Intra-Arterial Thrombolysis is Associated with Delayed Reperfusion of Remaining Vessel Occlusions following Incomplete Thrombectomy.

BACKGROUND AND PURPOSE: Intra-arterial thrombolytics may be used to treat distal vessel occlusions, which cause incomplete reperfusion following mechanical thrombectomy. Because immediate reperfusion after intra-arterial thrombolytics occurs rarely, the aim of this study was to assess the delayed effect of intra-arterial thrombolytics using follow-up perfusion imaging. MATERIALS AND METHODS: We included patients from a prospective stroke registry (February 2015 to September 2022) who had undergone mechanical thrombectomy and had incomplete reperfusion (expanded TICI 2a-2c) and available 24 hour perfusion imaging. Perfusion imaging was rated as delayed reperfusion if time-sensitive perfusion maps did not show wedge-shaped delays suggestive of persisting occlusions corresponding to the post-mechanical thrombectomy angiographic deficit. Patients treated with intra-arterial thrombolytics were compared with controls using multivariable logistic regression and inverse probability of treatment weighting matching for baseline differences and factors associated with delayed reperfusion. RESULTS: The median age of the final study population (n = 459) was 74 years (interquartile range, 63-81 years), and delayed reperfusion occurred in 61% of cases. Patients treated with additional intra-arterial thrombolytics (n = 40) were younger and had worse expanded TICI scores. After matching was performed, intra-arterial thrombolytics was associated with higher rates of delayed reperfusion (adjusted OR = 2.7; 95% CI, 1.1-6.4) and lower rates of new infarction in the residually hypoperfused territory after mechanical thrombectomy (adjusted OR = 0.3; 95% CI, 0.1-0.7). No difference was found in the rates of functional independence (90-day mRS, 0-2; adjusted OR = 1.4; 95% CI, 0.4-4.1). CONCLUSIONS: Rescue intra-arterial thrombolytics is associated with delayed reperfusion of remaining vessel occlusions following incomplete mechanical thrombectomy. The value of intra-arterial thrombolytics as a potential therapy for incomplete reperfusions after mechanical thrombectomy should be assessed in the setting of randomized controlled trials.

Endovascular therapy outcome in isolated posterior cerebral artery occlusion strokes: A multicenter analysis of the Swiss Stroke Registry.

PURPOSE: There is little data on the safety and efficacy of endovascular treatment (EVT) in comparison with intravenous thrombolysis (IVT) in acute ischemic stroke due to isolated posterior cerebral artery occlusion (IPCAO). We aimed to investigate the functional and safety outcomes of stroke patients with acute IPCAO treated with EVT (with or without prior bridging IVT) compared to IVT alone. METHODS: We did a multicenter retrospective analysis of data from the Swiss Stroke Registry. The primary endpoint was overall functional outcome at 3 months in patients undergoing EVT alone or as part of bridging, compared with IVT alone (shift analysis). Safety endpoints were mortality and symptomatic intracranial hemorrhage. EVT and IVT patients were matched 1:1 using propensity scores. Differences in outcomes were examined using ordinal and logistic regression models. FINDINGS: Out of 17,968 patients, 268 met the inclusion criteria and 136 were matched by propensity scores. The overall functional outcome at 3 months was comparable between the two groups (EVT vs IVT as reference category: OR = 1.42 for higher mRS, 95% CI = 0.78-2.57, p = 0.254). The proportion of patients independent at 3 months was 63.2% in EVT and 72.1% in IVT (OR = 0.67, 95% CI = 0.32-1.37, p = 0.272). Symptomatic intracranial hemorrhages were overall rare and present only in the IVT group (IVT = 5.9% vs EVT = 0%). Mortality at 3 months was also similar between the two groups (IVT = 0% vs EVT = 1.5%). CONCLUSION: In this multicenter nested analysis, EVT and IVT in patients with acute ischemic stroke due to IPCAO were associated with similar overall good functional outcome and safety. Randomized studies are warranted.

Risks of Undersizing Stent Retriever Length Relative to Thrombus Length in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Results regarding the association of thrombus length, stent retriever length, and recanalization success in patients with acute ischemic stroke are inconsistent. We hypothesized that the ratio of thrombus length to stent retriever length may be of particular relevance. MATERIALS AND METHODS: Patients with acute ischemic stroke undergoing stent retriever thrombectomy at our institution between January 2010 and December 2018 were reviewed retrospectively. Thrombus length was assessed by measuring the susceptibility vessel sign on SWI using a 1.5T or 3T MR imaging scanner. Multivariable logistic regression models were used to determine the association between thrombus length, stent retriever length, and thrombus length/stent retriever length ratio with first-pass recanalization, overall recanalization, and embolization in new territories. Results are shown as adjusted ORs with 95% CIs. Additional mediation analyses were performed to test for indirect effects on first-pass recanalization and overall recanalization success. RESULTS: The main analysis included 418 patients (mean age, 74.9 years). Increasing stent retriever length was associated with first-pass recanalization. Decreasing thrombus length and lower thrombus length/stent retriever length ratios were associated with first-pass recanalization and overall recanalization. Thrombus length and stent retriever length showed no association with first-pass recanalization or overall recanalization once thrombus length/stent retriever length ratio was factored in, while thrombus length/stent retriever length ratio remained a significant factor in both models (adjusted OR, 0.316 [95% CI, 0.112-0.892]; P = .030 and adjusted OR, = 0.366 [95% CI, 0.194-0.689]; P = .002). Mediation analyses showed that decreasing thrombus length and increasing stent retriever length had a significant indirect effect on first-pass recanalization mediated through thrombus length/stent retriever length ratio. The only parameter associated with embolization in new territories was an increasing thrombus length/stent retriever length ratio (adjusted OR, 5.079 [95% CI, 1.332-19.362]; P = .017). CONCLUSIONS: Information about thrombus and stent length is more valuable when combined. High thrombus length/stent retriever length ratios, which may raise the risk of unsuccessful recanalization and embolization in new territories, should be avoided by adapting stent retriever selection to thrombus length whenever possible.

SWI Susceptibility Vessel Sign in Patients Undergoing Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The frequency and clinical significance of the susceptibility vessel sign in patients with acute ischemic stroke remains unclear. We aimed to assess its prevalence in patients with acute ischemic stroke undergoing mechanical thrombectomy and to analyze its association with interventional and clinical outcome parameters in that group. MATERIALS AND METHODS: Six hundred seventy-six patients with acute ischemic stroke and admission MR imaging were reviewed retrospectively. Of those, 577 met the eligibility criteria for further analysis. Imaging was performed using a 1.5T or 3T MR imaging scanner. Associations between baseline variables, interventional and clinical outcome parameters, and susceptibility vessel sign were determined with multivariable logistic regression models. Results are shown as adjusted ORs with 95% CIs. RESULTS: The susceptibility vessel sign was present in 87.5% (n = 505) of patients and associated with tandem occlusion (adjusted OR, 3.3; 95% CI, 1.1-10.0; P = .032) as well as successful reperfusion, defined as an expanded TICI score of ≥2b (adjusted OR, 2.4; 95% CI, 1.28-4.6; P = .007). The susceptibility vessel sign was independently associated with functional independence (mRS ≤ 2: adjusted OR, 2.1; 95% CI, 1.1-4.0; P = .028) and lower mortality (adjusted OR, 0.4; 95% CI, 0.2-0.7; P = .003) at 90 days, even after adjusting for successful reperfusion. The susceptibility vessel sign did not influence the number of passes performed during mechanical thrombectomy, the first-pass reperfusion, or the risk of peri- or postinterventional complications. CONCLUSIONS: The susceptibility vessel sign is an MR imaging phenomenon frequently observed in patients with acute ischemic stroke and is associated with successful reperfusion after mechanical thrombectomy. However, superior clinical functional outcome and lower mortality noted in patients showing the susceptibility vessel sign could not be entirely attributed to higher reperfusion rates.

Room temperature organic exciton-polariton condensate in a lattice.

Interacting Bosons in artificial lattices have emerged as a modern platform to explore collective manybody phenomena and exotic phases of matter as well as to enable advanced on-chip simulators. On chip, exciton-polaritons emerged as a promising system to implement and study bosonic non-linear systems in lattices, demanding cryogenic temperatures. We discuss an experiment conducted on a polaritonic lattice at ambient conditions: We utilize fluorescent proteins providing ultra-stable Frenkel excitons. Their soft nature allows for mechanically shaping them in the photonic lattice. We demonstrate controlled loading of the coherent condensate in distinct orbital lattice modes of different symmetries. Finally, we explore the self-localization of the condensate in a gap-state, driven by the interplay of effective interaction and negative effective mass in our lattice. We believe that this work establishes organic polaritons as a serious contender to the well-established GaAs platform for a wide range of applications relying on coherent Bosons in lattices.

[Dizziness and vertigo in a tertiary ENT emergency department]. / Schwindelerkrankungen in einem tertiären HNO-Notfallzentrum.

BACKGROUND: Although vestibular symptoms are amongst the most frequent reasons for seeking emergency medical help, many patients remain undiagnosed. OBJECTIVE: In this cross-sectional study, we investigated the spectrum of vertigo and dizziness in a tertiary ear, nose, and throat (ENT) emergency department (ED). Furthermore, we investigated the attendant symptoms, clinical signs, and the diagnostic tests performed. METHODS: We screened all ED reports from 01/2013 to 12/2013 for adult patients with vestibular symptoms referred to the ENT department. RESULTS: In total, we found 2596 cases with reported vestibular symptoms in the ED as a main or accompanying complaint. Of these, 286 were referred to the ENT specialist directly (n = 98) or via other major medical specialties (n = 188). Benign paroxysmal positional vertigo (BPPV) was the most frequent diagnosis in our study (n = 46, 16.1%), followed by vestibular neuritis (n = 44, 15.4%), otitis media (n = 20, 7%), and 9 patients (3.1%) had an ischemic stroke or a transient ischemic attack. In 70 (24.5%) cases, dizziness was not further specified. CONCLUSION: BPPV is the most frequent diagnosis seen in the ED; however, physicians need to document nystagmus more precisely and perform diagnostic tests systematically, in order to make an accurate diagnosis. To avoid misdiagnoses, ED physicians and ENT specialists should be able to recognize central signs in patients with an acute vestibular syndrome. Every fourth patient does not receive a definitive diagnosis. Diagnostic ED workup for patients with dizziness needs further improvement.

How Do Physicians Approach Intravenous Alteplase Treatment in Patients with Acute Ischemic Stroke Who Are Eligible for Intravenous Alteplase and Endovascular Therapy? Insights from UNMASK-EVT.

BACKGROUND AND PURPOSE: With increasing use of endovascular therapy, physicians' attitudes toward intravenous alteplase in endovascular therapy-eligible patients may be changing. We explored current intravenous alteplase treatment practices of physicians in endovascular therapy- and alteplase-eligible patients with acute stroke using prespecified case scenarios and compared how their current local treatment practices differ compared with an assumed ideal environment. MATERIALS AND METHODS: In an international multidisciplinary survey, 607 physicians involved in acute stroke care were randomly assigned 10 of 22 case scenarios, among them 14 with guideline-based alteplase recommendations (9 with level 1A and 5 with level 2B recommendation) and were asked how they would treat the patient: A) under their current local resources, and B) under assumed ideal conditions. Answer options were the following: 1) anticoagulation/antiplatelet therapy, 2) endovascular therapy, 3) endovascular therapy plus intravenous alteplase, and 4) intravenous alteplase. Decision rates were calculated, and multivariable regression analysis was performed to determine variables associated with the decision to abandon intravenous alteplase. RESULTS: In cases with guideline recommendations for alteplase, physicians favored alteplase in 82.0% under current local resources and in 79.3% under assumed ideal conditions (P < .001). Under assumed ideal conditions, interventional neuroradiologists would refrain from intravenous alteplase most often (6.28%, OR = 2.40; 95% CI, 1.01-5.71). When physicians' current and ideal decisions differed, most would like to add endovascular therapy to intravenous alteplase in an ideal setting (196/3861 responses, 5.1%). CONCLUSIONS: In patients eligible for endovascular therapy and intravenous alteplase, we observed a slightly lower decision rate in favor of intravenous alteplase under assumed ideal conditions compared with the decision rate under current local resources.

Free propagation phase-contrast breast CT provides higher image quality than cone-beam breast-CT at low radiation doses: a feasibility study on human mastectomies.

In this study we demonstrate the first direct comparison between synchrotron x-ray propagation-based CT (PB-CT) and cone-beam breast-CT (CB-CT) on human mastectomy specimens (N = 12) including different benign and malignant lesions. The image quality and diagnostic power of the obtained data sets were compared and judged by two independent expert radiologists. Two cases are presented in detail in this paper including a comparison with the corresponding histological evaluation. Results indicate that with PB-CT it is possible to increase the level of contrast-to-noise ratio (CNR) keeping the same level of dose used for the CB-CT or achieve the same level of CNR reached by CB-CT at a lower level of dose. In other words, PB-CT can achieve a higher diagnostic potential compared to the commercial breast-CT system while also delivering a considerably lower mean glandular dose. Therefore, we believe that PB-CT technique, if translated to a clinical setting, could have a significant impact in improving breast cancer diagnosis.

Availability of secondary prevention services after stroke in Europe: An ESO/SAFE survey of national scientific societies and stroke experts.

BACKGROUND: Recurrent stroke is associated with increased disability and cognitive impairment, but the availability of secondary prevention measures after transient ischaemic attack (TIA) or stroke in Europe is uncertain. This limits prioritisation of investment and development of national stroke strategies. METHODS: National stroke representatives throughout Europe were surveyed. Consensus panels reported national data if available, or else expert opinion, estimating the availability of each intervention by quintiles of patients, dichotomised for analysis at 60%. Countries were classified into tertiles of gross domestic product per capita. RESULTS: Of 50 countries, 46 responded; 14/45 (31%) had national stroke registries and 25/46 (54.3%) had national stroke strategies incorporating secondary prevention. Respondents reported that the majority of TIA patients were assessed by specialist services within 48 hours in 74.4% of countries, but in nine countries more than 20% of patients were seen after more than seven days and usually assessed by non-specialists (7/46 countries). Eighty percent of countries deferred blood pressure assessment to primary care, whilst lifestyle management programmes were commonly available in only 46% of countries. Although basic interventions were widely available, interventions frequently not available to more than 60% of patients included: ambulatory cardiac monitoring (40% countries); prescription (26%) and continuation (46%) of statins; blood pressure control at follow-up (44%); carotid endarterectomy within one month (15%); face-to-face follow-up in hospital (33%); direct oral anticoagulants (21%). Gross domestic product per capita and reimbursement of interventions were the commonest predictors of availability of interventions. CONCLUSIONS: Provision of secondary prevention varied, with gaps in care prevalent throughout Europe, particularly in lower income countries.

Reasons for Reperfusion Failures in Stent-Retriever-Based Thrombectomy: Registry Analysis and Proposal of a Classification System.

BACKGROUND AND PURPOSE: In 5%-10% of patients with acute ischemic stroke with an intention to treat with mechanical thrombectomy, no reperfusion can be achieved (Thrombolysis in Cerebral Infarction score = 0/1). Purpose of this analysis was a systematic assessment of underlying reasons for reperfusion failures. MATERIALS AND METHODS: An intention-to-treat single-center cohort (n = 592) was re-evaluated for all patients in whom no reperfusion could be achieved (n = 63). Baseline characteristics of patients were compared between patients with and without reperfusion failures. After qualitative review of all cases with reperfusion failures, a classification system was proposed and relative frequencies were reported. In a second step, occurrence of delayed recanalization at 24 hours after reperfusion failure and dependency on IV-tPA were evaluated. RESULTS: In 63/592 patients with an intention to perform stent-retriever thrombectomy, no reperfusion was achieved (TICI 0/1, 10.6%, 95% CI, 8.2%-13.1%). Older patients (adjusted OR per yr = 1.03; 95% CI, 1.01-1.05) and patients with M2 occlusion (adjusted OR = 3.36; 95% CI, 1.82-6.21) were at higher risk for reperfusion failure. In most cases, no reperfusion was a consequence of technical difficulties (56/63, 88.9%). In one-third of these cases, reperfusion failures were due to the inability to reach the target occlusion (20/63, 31.7%), while "stent-retriever failure" occurred in 39.7% (25/63) of patients. Delayed recanalization was very rare (18.2%), without dependence on IV-tPA pretreatment status. CONCLUSIONS: Reasons for reperfusion failure in stent-retriever thrombectomy are heterogeneous. The failure to establish intracranial or cervical access is almost as common as stent-retriever failure after establishing intracranial access. Systematic reporting standards of reasons may help to further estimate relative frequencies and thereby guide priorities for technical development and scientific effort.

Multicentric Experience in Distal-to-Proximal Revascularization of Tandem Occlusion Stroke Related to Internal Carotid Artery Dissection.

BACKGROUND AND PURPOSE: Internal carotid dissection is a frequent cause of ischemic stroke in young adults. It may cause tandem occlusions in which cervical carotid obstruction is associated with intracranial proximal vessel occlusion. To date, no consensus has emerged concerning endovascular treatment strategy. Our aim was to evaluate our endovascular "distal-to-proximal" strategy in the treatment of this stroke subtype in the first large multicentric cohort. MATERIALS AND METHODS: Prospectively managed stroke data bases from 2 separate centers were retrospectively studied between 2009 and 2014 for records of tandem occlusions related to internal carotid dissection. Atheromatous tandem occlusions were excluded. The first step in the revascularization procedure was intracranial thrombectomy. Then, cervical carotid stent placement was performed depending on the functionality of the circle of Willis and the persistence of residual cervical ICA occlusion, severe stenosis, or thrombus apposition. Efficiency, complications, and radiologic and clinical outcomes were recorded. RESULTS: Thirty-four patients presenting with tandem occlusion stroke secondary to internal carotid dissection were treated during the study period. The mean age was 52.5 years, the mean initial NIHSS score was 17.29 ± 6.23, and the mean delay between onset and groin puncture was 3.58 ± 1.1 hours. Recanalization TICI 2b/3 was obtained in 21 cases (62%). Fifteen patients underwent cervical carotid stent placement. There was no recurrence of ipsilateral stroke in the nonstented subgroup. Twenty-one patients (67.65%) had a favorable clinical outcome after 3 months. CONCLUSIONS: Endovascular treatment of internal carotid dissection-related tandem occlusion stroke using the distal-to-proximal recanalization strategy appears to be feasible, with low complication rates and considerable rates of successful recanalization.

The Neutrons for Science Facility at SPIRAL-2.

The neutrons for science (NFS) facility is a component of SPIRAL-2, the new superconducting linear accelerator built at GANIL in Caen (France). The proton and deuteron beams delivered by the accelerator will allow producing intense neutron fields in the 100 keV-40 MeV energy range. Continuous and quasi-mono-kinetic energy spectra, respectively, will be available at NFS, produced by the interaction of a deuteron beam on a thick Be converter and by the 7Li(p,n) reaction on thin converter. The pulsed neutron beam, with a flux up to two orders of magnitude higher than those of other existing time-of-flight facilities, will open new opportunities of experiments in fundamental research as well as in nuclear data measurements. In addition to the neutron beam, irradiation stations for neutron-, proton- and deuteron-induced reactions will be available for cross-sections measurements and for the irradiation of electronic devices or biological cells. NFS, whose first experiment is foreseen in 2018, will be a very powerful tool for physics, fundamental research as well as applications like the transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors.

De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.

Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed in brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females and 2 affected males with a de novo variant in CLCN4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families with inherited CLCN4 variants (4 families previously unreported). Intellectual disability ranged from borderline to profound. Behavioral and psychiatric disorders were common in both child- and adulthood, and included autistic features, mood disorders, obsessive-compulsive behaviors and hetero- and autoaggression. Epilepsy was common, with severity ranging from epileptic encephalopathy to well-controlled seizures. Several affected individuals showed white matter changes on cerebral neuroimaging and progressive neurological symptoms, including movement disorders and spasticity. Heterozygous females can be as severely affected as males. The variability of symptoms in females is not correlated with the X inactivation pattern studied in their blood. The mutation spectrum includes frameshift, missense and splice site variants and one single-exon deletion. All missense variants were predicted to affect CLCN4's function based on in silico tools and either segregated with the phenotype in the family or were de novo. Pathogenicity of all previously unreported missense variants was further supported by electrophysiological studies in Xenopus laevis oocytes. We compare CLCN4-related disorder with conditions related to dysfunction of other members of the CLC family.

Impact of intravenous thrombolysis on recanalization rates in patients with stroke treated with bridging therapy.

BACKGROUND AND PURPOSE: Randomized controlled trials have shown that bridging endovascular therapy (EVT) after intravenous thrombolysis (IVT) therapy improves outcome in patients with stroke with large-artery anterior circulation stroke compared with IVT alone. It remains unknown whether IVT adds any benefit to EVT in these patients. The aim of this study was to assess recanalization rates and thrombus dislocation before initiation of EVT in patients receiving bridging therapy. METHODS: All patients in the Bernese stroke registry (2008-2015) in whom bridging therapy was considered were included in this analysis. Relevant recanalization before EVT, thrombus dislocation and increase in thrombus load between initial and control imaging were assessed retrospectively. RESULTS: A total of 319 patients were included. Relevant recanalization before EVT occurred in 8.8% and thrombus dislocation in 7.2% of patients before EVT. Recanalization rates were significantly higher in distal compared with large and more proximal vessel occlusions of the anterior circulation (occlusion of internal carotid artery, 5.4%; middle cerebral artery segment M1, 8.1%; middle cerebral artery segment M2, 17.6%) and in drip-and-ship patients compared with mother-ship patients. In multivariable regression analysis the occlusion site was the only independent predictor of relevant recanalization before EVT (P = 0.046). CONCLUSIONS: Relevant recanalization after IVT and prior to EVT in patients receiving bridging therapy was highly dependent on the occlusion site. These findings suggest that future randomized controlled trials should consider occlusion site and treatment paradigm to specify patients who benefit most from bridging therapy in comparison to EVT or IVT alone.

[Headache in the emergency department]. / Kopfschmerz in der Notaufnahme.

Headache is one of the most frequent symptoms leading to visits at the emergency department. Here, we aim at presenting a pragmatic algorithm for headache patients at the emergency department. The basic principle is taking a detailed history of the current headache with a focus on dynamics, phenotype and trigger factors as well as a possible preexisting headache. "Red flags" should be interrogated specifically. Hypotheses of the etiology of the headache should be generated in combination with the clinical examination (vital signs, neurological exam, otorhinolaryngological and ophthalmological exams) and should be tested appropriately with imaging, laboratory, cerebral spinal fluid studies and ultrasound. Secondary headache have to be treated with a causal approach, if necessary also symptomatically. When a secondary headache can be excluded, we recommend aiming for a primary headache diagnosis with subsequent specific therapy. When a headache patient can be discharged, we recommend scheduling a follow-up appointment to understand the development of a secondary headache and its cause. In case of a primary headache, optimizing prophylaxis and acute therapy is important to prevent future emergency department visits.

Impact of Anesthesia on the Outcome of Acute Ischemic Stroke after Endovascular Treatment with the Solitaire Stent Retriever.

BACKGROUND AND PURPOSE: General anesthesia during endovascular treatment of acute ischemic stroke may have an adverse effect on outcome compared with conscious sedation. The aim of this study was to examine the impact of the type of anesthesia on the outcome of patients with acute ischemic stroke treated with the Solitaire stent retriever, accounting for confounding factors. MATERIALS AND METHODS: Four-hundred one patients with consecutive acute anterior circulation stroke treated with a Solitaire stent retriever were included in this prospective analysis. Outcome was assessed after 3 months by the modified Rankin Scale. RESULTS: One-hundred thirty-five patients (31%) underwent endovascular treatment with conscious sedation, and 266 patients (69%), with general anesthesia. Patients under general anesthesia had higher NIHSS scores on admission (17 versus 13, P < .001) and more internal carotid artery occlusions (44.6% versus 14.8%, P < .001) than patients under conscious sedation. Other baseline characteristics such as time from symptom onset to the start of endovascular treatment did not differ. Favorable outcome (mRS 0-2) was more frequent with conscious sedation (47.4% versus 32%; OR, 0.773; 95% CI, 0.646-0.925; P = .002) in univariable but not multivariable logistic regression analysis (P = .629). Mortality did not differ (P = .077). Independent predictors of outcome were age (OR, 0.95; 95% CI, 0.933-0.969; P < .001), NIHSS score (OR, 0.894; 95% CI, 0.855-0.933; P < .001), time from symptom onset to the start of endovascular treatment (OR, 0.998; 95% CI, 0.996-0.999; P = .011), diabetes mellitus (OR, 0.544; 95% CI, 0.305-0.927; P = .04), and symptomatic intracerebral hemorrhage (OR, 0.109; 95% CI, 0.028-0.428; P = .002). CONCLUSIONS: In this single-center study, the anesthetic management during stent retriever thrombectomy with general anesthesia or conscious sedation had no impact on the outcome of patients with large-vessel occlusion in the anterior circulation.

Genomic profiling of Acute lymphoblastic leukemia in ataxia telangiectasia patients reveals tight link between ATM mutations and chromothripsis.

Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair. Using whole-genome sequencing, fluorescence in situ hybridization and RNA sequencing, we characterized the genomic landscape of Acute Lymphoblastic Leukemia (ALL) arising in patients with Ataxia Telangiectasia. We detected a high frequency of chromothriptic events in these tumors, specifically on acrocentric chromosomes, as compared with tumors from individuals with other types of DNA repair syndromes (27 cases total, 10 with Ataxia Telangiectasia). Our data suggest that the genomic landscape of Ataxia Telangiectasia ALL is clearly distinct from that of sporadic ALL. Mechanistically, short telomeres and compromised DNA damage response in cells of Ataxia Telangiectasia patients may be linked with frequent chromothripsis. Furthermore, we show that ATM loss is associated with increased chromothripsis prevalence in additional tumor entities.