While subarachnoid hemorrhage is the second most common hemorrhagic stroke in epidemiologic studies, the recent DISCHARGE-1 trial has shown that in reality, three-quarters of focal brain damage after subarachnoid hemorrhage is ischemic. Two-fifths of these ischemic infarctions occur early and three-fifths are delayed. The vast majority are cortical infarcts whose pathomorphology corresponds to anemic infarcts. Therefore, we propose in this review that subarachnoid hemorrhage as an ischemic-hemorrhagic stroke is rather a third, separate entity in addition to purely ischemic or hemorrhagic strokes. Cumulative focal brain damage, determined by neuroimaging after the first 2weeks, is the strongest known predictor of patient outcome half a year after the initial hemorrhage. Because of the unique ability to implant neuromonitoring probes at the brain surface before stroke onset and to perform longitudinal MRI scans before and after stroke, delayed cerebral ischemia is currently the stroke variant in humans whose pathophysiological details are by far the best characterized. Optoelectrodes located directly over newly developing delayed infarcts have shown that, as mechanistic correlates of infarct development, spreading depolarizations trigger (1) spreading ischemia, (2) severe hypoxia, (3) persistent activity depression, and (4) transition from clustered spreading depolarizations to a negative ultraslow potential. Furthermore, traumatic brain injury and subarachnoid hemorrhage are the second and third most common etiologies of brain death during continued systemic circulation. Here, we use examples to illustrate that although the pathophysiological cascades associated with brain death are global, they closely resemble the local cascades associated with the development of delayed cerebral infarcts.

BackgroundFetal alcohol syndrome (FAS) can result in cognitive dysfunction. Cognitive functions affected are subserved by few functional brain networks. Functional connectivity (FC) in these networks can be assessed with resting-state functional MRI (rs-fMRI). Alterations of FC have been reported in children and adolescents prenatally exposed to alcohol. Previous reports varied substantially regarding the exact nature of findings. The purpose of this study was to assess FC of cognition-related networks in young adults with FAS.MethodsCross-sectional rs-fMRI study in participants with FAS (n = 39, age: 20.9 ± 3.4 years) and healthy participants without prenatal alcohol exposure (n = 44, age: 22.2 ± 3.4 years). FC was calculated as correlation between cortical regions in ten cognition-related sub-networks. Subsequent modelling of overall FC was based on linear models comparing FC between FAS and controls. Results were subjected to a hierarchical statistical testing approach, first determining whether there is any alteration of FC in FAS in the full cognitive connectome, subsequently resolving these findings to the level of either FC within each network or between networks based on the Higher Criticism (HC) approach for detecting rare and weak effects in high-dimensional data. Finally, group differences in single connections were assessed using conventional multiple-comparison correction. In an additional exploratory analysis, dynamic FC states were assessed.ResultsComparing FAS participants with controls, we observed altered FC of cognition-related brain regions globally, within 7 out of 10 networks, and between networks employing the HC statistic. This was most obvious in attention-related network components. Findings also spanned across subcomponents of the fronto-parietal control and default mode networks. None of the single FC alterations within these networks yielded statistical significance in the conventional high-resolution analysis. The exploratory time-resolved FC analysis did not show significant group differences of dynamic FC states.ConclusionsFC in cognition-related networks was altered in adults with FAS. Effects were widely distributed across networks, potentially reflecting the diversity of cognitive deficits in FAS. However, no altered single connections could be determined in the most detailed analysis level. Findings were pronounced in networks in line with attentional deficits previously reported.

BackgroundAnti-NMDA-receptor GluN1 antibodies (NMDAR1-abs) are present in an autoimmune encephalitis with severe neuropsychiatric symptoms. We aimed to estimate the impact of serum NMDAR1-abs on depressive symptoms years after first-ever ischemic stroke (IS). MethodsData were used from the PROSpective Cohort with Incident Stroke-Berlin (PROSCIS-B; NCT01363856). Serum NMDAR1-abs (IgM/IgA/IgG) were measured within 7 days after IS using cell-based assays. We defined seropositivity as titers ≥1:10, thereof low titers as ≤1:100 and high titers as >1:100. We used the Center for Epidemiological Studies–Depression (CES-D) scale to measure depressive symptoms at year one, two and three following IS. We calculated crude and confounder adjusted weighted generalized linear models to quantify the impact of NMDAR1-abs on CES-D assessed at three annual time-points. ResultsNMDAR1-abs were measured in 583 PROSCIS-B IS patients (mean age = 67 [SD = 13]; 42%female; median NIHSS = 2 [IQR = 1–4]) of whom 76 (13%; IgM: n = 49/IgA: n = 43/IgG: n = 2) were seropositive, 55 (9%) with low and 21 (4%) with high titers. CES-D regarded over all follow-up time-points was higher in seropositive patients (βcrude = 2.56 [95%CI = −0.34 to 5.45]; βadjusted = 2.26 [95%CI = −0.68 to 5.20]) and effects were highest in patients with high titer (low titers: βcrude = 1.42 [95%CI = −1.79 to 4.62], βadjusted = 0.53 [95%CI = −2.47 to 3.54]; high titers: βcrude = 5.85 [95%CI = 0.20 to 11.50]; βadjusted = 7.20 [95%CI = 0.98 to 13.43]). ConclusionPatients with serum NMDAR1-abs (predominantly IgM&IgA) suffer more severe depressive symptoms after mild-to-moderate IS compared to NMDAR1-abs seronegative patients.

Certification of centers for weaning from aventilator in neurological neurosurgical early rehabilitation (NNER) by the German Society for Neurorehabilitation (DGNR) is possible since 1 October 2021. The results of certification of facilities in the first year after starting the procedure are presented. As part of the certification process 28criteria are assessed including aset of mandatory characteristics of the facility. The criteria are divided into structural criteria (i = 7), diagnostic criteria (i = 6), personnel criteria (i = 3), internal organization criteria (i = 7), and quality management criteria (i = 5). A total of 13 centers were certified in the first year, with acombined total of 283 beds for weaning from aventilator in the NNER and served 2278 persons to be weaned from aventilator in the year before certification, with amedian of 134 per facility (range 44-414). Only rarely was weaning unsuccessful, requiring conversion to home mechanical ventilation before discharge (invasive home mechanical ventilation median per facility 10persons, range 2-25; non-invasive home mechanical ventilation median 0persons, range 0-57). Ahigh level of process and structural quality was documented for the certified centers: across all areas of assessment, the individual certification criteria were met in the vast majority of cases (median degree of complete fulfilment 86%) or met with improvement potentials documented by the auditors (median 11%). Successful weaning in NNER and ahigh level of process and structural quality can be demonstrated by the certification results of centers that follow this integrative approach to weaning from aventilator in aNNER setting.

BackgroundThere is no assessment of the effects regarding the decision of the Federal Joint Committee from April 19th, 2018 which demands a central and interdisciplinary emergency room system under the control of a professionally and organizationally independent administration. The aim of this study was to solicit the current opinion of leading orthopedic surgeons regarding the above-mentioned decision. Material and methodsAn online questionnaire was sent to all 731 members of the Verband Leitender Orthopäden und Unfallchirurgen (www.vlou.de) to compare the opinion of these leading physicians on their current and future emergency room system. ResultsThe majority of the 179 responding surgeons consider emergency room systems with primary treatment of orthopedic patients by orthopedic surgeons in certain aspects to be more appropriate suitable than systems without such primary treatment. It is also not yet clear how work-related accidents should be treated according to the specifications of the German statutory accident insurance (DGUV®). The provision of training content could become more difficult if the ER rotation of orthopedic surgeons is not any longer part of these new ER concepts. ConclusionThe consequences of the decision of the Federal Joint Committee from April 19th, 2018 need to be reevaluated continuously and, if necessary, optimised accordingly, taking into account competing requirements, such as training regulations and the SGB VII.

IntroductionPatients with neurological or neurosurgical disease can suffer from impaired cough, which may result in life-threatening retention of tracheobronchial secretions, atelectasis, pneumonia and finally death. Due to a lack of alternatives and pathophysiological plausibility, the application of mechanical insufflation-exsufflation (MI-E) has already become international standard care in neuromuscular disease and spinal cord injury although a lack of evidence for efficacy. High-quality studies to support the use of MI-E in neurological and neurosurgical patients during weaning from mechanical ventilation are missing. The goal of this exploratory study is to display the effect size of MI-E intervention on the duration of mechanical ventilation and additional outcomes.Methods and analysisOne hundred adult patients with a cough deficiency or retention of secretion admitted to a neurological intensive care unit (ICU) are planned to be recruited for this randomised controlled trial. Patients are randomised 1:1 to receive either MI-E or best standard care. Observation will take place until discharge from the hospital, death or end of the study period. The primary endpoint of this trial is the duration of mechanical ventilation from randomisation until successful weaning. The outcome will be analysed with Kaplan-Meier estimation and competing risks analyses. Secondary endpoint is the proportion of patients with successful weaning. Further outcomes will include the incidence of hospital-acquired pneumonia, mortality, decannulation rate, length of stay on the ICU and the total score of the Glasgow Coma Scale.Ethics and disseminationThe study was approved by the Medical Ethics Committee of the University of Oldenburg. The findings of this study will be submitted for publication in a peer-reviewed journal.Trial registration numberDRKS00020981.

AbstractBackgroundFetal Alcohol Syndrome (FAS) can result in substantial cognitive dysfunction. Many of the cognitive functions affected are subserved by few functional brain networks. Functional connectivity (FC) in these networks can be assessed with resting state functional MRI (rs-fMRI). Alterations of FC have been reported in children and adolescents prenatally exposed to alcohol. However, previous reports varied substantially regarding which exact cognitive networks were affected, their interactions, and the directionalities of FC alterations. Despite persisting deficits, no previous studies have examined FC in older individuals. Purpose of this rs-fMRI study was to assess FC within and between cognition-related networks in young adults with FAS.MethodsCross-sectional study in patients with FAS (n = 39, age: 20.9 ± 3.4 years) and controls without prenatal alcohol exposure (n = 44, age: 22.2 ± 3.4 years). FC was calculated as correlation between cortical regions in ten cognition-related sub-networks. Subsequent modelling of overall FC was based on two-tailed t-tests comparing FC between FAS and controls. Results were subjected to a hierarchical statistical testing approach, first determining whether there is any alteration of FC in FAS (compared with controls) in the full cognitive connectome, subsequently resolving these findings to the level of either FC within each network or between networks, and finally to individual connections. The overall and network-level tests are based on the Higher Criticism (HC) approach for the detection of rare and week effects in high dimensional data. In an additional exploratory time- resolved FC analysis, potential group differences of dynamic FC states were assessed.ResultsComparing FAS subjects with controls, we observed altered FC of cognition-related brain regions globally, within 7 out of 10 networks, and between networks employing the HC statistic. This was most obvious in the dorsal attention A sub-network, followed by the salience / ventral attention A subnetwork. Findings also spanned subcomponents of the fronto-parietal control and default mode networks. None of the single FC alterations within these networks yielded statistical significance in the final high-resolution analysis. The exploratory time-resolved FC analysis did not show significant group differences in the temporal behavior of FC states.ConclusionsFC in cognition-related brain networks was altered in adults with FAS. Effects were widely distributed across these networks, potentially reflecting the diversity of cognitive deficits in these individuals. Findings were pronounced in attention-related networks in line with attentional deficits previously reported. An additional exploratory time-resolved FC analysis did not reveal altered dynamic FC patterns.