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  • 1
    In: The Lancet, Elsevier BV, Vol. 396, No. 10262 ( 2020-11), p. 1574-1584
    Type of Medium: Online Resource
    ISSN: 0140-6736
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2067452-1
    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 2
    In: American Heart Journal, Elsevier BV, Vol. 265 ( 2023-11), p. 66-76
    Type of Medium: Online Resource
    ISSN: 0002-8703
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2003210-9
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  • 3
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 14 ( 2023-3-10)
    Abstract: Acute disseminated encephalomyelitis (ADEM) is an autoimmune disorder of the central nervous system (CNS), which is commonly associated to previous viral infection or immunization. Cases of ADEM with a potential relationship to both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination have been reported. We recently published a rare case of a 65-year-old patient who suffered from a corticosteroid- and immunoglobulin-refractory multiple autoimmune syndrome including ADEM following Pfizer-BioNTech coronavirus disease (COVID)-19 vaccination, and whose symptoms largely resolved after repeated plasma exchange (PE). Four months later, the patient was diagnosed with SARS-CoV-2 omicron variant infection after experiencing mild upper respiratory tract symptoms. Few days later, the patient developed severe tetraparesis with magnetic resonance imaging (MRI) showing multiple new inflammatory contrast-enhancing lesions in the left middle cerebellar peduncle, cervical spinal cord, and ventral conus medullaris. Repeated cerebrospinal fluid (CSF) analyses indicated blood-brain barrier damage (increased albumin ratio) without signs of SARS-CoV-2 invasion (mild pleocytosis, no intrathecal antibody production). SARS-CoV-2 specific immunoglobulin G (IgG) were detected in serum and to a much lower degree in CSF with close correlation between both concentrations over time, reflecting antibody dynamics of vaccine- and infection-induced immune response, and blood-brain barrier patency. Daily PE therapy was initiated. Given the patient's lack of improvement after seven PE, treatment with rituximab was considered. After a first dose, however, the patient suffered epididymo-orchitis leading to sepsis, and declined rituximab continuation. At 3-months follow-up, clinical symptoms had dramatically improved. The patient regained walking ability without assistance. This case of recurrent ADEM after COVID-19-vaccination and after subsequent COVID-19-infection strongly supports the hypotheses of neuroimmunological complications in these conditions being promoted by a systemic immune response and mediated by molecular mimicry of, both, viral and vaccine SARS-CoV-2 antigens and CNS self-antigens.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564214-5
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  • 4
    In: International Journal of Stroke, SAGE Publications
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2211666-7
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  • 5
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 4 ( 2020-02-18)
    Abstract: Intravenous thrombolysis ( IVT ) in wake‐up stroke ( WUS ) or stroke with unknown onset ( SUO ) has been recently proven to be safe and effective using advanced neuroimaging (magnetic resonance imaging or computerized tomography‐perfusion) for patient selection. However, in most of the thrombolyzing centers advanced neuroimaging is not instantly available. We hypothesize that pragmatic non‐contrast computed tomography‐based IVT in WUS / SUO may be feasible and safe. Methods and Results TRUST ‐ CT (Thrombolysis in Stroke With Unknown Onset Based on Non‐Contrast Computerized Tomography) is an international multicenter registry‐based study. WUS / SUO patients undergoing non‐contrast computed tomography‐based IVT with National Institute of Health Stroke Scale ≥4 and initial Alberta Stroke Program Early Computerized Tomography score ≥7 were included and compared with propensity score matched non‐thrombolyzed WUS / SUO controls. Primary end point was the incidence of symptomatic intracranial hemorrhage; secondary end points included 24‐hour National Institute of Health Stroke Scale improvement of ≥4 and modified Rankin Scale at 90 days. One hundred and seventeen WUS / SUO patients treated with non‐contrast computed tomography‐based IVT were included. As compared with 112 controls, the median admission National Institute of Health Stroke Scale was 10 and the median Alberta Stroke Program Early Computerized Tomography score was 10 in both groups. Four (3.4%) IVT patients and one control patient (0.9%) suffered symptomatic intracranial hemorrhage (adjusted odds ratio 7.9, 95% CI 0.65–96, P =0.1). A decrease of ≥4 National Institute of Health Stroke Scale points was observed in 67 (57.3%) of IVT patients as compared with 25 (22.3%) in controls (adjusted odds ratio 5.8, CI 3.0–11.2, P 〈 0.001). A months, 39 (33.3%) IVT patients reached a modified Rankin Scale score of 0 or 1 versus 23 (20.5%) controls (adjusted odds ratio 1.94, CI 1.0–3.76, P =0.05). Conclusions Non‐contrast computed tomography‐based thrombolysis in WUS / SUO seems feasible and safe and may be effective. Randomized prospective comparisons are warranted. Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 03634748.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2653953-6
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  • 6
    In: Neurological Research and Practice, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2021-12)
    Abstract: Results of randomized controlled trials (RCT) do not provide definite guidance for secondary prevention after ischemic stroke (IS)/transient ischemic attack (TIA) attributed to patent foramen ovale (PFO). No recommendations can be made for patients 〉  60 years. We aimed to compare interventional and medical PFO-management in cryptogenic IS/TIA patients, including patients 〉  60 years. Methods Prospective case series including consecutive cryptogenic IS/TIA patients with PFO at Tuebingen university stroke unit, Germany. ‘PFO-closure’ was recommended in patients ≤70 years when featuring high-risk PFO (i.e., with atrial septal aneurysm, spontaneous, or high-grade right-to-left shunt during Valsalva). Primary (recurrent IS/intracranial hemorrhage) and secondary endpoints (e.g., disability) were assessed during ≥1-year follow-up; planned subgroup analyses of patients ≤60/ 〉  60 years. Results Among 236 patients with median age of 58 (range 18–88) years, 38.6% were females and median presenting National Institutes of Health Stroke Scale score was 1 (IQR 0–4). Mean follow-up was 2.8 ± 1.3 years. No intracranial hemorrhage was observed. Recurrent IS rate after ‘PFO-closure’ was 2.9% (95%CI 0–6.8%) and 7% (4–16.4) in high-risk PFO patients ≤60 ( n  = 103) and  〉  60 years ( n  = 43), respectively, versus 4% (0–11.5) during ‘medical therapy alone’ MTA ( n  = 28). 42 low-risk PFO patients treated with MTA experienced no recurrent IS/TIA. Conclusions In our real-world study, IS recurrence rate in ‘PFO-closure’ high-risk PFO patients ≤60 years was comparable to that observed in recent RCT. High-risk PFO patients 〉  60 years who underwent PFO-closure had similar IS recurrence rates than those who received MTA. MTA seems the appropriate treatment for low-risk PFO. Trial registration ClinicalTrials.gov, registration number: NCT04352790 , registered on: April 20, 2020 – retrospectively registered.
    Type of Medium: Online Resource
    ISSN: 2524-3489
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2947493-0
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  • 7
    In: Stroke: Vascular and Interventional Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 3, No. S2 ( 2023-11)
    Abstract: The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. Previous studies in LVO and MeVO have demonstrated a correlation between good clinical outcomes and the first pass effect (FPE, eTICI 2c/3 on the first pass) but no differences in FPE rates or clinical outcomes between first‐line endovascular therapy techniques.1‐6 We compared clinical and technical outcomes with first‐line stent‐retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international cohort study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion and pre‐stroke modified Rankin Scale (mRS) 0‐3, presenting within 24 hours of time last seen well from January 2015 to August 2022.7 The primary outcome was the first‐pass effect (FPE), defined as eTICI 2c/3 on the first pass. Secondary outcomes included final successful reperfusion (eTICI 2b‐3), 90‐day excellent outcome (mRS 0 to 1), 90‐day functional independence (mRS 0 to 2), sICH, and 90‐day mortality. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. This study was registered under NCT05291637. Results There were 326 patients who met inclusion criteria, consisting of 56.1% male, median age 75 (IQR 65‐82) years and median NIHSS 8 (5‐12). Occlusion segments were PCA P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. Compared to SR, FPE was lower in patients treated with first‐line combined technique and similar in patients treated with first‐line CA (combined vs. SR: aOR 0.35 [0.016‐0.80], p=0.01; CA vs. SR: aOR 0.45 [0.19‐1.06] , p=0.07). Final successful reperfusion (eTICI 2b‐3) was present in 81% of cases with no differences between treatment groups. Excellent outcome (mRS 0‐1) occurred in 30.7% of patients and functional independence (mRS 0‐2) occurred in 50.0% of patients. There were lower odds of functional independence in the first‐line CA versus SR alone group (aOR 0.52 [0.28‐0.95], p=0.04). FPE was associated with higher rates of favorable outcomes (mRS 0‐2: 58% vs. 43.4%, p=0.01; mRS 0‐1: 36.6% vs. 25.8%, p=0.05). sICH was observed in 5.6% (18/326) and mortality in 10.9% (35/326) with no differences between first‐line technique. Conclusion In patients with isolated PCA occlusion undergoing EVT, first line SR was associated with a higher rate of FPE compared to CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90‐days was more likely with first‐line SR compared to CA in adjusted analyses. FPE was associated with higher rates of 90‐day excellent outcomes and functional independence. No difference in sICH or mortality was noted across the three techniques. As the endovascular field evolves to treat patients with distal vessel occlusion and milder severity of stroke, optimizing the efficacy and safety of the procedure is essential.8
    Type of Medium: Online Resource
    ISSN: 2694-5746
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 3144224-9
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  • 8
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. Suppl_1 ( 2023-02)
    Abstract: Background: ATTICUS is the third prospective randomized controlled trial that compared a direct oral anticoagulant (DOAC) vs. acetylsalicylic acid (ASA) for secondary prevention after embolic stroke of undetermined source (ESUS). Aim of ATTICUS was to determine whether apixaban, initiated within 28 days after ESUS, is superior to ASA in preventing new ischemic lesions on 12-month follow- up MRI (primary endpoint) in subjects with remote atrial fibrillation (AF) monitoring. Methods: Multicenter (14 German centers) open-label randomized (1:1) controlled trial with blinded endpoint assessment. ESUS patients with at least one risk factor for AF/cardiac thromboembolism (i.e., left atrium (LA) size 〉 45 mm, spontaneous echo contrast in LA appendage, LA appendage flow velocity ≤ 0.2 m/s, atrial high-rate episodes, CHA2DS2-VASc ≥ 4, patent foramen ovale (PFO)) were enrolled. Study drug was initiated 3 to 28 days after minor/moderate stroke and ≥ 14 to 28 days after major stroke. ClinicalTrials.gov: NCT02427126. Funding by Bristol Meyers Squibb-Pfizer Alliance (Euro 2.2 Mio.) and Medtronic. Results: 352 patients were available for final analysis. New ischemic lesion(s) were found in 13.6% vs. 16.0% of patients in the apixaban and the ASA arm, respectively (p=0.57), intention-to-treat. AF was detected in 25.6 % of patients. No difference between study arms was found for other thromboembolism, death, SAE, major and clinically relevant bleeds. Conclusions: ATTICUS was the first trial testing the concept of DOAC vs. ASA in an enriched ESUS population. Mandatory cardiac monitoring, vessel imaging, and MRI in all ATTICUS patients will help to better understand this complex condition. We will present secondary analyses including on-treatment analysis, prevention of embolic/disabling lesions/strokes, association of stroke pattern with AF occurrence/macroangiopathic changes.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 9
    In: Acta Neurologica Scandinavica, Hindawi Limited, Vol. 2023 ( 2023-5-11), p. 1-13
    Abstract: Evidence for the management of asymptomatic carotid stenosis and possibly symptomatic nonstenosing carotid artery disease is limited. In contrary to calcified plaques, soft plaques are considered vulnerable and prone to rupture. Shear wave elastography (SWE), a novel ultrasound technique which uses acoustic wave force to propagate shear wave in tissues, can quantify tissue stiffness through the estimation of Young’s modulus (YM) in kPa or shear wave velocity in meter/second. This systematic review is aimed at evaluating the feasibility of SWE in carotid plaque risk stratification in relation to ischemic stroke (PROSPERO registration: CRD42022309709). 18 studies, obtained via search on PubMed, Cochrane, and Embase from inception until November 1, 2022, assessed SWE’s feasibility in carotid plaque risk stratification in humans (13 studies) and phantom models (5 studies). Human studies showed heterogeneity with respect to SWE devices, acquisition settings, and methodology, which consequently reflected in the between-study variability of YM values used for distinguishing vulnerable/symptomatic (27–52 kPa) and stable/asymptomatic (28–115 kPa) carotid plaques. However, within-study assessment of all human studies indicated SWE’s feasibility in carotid plaque risk stratification. Furthermore, four out of five carotid plaque phantom studies showed the potential of SWE to discriminate tissues of different stiffness comparable to the carotid vessel wall, soft and hard plaques, and with good reproducibility. SWE may potentially offer a bedside risk stratification tool for identifying patients with vulnerable carotid plaques, who may benefit from carotid surgery, stenting, or prolonged dual antiplatelet therapy. Patients with stable carotid plaques could be spared the risks of potentially harmful treatments and complications. However, available data are not enough to facilitate the immediate clinical application of SWE, and therefore, larger prospective clinical are warranted.
    Type of Medium: Online Resource
    ISSN: 1600-0404 , 0001-6314
    RVK:
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2023
    detail.hit.zdb_id: 2001898-8
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  • 10
    In: Annals of Neurology, Wiley, Vol. 93, No. 3 ( 2023-03), p. 479-488
    Abstract: Approximately 20% of strokes are embolic strokes of undetermined source (ESUS). Undetected atrial fibrillation (AF) remains an important cause. Yet, oral anticoagulation in unselected ESUS patients failed in secondary stroke prevention. Guidance on effective AF detection is lacking. Here, we introduce a novel, non‐invasive AF risk assessment after ESUS. Methods Catch‐Up ESUS is an investigator‐initiated, observational cohort study conducted between 2018 and 2019 at the Munich University Hospital. Besides clinical characteristics, patients received ≥72 h digital electrocardiogram recordings to generate the rhythm irregularity burden. Uni‐ and multivariable regression models predicted the primary endpoint of incident AF, ascertained by standardized follow‐up including implantable cardiac monitors. Predictors included the novel rhythm irregularity burden constructed from digital electrocardiogram recordings. We independently validated our model in ESUS patients from the University Hospital Tübingen, Germany. Results A total of 297 ESUS patients were followed for 15.6 ± 7.6 months. Incident AF (46 patients, 15.4%) occurred after a median of 105 days (25th to 75th percentile 31–33 days). Secondary outcomes were recurrent stroke in 7.7% and death in 6.1%. Multivariable‐adjusted analyses identified the rhythm irregularity burden as the strongest AF‐predictor (hazard ratio 3.12, 95% confidence interval 1.62–5.80, p   〈  0001) while accounting for the known risk factors age, CHA 2 DS 2 ‐VASc‐Score, and NT‐proBNP. Independent validation confirmed the rhythm irregularity burden as the most significant AF‐predictor (hazard ratio 2.20, 95% confidence interval 1.45–3.33, p   〈  0001). Interpretation The novel, non‐invasive, electrocardiogram‐based rhythm irregularity burden may help adjudicating AF risk after ESUS, and subsequently guide AF‐detection after ESUS. Clinical trials need to clarify if high‐AF risk patients benefit from tailored secondary stroke prevention. ANN NEUROL 2023;93:479–488
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2037912-2
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