Trial of Endovascular Thrombectomy for Large Ischemic Strokes.

BACKGROUND: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations. METHODS: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome. RESULTS: The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group. CONCLUSIONS: Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.).

Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial.

BACKGROUND: Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients. METHODS: SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18-85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3-5 [range 0-10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0-6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed. FINDINGS: The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53-0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14-1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71-1·11]). INTERPRETATION: In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up. FUNDING: Stryker Neurovascular.

Anticoagulation Use and Endovascular Thrombectomy in Patients with Large Core Stroke: A Secondary Analysis of the SELECT2 Trial.

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4-6] vs MM 5 [4-6], adjusted generalized odds ratio 0.89 [0.53-1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3-6] vs MM 5 [4-6], adjusted generalized odds ratio 1.87 [1.45-2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024.

Effect of gender on the evolution of pain and quality of life after treatment of symptomatic vertebral fragility fractures.

The evolution of pain and quality of life after a symptomatic vertebral fracture differs according to patient gender, with a worse evolution in women independently of the treatment received. PURPOSE: In a previous randomized clinical study comparing the effect of vertebroplasty (VP) vs. conservative therapy (CT) on pain evolution and quality of life (QoL) of patients with symptomatic vertebral fractures (VF), we observed the development of chronic back pain in 23% of subjects, independently of the therapy received. This study analyses the effect of gender on the evolution of pain and QoL in these subjects. METHODS: 118/125 randomized patients (27 males/91 females) with recent symptomatic VFs were evaluated. All received a standardized analgesic and antiosteoporotic format of treatment. Pain and QoL were evaluated by VAS and Qualeffo-41, respectively, at baseline, at 2 weeks and 2 and 6 months. We compared pain evolution and QoL after treatment (CT vs. VP) according to gender, and analysed factors including age, time of evolution, treatment received, baseline VAS, previous VFs (total and recent), incidental VFs, lumbar and femoral T-scores, and analgesic and antiosteoporotic treatment. RESULTS: At baseline, there were no differences in age (males 74.8 ± 11.2 vs. females:73.2 ± 8.7 years), time of evolution, number of VFs (males:3.8 ± 2.4 vs. females: 3.1 ± 2.4), treatment received (VP, males:59%, females:45%), lumbar or femoral T-score, baseline VAS (males:6.8 ± 2.1 vs. females:6.8 ± 2.2) or Qualeffo score (males:52.2 ± 24.4 vs. females:59.7 ± 20.6). Pain and QoL evolution differed according to gender, being better in males. These differences were significant after two months independently of the treatment and the development of incidental VF during follow-up. CONCLUSIONS: Pain and QoL evolution after a symptomatic VF differs according to gender, with a worse evolution in women independently of the treatment received.

Design of New BLE GAP Roles for Vehicular Communications.

Bluetooth Low Energy (BLE) is a prominent short-range wireless communication protocol widely extended for communications and sensor systems in consumer electronics and industrial applications, ranging from manufacturing to retail and healthcare. The BLE protocol provides four generic access profile (GAP) roles when it is used in its low-energy version, i.e., ver. 4 and beyond. GAP roles control connections and allow BLE devices to interoperate each other. They are defined by the Bluetooth special interest group (SIG) and are primarily oriented to connect peripherals wirelessly to smartphones, laptops, and desktops. Consequently, the existing GAP roles have characteristics that do not fit well with vehicular communications in cooperative intelligent transport systems (C-ITS), where low-latency communications in high-density environments with stringent security demands are required. This work addresses this gap by developing two new GAP roles, defined at the application layer to meet the specific requirements of vehicular communications, and by providing a service application programming interface (API) for developers of vehicle-to-everything (V2X) applications. We have named this new approach ITS-BLE. These GAP roles are intended to facilitate BLE-based solutions for real-world scenarios on roads, such as detecting road traffic signs or exchanging information at toll booths. We have developed a prototype able to work indistinctly as a unidirectional or bidirectional communication device, depending on the use case. To solve security risks in the exchange of personal data, BLE data packets, here called packet data units (PDU), are encrypted or signed to guarantee either privacy when sharing sensitive data or authenticity when avoiding spoofing, respectively. Measurements taken and their later evaluation demonstrated the feasibility of a V2X BLE network consisting of picocells with a radius of about 200 m.

Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles.

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort.

OBJECTIVE: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. METHODS: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial,  Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri ) were compared to those who received primary MM (MMpri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). RESULTS: Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MMpri : 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MMpri : 3 [2-4], p < 0.001). Functional independence was similar (EVTpri : 77.4% vs MMpri : 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri : 16.3% vs MMpri : 1.3%, p < 0.001) and neurological worsening (EVTpri : 19.6% vs MMpri : 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri : 77.4% vs MMpri : 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri : 77.4% vs MMpri : 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (pinteraction  = 0.06). Similar findings were observed in a propensity score-matched subpopulation. INTERPRETATION: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378.

Clinical Results of the Advanced Neurovascular Access Catheter System Combined With a Stent Retriever in Acute Ischemic Stroke (SOLONDA).

BACKGROUND: The Advanced Neurovascular Access (ANA) thrombectomy system is a novel stroke thrombectomy device comprising a self-expanding funnel designed to reduce clot fragmentation by locally restricting flow while becoming as wide as the lodging artery. Once deployed, the ANA device allows distal aspiration combined with a stent retriever to mobilize the clot into the funnel where it remains copped during extraction. We investigated the safety and efficacy of ANA catheter system. METHODS: SOLONDA (Solitaire in Combination With the ANA Catheter System as Manufactured by Anaconda) was a prospective, open, single-arm, multicenter trial with blinded assessment of the primary outcome by an independent core lab. Patients with anterior circulation vessel occlusion admitted within 8 hours from symptom onset were eligible. The primary end point was successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3) with ≤3 passes of the ANA device in combination with stent retriever, before the use of rescue therapy in the intention to treat population. Primary predefined analysis was noninferiority as compared to the performance end point observed in HERMES (High Effective Reperfusion Using Multiple Endovascular Devices). RESULTS: After enrollment of 74 patients, an interim analysis was conducted, and the trial Steering Committee decided to terminate recruitment due to safety and performance objectives were reached. Mean age was 71.6 (SD 8.9) years, 46.6% women and median National Institutes of Health Stroke Scale on admission 14 (interquartile range, 10-19). Successful reperfusion within 3 passes before rescue therapy was achieved in 60/72 (83.3% [95% CI, 74.7%-91.9%]) with a rate of complete reperfusion (modified Thrombolysis in Cerebral Infarction score 2c-3) of 60% (95% CI, 48.4%-71.1%; 43/72 patients). After noninferiority was confirmed (P<0.01), the ANA device also showed superiority in the rate of successful reperfusion with ≤3 passes (P=0.02). First-pass successful recanalization rate was 55.6% (95% CI, 44.1%-67.0%), with a first-pass complete recanalization rate of 38.9% (95% CI, 27.6%-50.1%). Rescue therapy to obtain a modified Thrombolysis in Cerebral Infarction score 2b-3 was needed in 12/72 (17%) patients. At 90 days, the rate of favorable functional outcome (modified Rankin Scale score 0-2) was 57.5% (95% CI, 46.2%-68.9%), and the rate of excellent functional outcome (modified Rankin Scale score 0-1) was 45.2% (95% CI, 33.8%-56.6%). The rate of severe adverse device related was 1.4%. CONCLUSIONS: In this clinical experience, the ANA device achieved a high rate of complete recanalization with a preliminary good safety profile and favorable 90 days clinical outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04095767.

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

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

Susceptibility Vessel Sign in Deep Perforating Arteries in Patients with Recent Small Subcortical Infarcts.

OBJECTIVES: Recent small subcortical infarcts (RSSI) are considered an acute manifestation of cerebral small vessel disease. Paramagnetic signals in perforating arteries supplying RSSI may be detected on T2*-relaxation derived sequences on MRI and is defined as susceptibility vessel sign (SVS). We aimed to study the prevalence of SVS in patients with RSSI, and explore whether its identification is related to cerebral small vessel disease markers. MATERIALS AND METHODS: We selected patients with RSSI identified on MRI during admission from a single-center stroke registry. The main demographic and clinical features, including vascular risk factors, were collected. Radiological features of RSSI and cerebral small vessel disease [white matter hyperintensities in deep and periventricular regions, enlarged perivascular spaces, lacunae, microbleeds, and brain atrophy] were described using validated qualitative scores. The presence of SVS was assessed on T2*gradient-echo or other susceptibility-weighted imaging. We compared the clinical and radiological features of patients with or without SVS in uni- and multivariate models. RESULTS: Out of 210 patients with an RSSI on an MRI, 35 (17%) showed SVS. The proportion of SVS+ patients was similar in different susceptibility imaging modalities (p=.64). Risk factor profiles and clinical course were similar in SVS+ and SVS- patients. SVS+ patients had a higher grade of deep white matter hyperintensities and brain atrophy, more lacunae (p=.001, p=.034, p=.022, respectively), and a similar degree of the rest of radiological variables, compared to SVS- patients. In the multivariate analysis, the grade of deep white matter hyperintensities was the only independent factor associated with SVS [OR 3.1 (95% CI, 1.5-6.4)]. CONCLUSIONS: SVS in patients with RSSI is uncommon and related to a higher grade of deep white matter hyperintensities. Pathophysiological mechanisms underlying the deposition of hemosiderin in the path of occluded perforating arteries are uncertain and might include endothelial dysfunction or embolic mechanisms.

Cerebral Venous Sinus Thrombosis in COVID-19 Patients: A Multicenter Study and Review of Literature.

BACKGROUND: COVID-19 infection has been known to predispose patients to both arterial and venous thromboembolic events such as deep venous thrombosis, pulmonary embolism, myocardial infarction, and stroke. A few reports from the literature suggest that Cerebral Venous Sinus Thrombosis (CVSTs) may be a direct complication of COVID-19. OBJECTIVE: To review the clinical and radiological presentation of COVID-19 positive patients diagnosed with CVST. METHODS: This was a multicenter, cross-sectional, retrospective study of patients diagnosed with CVST and COVID-19 reviewed from March 1, 2020 to November 8, 2020. We evaluated their clinical presentations, risk factors, clinical management, and outcome. We reviewed all published cases of CVST in patients with COVID-19 infection from January 1, 2020 to November 13, 2020. RESULTS: There were 8 patients diagnosed with CVST and COVID-19 during the study period at 7 out of 31 participating centers. Patients in our case series were mostly female (7/8, 87.5%). Most patients presented with non-specific symptoms such as headache (50%), fever (50%), and gastrointestinal symptoms (75%). Several patients presented with focal neurologic deficits (2/8, 25%) or decreased consciousness (2/8, 25%). D-dimer and inflammatory biomarkers were significantly elevated relative to reference ranges in patients with available laboratory data. The superior sagittal and transverse sinuses were the most common sites for acute CVST formation (6/8, 75%). Median time to onset of focal neurologic deficit from initial COVID-19 diagnosis was 3 days (interquartile range 0.75-3 days). Median time from onset of COVID-19 symptoms to CVST radiologic diagnosis was 11 days (interquartile range 6-16.75 days). Mortality was low in this cohort (1/8 or 12.5%). CONCLUSIONS: Clinicians should consider the risk of acute CVST in patients positive for COVID-19, especially if neurological symptoms develop.

Thrombectomy within 8 hours after symptom onset in ischemic stroke.

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

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

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

Diffuse Renal Cortical Hemorrhage in the Setting of Subcapsular Hematoma: Diagnosis and Treatment with Embolization.

PURPOSE: To describe radiologic findings, embolization technique, and clinical outcomes in patients with renal subcapsular hematoma and diffuse cortical hemorrhage. MATERIALS AND METHODS: Ten patients with renal subcapsular hematoma and diffuse cortical hemorrhage were reviewed. Nine of the 10 had undergone procedures (nephrostomy, n = 4; biopsy, n = 4; embolization of a cerebral aneurysm, n = 1) and 1 patient was receiving oral anticoagulation. Computed tomography (CT), angiography, and embolization of bleeding sites were performed in all patients. RESULTS: CT and angiography revealed subcapsular hematoma with diffuse cortical hemorrhage at the level of the interlobar and/or arcuate branches. Total embolization of intrarenal arterial branches was required in 3 patients. Partial embolization, which also resulted in permanent functional loss, was required in 4. The functional loss was likely caused by the embolization procedure and the underlying renal disease. In these 4 patients, renal failure was demonstrated by scintigraphy in 3 cases and based on the need to start chronic hemodialysis in 1 case. In the remaining three patients, embolization did not compromise renal function. CONCLUSIONS: Diffuse cortical hemorrhage unrelated to the site of puncture may be seen in some cases of subcapsular hematoma. The cause is likely the laceration of transcortical capsular arteries secondary to enlargement of the subcapsular hematoma. In the present case series, embolization achieved hemorrhage control, but loss of renal function was observed in patients with underlying renal disease.

Safety and Efficacy of Solitaire Stent Thrombectomy: Individual Patient Data Meta-Analysis of Randomized Trials.

BACKGROUND AND PURPOSE: Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. METHODS: Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0-2), symptomatic intracerebral hemorrhage, and mortality. RESULTS: The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0-3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29-5.99). Successful revascularization occurred in 77% treated with Solitaire device. The rate of symptomatic intracerebral hemorrhage and overall mortality did not differ between treatment groups. CONCLUSIONS: Solitaire thrombectomy for large vessel ischemic stroke was safe and highly effective with substantially reduced disability. Benefits were consistent in all prespecified subgroups.

Relevance of blood-brain barrier disruption after endovascular treatment of ischemic stroke: dual-energy computed tomographic study.

BACKGROUND AND PURPOSE: Computed tomographic (CT) high attenuation (HA) areas after endovascular therapy for acute ischemic stroke are a common finding indicative of blood-brain barrier disruption. Dual-energy CT allows an accurate differentiation between HA areas related to contrast staining (CS) or to brain hemorrhage (BH). We sought to evaluate the prognostic significance of the presence of CS and BH after endovascular therapy. METHODS: A prospective cohort of 132 patients treated with endovascular therapy was analyzed. According to dual-energy CT findings, patients were classified into 3 groups: no HA areas (n=53), CS (n=32), and BH (n=47). The rate of new hemorrhagic transformations was recorded at follow-up neuroimaging. Clinical outcome was evaluated at 90 days with the modified Rankin Scale (poor outcome, 3-6). RESULTS: Poor outcome was associated with the presence of CS (odds ratio [OR], 11.3; 95% confidence interval, 3.34-38.95) and BH (OR, 10.4; 95% confidence interval, 3.42-31.68). The rate of poor outcome despite complete recanalization was also significantly higher in CS (OR, 9.7; 95% confidence interval, 2.55-37.18) and BH (OR, 15.1; 95% confidence interval, 3.85-59.35) groups, compared with the no-HA group. Patients with CS disclosed a higher incidence of delayed hemorrhagic transformation at follow-up (OR, 4.5; 95% confidence interval, 1.22-16.37) compared with no-HA patients. CONCLUSIONS: Blood-brain barrier disruption, defined as CS and BH on dual-energy CT, was associated with poor clinical outcomes in patients with stroke treated with endovascular therapies. Moreover, isolated CS was associated with delayed hemorrhagic transformation. These results support the clinical relevance of blood-brain barrier disruption in acute stroke.

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

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

Functional outcome after primary endovascular therapy or IV thrombolysis alone for stroke. An observational, comparative effectiveness study.

BACKGROUND: Among the acute ischemic stroke patients with large vessel occlusions and contraindications for the use of IV thrombolysis, mainly on oral anticoagulation or presenting too late, primary endovascular therapy is often performed as an alternative to the standard therapy even though evidence supporting the use of endovascular reperfusion therapies is not yet established. Using different statistical approaches, we compared the functional independence rates at 3 months among patients undergoing primary endovascular therapy and patients treated only with IV thrombolysis. METHODS: We used data from a prospective, government-mandated and externally audited registry of reperfusion therapies for ischemic stroke (January 2011 to November 2012). Patients were selected if treated with either IV thrombolysis alone (n = 1,582) or primary endovascular thrombectomy (n = 250). A series of exclusions were made to homogenize the clinical characteristics among the two groups. We then carried out multivariate logistic regression and propensity score matching analyses on the final study sample (n = 1,179) to compare functional independence at 3 months, as measured by the modified Rankin scale scores 0-2, between the two groups. RESULTS: The unadjusted likelihood of good outcome was poorer among the endovascular group (OR: 0.69; 95% CI: 0.47-1.0). After adjustment, no differences by treatment modality were seen (OR: 1.51; 95% CI: 0.93-2.43 for primary endovascular therapy). Patients undergoing endovascular thrombectomy within 180-270 min (OR: 2.89; 95% CI: 1.17-7.15) and patients with severe strokes (OR: 1.84; 95% CI: 1.02-3.35) did better than their intravenous thrombolysis counterparts. The propensity score-matched analyses with and without adjustment by additional covariates showed that endovascular thrombectomy was as effective as intravenous thrombolysis alone in achieving functional independence (OR for unadjusted propensity score matched: 1.35; 95% CI: 0.9-2.02, OR for adjusted propensity score matched: 1.45; 95% CI: 0.91-2.32). CONCLUSION: This comparative effectiveness study shows that in ischemic stroke patients with contraindications for IV thrombolysis, primary endovascular treatment might be an alternative therapy at least as effective as IV thrombolysis alone. Randomized controlled trials are urgently needed.

Understanding the Importance of Blood-Brain Barrier Alterations in Brain Arteriovenous Malformations and Implications for Treatment: A Dynamic Contrast-Enhanced-MRI-Based Prospective Study.

BACKGROUND AND OBJECTIVES: The major clinical implication of brain arteriovenous malformations (bAVMs) is spontaneous intracranial hemorrhage. There is a growing body of experimental evidence proving that inflammation and blood-brain barrier (BBB) dysfunction are involved in both the clinical course of the disease and the risk of bleeding. However, how bAVM treatment affects perilesional BBB disturbances is yet unclear. METHODS: We assessed the permeability changes of the BBB using dynamic contrast-enhanced MRI (DCE-MRI) in a series of bAVMs (n = 35), before and at a mean of 5 (±2) days after treatment. A set of cerebral cavernous malformations (CCMs) (n = 16) was used as a control group for the assessment of the surgical-related collateral changes. The extended Tofts pharmacokinetic model was used to extract permeability (Ktrans) values in the lesional, perilesional, and normal brain tissues. RESULTS: In patients with bAVM, the permeability of BBB was higher in the perilesional of bAVM tissue compared with the rest of the brain parenchyma (mean Ktrans 0.145 ± 0.104 vs 0.084 ± 0.035, P = .004). Meanwhile, no significant changes were seen in the perilesional brain of CCM cases (mean Ktrans 0.055 ± 0.056 vs 0.061 ± 0.026, P = .96). A significant decrease in BBB permeability was evident in the perilesional area of bAVM after surgical resection (mean Ktrans 0.145 ± 0.104 vs 0.096 ± 0.059, P = .037). This benefit in BBB permeability reduction after surgery seemed to surpass the relative increase in permeability inherent to the surgical manipulation. CONCLUSION: In contrast to CCMs, BBB permeability in patients with bAVM is increased in the perilesional parenchyma, as assessed using DCE-MRI. However, bAVM surgical resection seems to reduce BBB permeability in the perilesional tissue. No evidence of the so-called breakthrough phenomenon was detected in our series. DCE-MRI could become a valuable tool to follow the longitudinal course of BBB damage throughout the natural history and clinical course of bAVMs.

Computer Aided Intracranial Aneurysm Treatment Based on 2D/3D Mapping, Virtual Deployment and Online Distal Marker Detection.

PURPOSE: To introduce a computational tool for peri-interventional intracranial aneurysm treatment guidance that maps preoperative planning information from simulation onto real-time X-Ray imaging. METHODS: Preoperatively, multiple flow diverter (FD) devices are simulated based on the 3D mesh of the vessel to treat, to choose the optimal size and location. In the peri-operative stage, this 3D information is aligned and mapped to the continuous 2D-X-Ray scan feed from the operating room. The current flow diverter position in the 3D model is estimated by automatically detecting the distal FD marker locations and mapping them to the treated vessel. This allows to visually assess the possible outcome of releasing the device at the current position, and compare it with the one chosen pre-operatively. RESULTS: The full pipeline was validated using retrospectively collected biplane images from four different patients (5 3D-DSA datasets in total). The distal FD marker detector obtained an average F1-score of 0.67 ( ± 0.224 ) in 412 2D-X-Ray scans. After aligning 3D-DSA + 2D-X-Ray datasets, the average difference between simulated and deployed positions was 0.832 mm ( ± 0.521 mm). Finally, we qualitatively show that the proposed approach is able to display the current location of the FD compared to their pre-operatively planned position. CONCLUSIONS: The proposed method allows to support the FD deployment procedure by merging and presenting preoperative simulation information to the interventionists, aiding them to make more accurate and less risky decisions.