The impact of general anesthesia versus non-general anesthesia on thrombectomy outcomes by occlusion location: insights from the ETIS registry.

OBJECTIVE: Identifying the optimal anesthetic technique for mechanical thrombectomy (MT) remains an unresolved issue. Prior research has not considered the influence of occlusion site when comparing general anesthesia (GA) with non-GA. This study evaluates the differential impacts of the anesthetic technique (GA vs non-GA) on outcomes according to the location of occlusion. METHODS: This is a retrospective analysis of the ETIS (Endovascular Treatment in Ischemic Stroke) registry. Patients with anterior circulation large-vessel occlusion treated with MT were included. Patients were divided into groups according to the location of occlusion. Inverse propensity score weighting analysis was used. RESULTS: Among 2783 patients included in the propensity score analysis, 669 (24%) received GA. In the total cohort, GA was not associated with favorable outcome, excellent outcome, successful reperfusion, or complete reperfusion. GA was associated with higher odds of parenchymal hemorrhage (OR 1.42, 95% 1.05-1.92) but not symptomatic intracranial hemorrhage. GA was associated with Alberta Stroke Program Early CT Score progression (OR 1.36, 95% CI 1.11-1.68). In the internal carotid artery occlusion group, GA was associated with higher odds of mortality (OR 1.94, 95% CI 1.15-3.27). In the M1 group, GA was associated with lower odds of complications (OR 0.41, 95% CI 0.19-0.92). In the M2 group, GA was associated with successful reperfusion (OR 2.79, 95% CI 1.02-7.64). In addition, the complication rate was lower with GA (2.7% vs 7%), although the association was not significant in adjusted analysis. CONCLUSIONS: While GA and non-GA techniques did not differ significantly in functional outcomes, the influence of GA on angiographic and procedural safety outcomes was location dependent, underscoring the importance of a tailored anesthesia technique in MT procedures.

ACCESS: ACtive Catheterization for EndovaScular TreatmentS-A First-in-Human, Single-Center, Nonrandomized, Open Clinical Study of the G60 Active Device for Endovascular Neurointerventions.

The catheterization of supra-aortic vessels during neuroendovascular interventions may be challenging in the setting of complex aortic arch anatomy. Evaluation of a new mechatronic controllable directional device in conjunction with different sheath and guide catheters to ease the cannulation of the supra-aortic vessels was conducted in the setting of a first-in-human clinical study. The evaluation assessment included access to the aortic arch, the technical success of the device in terms of time to target vessel, target vessel catheterization, adverse events, and clinical outcome. Ten subjects were enrolled at 1 site for treatment. Successful access, target vessel catheterization, and correct positioning of the catheter into the target vessel with the G60 device were achieved for all 10 procedures (7 from femoral access, 3 from radial access). One procedural complication, unrelated to the G60 device, was recorded during the investigation. The G60 is a polyvalent active device that facilitates guide catheter navigation in neuroendovascular interventions.

Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion.

Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells in intestinal Peyer's patches (PP) and lamina propria. Here we show that patients with stroke and myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid loss of IgA-producing plasma cells in PP and lamina propria. Reduced plasma IgG was detectable in patients and experimental mice 3-10 d after injury. Stroke/MI triggered the release of neutrophil extracellular traps (NETs). Depletion of neutrophils, NET degradation or blockade of NET release inhibited the loss of IgA+ cells and circulating IgA in experimental stroke and MI and in patients with stroke. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological Ig secretion and how this can be inhibited in patients.

Arterial hypotension "magnitude" and neurological outcome during mechanical thrombectomy under general anesthesia.

INTRODUCTION: Mechanical thrombectomy (MT) is the standard of care for the treatment of acute ischemic stroke (AIS) with large vessel occlusion (LVO), but unfavorable outcomes remain common. Procedural arterial hypotension is associated with poor patient outcome. This study aimed to assess the impact of arterial hypotension "magnitude" (a combination of the depth, defined as the percentage relative to baseline arterial blood pressure, and the duration of hypotensive episodes)" during MT on neurological outcome. METHODS: This is a monocentric retrospective study. Charts were reviewed between January 2018 and June 2021. "Patients were eligible if they were 18 years or older, anterior LVO was diagnosed on cerebral imaging" and MT performed under general anesthesia. Mean arterial pressure (MAP) was recorded every 5 min throughout the procedure, and the arterial hypotension "magnitude" was estimated by the area under the curve (AUC) for different thresholds of MAP drops. MAIN OUTCOME MEASURE: The modified Rankin Scale (mRS) at 90 days. MAIN RESULTS: Among the 117 patients analyzed, 46% had poor neurological outcome. Our study showed correlations between poor outcome and a greater procedural AUC of arterial hypotension for the different thresholds: 5% (k 0.18; 95% CI 0.06-0.30; P = 0.007), 10% (k 0.18; 95% CI 0.05-0.30; P = 0.008), 15% (k 0.18; 95% CI 0.04-0.30; P = 0.011), 20% (k 0.18; 95% CI 0.05-0.30; P = 0.010) and 30% (k 0.19; 95% CI 0.05-0.31; P = 0.010). This association persisted after controlling for age, baseline NIHSS score, and ASPECT score. CONCLUSION: The magnitude of hypotension during MT under general anesthesia for AIS is an independent factor of poor outcome at 90 days. These associations have been observed in patients with mild and severe hypotensive episodes.

Acute astrocytic reaction is associated with 3-month functional outcome after stroke treated with endovascular therapy.

INTRODUCTION: More than 50% of large vessel occlusion (LVO) acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT) remain severely disabled at 3 months. We hypothesized that acute astrocytic inflammatory response may play a pivotal role in post-AIS brain changes associated with poor functional outcome. We proposed to evaluate the level of YKL-40, a glycoprotein mainly released by reactive astrocytes. PATIENTS AND METHODS: A monocentric prospective cohort study was conducted on consecutive LVO AIS patients treated with EVT. Three blood samples (before, within 1 and 24-hour post-EVT) were collected to measure plasma YKL-40 concentrations. Functional outcome was assessed according to the modified Rankin Scale (mRS) score at 3 months. RESULTS: Between 2016 and 2020, 120 patients were included. The plasma concentration of YKL-40 before EVT was statistically and independently associated with 3-month worse functional outcome (adjusted cOR, 1.59; 95% CI [1.05-2.44], p = 0.027) but not the two following samples 1-hour and 24-hour post-EVT. Accordingly, we found that excellent functional outcome was associated with a lower level of YKL-40 before and within 1 h after EVT (p = 0.005 and p = 0.003, respectively) but not when measured 24 h after EVT (p = 0.2). DISCUSSION AND CONCLUSION: This study suggests that the astrocytic reaction to acute brain hypoxia, especially before recanalization, is associated with worse functional outcome. Such early biomarker of the astrocytic response in AIS may optimize individualized care in the future. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02900833.

Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial.

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.

Prognostic value of early EEG abnormalities in severe stroke patients requiring mechanical ventilation: a pre-planned analysis of the SPICE prospective multicenter study.

INTRODUCTION: Prognostication of outcome in severe stroke patients necessitating invasive mechanical ventilation poses significant challenges. The objective of this study was to assess the prognostic significance and prevalence of early electroencephalogram (EEG) abnormalities in adult stroke patients receiving mechanical ventilation. METHODS: This study is a pre-planned ancillary investigation within the prospective multicenter SPICE cohort study (2017-2019), conducted in 33 intensive care units (ICUs) in the Paris area, France. We included adult stroke patients requiring invasive mechanical ventilation, who underwent at least one intermittent EEG examination during their ICU stay. The primary endpoint was the functional neurological outcome at one year, determined using the modified Rankin scale (mRS), and dichotomized as unfavorable (mRS 4-6, indicating severe disability or death) or favorable (mRS 0-3). Multivariable regression analyses were employed to identify EEG abnormalities associated with functional outcomes. RESULTS: Of the 364 patients enrolled in the SPICE study, 153 patients (49 ischemic strokes, 52 intracranial hemorrhages, and 52 subarachnoid hemorrhages) underwent at least one EEG at a median time of 4 (interquartile range 2-7) days post-stroke. Rates of diffuse slowing (70% vs. 63%, p = 0.37), focal slowing (38% vs. 32%, p = 0.15), periodic discharges (2.3% vs. 3.7%, p = 0.9), and electrographic seizures (4.5% vs. 3.7%, p = 0.4) were comparable between patients with unfavorable and favorable outcomes. Following adjustment for potential confounders, an unreactive EEG background to auditory and pain stimulations (OR 6.02, 95% CI 2.27-15.99) was independently associated with unfavorable outcomes. An unreactive EEG predicted unfavorable outcome with a specificity of 48% (95% CI 40-56), sensitivity of 79% (95% CI 72-85), and positive predictive value (PPV) of 74% (95% CI 67-81). Conversely, a benign EEG (defined as continuous and reactive background activity without seizure, periodic discharges, triphasic waves, or burst suppression) predicted favorable outcome with a specificity of 89% (95% CI 84-94), and a sensitivity of 37% (95% CI 30-45). CONCLUSION: The absence of EEG reactivity independently predicts unfavorable outcomes at one year in severe stroke patients requiring mechanical ventilation in the ICU, although its prognostic value remains limited. Conversely, a benign EEG pattern was associated with a favorable 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.

Long-term outcome of endovascular treatment for indirect carotid-cavernous fistulas.

OBJECTIVE: Endovascular treatment (EVT) is the primary approach used to treat indirect carotid-cavernous fistulas (CCFs). In this study, the authors evaluated the immediate and long-term efficacy and safety of different endovascular techniques for indirect CCFs. METHODS: The databases of two endovascular centers were retrospectively reviewed to collect the patients with indirect CCFs treated using endovascular techniques between 2013 and 2023. Demographics, clinical presentation, CCF features, EVT characteristics, and clinical and radiological outcomes were evaluated and analyzed. The analysis was performed to compare the clinical and radiological data between different endovascular approaches and different embolic materials. RESULTS: Ninety-eight patients were included in the study. EVT was successful in 95 patients (96.9%). Immediate complete obliteration of the CCF was achieved in 93.9% of patients, with 98% undergoing embolization with liquid embolic agents (LEAs) and 95.6% undergoing coiling alone. Complete CCF obliteration was higher in the transvenous than in the transarterial approach (94.3% vs 75%, p = 0.010). At ≥ 6 months follow-up, complete CCF obliteration was achieved in all patients (100%). The rate of procedure-related complications was higher following LEAs than with coiling alone (32.0% vs 15.6%). New cranial nerve (CN) palsy was diagnosed in 26.0% and 2.2% after embolization with LEAs and coiling alone, respectively (p = 0.001), with complete CN palsy recovery in 78.6%. Procedure-related intracranial hemorrhage occurred in 3 patients (3.1%). Two patients experienced an ischemic stroke following Onyx migration into the internal carotid artery. Ocular symptoms improved in 93% (83/89) of the patients who were followed. CONCLUSIONS: In this study, complete obliteration of an indirect CCF was achieved in more than 90% of patients. Despite the occurrence of some new postprocedural ocular CN palsy, ocular symptoms improved in most patients in long-term follow-up. The transvenous approach was the most effective method for treating the indirect CCF. Coiling was safer than LEAs for the embolization of the indirect CCF.

Periodontitis in ischemic stroke: impact of Porphyromonas gingivalis on thrombus composition and ischemic stroke outcomes.

Background: Periodontitis is associated with an increased risk of ischemic stroke, but the mechanisms underlying this association remain unclear. Objectives: Our objective was to determine whether Porphyromonas gingivalis (Pg), a periodontal bacterium, could be detected within thrombus aspirates, modify thrombus composition, and endovascular therapy responses. Methods: The presence of Pg gingipain in 175 consecutive thrombi from patients with large vessel occlusion stroke enrolled in the multicenter research cohort compoCLOT was investigated by immunostaining. Thrombus blood cell composition according to gingipain status was analyzed in a subset of 63 patients. Results: Pg gingipain immunostaining was positive in 33.7% of thrombi (95% CI, 26.7%-40.8%). The percentage of near to complete reperfusion (modified Thrombolysis in Cerebral Infarction Score 2c/3) at the end of the procedure was lower in the Pgpos group than the Pgneg group (39.0% vs 57.8% respectively; adjusted odds ratio, 0.38; 95% CI, 0.19-0.77). At 3 months, 35.7% of patients in the Pgpos group had a favorable neurological outcome vs 49.5% in the Pgneg group (odds ratio, 0.65; 95% CI, 0.30-1.40). Quantitative analysis of a subset of 63 thrombi showed that neutrophil elastase content was significantly (P < .05) higher in Pgpos thrombi than in Pgneg thrombi. Conclusion: Our results indicate that intrathrombus Pg gingipain is associated with increased neutrophil content and resistance to endovascular therapy.

Exacerbation of thromboinflammation by JAK2V617F mutation worsens the prognosis of cerebral venous sinus thrombosis.

ABSTRACT: Cerebral venous sinus thrombosis (CVST) is an uncommon venous thromboembolic event accounting for <1% of strokes resulting in brain parenchymal injuries. JAK2V617F mutation, the most frequent driving mutation of myeloproliferative neoplasms, has been reported to be associated with worse clinical outcomes in patients with CVST. We investigated whether hematopoietic JAK2V617F expression predisposes to specific pathophysiological processes and/or worse prognosis after CVST. Using an in vivo mouse model of CVST, we analyzed clinical, biological, and imaging outcomes in mice with hematopoietic-restricted Jak2V617F expression, compared with wild-type Jak2 mice. In parallel, we studied a human cohort of JAK2V617F-positive or -negative CVST. Early after CVST, mice with hematopoietic Jak2V617F expression had increased adhesion of platelets and neutrophils in cerebral veins located in the vicinity of CVST. On day 1, Jak2V617F mice had a worse outcome characterized by significantly more frequent and severe intracranial hemorrhages (ICHs) and higher mortality rates. Peripheral neutrophil activation was enhanced, as indicated by higher circulating platelet-neutrophil aggregates, upregulated CD11b expression, and higher myeloperoxydase plasma level. Concurrently, immunohistological and brain homogenate analysis showed higher neutrophil infiltration and increased blood-brain barrier disruption. Similarly, patients with JAK2V617F-positive CVST tended to present higher thrombotic burden and had significantly higher systemic immune-inflammation index, a systemic thromboinflammatory marker, than patients who were JAK2V617F-negative. In mice with CVST, our study corroborates that Jak2V617F mutation leads to a specific pattern including increased thrombotic burden, ICH, and mortality. The exacerbated thromboinflammatory response, observed both in mice and patients positive for JAK2V617F, could contribute to hemorrhagic complications.

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.

Safety and efficacy of platelet glycoprotein VI inhibition in acute ischaemic stroke (ACTIMIS): a randomised, double-blind, placebo-controlled, phase 1b/2a trial.

BACKGROUND: Antagonists of glycoprotein VI-triggered platelet activation used in combination with recanalisation therapies are a promising therapeutic approach in acute ischaemic stroke. Glenzocimab is an antibody fragment that inhibits the action of platelet glycoprotein VI. We aimed to determine and assess the safety and efficacy of the optimal dose of glenzocimab in patients with acute ischaemic stroke eligible to receive alteplase with or without mechanical thrombectomy. METHODS: This randomised, double-blind, placebo-controlled study with dose-escalation (1b) and dose-confirmation (2a) phases (ACTIMIS) was done in 26 stroke centres in six European countries. Participants were adults (≥18 years) with disabling acute ischaemic stroke with a National Institutes of Health Stroke Scale score of 6 or higher before alteplase administration. Patients were randomly assigned treatment using a central electronic procedure. Total administered dose at the end of the intravenous administration was 125 mg, 250 mg, 500 mg, and 1000 mg of glenzocimab or placebo in phase 1b and 1000 mg of glenzocimab or placebo in phase 2a. Treatment was initiated 4·5 h or earlier from stroke symptom onset in patients treated with alteplase with or without mechanical thrombectomy. The sponsor, study investigator and study staff, patients, and central laboratories were all masked to study treatment until database lock. Primary endpoints across both phases were safety, mortality, and intracranial haemorrhage (symptomatic, total, and fatal), assessed in all patients who received at least a partial dose of study medication (safety set). The trial is registered on ClinicalTrials.gov, NCT03803007, and is complete. FINDINGS: Between March 6, 2019, and June 27, 2021, 60 recruited patients were randomly assigned to 125 mg, 250 mg, 500 mg, or 1000 mg glenzocimab, or to placebo in phase 1b (n=12 per group) and were included in the safety analysis. Glenzocimab 1000 mg was well tolerated and selected as the phase 2a recommended dose; from Oct 2, 2020, to June 27, 2021, 106 patients were randomly assigned to glenzocimab 1000 mg (n=53) or placebo (n=53). One patient in the placebo group received glenzocimab in error and therefore 54 and 52, respectively, were included in the safety set. In phase 2a, the most frequent treatment-emergent adverse event was non-symptomatic haemorrhagic transformation, which occurred in 17 (31%) of 54 patients treated with glenzocimab and 26 (50%) of 52 patients treated with placebo. Symptomatic intracranial haemorrhage occurred in no patients treated with glenzocimab compared with five (10%) patients in the placebo group. All-cause deaths were lower with glenzocimab 1000 mg (four [7%] patients) than with placebo (11 [21%] patients). INTERPRETATION: Glenzocimab 1000 mg in addition to alteplase, with or without mechanical thrombectomy, was well tolerated, and might reduce serious adverse events, intracranial haemorrhage, and mortality. These findings support the need for future research into the potential therapeutic inhibition of glycoprotein VI with glenzocimab plus alteplase in patients with acute ischaemic stroke. FUNDING: Acticor Biotech.

Neutrophil activation in patients treated with endovascular therapy is associated with unfavorable outcomes and mitigated by intravenous thrombolysis.

BACKGROUND: Accumulating evidence indicates that neutrophil activation (NA) contributes to microvascular thromboinflammation in acute ischemic stroke (AIS) due to a large vessel occlusion. Preclinical data have suggested that intravenous thrombolysis (IVT) before endovascular therapy (EVT) could dampen microvascular thromboinflammation. In this study we investigated the association between NA dynamics and stroke outcome, and the impact of IVT on NA in patients with AIS treated with EVT. METHODS: A single-center prospective study was carried out, including patients treated with EVT for whom three blood samples (before, within 1 hour, 24 hours post-EVT) were drawn to measure plasma myeloperoxidase (MPO) concentration as a marker of NA. Unfavorable outcome was defined as a modified Rankin score of 3-6 at 3 months. RESULTS: Between 2016 and 2020, 179 patients were included. The plasma MPO concentration peaked significantly 1 hour post-EVT (median increase 21.0 ng/mL (IQR -2.1-150)) and returned to pre-EVT baseline values 24 hours after EVT (median change from baseline -0.8 ng/mL (IQR -7.6-6.7)). This peak was strongly associated with unfavorable outcomes at 3 months (aOR 0.53 (95% CI 0.34 to 0.84), P=0.007). IVT before EVT abolished this 1 hour post-EVT MPO peak. Changes in plasma MPO concentration (baseline to 1 hour post-EVT) were associated with unfavorable outcomes only in patients not treated with IVT before EVT (aOR 0.54 (95% CI 0.33 to 0.88, P=0.013). However, we found no significant heterogeneity in the associations between changes in plasma MPO concentration and outcomes. CONCLUSIONS: A peak in plasma MPO concentration occurs early after EVT and is associated with unfavorable outcomes. IVT abolished the post-EVT MPO peak and may modulate the association between NA and outcomes.

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.

Assessment of inter-operator variability in peripheral monocyte subset gating strategy using flow cytometry in patients with suspected acute stroke.

BACKGROUND: Innovative tools to reliably identify patients with acute stroke are needed. Peripheral monocyte subsets, that is, classical-Mon1, intermediate-Mon2, and non-classical-Mon3, with their activation marker expression analyzed using flow-cytometry (FCM) could be interesting cell biomarker candidates. AIM: To assess the inter-operator variability in a new peripheral monocyte subset gating strategy using FCM in patients with suspected acute stroke. METHODS: In BOOST-study ("Biomarkers-algOrithm-for-strOke-diagnoSis-and Treatment-resistance-prediction," NCT04726839), patients ≥18 years with symptoms suggesting acute stroke within the last 24 h were included. Blood was collected upon admission to emergency unit. FCM analysis was performed using the FACS-CANTO-II® flow-cytometer and Flow-Jo™-software. Analyzed markers were CD45/CD91/CD14/CD16 (monocyte backbone) and CD62L/CD11b/HLA-DR/CD86/CCR2/ICAM-1/CX3CR1/TF (activation markers). Inter-operator agreement (starting from raw-data files) was quantified by the measure distribution and, for each patient, the coefficient of variation (CV). RESULTS: Three operators analyzed 20 patient blood samples. Median inter-operator CVs were below the pre-specified tolerance limits (10% [for Mon1 counts], 20% [Mon2, Mon3 counts], 15% [activation marker median-fluorescence-intensities]). We observed a slight, but systematic, inter-operator effect. Overall, absolute inter-operator differences in fractions of monocyte subsets were <0.03. CONCLUSION: Our gating strategy allowed monocyte subset gating with an acceptable inter-operator variability. Although low, the inter-operator effect should be considered in monocyte data analysis of BOOST-patients.

Treated unruptured cerebral aneurysm in elderly patients: a single center study.

INTRODUCTION: The increase in life expectancy raises the question of the treatment of unruptured intracranial aneurysms in extremely old patients (>80 years). We present results in terms of occlusion and complications in both symptomatic and asymptomatic aneurysm. METHODS: All patients aged >80 years admitted to the Foundation Adolphe de Rothschild between January 1, 2005 and March, 2023 were included. Aneurysms were grouped as compressive and non-compressive. Procedural complications were grouped as symptomatic (i.e., leading to any temporary or permanent neurological deficit) and severe (defined by modified Rankin Scale (mRS) ≥3 at follow-up). RESULTS: Forty-two aneurysms were treated in the study period. Coiling (with or without remodeling) was the treatment of choice in 30 patients. Eighteen patients had compressive aneurysm. Six complications occurred (14.2%), all ischemic. The majority of complications occurred in symptomatic aneurysms, in 4 patients (66.6%). One of the patients treated by flow-diverter had severe complications (mRs ≥3) with hemiplegia. CONCLUSION: In extremely specific cases, treatment of unruptured aneurysm in people older than 80 years may be considered. Compressive aneurysm is associated with a high risk of complications. Treatments can be endovascular. Further prospective studies are required to confirm this hypothesis.

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.

Early Intubation in Endovascular Therapy for Basilar Artery Occlusion: A Post Hoc Analysis of the BASICS Trial.

BACKGROUND: The optimal anesthetic management for endovascular therapy (EVT) in patients with posterior circulation stroke remains unclear. Our objective was to investigate the impact of early intubation in patients enrolled in the BASICS trial (Basilar Artery International Cooperation Study). METHODS: BASICS was a multicenter, randomized, controlled trial that compared the efficacy of EVT compared with the best medical care alone in patients with basilar artery occlusion. In this post hoc analysis, early intubation within the first 24 hours of the estimated time of basilar artery occlusion was examined as an additional covariate using regression modeling. We estimated the adjusted relative risks (RRs) for favorable outcomes, defined as modified Rankin Scale scores of 0 to 3 at 90 days. An adjusted common odds ratio was estimated for a shift in the distribution of modified Rankin Scale scores at 90 days. RESULTS: Of 300 patients in BASICS, 289 patients were eligible for analysis (151 in the EVT group and 138 in the best medical care group). compared with medical care alone, EVT was related to a higher risk of early intubation (RR, 1.29 [95% CI, 1.09-1.53]; P<0.01), and early intubation was negatively associated with favorable outcome (RR, 0.61 [95% CI, 0.45-0.84]; P=0.002). Whereas there was no overall treatment effect of EVT on favorable outcome (RR, 1.22 [95% CI, 0.95-1.55]; P=0.121), EVT was associated with favorable outcome (RR, 1.34 [95% CI, 1.05-1.71]; P=0.018) and a shift toward lower modified Rankin Scale scores (adjusted common odds ratio, 1.63 [95% CI, 1.04-2.57]; P=0.033) if adjusted for early intubation. CONCLUSIONS: In this post hoc analysis of the neutral BASICS trial, early intubation was linked to unfavorable outcomes, which might mitigate a potential benefit from EVT by indirect effects due to an increased risk of early intubation. This relationship may be considered when assessing the efficacy of EVT in patients with basilar artery occlusion in future trials.

Thrombus composition and thrombolysis resistance in stroke.

A State of the Art lecture titled "Thrombus Composition and Thrombolysis Resistance in Stroke" was presented at the ISTH Congress in 2022. Intravenous thrombolysis (IVT) remains the only pharmacologic option to re-establish cerebral perfusion at the acute phase of ischemic stroke. IVT is based on the administration of recombinant tissue plasminogen activator with the objective of dissolving fibrin, the major fibrillar protein component of thrombi. Almost 30 years on from its introduction, although the clinical benefits of IVT have been clearly demonstrated, IVT still suffers from a relatively low efficacy, with a rate of successful early recanalization below 50% overall. Analyses of thrombectomy-recovered acute ischemic stroke (AIS) thrombi have shown that apart from occlusion site, thrombus length, and collateral status, AIS thrombus structure and composition are also important modulators of IVT efficacy. In this article, after a brief presentation of IVT principle and current knowledge on IVT resistance, we review recent findings on how compaction and structural alterations of fibrin together with nonfibrin thrombus components such as neutrophil extracellular traps and von Willebrand factor interfere with IVT in AIS. We further discuss how these new insights could soon result in the development of original adjuvant therapies for improved IVT in AIS. Finally, we summarize relevant new data presented during the 2022 ISTH Congress.