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Background: Unfractionated heparin (UFH) bolus is occasionally administered during endovascular treatment (EVT) to reduce thrombotic complications in acute ischemic stroke patients. However, the MR CLEAN-MED trial showed an increase in symptomatic intracranial hemorrhages (sICH) and a non-significant shift towards worse functional outcome with UFH administration. We aimed to analyze the impact of periprocedural UFH bolus in a real-world setting in anterior (ACS) and posterior circulation stroke (PCS) patients., Methods: We analyzed data from the German Stroke Registry-Endovascular Treatment using propensity score matching. Primary outcome was the modified Rankin Scale at 3 months, and secondary outcome measures included mortality, angiographic outcomes, post-EVT National Institute of Health Stroke Scale scores and ICH at 24 hours., Results: Among 13,082 patients, 7948 with ACS (UFH bolus use in 15%) and 841 with PCS (UFH bolus use in 16.3%) were included in the propensity score matching analysis. Applying MR CLEAN-MED study criteria, UFH bolus was associated with worse functional outcomes (odds ratio [OR] 1.44; 95% CI 1.06-1.96). Analyzing all ACS and PCS patients, UFH bolus did not provide any net benefit. In ACS patients treated with intravenous thrombolysis (IVT), UFH bolus use was associated with worse functional outcomes (OR 2.40; 95% CI 1.34 to 5.06)., Conclusion: Our findings show transferability of the MR CLEAN-MED results into a real-world setting, confirming a negative effect of periprocedural UFH on functional outcome in this subgroup of patients. Considering all ACS and PCS patients, periprocedural UFH did not provide a net benefit and appears to be harmful, particularly in IVT-treated patients., Competing Interests: Competing interests: None declared., (© 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.)

Competing Interests: Conflict of interest: None declared.

Background: Comprehensive stroke centers (CSC) offer state-of-the-art stroke care in metropolitan centers. However, in rural areas, sufficient stroke expertise is much scarcer. Recently, telemedical stroke networks have offered instant consultation by stroke experts, enabling immediate administration of intravenous thrombolysis (IVT) on-site and decision on thrombectomy. While these immediate decisions are made during the consult, the impact of the network structures on stroke care in spoke hospitals is still not well described., Aims: This study was performed to determine if on-site performance in rural hospitals and patient outcome improve over time through participation and regular medical staff training within a telemedical stroke network., Methods: In this retrospective study, we analyzed data from stroke patients treated in four regional hospitals within the telemedical Neurovascular Network of Southwest Bavaria (NEVAS) between 2014 and 2019. We only included those patients that were treated in the regional hospitals until discharge at home or to neurorehabilitation. Functional outcome (modified Rankin scale) at discharge, mortality rate and periprocedural intracranial hemorrhage served as primary outcome parameters. Door-to-imaging and door-to-needle times were secondary outcome parameters., Results: In 2014-2019, 5,379 patients were treated for acute stroke with 477 receiving IVT. Most baseline characteristics were comparable over time. For all stroke patients, door-to-imaging times increased over the years, but significantly improved for potential IVT candidates and those finally treated with IVT. The percentage of patients with door-to-needle time <30 min increased from 10% to 25%. Clinical outcome at discharge improved for all stroke patients treated in the regional hospitals. Particularly for patients treated with IVT, good clinical outcome (modified Rankin scale 0-2) at discharge increased from 2014 to 2019 by 19% and mortality rates dropped from 13% to 5%., Conclusions: 24-h/7-day telemedical support and regular on-site medical staff training within a structured telemedicine stroke network such as NEVAS significantly improve on-site stroke care in rural areas, leading to a considerable benefit in clinical outcome., Data Access Statement: The data that support the findings of this study are available upon reasonable request and in compliance with the local and international ethical guidelines., 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.

Introduction: Akinetic mutism is a severe state of impaired volition that can result from a stroke. Its therapeutic evidence relies on single case reports that used atomoxetine or levodopa with variable latency and efficacy., Case Presentation: We present the case of a 54-year-old woman who developed akinetic mutism after infarction in the territory of the right anterior cerebral artery, successfully treated with methylphenidate and levodopa/benserazide. Clinical examination showed a patient lacking any spontaneous speech and movement while opening her eyes and fixating. Suspecting akinetic mutism after a comprehensive diagnostic work-up, we started an individual therapy attempt with methylphenidate 10 mg and levodopa/benserazide 100/25 mg twice daily. Both drugs affect the dopaminergic and noradrenergic transmission in the frontal-subcortical circuit, compromised in akinetic mutism. We saw rapid and sustained improvement in her volitional actions, devoid of side effects. Finally, the patient was actively communicating and moving her limbs., Conclusion: We discuss the patient's favorable clinical course in response to the synergistic combination of methylphenidate and levodopa/benserazide, emerging as a promising treatment strategy, and provide a brief literature review of treatment options in akinetic mutism following stroke., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Endovascular treatment has become the standard care for acute basilar artery occlusion (BAO). Uncertainty persists about the optimal thrombectomy technique., Objective: To compare aspiration thrombectomy with stent retriever thrombectomy in patients with BAO in a multicenter real-world patient population., Methods: We analyzed data from the German Stroke Registry-Endovascular Treatment (GSR-ET). Patients with isolated BAO who underwent either aspiration or stent retriever thrombectomy were compared, including propensity score matching (PSM). The primary outcome measure was the modified Rankin Scale shift analysis at 90 days. Secondary outcomes included symptomatic intracranial hemorrhage (sICH), procedure complications, and metrics., Results: Of 13 082 patients in the GSR-ET, 387 patients (mean age 72.0±13.1 years; 45.0% female) fulfilled the inclusion criteria. The thrombectomy technique was aspiration only in 195 (50.4%) and stent retriever only in 192 (49.6%) patients. Functional outcome did not differ between the groups, either before (common OR (cOR) 0.94; 95% CI 0.64 to 1.38) or after PSM (cOR=1.37; 95% CI 0.90 to 2.09). There was no significant difference in sICH (2.6 vs 5.5%; P=0.231; OR=0.46; 95% CI 0.14 to 1.47), but aspiration thrombectomy demonstrated fewer procedure-related complications (4.6% vs 12.5%; P=0.017), a shorter procedure duration (24 vs 48 min; P<0.001), and higher first pass recanalization rates (75.1% vs 44.8%; P<0.001)., Conclusions: In this study both aspiration and stent retriever thrombectomy showed equal efficacy in terms of functional outcome in patients with BAO. However, procedure complications and metrics might favor aspiration over stent retriever thrombectomy., Competing Interests: Competing interests: LKel has received funding for travel or speaker honoraria from Alexion, AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer outside of this study. CHN has received funding for travel or speaker honoraria from Alexion, Astra-Zeneca, Bayer Vital, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer, and Takeda., (© 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.)

Objective: Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment., Methods: This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing., Results: All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation., Interpretation: Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886-897., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Aims: Embolic stroke of undetermined source (ESUS) accounts for up to 20% of ischemic strokes annually. Undetected atrial fibrillation (AF) is one important potential underlying cause. For AF, oral anticoagulation has evolved as the most preferable means of secondary stroke prevention. To detect unrecognized paroxysmal AF, long-term ECG monitoring is required, and implantable cardiac monitors (ICM) appear most suitable. Yet, ICMs are particularly costly, implantation is invasive, and remote monitoring places a personnel burden on health care providers. Here, we use data from a large cohort of ESUS patients to systematically analyze the effort of ICM remote monitoring for AF diagnosis and the strain on health care providers., Methods and Results: From a prospective, single-center, observational ESUS registry, we analyzed all ICM-equipped patients post-ESUS (n = 172) between January 1st, 2018, and December 31st, 2019. Through January 2nd, 2023, 48 patients (27.9%) were diagnosed with AF by ICM remote monitoring. During follow-up, a total of 29,180 remote monitoring episodes were transmitted, of which 17,742 were alarms for AF. A systematic estimation of workload revealed that on average, 20.3 trained physician workhours are required to diagnose one patient with AF., Conclusion: ICM remote monitoring is useful to diagnose AF in cohort of post-ESUS patients. However, the number of ICM alarms is high, even in a cohort at known high risk of AF and in whom AF detection is therapeutically consequential. Improved automated event classification, clear recommendations for ICM interrogation after AF diagnosis, and a careful patient selection for ICM monitoring are warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 von Falkenhausen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objective: Post-stroke delirium (PSD) is a common complication in acute stroke patients, and guidelines recommend routine screening and various preventive and treatment measures. However, there is a substantial lack of standardized approaches in diagnostic and therapeutic management of PSD. Here, we aimed to develop a new pragmatic and easily assessable screening tool to predict PSD based on early parameters, which are already integral to acute stroke diagnostics., Methods: We enrolled acute stroke patients admitted to our stroke unit or intensive care unit and developed the scoring system using retrospective single-center patient data. The Confusion Assessment Method for the Intensive Care Unit was used for prospective score validation. Logistic regression models were employed to analyze the association of early clinical and paraclinical parameters with PSD development., Results: N = 525 patients (median age: 76 years; 45.7% female) were enrolled, with 29.7% developing PSD during hospitalization. The resulting score comprises 6 items, including medical history, clinical examination findings, and non-contrast computed tomography results at admission. Scores range from -15 to +15 points, with higher values indicating a higher likelihood of PSD, ranging from 4% to 79%. The accuracy was 0.85, and the area under the curve was 0.89., Conclusion: The new RAPID (Risk Assessment and PredIction of Delirium in acute stroke patients)-score shows high accuracy in predicting PSD among acute stroke patients and offers precise odds of PSD for each corresponding score value, utilizing routine early clinical and paraclinical parameters. It can identify high-risk populations for clinical study interventions and may be suitable to guide prophylactic PSD measures., Competing Interests: LK has received funding for travel or speaker honoraria from Alexion, AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol-Meyer-Squibb, Daiichi Sankyo, and Pfizer outside of this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wischmann, Kremer, Hinske, Tomasi, Becker-Pennrich and Kellert.)

The secondary prophylaxis of ischemic stroke provides an enormous therapeutic potential due to the high frequency of recurrent thrombembolic events and the exceptional importance of modifiable cardiovascular risk factors for the individual risk of stroke. In this respect, anti-thrombotic, interventional and surgical treatment options must be selected based on the respective etiology. Furthermore, meticulous optimization of risk factors is essential for effective long-term care. Close interdisciplinary and intersectoral collaboration is crucial, especially in the long-term treatment., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Experimental and neuroimaging studies suggest an influence of the time of day on acute infarct growth, but whether this could inform patient selection for acute treatments is uncertain. In a multicenter cohort of 9357 stroke patients undergoing endovascular treatment, morning treatment (05:00-10:59) was associated with lowest 90-day mRS scores (adjusted odds ratio, 1.27 [95% CI, 1.08-1.47]; p = 0.004). The association between successful recanalization and outcome was stronger in morning compared to evening-treated patients (p ia  = 0.046) with treatment benefit persisting until 24 h for morning-treated compared to 11.5 h for evening-treated patients suggesting that the time of day might inform patient selection for EVT., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Recent studies have implied that ongoing intravenous thrombolysis (IVT) during endovascular treatment (ET) improves functional outcomes in patients who have undergone stroke caused by a large vessel occlusion (LVO). In this study, we investigated the effect of ongoing IVT until completion of ET on procedure duration, first-pass thrombectomy rate, and periprocedural complications., Methods: We analyzed patients from the German Stroke Registry-Endovascular Treatment dataset, collected between June 2015 and December 2021. Primary outcomes were modified Rankin Scale (mRS) score after 3 months and achievement of a Thrombolysis In Cerebral Infarction (TICI) score of 2b-3. Secondary parameters included ET duration, first-pass thrombectomy, and periprocedural complications., Results: Of the 13,082 patients in the dataset, 1,639 met the study inclusion criteria. A total of n = 317 patients (19.3%) underwent ongoing IVT until completion of ET, while IVT was completed prior to ET in 1,322 patients (80.7%). Ongoing IVT was associated with higher rates of achievement of an mRS score of 0-2 (or a back-to-baseline) after 3 months [odds ratio (OR) 1.53; 95% confidence interval (CI) 1.08-2.17]. Furthermore, ongoing IVT was predictive of achievement of a TICI score of 2b-3 (OR 1.37; 95% CI 1.03-1.83) and of first-pass thrombectomy (OR 2.07; 95% CI 1.51-2.84), while reducing the rate of peri-interventional complications (OR 0.64; 95% CI 0.44-0.94) and reducing ET duration by 24 min [β = -24.35; 95% CI -32.92-(-15.79)]., Conclusion: Our findings suggest that ongoing IVT until ET completion has a favorable impact on both clinical and angiographic outcomes, as well as on periprocedural conditions, regardless of the overall time intervals involved. Therefore, rapid ET after IVT should be sought in order to take advantage of the additive effect of ongoing IVT during ET. Future studies should consider IVT timing in the context of ET as a potential confounder and treatment target., Competing Interests: LKel has received funding for travel or speaker honoraria from Alexion, AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol-Meyer-Squibb, Daiichi Sankyo, and Pfizer outside of this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wischmann, Pradhan, Zimmermann, Keidel, Tiedt, Dimitriadis, Liebig, Höglinger and Kellert.)

Background and Purpose: Acute ischemic stroke due to basilar artery occlusion (BAO) causes the most severe strokes and has a poor prognosis. Data regarding efficacy of endovascular thrombectomy in BAO are sparse. Therefore, in this study, we performed an analysis of the therapy of patients with BAO in routine clinical practice., Methods: Patients enrolled between June 2015 and December 2019 in the German Stroke Registry-Endovascular Treatment (GSR-ET) were analyzed. Primary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3), substantial neurological improvement (≥8-point National Institute of Health Stroke Scale [NIHSS] score reduction from admission to discharge or NIHSS score at discharge ≤1), and good functional outcome at 3 months (modified Rankin Scale [mRS] score of 0-2)., Results: Out of 6635 GSR-ET patients, 640 (9.6%) patients (age 72.2 ± 13.3, 43.3% female) experienced BAO (median [interquartile range] NIHSS score 17 [8, 27]). Successful reperfusion was achieved in 88.4%. Substantial neurological improvement at discharge was reached by 45.5%. At 3-month follow-up, good clinical outcome was observed in 31.1% of patients and the mortality rate was 39.2%. Analysis of mTICI3 versus mTICI2b groups showed considerable better outcome in those with mTICI3 (38.9% vs. 24.4%; p = 0.005). The strongest predictors of good functional outcome were intravenous thrombolysis (IVT) treatment (odds ratio [OR] 3.04, 95% confidence interval [CI] 1.76-5.23) and successful reperfusion (OR 4.92, 95% CI 1.15-21.11), while the effect of time between symptom onset and reperfusion seemed to be small., Conclusions: Acute reperfusion strategies in BAO are common in daily practice and can achieve good rates of successful reperfusion, neurological improvement and good functional outcome. Our data suggest that, in addition to IVT treatment, successful and, in particular, complete reperfusion (mTICI3) strongly predicts good outcome, while time from symptom onset seemed to have a lower impact., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

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.

Objective: 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., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Treatment of non-arteritic central retinal artery occlusion is still inconsistent. Therefore, the current study aimed to evaluate the efficacy of intravenous thrombolysis (IVT) and describe the prevalence of co-occurring ischemic brain lesions in patients with acute visual loss due to ischemia. Methods: We analysed 38 consecutive patients with acute visual loss between January 2015 and June 2020. Patients presenting within 4.5 h of symptom onset without any contraindication were treated with IVT. Patients underwent neurologic and ophthalmologic examination and diagnostic workup for the underlying aetiology. Follow-up was performed after 3 and 12 months. Results: Patients treated with IVT had a significantly better functional outcome at discharge compared to patients treated conservatively. No additional ischemic brain lesions were detected (0 of 38). Three patients had extracranial carotid artery stenosis ≥50%. Atrial fibrillation was present in four patients, three of whom already received oral anticoagulation. In the remaining 31 patients no embolic source was detected. However, the number of plaques were rated mild to moderate. Within three months, one patient developed transient visual loss while another suffered a contralateral transient ischemic attack. Conclusions: IVT may represent a safe and effective treatment option in patients with isolated visual loss due to ischemia. The aetiology was atherosclerotic burden rather than embolism caused by carotid stenosis or atrial fibrillation, bringing the current diagnostic procedure and therapy into question. Randomized trials are necessary to evaluate the efficacy and safety of IV thrombolysis and clarify the aetiology of isolated visual loss due to ischemia.

Background and Purpose: Reperfusion treatment in patients presenting with large vessel occlusion (LVO) and minor neurological deficits is still a matter of debate. We aimed to compare minor stroke patients treated with endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) or IVT alone., Methods: Patients enrolled in the German Stroke Registry-Endovascular Treatment (GSR-ET) and the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) between June 2015 and December 2019 were analyzed. Minor stroke was defined as National Institutes of Health Stroke Scale (NIHSS) score ≤5, and LVO as occlusion of the internal carotid, carotid-T, middle cerebral, basilar, vertebral or posterior cerebral arteries. GSR-ET and SITS-ISTR IVT-treated patients were matched in a 1:1 ratio using propensity-score (PS) matching. The primary outcome was good functional outcome at 3 months (modified Rankin Scale score 0-2)., Results: A total of 272 GSR-ET patients treated with EVT and IVT (age 68.6 ± 14.0 years, 43.4% female, NIHSS score 4 [interquartile range 2-5]) were compared to 272 IVT-treated SITS-ISTR patients (age 69.4 ± 13.7, 43.4% female, NIHSS score 4 [2-5]). Good functional outcome was seen in 77.0% versus 82.9% (p = 0.119), mortality in 5.9% versus 7.9% (p = 0.413), and intracranial hemorrhage in 8.8% versus 12.5% (p = 0.308) of patients in the GSR-ET versus the SITS-ISTR IVT group, respectively. In a second PS-matched analysis, 624 GSR-ET patients (IVT rate 56.7%) and 624 SITS-ISTR patients (IVT rate 100%), good outcome was more often observed in the SITS-ISTR patients (68.2% vs. 80.9%; p < 0.001), and IVT independently predicted good outcome (odds ratio 2.16, 95% confidence interval 1.43-3.28)., Conclusions: Our study suggests similar effectiveness of IVT alone compared to EVT with or without IVT in minor stroke patients. There is an urgent need for randomized controlled trials on this topic., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The adapter protein myeloid differentiation primary response gene 88 (MyD88) links the intracellular domains of interleukin receptors 1 and 18, and most Toll-like receptors (TLRs) to interleukin 1 receptor associated kinase (IRAK) signaling and subsequent NF-κB-mediated transcription. Previous work showed that mice with global deficiency of MyD88 (MyD88 -/- ) have osteopenic cancellous bone along with a reduction in osteoblastic but also osteoclastic surfaces. To further elucidate the role of MyD88 in bone, we utilized mice with osteoclast-restricted MyD88 expression in bone (MyD88 OC ). Bones of MyD88 OC and wild type (wt) mice were examined by microCT analysis. Mechanical properties of bones were tested by three-point bending, and gene expression measured using quantitative real-time polymerase chain reaction. In MyD88 OC mice, no osteopenic traits were observed, however, a drastic reduction in geometric parameters was detected. In trabecular bone a loss of connectivity density (-44%, p less than 0.0001) was measured and in cortical bone Imax (-31%, p less than 0.0001), Imin (-20%, p less than 0.001), J (-26%, p less than 0.0001) were reduced. Mechanical testing showed increased load to failure (77%, p less than 0.01) and decreased deflection at failure (-68%, p less than 0.01) of the femur. On the molecular level, relative gene expression analysis showed a (-29%, p less than 0.01) reduction in receptor activator of nuclear factor κ B ligand (RANKL) and no difference in osteoprotegerin (OPG) or RANK. Further, the bone resorption markers cathepsin K (CTSK) and tartrate-resistant acid phosphatase 5 (TRAP) were unchanged. In contrast, the bone formation markers collagen type 1 (COL1A1) and osteocalcin (OC) were decreased by -72% (p less than 0.0001) and -82% (p less than 0.0001), respectively. Together, our data suggests that the function of MyD88 in osteoclasts is sufficient to maintain bone mass, while it fails to preserve bone geometry, likely through dysfunctions in osteoblasts.

Osteoblasts are adherent cells, and under physiological conditions they attach to both mineralized and non-mineralized osseous surfaces. However, how exactly osteoblasts respond to these different osseous surfaces is largely unknown. Our hypothesis was that the state of matrix mineralization provides a functional signal to osteoblasts. To assess the osteoblast response to mineralized compared to demineralized osseous surfaces, we developed and validated a novel tissue surface model. We demonstrated that with the exception of the absence of mineral, the mineralized and demineralized surfaces were similar in molecular composition as determined, for example, by collagen content and maturity. Subsequently, we used the human osteoblastic cell line MG63 in combination with genome-wide gene set enrichment analysis (GSEA) to record and compare the gene expression signatures on mineralized and demineralized surfaces. Assessment of the 5 most significant gene sets showed on mineralized surfaces an enrichment exclusively of genes sets linked to protein synthesis, while on the demineralized surfaces 3 of the 5 enriched gene sets were associated with the matrix. Focusing on these three gene sets, we observed not only the expected structural components of the bone matrix, but also gene products, such as HMCN1 or NID2, that are likely to act as temporal migration guides. Together, these findings suggest that in osteoblasts mineralized and demineralized osseous surfaces favor intracellular protein production and matrix formation, respectively. Further, they demonstrate that the mineralization state of bone independently controls gene expression in osteoblastic cells., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Bone formation, for example during bone remodelling or fracture repair, requires mature osteoblasts to deposit bone with remarkable spatial precision. As osteoblast precursors derive either from circulation or resident stem cell pools, they and their progeny are required to migrate within the three-dimensional bone space and to navigate to their destination, i.e. to the site of bone formation. An understanding of this process is emerging based on in vitro and in vivo studies of several vertebrate species. Receptors on the osteoblast surface mediate cell adhesion and polarization, which induces osteoblast migration. Osteoblast migration is then facilitated along gradients of chemoattractants. The latter are secreted or released proteolytically by several cell types interacting with osteoblasts, including osteoclasts and vascular endothelial cells. The positions of these cellular sources of chemoattractants in relation to the position of the osteoblasts provide the migrating osteoblasts with tracks to their destination, and osteoblasts possess the means to follow a track marked by multiple chemoattractant gradients. In addition to chemotactic cues, osteoblasts sense other classes of signals and utilize them as landmarks for navigation. The composition of the osseous surface guides adhesion and hence migration efficiency and can also provide steering through haptotaxis. Further, it is likely that signals received from surface interactions modulate chemotaxis. Besides the nature of the surface, mechanical signals such as fluid flow may also serve as navigation signals for osteoblasts. Alterations in osteoblast migration and navigation might play a role in metabolic bone diseases such as osteoporosis., (© 2017 Cambridge Philosophical Society.)