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Marion Ortner,1 Christine Hauser,2 Christoph Schmaderer,2 Claudia Muggenthaler,1 Alexander Hapfelmeier,3 Christian Sorg,1,4 Janine Diehl-Schmid,1 Alexander Kurz,1 Hans Förstl,1 Benno Ikenberg,5 Konstantin Kotliar,6 Holger Poppert,5,7,* Timo Grimmer1,* 1Technical University of Munich, School of Medicine, Klinikum Rechts der Isar, Department of Psychiatry and Psychotherapy, Munich, Germany; 2Technical University of Munich, School of Medicine, Klinikum Rechts der Isar, Department of Nephrology, Munich, Germany; 3Technical University of Munich, School of Medicine, Klinikum Rechts der Isar, Institute for Medical Statistics and Epidemiology, Munich, Germany; 4Technical University of Munich, School of Medicine, Klinikum Rechts der Isar, Department of Diagnostic and Interventional Neuroradiology, Munich, Germany; 5Technical University of Munich, School of Medicine, Klinikum Rechts der Isar, Department of Neurology, Munich, Germany; 6Department of Medical Engineering and Technomathematics, FH Aachen, Jülich, Germany; 7Department of Neurology, Helios Dr. Horst Schmid Kliniken Wiesbaden, Wiesbaden, Germany*These authors contributed equally to this workCorrespondence: Marion OrtnerTechnical University of Munich, School of Medicine, Klinikum Rechts der Isar, Department of Psychiatry and Psychotherapy, Moehlstr. 26 81675, Muenchen, GermanyTel +49 89 4140 6463Fax +49 89 4140 4923Email marion.ortner@tum.dePurpose: Impaired paravascular drainage of β-Amyloid (Aβ) has been proposed as a contributing cause for sporadic Alzheimer’s disease (AD), as decreased cerebral blood vessel pulsatility and subsequently reduced propulsion in this pathway could lead to the accumulation and deposition of Aβ in the brain. Therefore, we hypothesized that there is an increased impairment in pulsatility across AD spectrum.Patients and Methods: Using transcranial color-coded duplex sonography (TCCS) the resistance and pulsatility index (RI; PI) of the middle cerebral artery (MCA) in healthy controls (HC, n=14) and patients with AD dementia (ADD, n=12) were measured. In a second step, we extended the sample by adding patients with mild cognitive impairment (MCI) stratified by the presence (MCI-AD, n=8) or absence of biomarkers (MCI-nonAD, n=8) indicative for underlying AD pathology, and compared RI and PI across the groups. To control for atherosclerosis as a confounder, we measured the arteriolar-venular-ratio of retinal vessels.Results: Left and right RI (p=0.020; p=0.027) and left PI (p=0.034) differed between HC and ADD controlled for atherosclerosis with AUCs of 0.776, 0.763, and 0.718, respectively. The RI and PI of MCI-AD tended towards ADD, of MCI-nonAD towards HC, respectively. RIs and PIs were associated with disease severity (p=0.010, p=0.023).Conclusion: Our results strengthen the hypothesis that impaired pulsatility could cause impaired amyloid clearance from the brain and thereby might contribute to the development of AD. However, further studies considering other factors possibly influencing amyloid clearance as well as larger sample sizes are needed.Keywords: pulsatility index, PI, resistance index, RI, biomarker, mild cognitive impairment, MCI, Alzheimer’s dementia

Background: Repeated mechanical thrombectomy for acute stroke treatment in individual patients has been proven feasible. However, less is known about the etiology of recurrent vessel occlusions after prior thrombectomy. We aimed to understand if the etiology of such recurrent events differs from the first stroke. Methods: Retrospectively, we identified all patients at our center who received a repeated mechanical thrombectomy between 2007 and 2019. Clinical data were retrieved from medical records. Etiology of stroke was evaluated retrospectively, and angiographic studies were revisited. Results: Twenty-three patients (1.5%) were identified. Median age was 68 years (IQR 56–77). Median NIHSS at first admission was 11 points (IQR 5–15). In nine cases (39.1%), the recurrent vessel occlusion was located exactly at the same position as the prior occlusion. Overall, five (21.7%) patients had a remarkable extracranial pathology as likely cause of stroke recurrence. In 16 patients (69.6%), the etiology of the first stroke and its recurrence was considered as likely being the same, mostly of cardioembolic or unknown origin. In the seven remaining patients (30.4%), the cause of stroke possibly differed from the first event, with five patients (21.7%) having a postinterventional intracranial intimal lesion as possible cause of stroke. Conclusion: Incidence of repeated thrombectomy was low. However, the high number of patients with known origin of stroke etiology raises the question how their monitoring may be optimized. The number of patients with remarkable extracranial pathologies or intracranial endothelial lesions supports current clinical practice to pay attention to final angiographic series. [ABSTRACT FROM AUTHOR]

Background: Evidence from randomized controlled trials has shown a benefit for endovascular treatment in basilar artery occlusion. We aimed to show the effect of the recanalization result on outcome and determine the role of underlying basilar stenosis in a real-world setting., Methods: A retrospective, single-center study of patients who received endovascular treatment for basilar artery occlusion from March 2008 to June 2022 was conducted. Clinical and outcome characteristics were gathered. Multivariate logistic regression analysis was performed to predict poor outcomes (post-treatment mRS 5 or 6). MRS shift analysis was performed., Results: This study includes 210 patients (mean age, 71.4 years +/- 13.3 [standard deviation]; 124 men). The variables age (OR, 1.04; 95% CI: 1.01-1.08; p = 0.014), underlying basilar stenosis (OR: 4.86; 95% CI: 2.15-10.98; p < 0.001), admission NHISS (OR: 1.09; 95% CI: 1.04-1.13; p < 0.001), and TICI (OR: 1.89; 95% CI: 1.09-3.25; p = 0.022) independently predicted a poor outcome. Patients with occlusions due to underlying stenosis had significantly worse recanalization rates. Median post-treatment mRS in all patients with embolic occlusion was 4; IQR, 2-5 (only patients with embolic occlusion: mTICI 0-2a, median: 5 [IQR, 4-5.5]; mTICI 2b, median: 4 [IQR, 2.5-6]; mTICI 3, median: 3 [IQR, 1-5]; p = 0.037). Median post-treatment mRS in all patients with occlusions due to underlying stenosis was 5; IQR, 4-6 (only patients with embolic occlusions: mTICI 0-2a, median: 6 [IQR, 4.5-6]; mTICI 2b, median: 6 [IQR, 4.25-6]; mTICI 3, median: 5 [IQR, 3.5-5.25]; p = 0.059)., Conclusions: Successful recanalization is essential for preventing poor outcomes in basilar artery occlusion. Underlying basilar stenosis diminishes the effect of successful recanalization on the overall outcome.

Introduction: While incident ischemic lesions (IILs) are not unusual on follow-up magnetic resonance imaging (MRI) following stroke, their risk factors and prognostic significance remain unknown., Methods: In a prospective multicenter study of 503 acute stroke patients, we assessed IILs on registered MRI images at baseline and 6 months, analyzing risk factors and clinical outcomes across 36 months., Results: At 6 months, 78 patients (15.5%) had IILs, mostly diffusion-weighted imaging-positive (72%) and clinically covert (91%). Older age and small vessel disease (SVD) lesions were baseline risk factors for IILs. IILs were associated with worse cognitive (beta for global cognition: -0.31, 95% confidence interval [CI]: -0.48 to -0.14) and functional outcomes (beta for modified Rankin scale [mRS]: 0.36, 95% CI: 0.14 to 0.58), and higher recurrent stroke risk (hazard ratio: 3.81, 95% CI: 1.35 to 10.69). IILs partially explained the relationship between SVD and poor cognition., Discussion: IILs are common and are associated with worse cognitive and functional outcomes and stroke recurrence risk. Assessing IILs following stroke might aid prognostication., Highlights: Incident ischemic lesions (IILs) were assessed with registered baseline and 6-month magnetic resonance imaging (MRI) scans in a stroke cohort. IILs 6 months after stroke are present in one-sixth of patients and are mostly clinically silent. Small vessel disease burden is the main baseline risk factor for IILs. IILs are associated with cognitive and functional impairment and stroke recurrence. Assessing IILs by follow-up MRI aids long-term prognostication for stroke patients., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: Basilar artery occlusion (BAO) may be etiologically attributed to embolism or in situ thrombosis due to basilar stenosis (BS). Patients with BAO due to BS (BAOS) are known to have worse outcomes than patients with embolic occlusions (BAOE). BAOS occurs more proximally in the basilar artery (BA) than BAOE. We hypothesize that differing brain stem infarct patterns contribute to outcome differences between these stroke etiologies., Methods: This retrospective study includes 199 consecutive patients with BAO who received endovascular treatment at a single center. Final infarction in brain parenchyma dependent on the posterior circulation was graded semiquantitatively on magnetic resonance imaging (MRI). Associations to underlying stenosis and angiographic and clinical outcome variables were tested. The primary endpoint was early good clinical outcome (EGCO, mRS score ≤ 3 at discharge)., Results: Infarct extension of the medulla oblongata (OR = 0.25; 95% CI = 0.07-0.86; p = 0.03), the inferior pons (OR = 0.328; 95% CI = 0.17-0.63; p = 0.001), the superior pons (OR = 0.57; 95% CI = 0.33-0.99; p = 0.046), and the occipital lobes (OR = 0.46; 95% CI = 0.26-0.80; p = 0.006) negatively predicted EGCO. Infarct extension for other posterior-circulation-dependent brain regions was not independently associated with unfavorable early outcomes. Patients with BAOS had more proximal occlusions and greater infarct volumes in the inferior brain stem. Successful reperfusion (mTICI 2b-3) occurred more often in patients with BAOE than in BAOS (BAOE: 131 (96.3%); BAOS: 47 (83.9%), p = 0.005)., Conclusion: Unfavorable early outcomes in patients with BAOS may be explained by a higher likelihood of inferior brain stem infarcts and lower rates of reperfusion success., Clinical Relevance Statement: Basilar artery occlusion due to underlying stenosis is associated with a poorer prognosis than that caused by embolism; these results suggest that aggressive endovascular therapy, usually involving the placement of a permanent stent, may be warranted in these patients., Key Points: Inferior brain stem and occipital infarcts are prognostically unfavorable in basilar artery occlusion. Basilar artery occlusion due to stenosis occurs more proximally and is associated with worse outcomes. Differentiating etiologies of basilar artery occlusion may influence how aggressively treated the occlusion is., (© 2024. The Author(s).)

Background: Nowadays, there is no method to quantitatively characterize the material composition of acute ischemic stroke thrombi prior to intervention, but dual-energy CT (DE-CT) offers imaging-based multimaterial decomposition. We retrospectively investigated the material composition of thrombi ex vivo using DE-CT with histological analysis as a reference., Methods: Clots of 70 patients with acute ischemic stroke were extracted by mechanical thrombectomy and scanned ex vivo in formalin-filled tubes with DE-CT. Multimaterial decomposition in the three components, i.e., red blood cells (RBC), white blood cells (WBC), and fibrin/platelets (F/P), was performed and compared to histology (hematoxylin/eosin staining) as reference. Attenuation and effective Z values were assessed, and histological composition was compared to stroke etiology according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria., Results: Histological and imaging analysis showed the following correlation coefficients for RBC (r = 0.527, p < 0.001), WBC (r = 0.305, p = 0.020), and F/P (r = 0.525, p < 0.001). RBC-rich thrombi presented higher clot attenuation in Hounsfield units than F/P-rich thrombi (51 HU versus 42 HU, p < 0.01). In histological analysis, cardioembolic clots showed less RBC (40% versus 56%, p = 0.053) and more F/P (53% versus 36%, p = 0.024), similar to cryptogenic clots containing less RBC (34% versus 56%, p = 0.006) and more F/P (58% versus 36%, p = 0.003) than non-cardioembolic strokes. No difference was assessed for the mean WBC portions in all TOAST groups., Conclusions: DE-CT has the potential to quantitatively characterize the material composition of ischemic stroke thrombi., Relevance Statement: Using DE-CT, the composition of ischemic stroke thrombi can be determined. Knowledge of histological composition prior to intervention offers the opportunity to define personalized treatment strategies for each patient to accomplish faster recanalization and better clinical outcomes., Key Points: • Acute ischemic stroke clots present different recanalization success according to histological composition. • Currently, no method can determine clot composition prior to intervention. • DE-CT allows quantitative material decomposition of thrombi ex vivo in red blood cells, white blood cells, and fibrin/platelets. • Histological clot composition differs between stroke etiology. • Insights into the histological composition in situ offer personalized treatment strategies., (© 2024. The Author(s).)

Background: Post-stroke diffusion weighted imaging (DWI) signal transformation of the infarct core, which results in high apparent diffusion coefficient (ADC) values and variable DWI signal intensity, is completed no later than 1 month after onset of ischemia. We observed frequent exceptions to this timeline of change in DWI signal, which led to uncertainties in further clinical patient management., Methods: A prospective single-center study of patients treated with mechanical thrombectomy of a large vessel occlusion in the anterior circulation was conducted. Patients received high-resolution MRI at 3T, including DWI, in the acute post-stroke phase and in the follow-up after 3-12 months., Results: Overall, 78 patients (45 men) of mean age 63.6 years were evaluated. We identified persisting or new diffusion restriction in 29 of the 78 patients (37.2%) on follow-up imaging. Diffusion restrictions in a different location from the infarct core, representing new (sub-)acute ischemia, were observed in four patients (5.1%). Smaller areas of persisting diffusion restriction (pDWI lesions with high DWI signal and reduced ADC values) within the former infarct core were observed in 25 patients (32.1%) without clinical evidence of recurrent stroke, but with worse outcome scores at follow-up compared with patients without pDWI lesions. The presence of pDWI lesions is associated with a large primary infarct core (multivariate regression OR 1.03 (95% CI 1.01 to 1.05); p<0.01), mediating the relationship between pDWI lesions and clinical outcome., Conclusion: Smaller foci of persisting diffusion restriction (pDWI lesions) in the follow-up after endovascular treatment for stroke are frequent and likely represent a slowed ADC signal progression within a formerly large infarct core., Competing Interests: Competing interests: Outside the submitted work, CZ has received speaker honoraria from Bayer-Schering. He serves as a co-editor on the advisory board of Clinical Neuroradiology and is president of the German Society of Neuroradiology (DGNR). All the other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Mechanical thrombectomy (MT) is frequently performed for distal medium vessel occlusions (DMVO) of the anterior circulation in acute stroke patients. However, evidence for its clinical benefit remains scarce. In this study, we aim to investigate clinical course and safety outcomes of MT in comparison to standard medical therapy (SMT) in DMVO. This single-center retrospective observational study included 138 consecutive patients treated for DMVO of the anterior circulation between 2015 and 2021. To reduce the risk of selection bias, propensity score matching (PSM) of patients with MT versus SMT was performed for the covariates NIHSS and mRS at admission. Out of all 138 patients, 48 (34.8%) received MT and 90 (65.2%) received SMT only. Overall, patients treated with MT showed significantly higher NIHSS and mRS scores at admission. Post 1:1 PSM, there was a trend toward a better NIHSS improvement in patients with MT (median 4 vs. 1, P = 0.1). No significant differences were observed in the occurrence of symptomatic intracranial hemorrhage or mortality between the groups before and after PSM. A subgroup analysis showed significantly higher NIHSS improvement (median 5 versus 1, P = 0.01) for patients with successful MT (≥ mTICI 2b). Mechanical thrombectomy for distal medium vessel occlusions (DMVO) in the anterior circulation appeared safe and feasible. Successful recanalization was associated with clinical improvement. Larger, multi-center, randomized-controlled trials are required to corroborate these findings., (© 2023. The Author(s).)

Introduction: It remains unknown whether the global small vessel disease (SVD) burden predicts post-stroke outcomes., Methods: In a prospective multicenter study of 666 ischemic and hemorrhagic stroke patients, we quantified magnetic resonance imaging (MRI)-based SVD markers (lacunes, white matter hyperintensities, microbleeds, perivascular spaces) and explored associations with 6- and 12-month cognitive (battery of 15 neuropsychological tests) and functional (modified Rankin scale) outcomes., Results: A global SVD score (range 0-4) was associated with cognitive impairment; worse performance in executive function, attention, language, and visuospatial ability; and worse functional outcome across a 12-month follow-up. Although the global SVD score did not improve prediction, individual SVD markers, assessed across their severity range, improved the calibration, discrimination, and reclassification of predictive models including demographic, clinical, and other imaging factors., Discussion: SVD presence and severity are associated with worse cognitive and functional outcomes 12 months after stroke. Assessing SVD severity may aid prognostication for stroke patients., Highlights: In a multi-center cohort, we explored associations of small vessel disease (SVD) burden with stroke outcomes. SVD burden associates with post-stroke cognitive and functional outcomes. A currently used score of SVD burden does not improve the prediction of poor outcomes. Assessing the severity of SVD lesions adds predictive value beyond known predictors. To add predictive value in assessing SVD in stroke patients, SVD burden scores should integrate lesion severity., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: Endovascular treatment of acute stroke patients with large vessel occlusions is well established. But tandem lesions of the internal carotid artery and the intracranial anterior circulation remain a challenge regarding the technical conditions and the putative higher risk of hemorrhage due to often required antiplatelet therapy.This study aims to evaluate the clinical outcome and the risk of hemorrhage after endovascular treatment of tandem lesions, with special regard to the periprocedural antiplatelet regimen., Materials and Methods: In this retrospective study, we included 63 consecutive stroke patients with endovascular treated tandem lesions. One hundred eleven patients with a solitary intracranial occlusion were matched using a "propensity score-matched analysis" with the covariates sex, age, wake-up stroke, iv-thrombolysis and NIHSS., Results: Rates of successful recanalization (mTICI 2b/3) and periprocedural complications were equal in both groups (P = 0.19; P = 0.35). The rate of good clinical outcome (mRS≤2) was similar, and the incidence of symptomatic hemorrhages was not significantly different (7.9% tandem lesions vs. 5.4% isolated intracranial occlusion, P = 0.51). Even intensified antiplatelet therapy in patients with tandem lesions did not increase the rate of symptomatic intracranial hemorrhages (P = 0.87)., Conclusions: Clinical outcome and symptomatic intracranial hemorrhages did not differ significantly between endovascular treated patients with tandem lesions and matched patients with solitary intracranial occlusions, regardless of the antiplatelet regimen. Therefore, the complex technical requirements for recanalization of a tandem lesion and the putative higher risk should not result in reluctant treatment that would decrease the chance of a good clinical outcome., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Published by Elsevier Ltd.)

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.

Magnetic resonance imaging (MRI) is an important imaging modality in stroke. Computer based automated medical image processing is increasingly finding its way into clinical routine. The Ischemic Stroke Lesion Segmentation (ISLES) challenge is a continuous effort to develop and identify benchmark methods for acute and sub-acute ischemic stroke lesion segmentation. Here we introduce an expert-annotated, multicenter MRI dataset for segmentation of acute to subacute stroke lesions ( https://doi.org/10.5281/zenodo.7153326 ). This dataset comprises 400 multi-vendor MRI cases with high variability in stroke lesion size, quantity and location. It is split into a training dataset of n = 250 and a test dataset of n = 150. All training data is publicly available. The test dataset will be used for model validation only and will not be released to the public. This dataset serves as the foundation of the ISLES 2022 challenge ( https://www.isles-challenge.org/ ) with the goal of finding algorithmic methods to enable the development and benchmarking of automatic, robust and accurate segmentation methods for ischemic stroke., (© 2022. The Author(s).)

The separation of mixtures of substances into their individual components plays an important role in many areas of science. In medical imaging, one method is the established analysis using dual-energy computed tomography. However, when analyzing mixtures consisting of more than three individual basis materials, a physical limit is reached that no longer allows this standard analysis. In addition, the X-ray attenuation coefficients of chemically complicated basis materials may not be known and also cannot be determined by other or previous analyses. To address these issues, we developed a novel theoretical approach and algorithm and tested it on samples prepared in the laboratory as well as on ex-vivo medical samples. This method allowed both five-material decomposition and determination or optimization of the X-ray attenuation coefficients of the sample base materials via optimizations of objective functions. After implementation, this new multimodal method was successfully tested on self-mixed samples consisting of the aqueous base solutions iomeprol, eosin Y disodiumsalt, sodium chloride, and pure water. As a first proof of concept of this technique for detailed material decomposition in medicine we analyzed exact percentage composition of ex vivo clots from patients with acute ischemic stroke, using histological analysis as a reference standard., (© 2022. The Author(s).)

Although a pathophysiological impact remains difficult to prove in individual patient care, a patent foramen ovale (PFO) is currently considered of high relevance for secondary prophylaxis in selected patients with cryptogenic ischemic stroke. By quantification of histological clot composition, we aimed to enhance pathophysiological understanding of PFO attributable ischemic strokes. Retrospectively, we evaluated all cerebral clots retrieved by mechanical thrombectomy for acute ischemic stroke treatment between 2011 and 2021 at our comprehensive stroke care center. Inclusion criteria applied were cryptogenic stroke, age (≤60 years), and PFO status according to transesophageal echocardiography, resulting in a study population of 58 patients. Relative clot composition was calculated using orbit image analysis to define the ratio of main histologic components (fibrin/platelets (F/P), red blood cell count (RBC), leukocytes). Cryptogenic stroke patients with PFO (PFO+, n = 20) displayed a significantly higher percentage of RBC (0.57 ± 0.17; p = 0.002) and lower percentage of F/P (0.38 ± 0.15; p = 0.003) compared to patients without PFO (PFO-, n = 38) (RBC: 0.41 ± 0.21; F/P: 0.52 ± 0.20). In conclusion, histologic clot composition in cryptogenic stroke varies depending on the presence of a PFO. Our findings histologically support the concept that a PFO may be of pathophysiological relevance in cryptogenic ischemic stroke.

Purpose: Acute basilar artery occlusion, a neurovascular emergency leading to high rates of morbidity and mortality, is usually diagnosed by CT imaging. The outcome is partly dependent on etiology, with a worse outcome in occlusions with underlying basilar artery stenosis. As this occlusion type requires a more complex angiographic therapy, this study aimed to develop new CT markers in emergency admission imaging to rapidly identify underlying stenosis. Methods: A total of 213 consecutive patients (female n = 91, age in years (mean/SD/range): 72/13/28−97), who received endovascular treatment at a single comprehensive stroke center for acute basilar artery occlusion, were included in this study. After applying strict inclusion criteria for imaging analyses, novel CT imaging markers, such as ‘absolute density loss’ (ADL) and relative thrombus attenuation (CTA-index), that measure perviousness, were assessed for n = 109 patients by use of CT-angiography and correlated to different occlusion patterns (thrombotic vs. embolic). Inter-observer agreement was assessed using an intraclass correlation coefficient for independent measures of a radiologist and a neuroradiologist. Associations between the imaging markers and clinical and interventional parameters were tested. Results: CT markers differ between the subgroups of basilar artery occlusions with and without underlying stenosis (for ADL: 169 vs. 227 HU (p = 0.03), for CTA-index: 0.55 vs. 0.70 (p < 0.001)), indicating a higher perviousness in the case of stenosis. A good inter-rater agreement was observed for ADL and CTA-index measures (ICC 0.92/0.88). For the case of embolic occlusions, a more pervious thrombus correlates to shorter time intervals, longer procedure times, and worse reperfusion success (p-values < 0.05, respectively). Conclusions: ADL and CTA-index are easy to assess in the emergency setting of acute basilar artery occlusion with the use of routinely acquired CT-angiography. They show a high potential to differentiate thrombotic from embolic occlusions, with an impact on therapeutic decisions and angiographic procedures. Measurements can be quickly performed with good reliability, facilitating implementation in clinical practice.

Long-term management after stroke has not been standardized in contrast to acute and rehabilitative stroke care. The fragmented outpatient sector of healthcare allows a high degree of flexibility but also variability in the quality of care provided. The commission on long-term stroke care of the German Stroke Society developed a concept on how to provide standardized multiprofessional long-term stroke care with a focus on patient-centered comprehensive care. We propose a diagnostic work-up in stages, with an initial patient-reported screening, followed by an adapted in-depth assessment of affected domains. This includes internistic domains (management of risk factors) and also genuine neurological domains (spasticity, cognitive deficits etc.) that must be considered. This information is then merged with patient expectations and prioritization to a standardized treatment plan. Special challenges for the implementation of such a comprehensive care system are the intersectoral and intrasectoral communication between healthcare providers, patients and relatives, the need to create a compensation system for providers and the establishment of appropriate quality management services. Digital health applications are helpful tools to provide aspects of diagnostics, treatment and communication in long-term stroke care., (© 2021. The Author(s).)

Introduction: Despite sufficient oral anticoagulation (OAC) to prevent cardioembolism, some patients suffer from cerebral ischemic strokes of suspected cardioembolic origin. Reasons for that are not clarified yet. In certain cases, the suspected cardioembolic origin of stroke is questioned. This study aimed to understand the thrombi origin and pathophysiology in patients suffering from stroke despite OAC by the analysis of histologic thrombus composition and imaging characteristics., Materials and Methods: On two distinct cohorts, we retrospectively analyzed histologic ( n = 92) and imaging features ( n = 64), i.e., thrombus perviousness in admission CT imaging, of cerebral thrombi retrieved by the endovascular treatment for a large vessel occlusion of the anterior circulation. In each group, patients with non-cardioembolic strokes and suspected cardioembolic strokes with or without anticoagulation were compared., Results: Fibrin/platelet content of suspected cardioembolic thrombi (mean/SD 57.2% ± 13) is higher than in non-cardioembolic thrombi (48.9% ± 17; p = 0.01). In suspected cardioembolic thrombi, the fibrin/platelet content does not differ in the subgroups of patients with (57.3% ± 13) and without prior OAC treatment (56.6% ±13; p = 0.8), both with higher values than non-cardioembolic thrombi. Thrombus perviousness (ε) of suspected cardioembolic OAC thrombi (mean/SD: 0.09 ± 0.06) differs significantly from non-cardioembolic thrombi (0.02 ± 0.02; p < 0.001). Further, ε is higher in suspected cardioembolic thrombi with OAC than in cardioembolic thrombi without OAC (0.06 ± 0.03; p = 0.04) and with insufficient OAC (0.04 ± 0.02; p = 0.07)., Conclusion: Thrombi of the suspected cardioembolic origin of patients with prior OAC do not differ in their histologic composition from those without prior OAC, but both differ from non-cardioembolic thrombi. These histologic results make a non-cardioembolic etiology for strokes despite prior OAC rather unlikely but favor other reasons for these ischemic events. Perviousness assessment reinforces the histologic findings, with additional information about the OAC thrombi, which present with higher perviousness. This suggests that OAC would not affect the relative histologic thrombus composition but may alter the microstructure, as reflected by perviousness., Competing Interests: The 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 © 2022 Ikenberg, Boeckh-Behrens, Maegerlein, Härtl, Hernandez Petzsche, Zimmer, Wunderlich and Berndt.)

Background and Purpose: Mechanical thrombectomy (MT) is standard care for patients suffering from an ischemic stroke due to a large vessel occlusion. Immediate and follow-up transcranial ultrasound examinations after MT were shown to have a diagnostic benefit. However, it is unclear whether repeated extracranial ultrasound after MT has an additional diagnostic yield, that is, depicts new findings., Methods: Retrospectively, from our prospective database we identified all patients after MT who presented for a follow-up examination between January 2017 and March 2020 and who had received an ultrasound examination after MT and at follow-up. Clinical data were extracted from our database. Ultrasound images of all patients were revisited to identify new findings at follow-up compared to examination after MT., Results: Ninety-one patients were identified appropriate for further analysis, with a mean age of 67.8 ± 16 years. Median National Institute of Health Stroke Scale at admission was 11 ± 8.5 points. At baseline ultrasound, 18 patients (19.8%) had no atherosclerotic alterations and 73 patients (82.2%) had a plaque burden of ≥1 plaque. During follow-up, in 5 patients (5.5%) a pathological finding presented in first examination evolved dynamically, that is, normalized. Vessel status of all other patients was stable, especially, in no patient a new relevant pathological finding occurred., Conclusions: Although sonographic normalization of pathologic findings was observed, pathologic new findings were not detected during follow-up. This study provides first data for a discussion of the role of ultrasound in a structured stroke care after MT. However, larger studies are required to improve the understanding., (© 2021 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) have been recently described as rare complications following vaccination against SARS-CoV-2 with vector vaccines. We report a case of a young woman who presented with VITT and cerebral CVST 7 days following vaccination with ChAdOx1 nCov-19 (AstraZeneca). While the initial MRI was considered void of pathological findings, MRI 3 days later revealed extensive CVST of the transversal and sigmoidal sinus with intracerebral haemorrhage. Diagnostic tests including a platelet-factor-4-induced platelet activation assay confirmed the diagnosis of VITT. Treatment with intravenous immunoglobulins and argatroban resulted in a normalisation of platelet counts and remission of CVST., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To compare the quality of free-text reports (FTR) and structured reports (SR) of brain magnetic resonance imaging (MRI) examinations in patients following mechanical thrombectomy for acute stroke treatment., Methods: A template for SR of brain MRI examinations based on decision trees was designed and developed in house and applied to twenty patients with acute ischemic stroke in addition to FTR. Two experienced stroke neurologists independently evaluated the quality of FTR and SR regarding clarity, content, presence of key features, information extraction, and overall report quality. The statistical analysis for the differences between FTR and SR was performed using the Mann-Whitney U-test or the Chi-squared test., Results: Clarity (p < 0.001), comprehensibility (p < 0.001), inclusion of relevant findings (p = 0.016), structure (p = 0.005), and satisfaction with the content of the report for immediate patient management (p < 0.001) were evaluated significantly superior for the SR by both neurologist raters. One rater additionally found the explanation of the patient's clinical symptoms (p = 0.003), completeness (p < 0.009) and length (p < 0.001) of SR to be significantly superior compared to FTR and stated that there remained no open questions, requiring further consultation of the radiologist (p < 0.001). Both neurologists preferred SR over FTR., Conclusions: The use of SR for brain magnetic resonance imaging may increase the report quality and satisfaction of the referring physicians in acute ischemic stroke patients following mechanical thrombectomy. Trial registration Retrospectively registered.

Background: Data on the frequency and outcome of repeated mechanical thrombectomy (MT) in patients with short-term re-occlusion of intracranial vessels is limited. Addressing this subject, we report our multicenter experience with a systematic review of the literature., Methods: A retrospective analysis was conducted of consecutive acute stroke patients treated with MT repeatedly within 30 days at 10 tertiary care centers between January 2007 and January 2020. Baseline demographics, etiology of stroke, angiographic outcome and clinical outcome evaluated by the modified Rankin Scale (mRS) at 90 days were noted. Additionally, a systematic review of reports with repeated MT due to large vessel occlusion (LVO) recurrence was performed., Results: We identified 30 out of 7844 (0.4%) patients who received two thrombectomy procedures within 30 days due to recurrent LVO. Through systematic review, three publications of 28 participants met the criteria for inclusion. Combined, a total of 58 participants were analyzed: cardioembolic events were the most common etiology for the first (65.5%) and second LVO (60.3%), respectively. Median baseline NIHSS (National Institutes of Health Stroke Scale) was 13 (IQR 8-16) before the first MT and 15 (IQR 11-19) before the second MT (p=0.031). Successful reperfusion was achieved in 91.4% after the first MT and in 86.2% patients after the second MT (p=0.377). The rate of functional independence (mRS 0-2) was 46% at 90 days after the second procedure., Conclusion: Repeated MT in short-term recurrent LVO is a rarity but appears to be safe and effective. The second thrombectomy should be pursued with the same extensive effort as the first procedure as these patients may achieve similar good outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The COVID-19 pandemic caused public lockdowns around the world. We analyzed if the public lockdown altered the referral pattern of Code Stroke patients by Emergency Medical Services (EMS) to our Comprehensive Stroke Center., Methods: Retrospective single-center study at a Bavarian Comprehensive Stroke Center. Patients who were directly referred to our stroke unit by EMS between the 1 st of January 2020 and the 19 th of April 2020 were identified and number of referrals, clinical characteristics and treatment strategies were analyzed during the public lockdown and before. The public lockdown started on 21 st of March and ended on 19 th April 2020., Results: In total 241 patients were referred to our center during the study period, i.e. 171 before and 70 during the lockdown. The absolute daily number of Code Stroke referrals and the portion of patients with stroke mimics remained stable. The portion of female stroke patients decreased (55% to 33%; p = 0.03), and stroke severity as measured by the National Institutes of Health Stroke Scale (median 3 (IQR 0-7) versus 6 (IQR 1-15.5) points; p = 0.04) increased during the lockdown. There was no difference of daily numbers of patients receiving thrombolysis and thrombectomy., Conclusions: Referral of Code Stroke patients by EMS could be maintained sufficiently despite the COVID-19 pandemic lockdown. However, patients' health care utilization of the EMS may have changed within the public lockdown. EMS remains a useful tool for Code Stroke patient referral during lockdowns, but public education about stroke is required prior to further lockdowns., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The relevance of motor evoked potential (MEP) recovery during mechanical endovascular thrombectomy (MT) in patients with ischemic stroke is unclear. We correlated MEP recovery during MT to symptom improvement and to ischemia in eloquent motor areas on magnetic resonance imaging (MRI) and compared the predictive value of MEPs to visual angiographic reperfusion status, classified by modified Thrombolysis in Cerebral Infarction grading (mTICI)., Methods: Patients with hemisyndrome and large-vessel occlusion undergoing MT were included (n35, 49% females; 73.9 ± 14.5 years; n31 anterior circulation). MEPs were elicited transcranially and recorded at the abductor pollicis brevis muscle bilaterally throughout the procedure. An MRI was acquired within 7 days after MT., Results: The median door-to-needle time was 3.5 hours. Median National Institutes of Health Stroke Scale at presentation was 16 (7 - 37). Median Modified Rankin Scale score was 4 at day 7 and 3 months. After MT, MEP-recovery occurred in 21 cases after a median time span of 4.5 min [range 2 - 11 min]. Symptom improvement at day 7 (3 months) was noted in 22 (21) cases. Absence of ischemia on postinterventional MRI was noted in 21 cases, 19 of whom showed MEP-recovery. Stratified for symptom improvement at day 7, sensitivity (specificity) of MEP-recovery was 86% (85%) and of mTICI ≥ 2b was 95% (23%). Stratified for absence of ischemia on postinterventional MRI, sensitivity (specificity) of MEP-recovery was 90% (86%) and of mTICI ≥ 2b was of 95% (21%)., Conclusions: MEP recovery occurs early after successful endovascular mechanical revascularization and is superior to mTICI grading in predicting postoperative neurological outcome and postoperative motor-pathway ischemia., Significance: This is a new, significant and clinically important study since it emphasizes the additional value of MEP monitoring in a field, which has been traditionally unaffiliated with neurophysiological monitoring., Competing Interests: Declaration of Competing Interest Electrophysiological monitoring was conducted on the ISIS system from Inomed Co. No author received compensation from the manufacturer., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Mechanical thrombectomy has been shown to be effective for acute stroke treatment, but lesions of cerebral vessels can develop thereafter. Such lesions of recanalized vessels and altered cerebral hemodynamics after mechanical thrombectomy are poorly investigated. In particular for neurosonography, data are sparse. We aimed to describe hemodynamic changes and incidence of de-novo stenosis after mechanical thrombectomy with neurosonography., Methods: Retrospective analysis of patients after successful mechanical thrombectomy for acute stroke therapy who received one neurosonography at baseline and during follow up. Peak systolic velocity (PSV) of all intracranial recanalized and reference vessels was extracted for analysis. Patients with an isolated increase or decrease of PSV (50% or 50 cm/second for anterior and 30% or 30 cm/second for posterior circulation) were identified and characterized., Results: Eighty-eight patients (mean age 64.4; 34.1% female) were included in this study. In 9 (10.2%) patients, the vessel occlusion was located in the posterior, and in 79 (89.9%) patients the vessel occlusion was located in the anterior circulation. With predominance to the recanalized vessel, mean PSV decreased at both, the recanalized and the reference vessel during follow up. In 3 (3.4%) patients, an isolated increase of PSV was observed in the recanalized vessel, and in 6 (6.8%) patients an isolated decrease of PSV was observed in the recanalized vessel., Conclusion: Sonographic incidence of de-novo stenosis following mechanical thrombectomy seems to be low, in line with prior angiographic studies. However, as measured by neurosonography, cerebral hemodynamic in the recanalized vessel is dynamic after thrombectomy. This result is of interest for further prospective analysis., (© 2019 by the American Society of Neuroimaging.)

Background: The first specific antidote for non-vitamin K antagonist oral anticoagulants (NOAC) has recently been approved. NOAC antidotes will allow specific treatment for 2 hitherto problematic patient groups: patients with oral anticoagulant therapy (OAT)-associated intracerebral hemorrhage (ICH) and maybe also thrombolysis candidates presenting on oral anticoagulation (OAT). We aimed to estimate the frequency of these events and hence the quantitative demand of antidote doses on a stroke unit., Methods: We extracted data of patients with acute ischemic stroke and ICH (<24 h after symptom onset) in the years 2012-2015 from a state-wide prospective stroke inpatient registry. We selected 8 stroke units and determined the mode of OAT upon admission in 2012-2013. In 2015, the mode of OAT became a mandatory item of the inpatient registry. From the number of anticoagulated patients and the NOAC share, we estimated the current and future demand for NOAC antidote doses on stroke units., Results: Eighteen percent of ICH patients within 6 h of symptom onset or an unknown symptom onset were on OAT. Given a NOAC share at admission of 40%, about 7% of all ICH patients may qualify for NOAC reversal therapy. Thirteen percent of ischemic stroke patients admitted within 4 h presented on anticoagulation. Given the availability of an appropriate antidote, a NOAC share of 50% could lead to a 6.1% increase in thrombolysis rate., Conclusions: Stroke units serving populations with a comparable demographic structure should prepare to treat up to 1% of all acute ischemic stroke patients and 7% of all acute ICH patients with NOAC antidotes. These numbers may increase with the mounting prevalence of atrial fibrillation and an increasing use of NOAC., (© 2016 S. Karger AG, Basel.)

Background: We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC)., Methods and Results: This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8-22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1-1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences., Conclusions: IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests., (© 2015 American Heart Association, Inc.)

Thrombin, a serine protease involved in the blood coagulation cascade has been shown to affect neural function following blood-brain barrier breakdown. However, several lines of evidence exist that thrombin is also expressed in the brain under physiological conditions, suggesting an involvement of thrombin in the regulation of normal brain functions. Here, we review ours' as well as others' recent work on the role of thrombin in synaptic transmission and plasticity through direct or indirect activation of Protease-Activated Receptor-1 (PAR1). These studies propose a novel role of thrombin in synaptic plasticity, both in physiology as well as in neurological diseases associated with increased brain thrombin/PAR1 levels.