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Background and Purpose: Endothelial dysfunction is considered an emerging therapeutic target to prevent complications during acute stroke and to prevent recurrent stroke. This review aims to provide an overview of the current knowledge on endothelial dysfunction, outline the diagnostic methods used to measure it and highlight the drugs currently being investigated for the treatment of endothelial dysfunction in acute ischemic stroke., Methods:  The PubMed® and ClinicalTrials.gov electronic databases were searched for eligible articles/studies dealing with endothelial dysfunction and stroke. The references of the articles were screened to identify additional sources. The data were abstracted and summarized., Findings and Discussion: Endothelial dysfunction can be measured by serum biomarkers as well as by ultrasound or plethysmography techniques. Drugs targeting endothelial dysfunction include widely used agents such as angiotensin-converting enzyme inhibitors or isosorbide mononitrate, but also experimental therapies such as endothelial progenitor cells., Conclusion: The role of endothelial dysfunction in acute ischemic stroke has been studied increasingly in recent years. It has been shown that there is a correlation between endothelial dysfunction and parenchymal hematoma after endovascular thrombectomy. Also, early clinical trials are conducted investigating, e.g., endothelial progenitor cells in the treatment of endothelial dysfunction in ischemic stroke. Current research focuses on the integration of novel markers of endothelial dysfunction into routine clinical practice to support decision making in the treatment of acute ischemic stroke., Competing Interests: Declarations. Conflicts of interest: The authors have no competing interests to declare that are relevant to the content of this article. Ethical approval: Not applicable. Informed consent: Not applicable., (© 2025. The Author(s).)

Background: Previously, T2-relaxation time (T2 app ) and proton spin density (ρ) detected nerve injury in a small group of ATTRv amyloidosis. Here, we aim to quantify peripheral nerve impairment in a large cohort of symptomatic and asymptomatic ATTRv amyloidosis and correlate T2-relaxometry markers with clinical parameters and nerve conduction studies (NCS)., Methods: Eighty participants with pathologic variants of the transthyretin gene ( TTRv ) and 40 controls prospectively underwent magnetic resonance neurography. T2-relaxometry was performed, allowing to calculate tibial ρ, T2 app and cross-sectional-area (CSA). Detailed clinical examinations and NCS of tibial and peroneal nerves were performed., Results: Forty participants were classified as asymptomatic TTRv -carriers, 40 as symptomatic patients with polyneuropathy. ρ, T2 app and CSA were significantly higher in symptomatic ATTRv amyloidosis (484.2 ± 14.8 a.u.; 70.6 ± 1.8 ms; 25.7 ± 0.9 mm 2 ) versus TTRv- carriers (413.1 ± 9.4 a.u., p  < 0.0001; 62.3 ± 1.3 ms, p  = 0.0002; 19.0 ± 0.8 mm 2 , p  < 0.0001) and versus controls (362.6 ± 7.5 a.u., p  < 0.0001; 59.5 ± 1.0 ms, p  < 0.0001; 15.4 ± 0.5 mm 2 , p  < 0.0001). Only ρ and CSA differentiated TTRv- carriers from controls. ρ and CSA correlated with NCS in TTRv -carriers, while T2 app correlated with NCS in symptomatic ATTRv amyloidosis. Both ρ and T2 app correlated with clinical score., Conclusion: ρ and CSA can detect early nerve injury and correlate with electrophysiology in asymptomatic TTRv -carriers. T2 app increases only in symptomatic ATTRv amyloidosis in whom it correlates with clinical scores and electrophysiology. Our results suggest that T2-relaxometry can provide biomarkers for disease- and therapy-monitoring in the future.

Intravenous thrombolysis is not recommended in anticoagulated patients receiving direct oral anticoagulants (DOACs) and a recent intake within the last 48 hours in US and European guidelines. However, three observational studies now suggest safety of thrombolysis in patients with recent intake of DOACs, and thus support previous experimental data. In this perspective, the current evidence and practical consequences are discussed., Competing Interests: Competing interests: JCP has received consultation fees and travel expenses from Akcea, Bayer, Boehringer Ingelheim, Daiichi Sankyo and BMS/Pfizer, outside the submitted work. TRM reports grants from Bangerter-Rhyner Foundation. YX has received a research grant from the National Institute on Aging, American Heart Association and Genentech, and honorarium from Boehringer Ingelheim. DJS is on the advisory board of Bayer Switzerland and Portola/Alexion. He reports research funding from the Swiss National Science Foundation, Swiss Heart Foundation, Bangerter-Rhyner Foundation, Bayer Foundation and Portola/Alexion. All other authors report no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: For patients experiencing ischemic stroke despite receiving therapy with direct oral anticoagulants (DOAC) and without endovascular treatment options, therapeutic prospects are currently dismal. Current guidelines recommend intravenous thrombolysis (IVT) only for patients who have received DOAC in very restricted settings, as an increased risk of bleeding is suspected. However, recent retrospective observational studies suggest that IVT is safe despite DOAC pretreatment., Objectives: To provide further evidence that IVT despite previous DOAC treatment is not associated with an increased risk of bleeding., Design: Observational retrospective study., Methods: Demographic, clinical, and radiological data of patients who received IVT (+/- endovascular thrombectomy) despite DOAC pretreatment between June 2021 and January 2024 were analyzed using descriptive statistics, including DOAC plasma concentration at admission. Secondary intracranial hemorrhages and functional outcomes at 3 months were assessed. Since 2023, patients have been treated according to a modified local standard operating procedure at our hospital, allowing for IVT despite DOAC pretreatment regardless of DOAC plasma levels or the use of reversal agents., Results: Of 1821 patients treated with acute recanalization procedures during the study period, N  = 35 had received IVT with (18) or without (17) additional endovascular therapy. Among these patients with a wide age range (42-97 years) and DOAC plasma concentrations up to 369 ng/ml, only one developed symptomatic intracranial hemorrhage. A favorable outcome (modified Rankin scale score 0-2) after 3 months was observed in 57% (20) of the patients., Conclusion: IVT despite direct oral anticoagulation seems to be safe, even at advanced age and high DOAC plasma levels., (© The Author(s), 2024.)

Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs., Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion., Methods and Design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial., Study Outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted., Sample Size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation., Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia., Trial Registrations: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

BACKGROUND: Rivaroxaban and dabigatran were not superior to aspirin in trials of patients with embolic stroke of undetermined source (ESUS). It is unknown whether apixaban is superior to aspirin in patients with ESUS and known risk factors for cardioembolism. METHODS: We conducted a multicenter, randomized, open-label, blinded-outcome trial of apixaban (5 mg twice daily) compared with aspirin (100 mg once daily) initiated within 28 days after ESUS in patients with at least one predictive factor for atrial fibrillation or a patent foramen ovale. Cardiac monitoring was mandatory, and aspirin treatment was switched to apixaban in case of atrial fibrillation detection. The primary outcome was any new ischemic lesion on brain magnetic resonance imaging (MRI) during 12-month follow-up. Secondary outcomes included major and clinically relevant nonmajor bleeding. RESULTS: A total of 352 patients were randomly assigned to receive apixaban (178 patients) or aspirin (174 patients) at a median of 8 days after ESUS. At 12-month follow-up, MRI follow-up was available in 325 participants (92.3%). New ischemic lesions occurred in 23 of 169 (13.6%) participants in the apixaban group and in 25 of 156 (16.0%) participants in the aspirin group (adjusted odds ratio, 0.79; 95% confidence interval, 0.42 to 1.48; P=0.57). Major and clinically relevant nonmajor bleeding occurred in five and seven participants, respectively (1-year cumulative incidences, 2.9 and 4.2; hazard ratio, 0.68; 95% confidence interval, 0.22 to 2.16). Serious adverse event rates were 43.9 per 100 person-years in those given apixaban and 45.7 per 100 person-years in those given aspirin. The Apixaban for the Treatment of Embolic Stroke of Undetermined Source trial was terminated after a prespecified interim analysis as a result of futility. CONCLUSIONS: Apixaban treatment was not superior to cardiac monitoring-guided aspirin in preventing new ischemic lesions in an enriched ESUS population. (Funded by Bristol-Myers Squibb and Medtronic Europe; ClinicalTrials.gov number, NCT02427126.)

Purpose: Acute intraprocedural thrombosis (AIT) is a severe complication of flow diverter stent (FDS) implantation for the treatment of intracranial aneurysms. Even though device-related thromboembolic complications are well known, there are no acknowledged risk factors nor defined surveillance protocols for their early detection. This study aimed to demonstrate that an angiographic active surveillance is effective to detect and treat AIT. Furthermore, we investigated risk factors for the occurrence of AIT., Methods: A prospective institutional protocol consisting of a defined observation period of 30 min following FDS deployment was established to detect AIT. Overall incidence, as well as the efficacy and safety of AIT treatment were assessed. Moreover, radiological and clinical outcomes of patients with AIT were analyzed. The influence of various patient- and procedure-related factors on the occurrence of AIT was investigated using multivariable forward logistic regression., Results: During active surveillance twelve cases of AIT were observed among a total of 161 procedures (incidence: 7.5%). The median time of first observation was 15.5 min (IQR 9.5) after FDS implantation. The early recognition of AIT ensured a prompt treatment with intravenous application of a glycoprotein IIb/IIIa inhibitor, which led to complete thrombus resolution in all cases without hemorrhagic complications. Patients with pre-existing arterial hypertension and side branches originating from the aneurysmal sac had a higher risk of AIT (respectively OR, 9.844; OR, 3.553). There were two cases of re-thrombosis in the short-term postoperative period, of whom one died. The remaining patients with AIT had a good clinical outcome., Conclusion: Active surveillance for 30 min after FDS implantation is an effective strategy for early detection and ensuing treatment of AIT and can thus prevent secondary sequalae. Hypertension and side branches originating from the aneurysmal sac may increase the risk of AIT., (© 2022. The Author(s).)

Impaired consciousness is a frequent phenomenon after general anesthesia. In addition to the classical causes (e.g., overhang of sedatives), an impairment of consciousness can also be an adverse side effect of drugs. Many drugs used in anesthesia can trigger these symptoms. Alkaloids, such as atropine can trigger a central anticholinergic syndrome, opioids can promote the occurrence of serotonin syndrome and the administration of a neuroleptic can lead to neuroleptic malignant syndrome. These three syndromes are difficult to diagnose due to the individually very heterogeneous symptoms. Mutual symptoms, such as impaired consciousness, tachycardia, hypertension and fever further complicate the differentiation between the syndromes; however, more individual symptoms, such as sweating, muscle tension or bowl sounds can be helpful in distinguishing these syndromes. The time from the trigger event can also help to differentiate the syndromes. The central anticholinergic syndrome is the fastest to appear, usually taking just a few of hours from trigger to clinical signs, serotonin syndrome takes several hours up to 1 day to show and neuroleptic malignant syndrome usually takes days. The clinical symptoms can range from mild to life-threatening. Generally, mild cases are treated with discontinuation of the trigger and extended observation. More severe cases can require specific antidotes. The specific treatment recommended for central anticholinergic syndrome is physostigmine with an initial dose of 2 mg (0.04 mg/kg body weight, BW) administered over 5 min. For serotonin syndrome an initial dose of 12 mg cyproheptadine followed by 2 mg every 2 h is recommended (maximum 32 mg/day or 0.5 mg/kgBW day -1 ) but this medication is only available in Germany as an oral formulation. For neuroleptic malignant syndrome 25-120 mg dantrolene (1-2.5 mg/kgBW maximum 10 mg/kgBW day -1 ) is the recommended treatment., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Importance: International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC)., Objective: To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion., Design, Setting, and Participants: This international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021., Exposures: Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation., Main Outcomes and Measures: The main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses., Results: Of 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion., Conclusions and Relevance: In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

Impaired consciousness is a frequent phenomenon after general anesthesia. In addition to the classical causes (e.g., overhang of sedatives), an impairment of consciousness can also be an adverse side effect of drugs. Many drugs used in anesthesia can trigger these symptoms. Alkaloids, such as atropine can trigger a central anticholinergic syndrome, opioids can promote the occurrence of serotonin syndrome and the administration of a neuroleptic can lead to neuroleptic malignant syndrome. These three syndromes are difficult to diagnose due to the individually very heterogeneous symptoms. Mutual symptoms, such as impaired consciousness, tachycardia, hypertension and fever further complicate the differentiation between the syndromes; however, more individual symptoms, such as sweating, muscle tension or bowl sounds can be helpful in distinguishing these syndromes. The time from the trigger event can also help to differentiate the syndromes. The central anticholinergic syndrome is the fastest to appear, usually taking just a few of hours from trigger to clinical signs, serotonin syndrome takes several hours up to 1 day to show and neuroleptic malignant syndrome usually takes days. The clinical symptoms can range from mild to life-threatening. Generally, mild cases are treated with discontinuation of the trigger and extended observation. More severe cases can require specific antidotes. The specific treatment recommended for central anticholinergic syndrome is physostigmine with an initial dose of 2 mg (0.04 mg/kg body weight, BW) administered over 5 min. For serotonin syndrome an initial dose of 12 mg cyproheptadine followed by 2 mg every 2 h is recommended (maximum 32 mg/day or 0.5 mg/kgBW day -1 ) but this medication is only available in Germany as an oral formulation. For neuroleptic malignant syndrome 25-120 mg dantrolene (1-2.5 mg/kgBW maximum 10 mg/kgBW day -1 ) is the recommended treatment., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, ein Teil von Springer Nature 2023.)

Background: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes., Methods: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE)., Results: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome., Conclusions: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

Background: There is little evidence of endovascular therapy (EVT) being performed in acute ischemic stroke beyond 24 h, and that evidence is limited to anterior circulation stroke., Objective: To extend evidence of efficacy and safety of EVT after more than 24 h in both anterior and posterior circulation stroke., Methods: Local, prospectively collected registries were screened for patients with acute ischemic stroke and large-vessel occlusion who had received either EVT > 24 h after last-seen-well but <24 h after symptom recognition (EVT >24LSW ) or EVT > 24 h since first (definitive) symptom recognition (EVT >24DEF ). Patients treated <24 h served as a group for comparison. Favorable outcome was defined as modified Rankin scale (mRS) 0-2 or return to prestroke mRS at 3 months., Results: Between January 2014 and August 2021, N  = 2347 were treated with EVT at our comprehensive stroke center, of whom n  = 43 met the inclusion criteria (EVT >24LSW , n  = 16, EVT >24DEF , n  = 27). EVT >24LSW patients were treated at a median of 28.7 h [interquartile range (IQR) = 27.3-32.8] after last-seen-well and 7.3 h (IQR = 2.8-14.3) after symptom recognition; EVT >24DEF patients were treated 52.5 h (IQR = 26.5-94.2) after first symptoms. Favorable outcome was achieved by 23.3% (10/43) in the EVT > 24 compared with 39.4% (886/2250) in the EVT < 24 group ( p  = 0.04). Bleeding rates were similar across groups. Mortality was also similar [EVT > 24, 27.9% (12/43) versus EVT < 24, 25.7% (584/2264), p  = 0.727; posterior circulation, EVT > 24, 41.7% (5/12) versus EVT < 24, 36.5% (92/252) p  = 0.764]., Conclusion: In selected patients, EVT seems effective and safe beyond 24 h for both anterior and posterior circulation stroke., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JCP has received consultation fees and travel expenses from Akcea, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer. PAR received speaker fees from Bayer, Boehringer Ingelheim, Daiichi Sanyko, and Pfizer. SN reports consulting fees from Brainomix and lecture fees from Boehringer Ingelheim and BMS Pfizer. MM has received consulting honoraria, speaker honoraria, and travel support outside this work from Covidien/Medtronic, MicroVention, and Stryker. The other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Objectives: Multi spin echo (MSE) sequences are often used for obtaining T2-relaxometry data as they provide defined echo times (TEs). Due to their time-consuming acquisition, they are frequently replaced by turbo spin echo (TSE) sequences that in turn bear the risk of systematic errors when analyzing small structures or lesions. With this study, we aim to test whether T2-relaxometry data derived from either dual-echo TSE or 12-echo MSE sequences are equivalent for quantifying peripheral nerve lesions. Hereditary transthyretin (ATTRv) amyloidosis was chosen as a surrogate disease, as it allows the inclusion of both asymptomatic carriers of the underlying variant transthyretin gene (varTTR) and symptomatic ATTRv amyloidosis patients., Materials and Methods: Overall, 50 participants with genetically confirmed varTTR (20 clinically symptomatic ATTRv amyloidosis; 4 females, 16 males; mean age, 61.8 years; range, 33-76 years; and 30 asymptomatic varTTR-carriers; 18 females, 12 males; mean age, 43.1 years; range, 21-62 years), and 30 healthy volunteers (13 females, 17 males, mean age 41.3 years, range 22-73) were prospectively included and underwent magnetic resonance neurography at 3 T. T2-relaxometry was performed by acquiring an axial 2-dimensional dual-echo TSE sequence with spectral fat saturation (TE1/TE2, 12/73 milliseconds; TR, 5210 milliseconds; acquisition time, 7 minutes, 30 seconds), and an axial 2-dimensional MSE sequence with spectral fat saturation and with 12 different TE (TE1, 10 milliseconds to TE12, 120 milliseconds; ΔTE, 10 milliseconds; TR, 3000 milliseconds; acquisition time, 11 minutes, 23 seconds) at the right mid to lower thigh. Sciatic nerve regions of interest were manually drawn in ImageJ on 10 central slices per participant and sequence, and the apparent T2-relaxation time (T2app) and proton spin density (ρ) were calculated individually from TSE and MSE relaxometry data., Results: Linear regression showed that T2app values obtained from the dual-echo TSE (T2appTSE), and those calculated from the 12-echo MSE (T2appMSE) were mathematically connected by a factor of 1.3 throughout all groups (controls: 1.26 ± 0.02; varTTR-carriers: 1.25 ± 0.02; symptomatic ATTRv amyloidosis: 1.28 ± 0.02), whereas a factor of 0.5 was identified between respective ρ values (controls: 0.47 ± 0.01; varTTR-carriers: 0.47 ± 0.01; symptomatic ATTRv amyloidosis: 0.50 ± 0.02). T2app calculated from both TSE and MSE, distinguished between symptomatic ATTRv (T2appTSE 66.38 ± 2.6; T2appMSE 84.6 ± 3.3) and controls (T2appTSE 58.1 ± 1.0, P = 0.0028; T2appMSE 72.8 ± 0.7, P < 0.0001), whereas differences between varTTR-carriers (T2appTSE 61.8 ± 1.5; T2appMSE 76.7 ± 1.3) and ATTRv amyloidosis were observed only for T2appMSE (P = 0.0082). The ρ value differentiated well between healthy controls (ρTSE 365.1 ± 7.2; ρMSE 170.4 ± 3.8) versus varTTR-carriers (ρTSE 415.7 ± 9.8, P = 0.0027; ρMSE 193.7 ± 5.3, P = 0.0398) and versus symptomatic ATTRv amyloidosis (ρTSE 487.8 ± 17.9; ρMSE 244.7 ± 13.1, P < 0.0001, respectively), but also between varTTR-carriers and ATTRv amyloidosis (ρTSEP = 0.0001; ρMSEP < 0.0001)., Conclusions: Dual-echo TSE and 12-echo MSE sequences provide equally robust and reliable T2-relaxometry data when calculating T2app and ρ. Due to their shorter acquisition time and higher resolution, TSE sequences may be preferred in future magnetic resonance imaging protocols. As a secondary result, ρ can be confirmed as a sensitive biomarker to detect early nerve lesions as it differentiated best among healthy controls, asymptomatic varTTR-carriers, and symptomatic ATTRv amyloidosis, whereas T2app might be beneficial in already manifest ATTRv amyloidosis., Competing Interests: Conflicts of interest and sources of funding: M.W. advises for Akcea Therapeutics, Alnylam Pharmaceuticals, Biogen, Pfizer, and Roche; received lecture honoraria from Akcea Therapeutics, Alnylam Pharmaceuticals, and Biogen; and received financial support for conference attendance from Biogen and Pfizer. U.H. advises for Pfizer and received lecture honoraria from Pfizer, Akcea Therapeutics, and Alnylam Pharmaceuticals. J.C.P. was supported by Abbott, Akcea, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer, all outside the submitted work. E.H. received financial reimbursement for consulting and advisory board activities and/or travel support by Akcea, Alnylam, and Pfizer. S.H. was supported by the German Research Council (DFG, SFB 1118). M.B. reports personal fees from Teva, BBraun, Vascular Dynamics, Bayer, Grifols, Merck, Neuroscios, Boehringer Ingelheim, Novartis, research grants from Hopp Foundation, DFG, BMBF, European Union, Stryker, and Siemens, all outside the submitted work. J.K. reports a research grant from Alnylam Pharmaceuticals; the Olympia Morata grant from the Medical Faculty of the University of Heidelberg; personal fees, lecture honoraria, and financial support for conference attendance from Alnylam Pharmaceuticals; lecture honoraria and financial support for conference attendance from Pfizer; and advises for Akcea Therapeutics. For the remaining authors, no conflicts of interest were declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Data regarding the efficacy and safety of bridging thrombolysis (BT) initiated before transfer for evaluation of endovascular therapy is heterogeneous. We, therefore, analyse efficacy and safety of BT in patients treated within a drip-and-ship stroke service., Methods: Consecutive adult patients suffering from acute ischaemic stroke and large-vessel occlusions (LVO) transferred to our comprehensive stroke centre for evaluation of endovascular therapy in 2017-2020 were identified from a local prospective stroke database and categorised according to BT and no-BT. BT was defined as intravenous thrombolysis initiated before transfer. LVO was assessed before and after transfer. Functional outcome before stroke and at 3 months using the modified Rankin scale (mRS) was determined. Excellent outcome was defined as mRS 0-1 or return to prestroke mRS. For safety analysis, intracranial haemorrhages and mortality at 3 months were analysed. Main analysis was limited to patients with anterior circulation stroke., Results: Of N=714 patients, n=394 (55.2%) received BT. More patients in the BT group with documented LVO before transfer recanalised without endovascular therapy (n=46, 11.7%) than patients who did not receive BT before transfer (n=4, 1.3%, p<0.001). In multivariate analysis, BT was the strongest independent predictor of early recanalisation (adjusted OR 10.9, 95% CI 3.8 to 31.1, p<0.001). BT tended to be an independent predictor of an excellent outcome at 3 months (adjusted OR 1.38, 95% CI 0.97 to 1.96, p=0.077). There were no differences in safety between the BT and no-BT groups., Conclusions: BT initiated before transfer was a strong independent predictor of early recanalisation., Competing Interests: Competing interests: JCP has received consultation fees and travel expenses from Akcea, Bayer, Boehringer Ingelheim, Daiichi Sankyo and Pfizer. MM reports grants/grants pending from Balt, Medtronic, MicroVention, Stryker (money paid to the institution). PAR received travel support and lecture fees from Boeheringer Ingelheim, Daiichi Sankyo, Pfizer, and Bayer. SN has received consulting fees from Brainomix and Boehringer Ingelheim and lecture fees and travel expenses from Medtronic and Pfizer. CG is speaker of the commission telemedicine service of the German Stroke Society., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)