Apixaban versus Aspirin for Embolic Stroke of Undetermined Source.

Apixaban versus Aspirin for Embolic StrokeIn a trial of 352 patients with embolic stroke of undetermined source, 5 mg of apixaban administered twice daily was compared with 100 mg of aspirin administered once daily for the prevention of recurrent ischemic strokes. At 12 months, 13.6% of patients given apixaban had new ischemic lesions on magnetic resonance imaging compared with 16.0% of patients given aspirin, and the rates of clinically relevant bleeding were also comparable.

PREDICT-juvenile-stroke: PRospective evaluation of a prediction score determining individual clinical outcome three months after ischemic stroke in young adults - a study protocol.

BACKGROUND: Although of high individual and socioeconomic relevance, a reliable prediction model for the prognosis of juvenile stroke (18-55 years) is missing. Therefore, the study presented in this protocol aims to prospectively validate the discriminatory power of a prediction score for the 3 months functional outcome after juvenile stroke or transient ischemic attack (TIA) that has been derived from an independent retrospective study using standard clinical workup data. METHODS: PREDICT-Juvenile-Stroke is a multi-centre (n = 4) prospective observational cohort study collecting standard clinical workup data and data on treatment success at 3 months after acute ischemic stroke or TIA that aims to validate a new prediction score for juvenile stroke. The prediction score has been developed upon single center retrospective analysis of 340 juvenile stroke patients. The score determines the patient's individual probability for treatment success defined by a modified Rankin Scale (mRS) 0-2 or return to pre-stroke baseline mRS 3 months after stroke or TIA. This probability will be compared to the observed clinical outcome at 3 months using the area under the receiver operating characteristic curve. The primary endpoint is to validate the clinical potential of the new prediction score for a favourable outcome 3 months after juvenile stroke or TIA. Secondary outcomes are to determine to what extent predictive factors in juvenile stroke or TIA patients differ from those in older patients and to determine the predictive accuracy of the juvenile stroke prediction score on other clinical and paraclinical endpoints. A minimum of 430 juvenile patients (< 55 years) with acute ischemic stroke or TIA, and the same number of older patients will be enrolled for the prospective validation study. DISCUSSION: The juvenile stroke prediction score has the potential to enable personalisation of counselling, provision of appropriate information regarding the prognosis and identification of patients who benefit from specific treatments. TRIAL REGISTRATION: The study has been registered at https://drks.de on March 31, 2022 ( DRKS00024407 ).

Multistage classification identifies altered cortical phase- and amplitude-coupling in Multiple Sclerosis.

Distinguishing groups of subjects or experimental conditions in a high-dimensional feature space is a common goal in modern neuroimaging studies. Successful classification depends on the selection of relevant features as not every neuronal signal component or parameter is informative about the research question at hand. Here, we developed a novel unsupervised multistage analysis approach that combines dimensionality reduction, bootstrap aggregating and multivariate classification to select relevant neuronal features. We tested the approach by identifying changes of brain-wide electrophysiological coupling in Multiple Sclerosis. Multiple Sclerosis is a demyelinating disease of the central nervous system that can result in cognitive decline and physical disability. However, related changes in large-scale brain interactions remain poorly understood and corresponding non-invasive biomarkers are sparse. We thus compared brain-wide phase- and amplitude-coupling of frequency specific neuronal activity in relapsing-remitting Multiple Sclerosis patients (n = 17) and healthy controls (n = 17) using magnetoencephalography. Changes in this dataset included both, increased and decreased phase- and amplitude-coupling in wide-spread, bilateral neuronal networks across a broad range of frequencies. These changes allowed to successfully classify patients and controls with an accuracy of 84%. Furthermore, classification confidence predicted behavioral scores of disease severity. In sum, our results unravel systematic changes of large-scale phase- and amplitude coupling in Multiple Sclerosis. Furthermore, our results establish a new analysis approach to efficiently contrast high-dimensional neuroimaging data between experimental groups or conditions.

Comparison of Risk Factors, Safety, and Efficacy Outcomes of Mechanical Thrombectomy in Posterior vs. Anterior Circulation Large Vessel Occlusion.

Background and Purpose: It is believed that stroke occurring due to posterior circulation large vessel occlusion (PCLVO) and that occurring due to anterior circulation large vessel occlusion (ACLVO) differ in terms of their pathophysiology and the outcome of their acute management in relation to endovascular mechanical thrombectomy (MT). Limited sample size and few randomized controlled trials (RCTs) with respect to PCLVO make the safety and efficacy of MT, which has been confirmed in ACLVO, difficult to assess in the posterior circulation. We therefore conducted a meta-analysis to study to which extent MT in PCLVO differs from ACLVO. Materials and Methods: We searched the databases PubMed, Cochrane, and EMBASE for studies published between 2010 and January 2021, with information on risk factors, safety, and efficacy outcomes of MT in PCLVO vs. ACLVO and conducted a systematic review and meta-analysis; we compared baseline characteristics, reperfusion treatment profiles [including rates of intravenous thrombolysis (IVT) and onset-to-IVT and onset-to-groin puncture times], recanalization success [Thrombolysis In Cerebral Infarction scale (TICI) 2b/3], symptomatic intracranial hemorrhage (sICH), and favorable functional outcome [modified Rankin Score (mRS) 0-2] and mortality at 90 days. Results: Sixteen studies with MT PCLVO (1,172 patients) and ACLVO (7,726 patients) were obtained from the search. The pooled estimates showed higher baseline National Institutes of Health Stroke Scale (NIHSS) score (SMD 0.32, 95% CI 0.15-0.48) in the PCLVO group. PCLVO patients received less often IVT (OR 0.65, 95% CI 0.53-0.79). Onset-to-IVT time (SMD 0.86, 95% CI 0.45-1.26) and onset-to-groin puncture time (SMD 0.59, 95% CI 0.33-0.85) were longer in the PCLVO group. The likelihood of obtaining successful recanalization and favorable functional outcome at 90 days was comparable between the two groups. PCLVO was, however, associated with less sICH (OR 0.56, 95% CI 0.37-0.85) but higher mortality (OR 1.92, 95% CI 1.46-2.53). Conclusions: This meta-analysis indicates that MT in PCLVO may be comparably efficient in obtaining successful recanalization and 90 day favorable functional outcome just as in ACLVO. Less sICH in MT-treated PCLVO patients might be the result of the lower IVT rate in this group. Higher baseline NIHSS and longer onset-to-IVT and onset-to-groin puncture times may have contributed to a higher 90 day mortality in PCLVO patients.

Structured Reporting of Acute Ischemic Stroke - Consensus-Based Reporting Templates for Non-Contrast Cranial Computed Tomography, CT Angiography, and CT Perfusion. / Strukturierte Befundung beim ischämischen Schlaganfall: Konsensbasierte Befundvorlagen für die native Computertomografie, CT-Angiografie und CT-Perfusion des Neurokraniums.

PURPOSE: Structured reporting is an essential step in establishing standardized quality standards in diagnostic radiology. The German Society of Radiology and the German Society of Neuroradiology aim to provide templates for the structured reporting of different radiological examinations. METHOD: The Information Technology working group of the German Society of Radiology developed structured templates for the radiological reporting of different indications in consensus with specialist support by experts. RESULTS: We present a template for the structured reporting of examinations of patients with acute ischemic stroke by non-contrast computed tomography, CT angiography, and CT perfusion. This template is provided on the website www.befundung.drg.de for free use. CONCLUSION: Implementation of the structured template may increase quality and provide a minimum standard for radiological reports in patients with acute ischemic stroke. KEY POINTS: · The German Society of Radiology and the German Society of Neuroradiology are providing support for the development of structured templates in German.. · We present a template for the structured reporting of examinations of patients with acute ischemic stroke by non-contrast computed tomography, CT angiography, and CT perfusion. This template is provided on the website www.befundung.drg.de for free use.. · Implementation of the structured template may increase quality and provide a minimum standard for radiological reports in patients with acute ischemic stroke.. CITATION FORMAT: · Brendle C, Bender B, Selo N et al. Structured Reporting of Acute Ischemic Stroke - Consensus-Based Reporting Templates for Non-Contrast Cranial Computed Tomography, CT Angiography, and CT Perfusion. Fortschr Röntgenstr 2021; 193: 1315 - 1317.

Cerebrospinal fluid findings in patients with psychotic symptoms-a retrospective analysis.

In current international classification systems (ICD-10, DSM5), the diagnostic criteria for psychotic disorders (e.g. schizophrenia and schizoaffective disorder) are based on symptomatic descriptions since no unambiguous biomarkers are known to date. However, when underlying causes of psychotic symptoms, like inflammation, ischemia, or tumor affecting the neural tissue can be identified, a different classification is used ("psychotic disorder with delusions due to known physiological condition" (ICD-10: F06.2) or psychosis caused by medical factors (DSM5)). While CSF analysis still is considered optional in current diagnostic guidelines for psychotic disorders, CSF biomarkers could help to identify known physiological conditions. In this retrospective, partly descriptive analysis of 144 patients with psychotic symptoms and available CSF data, we analyzed CSF examinations' significance to differentiate patients with specific etiological factors (F06.2) from patients with schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F2). In 40.3% of all patients, at least one CSF parameter was out of the reference range. Abnormal CSF-findings were found significantly more often in patients diagnosed with F06.2 (88.2%) as compared to patients diagnosed with F2 (23.8%, p < 0.00001). A total of 17 cases were identified as probably caused by specific etiological factors (F06.2), of which ten cases fulfilled the criteria for a probable autoimmune psychosis linked to the following autoantibodies: amphiphysin, CASPR2, CV2, LGl1, NMDA, zic4, and titin. Two cases presented with anti-thyroid tissue autoantibodies. In four cases, further probable causal factors were identified: COVID-19, a frontal intracranial tumor, multiple sclerosis (n = 2), and neurosyphilis. Twenty-one cases remained with "no reliable diagnostic classification". Age at onset of psychotic symptoms differed between patients diagnosed with F2 and F06.2 (p = 0.014), with the latter group being older (median: 44 vs. 28 years). Various CSF parameters were analyzed in an exploratory analysis, identifying pleocytosis and oligoclonal bands (OCBs) as discriminators (F06.2 vs. F2) with a high specificity of > 96% each. No group differences were found for gender, characteristics of psychotic symptoms, substance dependency, or family history. This study emphasizes the great importance of a detailed diagnostic workup in diagnosing psychotic disorders, including CSF analysis, to detect possible underlying pathologies and improve treatment decisions.

Point-of-care testing for emergency assessment of coagulation in patients treated with direct oral anticoagulants including edoxaban.

BACKGROUND: Direct oral anticoagulants (DOAC) including edoxaban are increasingly used for stroke prevention in atrial fibrillation. Despite treatment, annual stroke rate in these patients remains 1-2%. Rapid assessment of coagulation would be useful to guide thrombolysis or reversal therapy in this growing population of DOAC/edoxaban-treated stroke patients. Employing the Hemochron™ Signature Elite point-of-care test system (HC-POCT), clinically relevant plasma concentrations of dabigatran and rivaroxaban can be excluded in a blood sample. However, no data exists on the effect of edoxaban on HC-POCT results. We evaluated whether edoxaban plasma concentrations above the current treatment thresholds for thrombolysis or anticoagulation reversal (i.e., 30 and 50 ng/mL) can be ruled out with the HC-POCT. METHODS: We prospectively studied patients receiving a first dose of edoxaban. Six blood samples were collected from each patient: before, 0.5, 1, 2, 8, and 24 h after drug intake. HC-POCT-based INR (HC-INR), activated clotting time (HC-ACT+ and HC-ACT-LR), activated partial thromboplastin time (HC-aPTT), and mass spectrometry for edoxaban plasma concentrations were performed at each time-point. We calculated correlations, receiver operating characteristics (ROC) and test-specific cut-offs for ruling out edoxaban concentrations > 30 and > 50 ng/mL in a blood sample. RESULTS: One hundred twenty blood samples from 20 edoxaban-treated patients were analyzed. Edoxaban plasma concentrations ranged from 0 to 512 ng/mL. HC-INR/HC-ACT+/HC-ACT-LR/HC-aPTT ranged from 0.7-8.3/78-310 s/65-215 s/19-93 s, and Pearson's correlation coefficients showed moderate to very strong correlations with edoxaban concentrations (r = 0.95/0.79/0.70/0.60). With areas under the ROC curve of 0.997 (95% confidence interval: 0.991-0.971) and 0.989 (0.975-1.000), HC-INR most reliably ruled out edoxaban concentrations > 30 and > 50 ng/mL, respectively, and HC-INR results ≤1.5 and ≤ 2.1 provided specificity/sensitivity of 98.6% (91.2-99.9)/98.0% (88.0-99.9) and 96.8% (88.0-99.4)/96.5% (86.8-99.4). CONCLUSIONS: Our study represents the first systematic evaluation of the HC-POCT in edoxaban-treated patients. Applying sufficiently low assay-specific cut-offs, the HC-POCT may not only be used to reliably rule out dabigatran and rivaroxaban, but also very low edoxaban concentrations in a blood sample. Because the assay-specific cut-offs were retrospectively defined, further investigation is warranted. TRIAL REGISTRATION: ClinicalTrials.gov, registration number: NCT02825394 , registered on: 07/07/2016, URL.

Early corticospinal tract damage in prodromal SCA2 revealed by EEG-EMG and EMG-EMG coherence.

OBJECTIVE: Clinical data suggest early involvement of the corticospinal tract (CST) in spinocerebellar ataxia type 2 (SCA2). Here we tested if early CST degeneration can be detected in prodromal SCA2 mutation carriers by electrophysiological markers of CST integrity. METHODS: CST integrity was tested in 15 prodromal SCA2 mutation carriers, 19 SCA2 patients and 25 age-matched healthy controls, using corticomuscular (EEG-EMG) and intermuscular (EMG-EMG) coherence measures in upper and lower limb muscles. RESULTS: Significant reductions of EEG-EMG and EMG-EMG coherences were observed in the SCA2 patients, and to a similar extent in the prodromal SCA2 mutation carriers. In prodromal SCA2, EEG-EMG and EMG-EMG coherences correlated with the predicted time to ataxia onset. CONCLUSIONS: Findings indicate early CST neurodegeneration in SCA2. EEG-EMG and EMG-EMG coherence may serve as biomarkers of early CST neurodegeneration in prodromal SCA2 mutation carriers. SIGNIFICANCE: Findings are important for developing preclinical disease markers in the context of currently emerging disease-modifying therapies of neurodegenerative disorders.

Corticomuscular Coherence: a Novel Tool to Assess the Pyramidal Tract Dysfunction in Spinocerebellar Ataxia Type 2.

Clinical signs of corticospinal tract dysfunction are a common feature of spinocerebellar ataxia type 2 (SCA2) patients. The objective of this study is to assess dysfunction of the corticospinal tract in SCA2 using corticomuscular coherence. Testing corticomuscular coherence and rating of ataxia severity and non-ataxia symptoms were performed in 19 SCA2 patients and 24 age-matched controls. Central motor conduction times (CMCT) to upper and lower right limbs were obtained for the SCA2 group using Transcraneal magnetic stimulation (TMS). SCA2 patients exhibited a significant reduction of corticomuscular coherence for lower limbs, but not for upper limbs. This difference remained significant, even when excluding those individuals with clinical signs of corticospinal tract dysfunction. Corticomuscular coherence for lower limbs correlated inversely with CMCT to tibialis anterior muscle. Corticomuscular coherence could be a valuable electrophysiological tool to assess the corticospinal tract involvement in SCA2, even in the absence of clinical signs of corticospinal tract dysfunction.

Concurrent TMS-fMRI Reveals Interactions between Dorsal and Ventral Attentional Systems.

Adaptive behavior relies on combining bottom-up sensory inputs with top-down control signals to guide responses in line with current goals and task demands. Over the past decade, accumulating evidence has suggested that the dorsal and ventral frontoparietal attentional systems are recruited interactively in this process. This fMRI study used concurrent transcranial magnetic stimulation (TMS) as a causal perturbation approach to investigate the interactions between dorsal and ventral attentional systems and sensory processing areas. In a sustained spatial attention paradigm, human participants detected weak visual targets that were presented in the lower-left visual field on 50% of the trials. Further, we manipulated the presence/absence of task-irrelevant auditory signals. Critically, on each trial we applied 10 Hz bursts of four TMS (or Sham) pulses to the intraparietal sulcus (IPS). IPS-TMS relative to Sham-TMS increased activation in the parietal cortex regardless of sensory stimulation, confirming the neural effectiveness of TMS stimulation. Visual targets increased activations in the anterior insula, a component of the ventral attentional system responsible for salience detection. Conversely, they decreased activations in the ventral visual areas. Importantly, IPS-TMS abolished target-evoked activation increases in the right temporoparietal junction (TPJ) of the ventral attentional system, whereas it eliminated target-evoked activation decreases in the right fusiform. Our results demonstrate that IPS-TMS exerts profound directional causal influences not only on visual areas but also on the TPJ as a critical component of the ventral attentional system. They reveal a complex interplay between dorsal and ventral attentional systems during target detection under sustained spatial attention. SIGNIFICANCE STATEMENT: Adaptive behavior relies on combining bottom-up sensory inputs with top-down attentional control. Although the dorsal and ventral frontoparietal systems are key players in attentional control, their distinct contributions remain unclear. In this TMS-fMRI study, participants attended to the left visual field to detect weak visual targets presented on half of the trials. We applied brief TMS bursts (or Sham-TMS) to the dorsal intraparietal sulcus (IPS) 100 ms after visual stimulus onset. IPS-TMS abolished the visual induced response suppression in the ventral occipitotemporal cortex and the response enhancement to visual targets in the temporoparietal junction. Our results demonstrate that IPS causally influences neural activity in the ventral attentional system 100 ms poststimulus. They have important implications for our understanding of the neural mechanisms underlying attentional control.