, 95% CI 0.19 to 0.83; p=0.014) despite similar recanalization rates. Conversely, in distal occlusions there was no difference in clinical outcomes although recanalization rates were higher with CA (modified Thrombolysis in Cerebral Infarction score (mTICI 2b/3): 97.7% vs 91.7%; OR=0.17, 95% CI 0.05 to 0.66; p=0.01). CONCLUSIONS: In our BAO population, CA demonstrated better angiographic outcomes in middle and distal occlusions and better clinical outcomes in proximal occlusions. This translated into better angiographic and clinical results in the global study population. Clinical results were particularly influenced by the negative impact of SR on 90-day mRS, independently of recanalization rates in proximal BAO.

Impact of Day 1 carotid patency on outcome in dissection-related tandem occlusions treated with mechanical thrombectomy.

BACKGROUND: The clinical benefit of mechanical thrombectomy(MT) for stroke patients with tandem occlusion is similar to that of isolated intracranial occlusions. However, the management of cervical internal carotid artery(ICA) occlusion during the MT, particularly in the setting of carotid dissection, remains controversial. We aimed to investigate the clinical impact of cervical ICA patency at day 1 on 3-month functional outcome. METHODS: We collected data from the Endovascular Treatment in Ischemic Stroke, a prospective national registry in 30 French centers performing MT between January 2015 and January 2022. Inclusion criteria were consecutive tandem occlusions related to cervical ICA dissection treated with MT. Tandem occlusions of other etiology, isolated cervical ICA occlusions without intracranial thrombus and patients without day-1 ICA imaging were excluded. Primary endpoint was the 3-month functional outcome. Secondary endpoints included intracranial hemorrhage(ICH), excellent outcome, mortality and early neurological improvement. A sensitivity analysis was performed in patients with intracranial favorable recanalization after MT. RESULTS: During the study period, 137 patients were included of which 89(65%) presented ICA patency at day 1. The odds of favorable outcome did not significantly differ between patients with patent and occluded ICA at day 1(68.7 vs 59.1%;aOR=1.30;95%CI 0.56-3.00,p=0.54). Excellent outcome, early neurological improvement, mortality and ICH were also comparable between groups. Sensitivity analysis showed similar results. CONCLUSION: ICA patency at day 1 in patients with tandem occlusions related to dissection did not seem to influence functional outcome. Endovascular recanalization of the cervical ICA including stenting might not be systematically required in this setting.

Endovascular therapy of acute vertebrobasilar occlusions: influence of first-line strategy in the Endovascular Treatment in Ischemic Stroke (ETIS) Registry.

BACKGROUND: The choice of the first-line technique in vertebrobasilar occlusions (VBOs) remains challenging. We aimed to report outcomes in a large cohort of patients and to compare the efficacy and safety of contact aspiration (CA) and combined technique (CoT) as a first-line endovascular technique in patients with acute VBOs. METHODS: We retrospectively analyzed clinical and neuroradiological data of patients with VBOs from the prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke (ETIS) Registry in France between January 2015 and August 2023. The primary outcome was the first pass effect (FPE) rate, whereas modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3 and 2c-3, number of passes, need for rescue strategy, modified Rankin Scale (mRS) 0-2, mortality, and symptomatic intracranial hemorrhage (sICH) were secondary outcomes. We performed univariate and multivariate analyses to investigate differences between the two groups. RESULTS: Among the 583 included patients (mean age 66.2 years, median National Institutes of Health Stroke Scale (NIHSS) 13, median posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) 8), 393 were treated with CA alone and 190 with CoT. Procedures performed with CA were shorter compared with CoT (28 vs 47 min, P<0.0001); however, no differences were observed in terms of FPE (CA 43.3% vs CoT 38.4%, P=0.99), and successful final recanalization (mTICI 2b-3, CA 92.4% vs CoT 91.8%, P=0.74) did not differ between the two groups. Functional independence and sICH rates were also similar, whereas mortality was significantly lower in the CA group (34.5% vs 42.9%; OR 1.79, 95% CI 1.03 to 3.11). CONCLUSIONS: We observed no differences in FPE, mTICI 2b-3, sICH, and functional independence between the two study groups. First-line CA was associated with shorter procedures and lower mortality rates than CoT.

MRI vs CT for Baseline Imaging Evaluation in Acute Large Artery Ischemic Stroke: A Subanalysis of the SWIFT-DIRECT Trial

BACKGROUND AND OBJECTIVES: Whether MRI or CT is preferable for the evaluation of patients with suspected stroke remains a matter of debate, given that the imaging modality acquired at baseline may be a relevant determinant of workflow delays and outcomes with it, in patients with stroke undergoing acute reperfusion therapies. METHODS: In this post hoc analysis of the SWIFT-DIRECT trial that investigated noninferiority of thrombectomy alone vs IV thrombolysis (IVT) + thrombectomy in patients with an acute ischemic anterior circulation large vessel occlusive stroke eligible to receive IVT within 4.5 hours after last seen well, we tested for a potential interaction between baseline imaging modality (MRI/MR-angiography [MRA] vs CT/CT-angiography [CTA]) and the effect of acute treatment (thrombectomy vs IVT + thrombectomy) on clinical and safety outcomes and procedural metrics (primary analysis). Moreover, we examined the association between baseline imaging modality and these outcomes using regression models adjusted for age, sex, baseline NIH Stroke Scale (NIHSS), occlusion location, and Alberta Stroke Program Early CT Score (ASPECTS) (secondary analysis). Endpoints included workflow times, the modified Rankin scale (mRS) score at 90 days, the rate of successful reperfusion, the odds for early neurologic deterioration within 24 hours, and the risk of symptomatic intracranial hemorrhage. The imaging modality acquired was chosen at the discretion of the treating physicians and commonly reflects center-specific standard procedures. RESULTS: Four hundred five of 408 patients enrolled in the SWIFT-DIRECT trial were included in this substudy. Two hundred (49.4%) patients underwent MRI/MRA, and 205 (50.6%) underwent CT/CTA. Patients with MRI/MRA had lower NIHSS scores (16 [interquartile range (IQR) 12-20] vs 18 [IQR 14-20], p = 0.012) and lower ASPECTS (8 [IQR 6-9] vs 8 [IQR 7-9], p = 0.021) compared with those with CT/CTA. In terms of the primary analysis, we found no evidence for an interaction between baseline imaging modality and the effect of IVT + thrombectomy vs thrombectomy alone. Regarding the secondary analysis, MRI/MRA acquisition was associated with workflow delays of approximately 20 minutes, higher odds of functional independence at 90 days (adjusted odds ratio [aOR] 1.65, 95% CI 1.07-2.56), and similar mortality rates (aOR 0.73, 95% CI 0.36-1.47) compared with CT/CTA. DISCUSSION: This post hoc analysis does not suggest treatment effect heterogeneity of IVT + thrombectomy vs thrombectomy alone in large artery stroke patients with different imaging modalities. There was no evidence that functional outcome at 90 days was less favorable following MRI/MRA at baseline compared with CT/CTA, despite significant workflow delays. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03192332.

First-ever acute ischemic strokes in HIV-infected persons: A case-control study from stroke units.

OBJECTIVE: The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke-unit (SU)-access, acute reperfusion therapy-use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce. METHODS: AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris-area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age-, initial NIHSS- and sex-matched HIV-uninfected controls (HUCs). Outcome was the 90-day modified Rankin Scale score. RESULTS: Among 126 PLHIVs with confirmed first-ever AIS, ~80% were admitted outside the thrombolysis-administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small-vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%-30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well-tolerated. INTERPRETATION: The high uncontrolled HIV-infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk.

Evaluation of acute mechanical revascularization in large stroke (ASPECTS ⩽5) and large vessel occlusion within 7 h of last-seen-well: The LASTE multicenter, randomized, clinical trial protocol.

RATIONALE: Mechanical thrombectomy (MT), the standard of care for acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO), is generally not offered to patients with large baseline infarct (core). Recent studies demonstrated MT benefit in patients with anterior circulation stroke and large core (i.e. Alberta Stroke Program Early Computed Tomography Score, ASPECTS 3-5). However, its benefit in patients with the largest core (ASPECTS 0-2) remains unproven. AIM: To compare the efficacy and safety of MT plus best medical treatment (BMT) and of BMT alone in patients with ASPECTS 0-5 (baseline computed tomography (CT) or magnetic resonance imaging (MRI)) and anterior circulation LVO within 7 h of last-seen-well. SAMPLE SIZE ESTIMATE: To detect with a two-sided test at 5% significance level (80% power) a common odds ratio of 1.65 for 1-point reduction in the 90-day modified Rankin Scale (mRS) score in the MT + BMT arm versus BMT arm and to anticipate 10% of patients with missing primary endpoint, 450 patients are planned to be included by 36 centers in France, Spain, and the United States. METHODS AND DESIGN: LArge Stroke Therapy Evaluation (LASTE) is an international, multicenter, Prospectively Randomized into two parallel (1:1) arms, Open-label, with Blinded Endpoint (PROBE design) trial. Eligibility criteria are diagnosis of AIS within 6.5 h of last-seen-well (or negative fluid-attenuated inversion recovery (FLAIR) if unknown stroke onset time), ASPECTS 0-5 (ASPECTS 4-5 for ⩾80-year-old patients), and LVO in the anterior circulation (intracranial internal carotid artery (ICA) and M1 or M1-M2 segment of the middle cerebral artery (MCA)). STUDY OUTCOMES: The primary endpoint is the day-90 mRS score distribution (shift analysis) with mRS categories 5 and 6 coalesced into one category. Secondary endpoints include day-180 mRS score, rates of 90-day and 180-day mRS score = 0-2 and 0-3, rate of decompressive craniectomy, the National Institutes of Health Stroke Scale (NIHSS) score change, revascularization and infarct volume growth at 24 h, and quality of life at day 90 and 180. Safety outcomes (90-day all-cause mortality, procedural complications, symptomatic intracerebral hemorrhage, and early NIHSS score worsening) are recorded. A dynamic balanced randomization (1:1) is used to distribute eligible patients into the experimental arm and control arm, by incorporating the center and these pre-specified factors: baseline ASPECTS (0-3 vs 4-5), age (⩽70 vs >70 years), baseline NIHSS (<20 vs ⩾20), intravenous thrombolysis (no vs yes), admission mode (Drip-and-Ship vs Mothership), occlusion site (intracranial ICA vs MCA-M1 or M1-M2), intravenous fibrinolysis (no vs yes), and last-seen-well to randomization time (0-4.5 vs >4.5-6.5 h). DISCUSSION: The LASTE trial will determine MT efficacy and safety in patients with ASPECTS 0-5 and LVO in the anterior circulation. TRIAL REGISTRATION: LASTE Trial NCT03811769.

Intravenous thrombolysis with tenecteplase versus alteplase combined with endovascular treatment of anterior circulation tandem occlusions: A pooled analysis of ETIS and TETRIS.

BACKGROUND: Tandem occlusions are a singular large vessel occlusion entity involving specific endovascular and perioperative antithrombotic management. In this context, data on safety and efficacy of prior intravenous thrombolysis (IVT) with tenecteplase is scarce. We aimed to compare IVT with tenecteplase or alteplase in patients with acute tandem occlusions intended for endovascular treatment. PATIENTS AND METHODS: A retrospective pooled analysis of two large observational registries (ETIS (Endovascular Treatment of Ischemic Stroke) and TETRIS (Tenecteplase Treatment in Ischemic Stroke)) was performed on consecutive patients presenting with anterior circulation tandem occlusion treated with IVT using either alteplase (ETIS) or tenecteplase (TETRIS) followed by endovascular treatment between January 2015 and June 2022. Sensitivity analyses on atherosclerosis related tandem occlusions and on patient treated with emergent carotid stenting were conducted. Propensity score overlap weighting analyses were performed. RESULTS: We analyzed 753 patients: 124 in the tenecteplase and 629 in the alteplase group. The overall odds of favorable outcome (3-month modified Rankin score 0-2) were comparable between both groups (49.4% vs 47.1%; OR = 1.10, 95%CI 0.85-1.41). Early recanalization, final successful recanalization and mortality favored the use of tenecteplase. The occurrence of any intracranial hemorrhage (ICH) was more frequent after tenecteplase use (OR = 2.24; 95%CI 1.75-2.86). However, risks of symptomatic ICH and parenchymal hematoma remained similar. In atherosclerotic tandems, favorable outcome, mortality, parenchymal hematoma, early recanalization, and final successful recanalization favored the tenecteplase group. In the carotid stenting subgroup, PH were less frequent in the tenecteplase group (OR = 0.18; 95%CI 0.05-0.69). CONCLUSION: In patients with tandem occlusions, IVT with tenecteplase seemed reasonably safe in particular with increased early recanalization rates. These findings remain preliminary and should be further confirmed in randomized trials.

Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial.

RATIONALE: Mechanical thrombectomy (MT) associated with the best medical treatment (BMT) has recently shown efficacy for the management of acute ischemic stroke (AIS) secondary to a large vessel occlusion. However, evidence is lacking regarding the benefit of MT for more distal occlusions. AIM: To evaluate the efficacy in terms of good clinical outcome at 3 months of MT associated with the BMT over the BMT alone in AIS related to a distal occlusion. METHODS: The DISCOUNT trial is a multicenter open-label randomized controlled trial involving French University hospitals. Adult patients (⩾18 years) with an AIS involving the anterior or posterior circulation secondary to a distal vessel occlusion within 6 h of symptom onset or within 24 h if no hyperintense signal on fluid attenuation inversion recovery acquisition will be randomized 1:1 to receive either MT associated with the BMT (experimental group) or BMT alone (control group). The number of patients to be included is 488. STUDY OUTCOMES: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin scale (mRS) ⩽2 and evaluated by an independent assessor blinded to the intervention arm. Secondary outcomes include recanalization of the occluded vessel within 48 h, angiographic reperfusion in the experimental group, 3-month excellent clinical outcome (mRS ⩽ 1), all adverse events, and death. A cost utility analysis will estimate the incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION: If positive, this study will open new insights in the management of AISs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05030142 registered on 1 September 2021.

Rescue intracranial permanent stenting for refractory occlusion following thrombectomy: a propensity matched analysis.

BACKGROUND: Rescue intracranial stenting (RIS) can be used in refractory large vessel occlusion (LVO) after mechanical thrombectomy (MT). We aimed to assess the safety and efficacy of RIS versus a propensity matched sample of patients with persistent LVO. METHODS: We retrospectively analysed a multicenter retrospective pooled cohort of patients with anterior LVO (2015-2021) treated with MT, and identified patients with at least three passes and a modified Thrombolysis In Cerebral Infarction (mTICI) score of 0 to 2a. Propensity score matching was used to account for determinants of outcome in patients with or without RIS. The study outcomes included 3 months modified Rankin Scale (mRS) and symptomatic hemorrhagic transformation (HT). RESULTS: 420 patients with a refractory anterior occlusion were included, of which 101 were treated with RIS (mean age 69 years). Favorable outcome (mRS 0-2) was more frequent in patients with a patent stent at day 1 (53% vs 6%, P<0.001), which was independently associated with an early dual antiplatelet regimen (P<0.05). In the propensity matched sample, patients treated with RIS versus without RIS had similar rates of favorable outcomes (36.8% vs 30.3%, P=0.606). Patients with RIS showed a favorable shift in the overall mRS distributions (common adjusted OR 0.74, 95% CI 0.60 to 0.91, P=0.006). Symptomatic HT was marginally more frequent in the RIS group (9% vs 3%, P=0.07), and there was no difference in 3-month mortality. CONCLUSION: In selected patients with a refractory intracranial occlusion despite at least three thrombectomy passes, RIS may be associated with an overall shift towards more favorable clinical outcome, and no significant increase in the odds of symptomatic HT or death.

Combined Technique for Internal Carotid Artery Terminus or Middle Cerebral Artery Occlusions in the ASTER2 Trial.

BACKGROUND: The aim of this study was to report the results of a subgroup analysis of the ASTER2 trial (Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion) comparing the safety and efficacy of the combined technique (CoT) and stent retriever as a first-line approach in internal carotid artery (ICA) terminus±M1-middle cerebral artery (M1-MCA) and isolated M1-MCA occlusions. METHODS: Patients enrolled in the ASTER2 trial with ICA terminus±M1-MCA and isolated M1-MCA occlusions were included in this subgroup analysis. The effect of first-line CoT versus stent retriever according to the occlusion site was assessed on angiographic (first-pass effect, expanded Treatment in Cerebral Infarction score ≥2b50, and expanded Treatment in Cerebral Infarction score ≥2c grades at the end of the first-line strategy and at the end of the procedure) and clinicoradiological outcomes (24-hour National Institutes of Health Stroke Scale, ECASS-III [European Cooperative Acute Stroke Study] grades, and 3-month modified Rankin Scale). RESULTS: Three hundred sixty-two patients were included in the postsubgroup analysis according to the occlusion site: 299 were treated for isolated M1-MCA occlusion (150 with first-line CoT) and 63 were treated for ICA terminus±M1-MCA occlusion (30 with first-line CoT). Expanded Treatment in Cerebral Infarction score ≥2b50 (odds ratio, 11.83 [95% CI, 2.32-60.12]) and expanded Treatment in Cerebral Infarction score ≥2c (odds ratio, 4.09 [95% CI, 1.39-11.94]) were significantly higher in first-line CoT compared with first-line stent retriever in patients with ICA terminus±M1-MCA occlusion but not in patients with isolated M1-MCA. CONCLUSIONS: First-line CoT was associated with higher reperfusion grades in patients with ICA terminus±M1-MCA at the end of the procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03290885.

Intravenous Thrombolysis before Complete Angiographic Reperfusion: Beyond Angiographic Assessment to Target Microvascular Obstruction?

OBJECTIVE: Recent data have suggested that ineffective tissue reperfusion despite successful angiographic reperfusion was partly responsible for unfavorable outcomes after endovascular therapy (EVT) and might be modulated by intravenous thrombolysis (IVT) use before EVT. To specifically decipher the effect played by IVT before EVT, we compared the clinical and safety outcomes of patients who experienced a complete reperfusion at the end of EVT according to IVT use before EVT. METHODS: The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing, prospective, observational study at 21 centers that perform EVT in France. Patients were included if they had an anterior large vessel occlusion of the intracranial internal carotid artery or middle cerebral artery (M1/M2 segments) and complete reperfusion (expanded Thrombolysis in Cerebral Infarction score = 3) with EVT within 6 hours, between January 2015 and December 2021. The cohort was divided into two groups according to IVT use before EVT, and propensity score matching (PSM) was used to balance the two groups. Primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included favorable outcome (mRS 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. Outcomes were estimated with multivariate logistic models adjusted for age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and time from symptom onset to puncture. RESULTS: Among 5,429 patients included in the ETIS registry, 1,093 were included in the study, including 651 patients with complete recanalization treated with IVT before EVT. After PSM, 488 patients treated with IVT before EVT were compared to 337 patients without IVT. In the matched cohort analysis, the IVT+EVT group had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR] = 1.41, 95% confidence interval [CI] = 1.04-1.91, p = 0.023) and higher rates of favorable outcome (61.1% vs 48.7%, aOR = 1.49, 95% CI = 1.02-2.20, p = 0.041) at 90 days compared with the EVT alone group. Rates of symptomatic intracerebral hemorrhage were comparable between both groups (6.0% vs 4.3%, aOR = 1.16, 95% CI = 0.53-2.54, p = 0.709). INTERPRETATION: In clinical practice, even after complete angiographic reperfusion by EVT, prior IVT use improves clinical outcomes of patients without increasing bleeding risk. ANN NEUROL 2024;95:762-773.