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Aims: Urochloa species are the most planted forage used for cattle production in the tropics. Plant-bacteria interaction is cultivar dependent, and a better understanding of this fine-tuning can be useful to improve the plant growth benefits of this association. Therefore, the current study aimed at testing the performance of six Urochloa cultivars inoculated with α (Azospirillum baldaniorum Ab-Sp245 and Nitrospirillum amazonense Na-CBAmC) and β (Herbaspirillum seropedicae Hs-HRC54) Proteobacteria by evaluating plant initial growth and root colonization. Methods: Three experiments using Hoagland's solution, with and without N as nitrate (0-, 0.3-, and 3-mM N) and a pot experiment using soil with 0, 30, and 60 kg ha−1 of urea measured after two harvests were described. The root colonization pattern of AFP-labelled Ab-Sp245 and Hs-HRC54 in four cultivars was studied by confocal laser scanning microscope. A randomized block design evaluated biomass accumulation, roots analysis, bacterial colonization, and N, P and K accumulation. Results: The root architecture was modified according to the strain used and Ab-Sp245 was the one with the highest growth response, especially at N middle level. This bacterium revealed a wide colonization pattern on the cultivars' roots, except cv. Llanero. The bacterial response was dependent on the bacterial strain, plant cultivar, and nitrogen supply. Conclusions: From the results shown, we predict that Urochloa pastures limited in N supply will benefit if inoculation using a selected strain is applied as a seed cover. Benefits can be visualized by higher biomass production and N accumulated in a shorter period of growth. [ABSTRACT FROM AUTHOR]

The adoption of bioinputs in agriculture has aroused great interest in recent years and, in this scenario, the inoculation of crops with synthetic microbial communities (SynComs) has shown to be promising. In sugarcane crop, inoculation with nitrogen-fixing bacteria (NFB) in consortium with arbuscular mycorrhizal fungi (AMF) has shown positive results on plant development and nutrition. However, considering that the microbiota plays a fundamental role in the growth and health of the host plant, especially the endophytes, which are closely associated, few studies have explored the effects of SynCom inoculation on the endophytic microbiota of sugarcane. This study aimed to evaluate the impact of SynCom inoculation on the structure of the endophytic microbiota of sugarcane. The results of the analyses revealed that the microbiota diversity remained unchanged due to the inoculation treatment, while differences in microbial communities were found between the two evaluated commercial cultivars, RB867515 and RB92579, and between the two plant organs, roots and culms, under field conditions at the end of the first crop growth cycle (~360 days). Furthermore, microbes specifically detected in roots or culms present potential valuable applications in sugarcane cultivation in the future. Altogether, our data support that the inoculated microorganisms exerted their beneficial effects during the initial stages of plant development, which opens up space for new research with SynComs in these primordial stages of cane cropping. • Inoculation of a SynCom onto sugarcane does not alter its microbiota after 360 days. • There are differences in alpha diversity of bacteria between two commercial cultivars. • There are differences in beta diversity of bacteria and fungi between roots and stems. [ABSTRACT FROM AUTHOR]

Nitrospirillum amazonense is a nitrogen-fixing bacterium that shows potential to promote plant growth when inoculated into sugarcane and rice plants. This microorganism has been the subject of biochemical and genetic characterization to elucidate important functions related to host plant interaction and growth promotion, including the determination of draft genome sequences of two strains, Y2 and CBAmC, the second of which is the aim of the present study. CBAmC has been isolated from sugarcane (Saccharum spp.), and is currently used in a sugarcane consortium inoculant with four other nitrogen-fixing bacterial strains. The present paper describes a significant improvement in the genome sequence and assembly for the N. amazonense strain CBAmC, and determination for the first time of a complete genome sequence for this bacterial species, using PacBio technology. The analysis of the genomic data obtained allowed the discovery of genes coding for metabolic pathways and cellular structures that may be determinant for the success of the bacterial establishment and colonization into the host sugarcane plant, besides conferring important characteristics to the inoculant. These include genes for the use of sucrose and N-glycans, biosynthesis of autoinducer molecules, siderophore production and acquisition, auxin and polyamine biosynthesis, flagellum, σ-fimbriae, a variety of secretion systems, and a complete denitrification system. Concerning genes for nitrogenase and auxiliary proteins, it was possible to corroborate literature data that in N. amazonense these probably had originated from horizontal gene transfer, from bacteria of the Rhizobiales order. The complete genomic sequence of the CBAmC strain of N. amazonense revealed that the bacterium harbors four replicons, including three chromosomes and one chromid, a profile that coincides with that of other two strains, according to literature data, suggesting that as a replicon pattern for the species. Finally, results of phylogenomic analyses in this work support the recent reclassification of the species, separating it from the Azospirillum genus. More importantly, results of the present work shall guide subsequent studies on strain CBAmC as well as the development of a sugarcane inoculant. [ABSTRACT FROM AUTHOR]

Gluconacetobacter diazotrophicus is a nitrogen-fixing, endophytic bacterium that has the potential to promote plant growth and increase yield. Genetically modified strains might get more benefits to host plants, including through expression of useful proteins, such as Cry toxins from B. thuringiensis, or enzymes involved in phytohormone production, proteins with antagonistic activity for phytopathogens, or that improve nutrient utilization by the plant. For that, expression systems for G. diazotrophicus are needed, which requires active promoters fused to foreign (or innate) genes. This article describes the construction of a G. diazotrophicus PAL5 promoter library using a promoter-less lacZ-bearing vector, and the identification of six active promoters through β-galactosidase activity assays, sequencing and localization in the bacterial genome. The characterized promoters, which are located on distinct regions of the bacterial genome and encoding either sense or antisense transcripts, present variable expression strengths and might be used in the future for expressing useful proteins. [ABSTRACT FROM AUTHOR]

Hypothermia and its possible neuroprotective effects have been investigated in different conditions of acute ischemic stroke, including awake patients and patients undergoing hemicraniectomy due to malignant middle cerebral artery infarction. For acute ischemic stroke patients with large vessel occlusion, EVT is a highly effective therapy [4] and therefore detection of additional therapy effects in EVT patients might be difficult. It well may be that inadvertent hypothermia in this patient cohort is a surrogate marker for worse medical pre-condition and more severely affected stroke patients, as hypothermia was associated with older age and use of general anesthesia for EVT. [Extracted from the article]

Introduction: Sonography in classical nerve entrapment syndromes is an established and validated method. In contrast, few publications highlight lesions of the radial nerve, particularly of the posterior interosseus nerve (PIN). Method: Five patients with a radial nerve lesion were investigated by electromyography, nerve conduction velocity and ultrasound. Further normative values of 26 healthy subjects were evaluated. Results: Four patients presented a clinical and electrophysiological proximal axonal radial nerve lesion and one patient showed a typical posterior interosseous nerve syndrome (PINS). The patient with PINS presented an enlargement of the PIN anterior to the supinator muscle. However four patients with proximal lesions showed an unexpected significant enlargement of the PIN within the supinator muscle. Conclusion: High-resolution sonography is a feasible method to demonstrate the radial nerve including its distal branches. At least in axonal radial nerve lesions, sonography might reveal abnormalities far distant from a primary proximal lesion site clearly distinct from the appearance in classical PINS. [ABSTRACT FROM AUTHOR]

Background The magnitude of treatment effect in acute stroke depends on several factors, including time from symptom onset (TFSO) to treatment and severity of the initial insult.Objective To report further evaluation of NeuroFlo therapy, focusing on the effect of time and stroke severity. Methods SENTIS was a prospective randomized trial (N=515) comparing standard medical therapy with/without NeuroFlo therapy. For this analysis, we evaluated outcomes in groups of patients based on TFSO and stroke severity: patients randomized <6 h, 6-10 h, and >10 h with mild (NIHSS<8), moderate (8-14), and severe (>14) symptoms at randomization. 90-Day mRS (modified Rankin Scale) scores and stroke-related death rates were compared between treatment groups. Results For patients randomized <6 h TFSO (n=128),the OR for mRS 0-2 was 3.11 (CI 1.30 to 7.46, p=0.011) for treated versus non-treated patients. In patients with disease of moderate severity (NIHSS 8-14, n=214), NeuroFlo-treated patients were more likely to have a good outcome (mRS 0-2; OR=1.84, CI 1.02 to 3.33, p=0.043). The stroke-related death rate was better in the treated group with TFSO >10 h and NIHSS >14(n=42) (OR=7.10, CI 1.13 to 44.55, p=0.036). Conclusions The results of our analysis support the importance of careful selection of outcome measures and the impact that rapid treatment and initial stroke severity have on outcome. Clinical trial registration URL://http.clinicaltrials.gov.Unique identifier: NCT00119717. [ABSTRACT FROM AUTHOR]

Posterior reversible encephalopathy syndrome (PRES) is characterized by headache, altered mental status, visual disturbances, and seizures. Radiological features typically include edema of the posterior cerebral regions, especially of the parietooccipital lobes. Atypical imaging features, such as involvement of anterior cerebral regions, deep white matter, and the brain stem are also frequently seen. Vasoconstriction is common in vascular imaging. Different conditions have been associated with PRES, but toxemia of pregnancy, solid organ or bone marrow transplantation, immunosuppressive treatment, cancer chemotherapy, autoimmune diseases, and hypertension are most commonly described. The pathophysiology of PRES is unclear and different hypotheses are being discussed. Posterior reversible encephalopathy syndrome is best managed by monitoring and treatment in the setting of a neurointensive care unit. The prognosis is usually benign with complete reversal of clinical symptoms within several days, when adequate treatment is immediately initiated. Treatment of severe hypertension, seizures, and withdrawal of causative agents represent the hallmarks of specific therapy in PRES. Delay in diagnosis and treatment may lead to permanent neurological sequelae. Therefore, awareness of PRES is of crucial importance for the intensivist. [ABSTRACT FROM PUBLISHER]

Abstract: The Cydia pomonella granulovirus (CpGV) is deployed worldwide in commercial (organic) apple orchards to control the pest codling moth (Cydia pomonella). Due to its strong UV sensitiveness and its low uptake the encapsulation of the untreated CpGV within an organic matrix together with admixed UV protectants and phago-stimulants is needed. The Particles from Gas Saturated Solutions (PGSS) process was further developed in order to meet the requirements for the encapsulation of the CpGV with respect to temperature sensitivity and environmental compatibility. The produced virus-loaded microcapsules are characterized by scanning electron microscopy (SEM), laser diffraction, and UV spectroscopy. Finally, the efficiency and sprayability of the encapsulated CpGV formulation as biological plant protection agent were successfully verified in laboratory bioassays. [Copyright &y& Elsevier]

Summary: Space-occupying, malignant middle cerebral artery (MCA) infarctions are still one of the most devastating forms of ischaemic stroke, with a mortality of up to 80% in untreated patients. An early diagnosis is essential and depends on CT and MRI to aid the prediction of a malignant course. Several pharmacological strategies have been proposed but the efficacy of these approaches has not been supported by adequate evidence from clinical trials and, until recently, treatment of malignant MCA infarctions has been a major unmet need. Over the past 3 years, results from randomised controlled trials and their pooled analyses have provided evidence that an early hemicraniectomy leads to a substantial decrease in mortality at 6 and 12 months and is likely to improve functional outcome. Hemicraniectomy is now in routine use for the clinical management of malignant MCA infarction in patients younger than 60 years of age. However, there are still important questions about the individual indication for decompressive surgery, particularly with regard to the ideal timing of hemicraniectomy, a potential cut-off age for the procedure, the hemisphere affected, and ethical considerations about functional outcome in surviving patients. [Copyright &y& Elsevier]

Abstract: Acetylsalicylic acid (ASA; Aspirin) has a neuroprotective potential by its anti-excitotoxic and anti-inflammatory effects. A temporary middle cerebral artery occlusion (tMCAO) model was used in 80 Wistar rats to evaluate whether a high dose of Aspirin (40 mg/kg) applied with different initiation time points after stroke onset (30 min, 3 h, 6 h, 12 h, 20 rats for each time group) and followed by repeated administration (1, 2 and 3 days) is neuroprotective. Neurological score and brain infarct volume were analyzed and indicated that postischemic therapy initiation at 30 min and as late as 6 h led to better neurological recovery (6 h, p =0.0046) and significant smaller infarct size (6 h, 57±9 mm3, n =10, p =0.0043) compared to the saline control group (110±13 mm3, n =10). Thus, there may be a relatively wide time window for acute stroke therapy with high dose Aspirin. [Copyright &y& Elsevier]

Random mutagenesis using transposons with promoterless reporter genes has been widely used to examine differential gene expression patterns in bacteria. Using this approach, we have identified 26 genes of the endophytic nitrogen-fixing bacterium Herbaspirillum seropedicae regulated in response to ammonium content in the growth medium. These include nine genes involved in the transport of nitrogen compounds, such as the high-affinity ammonium transporter AmtB, and uptake systems for alternative nitrogen sources; nine genes coding for proteins responsible for restoring intracellular ammonium levels through enzymatic reactions, such as nitrogenase, amidase, and arginase; and a third group includes metabolic switch genes, coding for sensor kinases or transcription regulation factors, whose role in metabolism was previously unknown. Also, four genes identified were of unknown function. This paper describes their involvement in response to ammonium limitation. The results provide a preliminary profile of the metabolic response of Herbaspirillum seropedicae to ammonium stress. [ABSTRACT FROM AUTHOR]

Herbaspirillum seropedicae is an endophytic bacterium that fixes nitrogen under microaerophilic conditions. The putative promoter sequences glnAp1 (σ70-dependent) and glnAp2 (σ54), and two NtrC-binding sites were identified upstream from the glnA, ntrB and ntrC genes of this microorganism. To study their transcriptional regulation, we used lacZ fusions to the H. seropedicae glnA gene, and the glnA-ntrB and ntrB-ntrC intergenic regions. Expression of glnA was up-regulated under low ammonium, but no transcription activity was detected from the intergenic regions under any condition tested, suggesting that glnA, ntrB and ntrC are co-transcribed from the promoters upstream of glnA. Ammonium regulation was lost in the ntrC mutant strain. A point mutation was introduced in the conserved –25/–24 dinucleotide (GG→TT) of the putative σ54-dependent promoter (glnAp2). Contrary to the wild-type promoter, glnA expression with the mutant glnAp2 promoter was repressed in the wild-type strain under low ammonium levels, but this repression was abolished in an ntrC background. Together our results indicate that the H. seropedicae glnAntrBC operon is regulated from two functional promoters upstream from glnA, which are oppositely regulated by the NtrC protein. [ABSTRACT FROM AUTHOR]

The article reflects on the conditions of neurological, neurosurgical and neuro-intensive care units (NICU) of Germany. Topics include the lack of industry-sponsored trials of neuro critical care, a survey on admission diagnoses, use of standard operating procedures, protocols and modalities of multimodal neuromonitoring in German hospitals, as of April 2014 and initiation of neuro-monitoring (NM) due to traumatic brain injury and rise in intracranial pressure (ICP) or coma.

Acute ischemic stroke (AIS) is a leading global cause of mortality and morbidity. Improving long-term outcome predictions after thrombectomy can enhance treatment quality by supporting clinical decision-making. With the advent of interpretable deep learning methods in recent years, it is now possible to develop trustworthy, high-performing prediction models. This study introduces an uncertainty-aware, graph deep learning model that predicts endovascular thrombectomy outcomes using clinical features and imaging biomarkers. The model targets long-term functional outcomes, defined by the three-month modified Rankin Score (mRS), and mortality rates. A sample of 220 AIS patients in the anterior circulation who underwent endovascular thrombectomy (EVT) was included, with 81 (37%) demonstrating good outcomes (mRS ≤ 2). The performance of the different algorithms evaluated was comparable, with the maximum validation under the curve (AUC) reaching 0.87 using graph convolutional networks (GCN) for mRS prediction and 0.86 using fully connected networks (FCN) for mortality prediction. Moderate performance was obtained at admission (AUC of 0.76 using GCN), which improved to 0.84 post-thrombectomy and to 0.89 a day after stroke. Reliable uncertainty prediction of the model could be demonstrated. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of unknown etiology that affects the central nervous system and can lead to neurological impairment. Our aim was to determine whether MS patients also show inflammatory changes in the oral cavity more frequently than healthy individuals. For this purpose, we examined plaque samples for various mediators and their correlation with clinical findings. A study group (MS) and a control group were examined and compared. The plaque samples were analyzed for the expression of interleukins (IL-2, -6, -10), matrix metalloproteinases (MMP-7, MMP-9), and a surface antigen CD90 by quantitative real-time PCR. The clinical parameters examined were the Mombelli plaque index; bleeding on probing (BOP) index; periodontal pocket depth; and decayed, missing, and filled tooth (DMFT) index. The expression of MMP9 was significantly (p = 0.035) higher in the control group. The expression of IL-2 was increased four-fold in the MS group; however, this difference was not statistically significant. The mean PD (p < 0.001) and BOP index (p = 0.029) values were increased in the study group. The clinical parameters of the BOP index and PD were significantly amplified in the MS patients. However, no causal relationship between the investigated inflammatory mediators and the clinical findings could be established in this case series. [ABSTRACT FROM AUTHOR]

The extracellular space in plants, termed the apoplast, has a pH and sugar content that enables bacterial growth and represents a possible niche for the establishment of endophytic bacteria. Previous studies have investigated the effects of diazotrophic bacteria inoculation in sugarcane varieties, but it has not yet been analyzed how the microbial community of apoplast fluid of sugarcane is affected. High-throughput next generation sequencing of the 16S rRNA gene was used throughout this study to determine the effect of inoculation with a diazotrophic bacteria consortium, previously isolated from sugarcane, on the native bacterial population of sugarcane variety RB867515 grown in the field. The analyses were carried out 450 days after inoculation. The results revealed the presence of 22 phyla, with predominance of Proteobacteria phylum. It was observed that the inoculated consortium changed the indigenous bacterial community structure of sugarcane apoplast fluid by decreasing diversity and evenness, interfering in the composition of rare species. Microbial community composition analysis revealed differences between treatments. The differential abundance test showed there were 43 amplicon sequence variants (ASVs) which were relatively more abundant in the inoculated treatment, with predominance of the Sphingomonas genus. The predicted functions of the most abundant ASVs revealed the presence of genera related to plant growth promotion and protection against phytopathogens. Analysis to evaluate the occurrence of inoculated strains in the recovered data was not conclusive since the ASVs taxonomically close to the inoculated bacteria were observed in low abundance. The present study is the first report to elucidate the bacterial community in sugarcane apoplast fluid using a culture-independent approach. It demonstrated that the diazotrophic bacterial consortium interferes in the natural bacterial community in sugarcane variety RB867515. [ABSTRACT FROM AUTHOR]

Background and purpose: Sarcoidosis is a granulomatous disease of unknown etiology affecting the central nervous system in up to 15% of the patients. Diagnosis of neurosarcoidosis is very challenging due to the heterogeneity of its clinical manifestation. This study intended to evaluate the distribution of cerebral lesion sites and the potential presence of specific lesion clusters in neurosarcoidosis patients using voxel-based lesion symptom mapping (VLSM). Methods: Patients with neurosarcoidosis were retrospectively identified and included between 2011 and 2022. Cerebral lesion sites were correlated voxel-wise with presence and absence of neurosarcoidosis using non-parametric permutation test. Multiple sclerosis patients served as controls for the VLSM-analysis. Results: Thirty-four patients (mean age 52 ± 15 years) of whom 13 were diagnosed with possible, 19 with probable and 2 with confirmed neurosarcoidosis were identified. Lesion overlap of neurosarcoidosis patients demonstrated a distribution of white matter lesions in all brain areas, with a periventricular predilection similar to multiple sclerosis. In contrast to multiple sclerosis controls, no propensity for lesions in proximity of the corpus callosum was observed. Neurosarcoidosis lesions appeared smaller and lesion volume was lower in the neurosarcoidosis cohort. The VLSM analysis showed minor associations between neurosarcoidosis and damaged voxels in the bilateral frontobasal cortex. Conclusions: The VLSM analysis yielded significant associations in the bilateral frontal cortex, suggesting that leptomeningeal inflammatory disease with following cortical involvement is a quite specific feature in neurosarcoidosis. Lesion load was lower in neurosarcoidosis than in multiple sclerosis. However, no specific pattern of subcortical white matter lesions in neurosarcoidosis was revealed. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic hypothermia is a promising candidate for stroke treatment although its efficacy has not yet been demonstrated in patients. Changes in blood molecules could act as surrogate markers to evaluate the efficacy and safety of therapeutic cooling. Methods: Blood samples from 54 patients included in the EuroHYP‐1 study (27 treated with hypothermia, and 27 controls) were obtained at baseline, 24 ± 2 h, and 72 ± 4 h. The levels of a panel of 27 biomarkers, including matrix metalloproteinases and cardiac and inflammatory markers, were measured. Results: Metalloproteinase‐3 (MMP‐3), fatty‐acid‐binding protein (FABP), and interleukin‐8 (IL‐8) increased over time in relation to the hypothermia treatment. Statistically significant correlations between the minimum temperature achieved by each patient in the hypothermia group and the MMP‐3 level measured at 72 h, FABP level measured at 24 h, and IL‐8 levels measured at 24 and 72 h were found. No differential biomarker levels were observed in patients with poor or favorable outcomes according to modified Rankin Scale scores. Conclusion: Although the exact roles of MMP3, FABP, and IL‐8 in hypothermia‐treated stroke patients are not known, further exploration is needed to confirm their roles in brain ischemia. [ABSTRACT FROM AUTHOR]

Background and purpose: Previous studies in neurological emergency rooms (nERs) have reported many non‐acute, self‐presenting patients, patients with delayed presentation of stroke, and frequent visits of persons with seizures (PWS). The aim of this study was to evaluate trends during the last decade, with special focus on PWS. Methods: We retrospectively analyzed patients who presented to our specialized nER during the course of 5 months in 2017 and 2019, and included information on admission/referral, hospitalization, discharge diagnosis, and diagnostic tests/treatment in the nER. Results: A total of 2791 patients (46.6% male, mean age 57 ± 21 years) were included. The most common diagnoses were cerebrovascular events (26.3%), headache (14.1%), and seizures (10.5%). Most patients presented with symptoms lasting >48 h (41.3%). The PWS group included the largest proportion of patients presenting within 4.5 h of symptom onset (171/293, 58.4%), whereas only 37.1% of stroke patients presented within this time frame (273/735). Self‐presentation was the most common admission pathway (31.1%), followed by emergency service referral (30.4%, including the majority of PWS: 197/293, 67.2%). Despite known diagnosis of epilepsy in 49.2%, PWS more often underwent accessory diagnostic testing including cerebral imaging, compared to the overall cohort (accessory diagnostics 93.9% vs. 85.4%; cerebral imaging 70.1% vs. 64.1%). Electroencephalography in the nER was only performed in 20/111 patients (18.0%) with a first seizure. Nearly half of the patients (46.7%) were discharged home after nER work‐up, including most self‐presenters (632/869, 72.7%) and headache patients (377/393, 88.3%), as well as 37.2% (109/293) of PWS. Conclusion: After 10 years, nER overuse remains a problem. Stroke patients still do not present early enough, whereas PWS, even those with known epilepsy, often seek acute and extensive assessment, indicating gaps in pre‐hospital management and possible over‐assessment. [ABSTRACT FROM AUTHOR]

Introduction: Chronic refractory pain of various origin occurs in 30–45% of pain patients, and a considerable proportion remains resistant to pharmacological and behavioral therapies, requiring adjunctive neurostimulation therapies. Chronic pain is known to stimulate sympathetic outflow, yet the impact of burst motor cortex stimulation (burstMCS) on objectifiable autonomic cardiovascular parameters in chronic pain remains largely unknown. Methods: In three patients with chronic pain (2 facial pain/1 post-stroke pain), we compared pain intensity using a visual analog scale (VAS 1–10) and parameters of autonomic cardiovascular modulation at supine rest, during parasympathetic challenge with six cycles per minute of metronomic deep breathing, and during sympathetic challenge (active standing) at baseline and after 4 months of burstMCS compared to age-/gender-matched healthy controls. Results: While two out of three patients were responsive after 4 months of adjunctive burstMCS (defined as pain reduction of > 30%), no differences were found in any of the three patients regarding the R-R intervals of adjacent QRS complexes (RRI, 642 vs. 676 ms) and blood pressure (BP, 139/88 vs. 141/90 mmHg). Under resting conditions, parameters of parasympathetic tone [normalized units of high-frequency oscillations of RRI (RRI-HFnu power) 0.24 vs. 0.38, root-mean-square differences of successive RRI (RRI-RMSSD) 7.7 vs. 14.7 ms], total autonomic cardiac modulation [RRI total power 129.3 vs. 406.2 ms2, standard deviation of RRI (RRI-SD) 11.6 vs. 18.5 ms, coefficient of variation of RRI (RRI-CV) 1.9 vs. 3.7%], and baroreceptor reflex sensitivity (BRS, 1.9 vs. 2.3 ms/mmHg) increased, and parameters of sympathetic tone [normalized units of low-frequency oscillations of RRI (RRI-LFnu power) 0.76 vs. 0.62] and sympatho-vagal balance [ratio of RR-LF to RRI-HF power (RRI-LF/HF ratio) 3.4 vs. 1.9] decreased after 4 months of burstMCS. Low-frequency oscillations of systolic blood pressure (SBP-LF power), a parameter of sympathetic cardiovascular modulation, increased slightly (17.6 vs. 20.4 mmHg2). During parasympathetic stimulation, the expiratory–inspiratory ratio (E/I ratio) increased slightly, while upon sympathetic stimulation, the ratio between the shortest RRI around the 15th heartbeat and the longest RRI around the 30th heartbeat after standing up (RRI 30/15 ratio) remained unchanged. Conclusion: Four months of adjunctive burstMCS was associated with an increase in parameters reflecting both total and parasympathetic autonomic modulation and baroreceptor reflex sensitivity. In contrast, sympathetic tone declined in our three patients, suggesting stimulation-associated improvement not only in subjectively perceived VAS pain scores, but also in objectifiable parameters of autonomic cardiovascular modulation. [ABSTRACT FROM AUTHOR]

Age at onset of epilepsy is an important predictor of deterioration in naming ability following epilepsy surgery. In 141 patients with left hemispheric epilepsy and language dominance who received epilepsy surgery at the Epilepsy Centre Erlangen, naming of objects (Boston naming test, BNT) was assessed preoperatively and 6 months postoperatively. Surgical lesions were plotted on postoperative MRI and normalized for statistical analysis using voxel-based lesion-symptom mapping (VBLSM). The correlation between lesion and presence of postoperative naming deterioration was examined varying the considered age range of epilepsy onsets. The VBLSM analysis showed that volumes of cortex areas in the left temporal lobe, which were associated with postoperative decline of naming, increased with each year of later epilepsy onset. In patients with later onset, an increasing left posterior temporobasal area was significantly associated with a postoperative deficit when included in the resection. For late epilepsy onset, the temporomesial expansion also included the left hippocampus. The results underline that early onset of epilepsy is a good prognostic factor for unchanged postoperative naming ability following epilepsy surgery. For later age of epilepsy onset, the extent of the area at risk of postoperative naming deficit at 6 months after surgery included an increasing left temporobasal area which finally also comprised the hippocampus. [ABSTRACT FROM AUTHOR]

Background: Despite benefits of endovascular treatment (EVT) for large vessel occlusion (LVO) ischemic stroke, space-occupying brain edema (BE) represents a detrimental complication. In critical-care settings, CT-imaging is needed for monitoring these patients. Yet, bed-side techniques with the potential to predict whether patients develop BE or not would facilitate a time- and cost-efficient patient care. We assessed clinical significance of automated pupillometry in the follow-up of patients undergoing EVT. Methods: From 10/2018 to 10/2021, neurocritical-care-unit patients were retrospectively enrolled after EVT of anterior circulation LVO. We monitored parameters of pupillary reactivity [light-reflex-latency (Lat), constriction- and redilation-velocities (CV, DV), percentage-change-of-apertures (per-change); NeurOptics-pupilometer®] up to every hour on day 1–3 of ICU stay. BE was defined as midline shift ≥ 5 mm on follow-up imaging 3–5 days after EVT. We calculated mean values of intra-individual differences between successive pairs of parameters (mean-deltas), determined best discriminative cut-off values for BE development (ROC-analyses), and evaluated prognostic performance of pupillometry for BE development (sensitivity/specificity/positive-/negative-predictive-values). Results: 3241 pupillary assessments of 122 patients [67 women, 73 years (61.0–85.0)] were included. 13/122 patients developed BE. Patients with BE had significantly lower CVs, DVs, and smaller per-changes than patients without BE. On day 1 after EVT mean-deltas of CV, DV, and per-changes were significantly lower in patients with than without BE. Positive-predictive-values of calculated thresholds to discriminate both groups were considerably low, yet, we found high negative-predictive-values for CV, DV, per-changes, and mean-deltas (max.: 98.4%). Conclusion: Our data suggest associations between noninvasively detected changes in pupillary reactivity and BE early after LVO-EVT. Pupillometry may identify patients who are unlikely to develop BE and may not need repetitive follow-up-imaging or rescue-therapy. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses reports within the issue regarding decompressive hemicraniectomy during malignant cerebrovascular accident.

Aim: The aim of this study was to re‐evaluate risk factors for post‐ICH epilepsy (PICHE) and examine the impact of surgical hematoma evacuation on epilepsy development after ICH. Background and purpose: Epilepsy is a common complication after intracerebral hemorrhage (ICH). Information on risk factors is still scarce and the role of ICH evacuation remains uncertain. Methods: We retrospectively included patients with spontaneous ICH treated in our hospital in 2006–2019. Patients' medical records were analyzed. In addition, mailed questionnaires and telephone interviews were used to complete the dataset. Uni‐ and multivariable hazard ratios (HRs) were applied to investigate risk factors for PICHE and the impact of surgical ICH evacuation. Results: Among 587 ICH patients available for analyses, 139 (23.7%) developed PICHE (mean follow‐up 1795 ± 1378 days). The median time of epilepsy onset was 7 months after ICH (range 1–132 months). Risk factors associated with PICHE were cortical hemorrhage (multivariable HR 1.65 [95% CI 1.14–2.37]; p = 0.008), ICH volume > 10 ml (multivariable HR 1.91 [95% CI 1.33–2.73]; p < 0.001) and acute symptomatic seizures (multivariable HR 1.81 [95% CI 1.20–2.75]; p = 0.005). Patients with cortical ICH > 10 ml who underwent surgical hematoma evacuation were less likely to develop epilepsy than those with conservative treatment alone (multivariable HR 0.26 [95% CI 0.08–0.84]; p = 0.025). Conclusions: Post‐ICH epilepsy is frequent and predicted by large cortical ICH and acute symptomatic seizures. Hematoma evacuation reduced the risk of PICHE by more than 70% in patients with large cortical ICH. This finding could be considered in the clinical decision making on the acute treatment of ICH. [ABSTRACT FROM AUTHOR]

Background and Purpose: The relationship between ischemic stroke site and occurrence of poststroke epilepsy (PSE) is incompletely understood. This study intended to evaluate incidence and temporal profiles of seizures and to correlate ischemic lesion sites with PSE using voxel‐based lesion symptom mapping (VLSM). Methods: Patients with imaging‐confirmed first‐ever ischemic stroke without prior history of epilepsy were prospectively included. Demographic data, cardiovascular risk factors, and National Institute of Health Stroke Scale (NIHSS) scores were assessed. Data on seizures and modified Rankin scale scores were determined within a 90‐day period after stroke onset. Ischemic lesion sites were correlated voxel wise with occurrence of PSE using nonparametric permutation test. Age‐ and sex‐matched patients with first‐ever ischemic strokes without PSE after 90 days served as controls for the VLSM analysis. Results: The stroke database contained 809 patients (mean age: 68.4 ± 14.2 years) with first‐ever imaging‐confirmed ischemic strokes without history of epilep. Incidence of PSE after 90‐day follow‐up was 2.8%. Five additional patients were admitted to the emergency department with a seizure after 90‐day follow‐up. Fifty percent of the seizures occurred in the acute phase after stroke. PSE patients had higher NIHSS scores and infarct volumes compared to controls without PSE (p <.05). PSE patients had infarcts predominantly involving the cerebral cortex. The hemisphere‐specific VLSM analysis shows associations between PSE and damaged voxels in the left‐hemispheric temporo‐occipital transition zone. Conclusions: The data indicate that PSE occurs in a small proportion of patients with rather large ischemic strokes predominantly involving the cerebral cortex. Especially patients with ischemic lesions in the temporo‐occipital cortex are vulnerable to develop PSE. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy is a common comorbidity of glioblastoma. Seizures may occur in various phases of the disease. We aimed to assess potential risk factors for seizures in accordance with the point in time at which they occurred. Methods: We retrospectively analyzed medical files of adult patients with de novo glioblastoma treated at our institution between January 2006 and January 2020. We categorized seizures as preoperative seizures (POS), early postoperative seizures (EPS; before initiation of radio[chemo]therapy [RCT]), seizures during radiotherapy (SDR; during or <30 days after RCT), and posttherapeutic seizures (PTS; ≥30 days after completion of RCT). We addressed associations between patients' characteristics and their seizures. Results: In the final cohort (N = 520), 292 patients experienced seizures. POS, EPS, SDR, and/or PTS occurred in 29.6% (154/520), 6.0% (31/520), 13.8% (70/509), and 36.1% (152/421) of patients, respectively. POS occurred more frequently in patients with higher Karnofsky Performance Scale scores (odds ratio [OR] = 3.27, p =.001) and tumor location in the temporal lobe (OR = 1.51, p =.034). None of the parameters we analyzed was related to the occurrence of EPS. SDR were independently associated with tumor location (parietal lobe, OR = 1.86, p =.027) and POS, but not EPS, and were independent of RCT. PTS were independently associated with tumor progression (OR = 2.32, p <.001) and with occurrence of SDR (OR = 3.36, p <.001), and negatively correlated with temporal lobe location (OR =.58, p <.014). In patients with tumors exclusively located in the temporal lobe, complete tumor resection was associated with a decreased risk of postoperative seizures. Significance: Seizures in glioblastoma patients have various, time‐dependent risk factors. Temporal lobe localization was a risk factor for preoperative seizures; surgery may have had a protective effect in these patients. RCT did not have dose‐dependent pro‐ or anticonvulsive effects. PTS were associated with tumor progression. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies postulate a high prognostic value of the Alberta Stroke Programme Early CT Score (ASPECTS) applied on non-contrast whole-brain flat-detector CT (FDCT) after successful endovascular treatment (EVT). The aim of this study was the evaluation of long-term patient outcome after endovascular treatment using postinterventional FDCT. Methods: Using a local database (Stroke Research Consortium in Northern Bavaria, STAMINA), 517 patients with successful endovascular treatment (modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2B) due to acute ischaemic stroke (AIS) and large vessel occlusion (LVO) of the anterior circulation were recruited retrospectively. In all cases, non-contrast FDCT after EVT was analysed with special focus at ASPECTS. These results were correlated with the functional outcome in long-term (modified Rankin Scale (mRS) shift from pre-stroke to 90 days after discharge). Results: A significant difference in FDCT-ASPECTS compared to the subgroup of favourable vs. unfavourable outcome (Δ mRS) (median ASPECTS 10 (10–9) vs. median ASPECTS 9 (10–7); p = 0,001) could be demonstrated. Multivariable regression analysis revealed FDCT-ASPECTS (OR 0.234, 95% CI − 0.102–0.008, p = 0.022) along with the NHISS at admission (OR 0.169, 95% CI 0.003–0.018, p = 0.008) as independent factors for a favourable outcome. Cut-off point for a favourable outcome (Δ mRS) was identified at an ASPECTS ≥ 8 (sensitivity 90.6%, specificity 35%). Conclusion: For patients with LVO and successful EVT, FDCT-ASPECTS was found to be highly reliable in predicting long-term outcome. [ABSTRACT FROM AUTHOR]

Objective: Discrimination against persons with epilepsy (PWEs) may persist. The aim of this study was to examine whether epilepsy is an obstacle to desired friendship. Methods: A factorial survey (vignettes), which is less biased by social desirability, was applied to PWEs, their relatives, and lay persons. The vignettes described a person who was varied by the dimensions of age (younger, same age, older), gender (male, female), disease (healthy, mild epilepsy, severe epilepsy [generalized tonic–clonic seizures], diabetes), origin (German, non‐German), contact (phone/internet, activities at home, activities outside), frequency of contacts (weekly, monthly), and distance (around the corner, 10 km away). Respondents rated their willingness to befriend the person on a 10‐point Likert scale. Multivariate regression determined the contribution of each dimension on the judgment. Results: Participants were 64 PWEs (age = 37.1 ± 14.0 years), 64 relatives of PWEs (age = 45.1 ± 13.6 years), and 98 controls without contact with PWEs (age = 24.4 ± 10.1 years). Controls were less interested in a friendship with a PWE with mild epilepsy (−3.4%) and even more avoided PWEs with severe epilepsy (−11.7%), whereas in PWEs with tonic–clonic seizures, a mild form of epilepsy was actually conducive to friendship (+7.0%). Controls preferred females (+5.0%) and disliked younger people (−12.3%) and contacts via the internet or telephone (−7.3%). PWEs were also less interested in younger people (−5.8%), and relatives of PWEs had a lower preference for friendships with longer distance (−2.3%). Significance: PWEs still suffer from a risk of social avoidance, and this becomes more evident with generalized motor seizures. [ABSTRACT FROM AUTHOR]

Vestibular neuritis is a common neuro‐otological entity. Therapeutically, corticosteroids are advised, although the evidence is limited. The objective of this review is to update meta‐analyses of clinical trials that address the question of whether patients with vestibular neuritis treated with corticosteroids show better recovery than control patients. The electronic databases Medline, Scopus and Cochrane were searched for clinical trials for the years 1970–2020 without language restriction. Data were extracted, and outcome parameters were subjected to conventional and cumulative meta‐analysis using a commercially available software program (www.meta‐analysis.com). Finally, 15 trials with 363 participants in the treatment and 489 in the control groups were identified and could be included. Eight studies were judged to be at high risk of bias. The odds ratio (OR) for good outcome in the acute phase was 3.1 (95% CI 1.2–7.8; p =.015) in favour of steroid treatment leading to the number needed to treat (NNT) = 6 (95% CI 4–23). The odds ratio (OR) for restoration of vestibular function in the follow‐up was 2.4 (95% CI 1.3–4.4; p =.004) for the benefit of steroid treatment resulting in a NNT = 7 (95% CI 5–18). The results of the cumulative statistics did not differ. The risk of adverse effects was higher in patients treated with steroids with an OR of 10.9 (95% CI 1.3–93.8; p =.015) and an estimated number needed to harm (NNH) = 4 (95% CI 3–19). The advantage for corticosteroids remained when differentiating between patients who participated in randomized or non‐randomized clinical trials. Steroid treatment in vestibular neuritis resulted in a statistically significant benefit compared to control therapies. However, broad heterogeneity of the studies, mostly low‐grade quality of studies, high risk of bias and broad confidence intervals put the findings into perspective allowing only a careful judgement of some benefit of corticosteroids. The findings, however, support the call for an adequately powered and well‐designed randomized controlled trial to re‐evaluate the effectiveness of corticosteroids. [ABSTRACT FROM AUTHOR]

Background: Stroke may compromise cardiovascular–autonomic modulation (CAM). The longitudinal post-stroke CAM alterations remain unclear as previous studies excluded patients with cardiovascular medication. This study evaluated whether CAM dysfunction improves after several months in patients under typical clinical conditions, i.e., without excluding patients with cardiovascular medication. Methods: In 82 ischemic stroke patients [33 women, 64.9 ± 8.9 years, NIHSS-scores 2 (interquartile range 1–5)], we evaluated the applications of cardiovascular medication before stroke, during autonomic tests performed within 1 week, 3 and 6 months after stroke onset. We determined resting RR intervals (RRI), systolic, diastolic blood pressures (BPsys), respiration, parameters reflecting total CAM [RRI-standard deviation (RRI-SD), RRI-total powers], sympathetic [RRI-low-frequency powers (RRI-LF), BPsys-LF powers] and parasympathetic CAM [RMSSD, RRI-high-frequency powers (RRI-HF powers)], and baroreflex sensitivity. ANOVA or Friedman tests with post hoc analyses compared patient data with data of 30 healthy controls, significance was assumed for P < 0.05. Results: More patients had antihypertensive medication after than before stroke. First-week CAM testing showed lower RRIs, RMSSD, RRI-SDs, RRI-total powers, RRI-HF powers, and baroreflex sensitivity, but higher BPsys-LF powers in patients than controls. After 3 and 6 months, patients had significantly higher RRIs, RRI-SDs, RRI-total powers, RMSSDs, RRI-HF powers, and baroreflex sensitivity, but lower BPsys-LF powers than in the 1st week; RMSSDs and RRI-HF powers no longer differed between patients and controls. However, 6-month values of RRIs, RRI-SDs, and baroreflex sensitivity were again lower in patients than controls. Conclusions: Even mild strokes compromised cardiovagal modulation and baroreflex sensitivity. After 3 months, CAM had almost completely recovered. Recovery might be related to the mild stroke severity. Presumably, CAM recovery was also promoted by the increased application of cardiovascular medication. Yet, slight CAM dysfunction after 6 months suggests continuing autonomic vulnerability. [ABSTRACT FROM AUTHOR]

Background and aim: To assess associations between clinical severity and possible dysfunction of autonomic cardiovascular modulation within the acute phase after spontaneous subarachnoid hemorrhage (SAH). Methods: In this prospective observational study, in 51 patients with spontaneous SAH, Hunt-and-Hess scores (H&H) were assessed and cardiovascular autonomic modulation was monitored within 24 h after SAH-onset. From 5 min time-series of R–R-intervals (RRI) and blood-pressure (BP) recordings, we calculated autonomic parameters including time-domain [RRI-coefficient-of-variation (RRI-CV) and square-root-of-the-mean-squared-differences-of-successive-RRIs (RMSSD)] and frequency-domain parameters [low- and high-frequency-powers of RRI- and BP-modulation (RRI-LF-, RRI-HF-, SBP-LF-powers) and RRI-total-powers]. Data were compared to those of 20 healthy volunteers. Results: RRI- and BP-values did not differ between groups. Yet, parameters of sympathetic (RRI-LF-powers 141.0 (18.9–402.4) ms2 vs 442.3 (246.8–921.2) ms2, p = 0.001) and total autonomic modulation (RRI-CV 2.4 (1.2–3.7) ms2 vs 3.7 (3.1–5.3) ms2, p = 0.001) were significantly lower in patients than in controls. Subgroup analyses (patients with H&H < 3 vs H&H ≥ 3) and Spearman-rank-correlations revealed increasing loss of sympathetic (RRI-LF-powers 338.6 (179.7–710.4) ms2 vs 72.1 (10.1–175.9) ms2, p = 0.001, rho = − 0.524) and total autonomic modulation (RRI-CV 3.5 (2.3–5.4) ms2 vs 1.6 (1.0–2.8) ms2, p < 0.001, rho = − 0.519) with higher H&H-scores. Multiple-logistic-regression underlined the significant influence of H&H-scores on sympathetic (RRI-LF-powers, p = 0.033) and total autonomic modulation (RRI-CV, p = 0.040) compared to possible confounders (e.g., age, intubation). Conclusion: Within the acute phase, spontaneous SAH induces a decrease in sympathetic and total autonomic cardiovascular modulation. Higher H&H-scores were associated with increasing autonomic dysfunction and may therefore augment the risk of cardiovascular complications and poor clinical outcome. [ABSTRACT FROM AUTHOR]

Objective: Because resources are limited in modern health care systems, the decision on the allocation of expensive drugs can be supported by a public consent. This study examines how various factors influence subjectively perceived "fair" pricing of antiseizure medication (ASM) among four groups including physicians, persons with epilepsy (PWEs), their relatives, and a control group. Methods: We conducted a factorial survey. Vignettes featured a fictional PWE receiving a fictional ASM. The characteristics of the fictional PWE, ASM, and epilepsy varied. Participants were asked to assess the subjectively appropriate annual cost of ASM treatment per year for each scenario. Results: Fifty‐seven PWEs (mean age (SD) 37.7 ± 12.3, 45.6% female), 44 relatives (age 48.4 ± 15.7, 51.1% female), 46 neurologists (age 37.1 ± 9.6, 65.2% female), and 47 persons in the control group (age 31.2 ± 11.2, 68.1% female) completed the questionnaire. The amount of money that respondents were willing to spend for ASM treatment was higher than currently needed in Germany and increased with disease severity among all groups. All groups except for PWEs accepted higher costs of a drug with better seizure control. Physicians and the control group, but not PWEs and their relatives, tended to do so also for minor or no side effects. Physicians reduced the costs for unemployed patients and the control group spent less money for older patients. Significance: ASM effectiveness appears to justify higher costs. However, the control group attributed less money to older PWEs and physicians allocated fewer drug costs to unemployed PWEs. [ABSTRACT FROM AUTHOR]

Background and purpose: Ischemic stroke may induce cardiovascular autonomic dysfunction, but most previous studies have included patients with anterior circulation ischemic stroke or brainstem stroke. It remains unclear whether posterior circulation ischemic stroke (PCIS) without brainstem involvement also compromises cardiovascular autonomic modulation (CAM). Therefore, we aimed to assess CAM in PCIS patients with and without brainstem involvement. Methods: In four subgroups of 61 PCIS patients (14 occipital lobe, 16 thalamic, 12 cerebellar, and 19 brainstem strokes) and 30 healthy controls, we recorded RR intervals (RRIs), systolic (SBP) and diastolic blood pressure (DBP), and respiration at supine rest during the first week after stroke onset. We calculated parameters reflecting total CAM (RRI‐standard deviation [RRI‐SD], RRI‐total powers), predominantly sympathetic CAM (RRI‐low‐frequency [LF] powers and SBP‐LF powers] and parasympathetic CAM (root mean square of successive RRI differences [RMSSD], RRI‐high‐frequency [HF] powers), sympathetic‐parasympathetic balance (RRI‐LF/HF ratios), and baroreflex sensitivity (BRS). Values were compared among the four PCIS groups and controls using one‐way ANOVA Kruskal–Wallis tests, with post‐hoc analyses. Significance was assumed for p < 0.05. Results: In each PCIS subgroup, values for RRI, RRI‐SD, RMSSD, RRI‐HF powers, and BRS were significantly lower, while SBP‐LF powers were higher than in the controls. Only in patients with occipital lobe stroke were RRI‐LF/HF ratios significantly higher than in controls. Otherwise, autonomic variables did not differ among the four PCIS subgroups. Conclusions: During the first week after stroke onset, our PCIS patients with occipital lobe, thalamic, cerebellar, or brainstem strokes all had reduced cardiovagal modulation, compromised baroreflex, and increased peripheral sympathetic modulation. The RRI‐LF/HF ratios suggest that sympathetic predominance is slightly more prominent after occipital lobe stroke. PCIS may trigger cardiovascular autonomic dysfunction even without brainstem involvement. [ABSTRACT FROM AUTHOR]

Cetuximab is a chimeric IgG1 monoclonal antibody against epidermal growth factor receptor. It is approved by the European medical agency for the treatment of RAS wild-type metastatic colorectal cancer and metastatic squamous cell cancer of the head and neck. Few cases of aseptic meningitis, primarily associated with the first administration of cetuximab in patients with squamous cell cancer, have been reported. So far, there was only 1 case in a patient with metastatic colorectal cancer. We report on a 50-year-old Caucasian patient with metastatic rectum carcinoma who suffered from headache, fever, and neck stiffness 3 h after the first administration of cetuximab (400 mg/m2). CSF examination revealed an excessive pleocytosis with a white blood cell count of 2,433/µL. He was diagnosed with cetuximab-induced aseptic meningitis since clinical symptoms and CSF pleocytosis resolved within days, and further diagnostic workup revealed no infectious cause. Cetuximab-induced aseptic meningitis is a rare and severe drug reaction with predominance in treating squamous cell cancer of the head and neck. Clinical presentation and CSF findings suggest acute meningoencephalitis. In all reported cases, the course of the disease was benign and self-limited. Empiric antimicrobial and antiviral therapy are suggested until infectious causes can be ruled out. A lower dosage of cetuximab and a premedication including antihistamines and glucocorticosteroids may lower the risk of a re-occurrence if cetuximab therapy is continued. [ABSTRACT FROM AUTHOR]

Background and purpose: Atrial fibrillation (AF) in stroke patients can be classified as either "known AF" (KAF), defined as AF confirmed before stroke onset, or "AF detected after stroke" (AFDAS), defined as AF diagnosed after stroke onset. While KAF is considered primarily cardiogenic, AFDAS includes patients with stroke‐triggered neurogenic arrhythmias. This study aimed to investigate the clinical course of stroke, functional outcomes and the value of oral anticoagulation (OAC) for secondary prevention according to AF subtype. Methods: Acute ischemic stroke patients were consecutively enrolled and AF was classified as AFDAS or KAF. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and 3‐month functional outcomes were measured on the modified Rankin scale. Inverse probability weighting was applied to adjust for baseline confounders in patients with AFDAS and KAF. Multivariate logistic regression models were calculated to investigate the value of OAC for secondary prevention. Results: A total of 822 stroke patients with AF were included, of whom 234 patients (28.5%) had AFDAS. AFDAS patients had a lower prevalence of coronary artery disease, heart failure, and sustained AF, but higher rates of large vessel occlusion compared to KAF patients. NIHSS scores were lower in patients on pre‐stroke anticoagulation. OAC for secondary prevention was associated with favorable 3‐month functional outcome (odds ratio 7.60, 95% confidence interval 3.42–16.88) independently of AF subtype. The rate of stroke recurrence did not differ significantly. Conclusions: Clinical characteristics suggest that AFDAS might comprise a distinct pathophysiological and clinical entity among stroke patients with AF. The benefit of anticoagulation for secondary prevention was not affected by AF subtype. [ABSTRACT FROM AUTHOR]

Neurocritical patients suffer from a substantial risk of extubation failure. The aim of this prospective study was to analyze if quantitative EEG (qEEG) monitoring is able to predict successful extubation in these patients. We analyzed EEG-monitoring for at least six hours before extubation in patients receiving mechanical ventilation (MV) on our neurological intensive care unit (NICU) between November 2017 and May 2019. Patients were divided in 2 groups: patients with successful extubation (SE) versus patients with complications after MV withdrawal (failed extubation; FE), including reintubation, need for non-invasive ventilation (NIV) or death. Bipolar six channel EEG was applied. Unselected raw EEG signal underwent automated artefact rejection and Short Time Fast Fourier Transformation. The following relative proportions of global EEG spectrum were analyzed: relative beta (RB), alpha (RA), theta (RT), delta (RD) as well as the alpha delta ratio (ADR). Coefficient of variation (CV) was calculated as a measure of fluctuations in the different power bands. Mann–Whitney U test and logistic regression were applied to analyze group differences. 52 patients were included (26 male, mean age 65 ± 17 years, diagnosis: 40% seizures/status epilepticus, 37% ischemia, 13% intracranial hemorrhage, 10% others). Successful extubation was possible in 40 patients (77%), reintubation was necessary in 6 patients (12%), 5 patients (10%) required NIV, one patient died. In contrast to FE patients, SE patients showed more stable EEG power values (lower CV) considering all EEG channels (RB: p < 0.0005; RA: p = 0.045; RT: p = 0.045) with RB as an independent predictor of weaning success in logistic regression (p = 0.004). The proportion of the EEG frequency bands (RB, RA RT, RD) of the entire EEG power spectrum was not significantly different between SE and FE patients. Higher fluctuations in qEEG frequency bands, reflecting greater fluctuation in alertness, during the hours before cessation of MV were associated with a higher rate of complications after extubation in this cohort. The stability of qEEG power values may represent a non-invasive, examiner-independent parameter to facilitate weaning assessment in neurocritical patients. [ABSTRACT FROM AUTHOR]

Background: Clinical characteristics, outpatient situation, and outcome in patients with psychogenic nonepileptic seizures (PNES) remain to be elucidated. Methods: Patients diagnosed with PNES after video‐electroencephalography (EEG) monitoring (VEM) 03/2000–01/2016 at the Erlangen Epilepsy Center were surveyed between June 2016 and February 2017. Primary outcome was PNES cessation defined as no PNES episodes within > = 12 months prior to the interview. Secondary outcome variables included quality of life (QoL) and dependency. Sensitivity analysis included patients with proven PNES during VEM without comorbid epilepsy. Results: Ninety‐nine patients were included (median age 38 (interquartile range (IQR 29–52)) years; 68 (69%) females, follow‐up 4 (IQR 2.1–7.7) years). Twenty‐eight (28%) patients suffered from comorbid epilepsy. Twenty‐five (25%) patients reported PNES cessation. Older age at symptom onset (odds ratio (OR) related to PNES cessation: 0.95 (95% CI 0.90–0.99)), comorbid epilepsy (OR 0.16 (95% CI 0.03–0.83)), anxiety disorder (OR 0.15 (95% CI 0.04–0.61)), and tongue biting (OR 0.22 (95% CI 0.03–0.91)) remained independently associated with ongoing PNES activity after adjustment. Sensitivity analysis (n = 63) revealed depressive disorder (OR 0.03 (95% CI 0.003–0.34)) instead of anxiety as independent predictor, while this seemed relevant only in patients older than 26 years at onset (OR 0.04 (95% CI 0.002–0.78) versus OR 0.21 (95% CI 0.02–1.84) in patients younger than 26 years). PNES cessation was associated with increased median QoL (8 (IQR 7–9) versus 5.5 (IQR 4–7); p <.001) and an increased frequency of financial independency (14 (56%) versus 21 (28%); p =.01). Conclusions: We found poor outcomes in PNES especially in older patients at onset with comorbid depressive disorder. Comorbid epilepsy also seems to be a major risk factor of ongoing PNES activity, which in turn affects patients' daily living. [ABSTRACT FROM AUTHOR]

Introduction Anti–N-methyl-D-aspartate receptor immunoglobulin G antibodies directed against the GluN1 subunit are considered highly specific for anti-N-methyl-D-aspartate receptor encephalitis, a severe clinical syndrome characterized by seizures, psychiatric symptoms, orofacial dyskinesia and autonomic dysfunction. Case presentation Here we report a 33 year old Caucasian male patient with clinically definite multiple sclerosis who was found to be positive for anti-N-methyl-D-aspartate receptor antibodies. Rituximab therapy was initiated. On the 18 months follow-up visit the patient was found to be clinically stable, without typical signs of anti-N-methyl-D-aspartate receptor encephalitis. Conclusion Our findings add to the growing evidence for a possible association between anti-N-methyl- D-aspartate receptor encephalitis and demyelinating diseases. [ABSTRACT FROM AUTHOR]

The human amygdala is involved in processing of memory, decision-making, and emotional responses. Previous studies suggested that the amygdala may represent a neurogenic niche in mammals. By combining two distinct methodological approaches, lipofuscin quantification and 14C-based retrospective birth dating of neurons, along with mathematical modelling, we here explored whether postnatal neurogenesis exists in the human amygdala. We investigated post-mortem samples of twelve neurologically healthy subjects. The average rate of lipofuscin-negative neurons was 3.4%, representing a substantial proportion of cells substantially younger than the individual. Mass spectrometry analysis of genomic 14C-concentrations in amygdala neurons compared with atmospheric 14C-levels provided evidence for postnatal neuronal exchange. Mathematical modelling identified a best-fitting scenario comprising of a quiescent and a renewing neuronal population with an overall renewal rate of >2.7% per year. In conclusion, we provide evidence for postnatal neurogenesis in the human amygdala with cell turnover rates comparable to the hippocampus. Lipofuscin labeling and 14 C retrospective birth-dating of neurons, along with mathematical modelling, here suggest continued postnatal neurogenesis in the human amygdala, rather than protracted maturation of developmentally generated neurons. [ABSTRACT FROM AUTHOR]

Purpose: Endovascular therapy (EVT) of large-vessel occlusion in acute ischemic stroke (AIS) may be performed in general anesthesia (GA) or conscious sedation (CS). We intended to determine the contribution of ischemic cerebral lesion sites on the physician's decision between GA and CS using voxel-based lesion symptom mapping (VLSM). Methods: In a prospective local database, we sought patients with documented AIS and EVT. Age, stroke severity, lesion volume, vigilance, and aphasia scores were compared between EVT patients with GA and CS. The ischemic lesions were analyzed on CT or MRI scans and transformed into stereotaxic space. We determined the lesion overlap and assessed whether GA or CS is associated with specific cerebral lesion sites using the voxel-wise Liebermeister test. Results: One hundred seventy-nine patients with AIS and EVT were included in the analysis. The VLSM analysis yielded associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas. Stroke severity and lesion volume were significantly higher in the GA group. The prevalence of aphasia and aphasia severity was significantly higher and parameters of vigilance lower in the GA group. Conclusions: The VLSM analysis showed associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas including the thalamus that are known to cause neurologic deficits, such as aphasia or compromised vigilance, in AIS-patients with EVT. Our data suggest that higher disability, clinical impairment due to neurological deficits like aphasia, or reduced alertness of affected patients may influence the physician's decision on using GA in EVT. [ABSTRACT FROM AUTHOR]

Background: For outcome assessment in patients surviving subarachnoid hemorrhage (SAH), the modified Rankin scale (mRS) represents the mostly established outcome tool, whereas other dimensions of outcome such as mood disorders and impairments in social life remain unattended so far. Objective: The aim of our study was to correlate 12-month functional and subjective health outcomes in SAH survivors. Methods: All SAH patients treated over a 5-year period received outcome assessment at 12 months, including functional scores (mRS and Barthel Index [BI]), subjective health measurement (EQ-5D), and whether they returned to work. Analyses – including utility-weighted mRS – were conducted to detect associations and correlations among different outcome measures, especially in patients achieving good functional outcome (i.e., mRS 0-2) at 12 months. Results: Of 351 SAH survivors, 287 (81.2%) achieved favorable functional outcome at 12 months. Contrary to the BI, the EQ-5D visual analog scale (VAS) showed a strong association with different mRS grades, accentuated in patients with favorable functional outcome. Despite favorable functional outcome, patients reported a high rate of impairments in activities (24.0%), pain (33.4%), and anxiety/depression (42.5%). Further, multivariable analysis revealed (i) impairments in activities (odds ratio [OR] [95% confidence interval {CI}]: 0.872 [0.817–0.930]), (ii) presence of depression or anxiety (OR [95% CI]: 0.836 [0.760–0.920]), and (iii) return to work (OR [95% CI]: 1.102 [0.1.013–1.198]) to be independently associated with self-reported subjective health. Conclusion: Established stroke scores mainly focusing on functional outcomes do poorly reflect the high rate of subjective impairments reported in SAH survivors, specifically in those achieving good functional outcome. Further studies are needed to investigate whether psychoeducational approaches aiming at improving coping mechanisms and perceived self-efficacy may result in higher subjective health in these patients. [ABSTRACT FROM AUTHOR]

Background: Prehospital cooling of acute stroke patients would be ideal when associated with minor or no side effects. Therefore, we evaluated a cooling cap for the surface of head and cervical regions in awake volunteers. Methods: 10 healthy volunteers were treated by external cooling for 190 min using a gel-based cooling device. Vital signs, rectal temperature, tympanic temperature, the extent of shivering and individual perception of frostiness and discomfort were measured. Results: All participants (median age 35 years) successfully completed the treatment and experienced only mild to moderate discomfort. No serious adverse events and no shivering were noticed. There was a significant drop in the tympanic temperature to 34.68°C (difference from baseline: 1.7°C, 95% CI: 0.61-2.7°C, p = 0.001), in the rectal temperature to 36.65°C (difference from baseline: 0.65°C, 95% CI: 0.06-1.2°C, p = 0.019) and in the heart rate (difference from baseline: 15 beats/min, 95% CI: 0.63-30 beats/min, p = 0.035). Conclusion: Treatment with the cooling device was well tolerated by all participants. The technique had measurable effects on core body temperature (rectal) and tympanic temperature (may reflect temperature at the external ear and skin rather than intracranial). It can be considered as a simple therapeutic approach to patients with suspected stroke in the prehospital setting. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Since pravastatin, a HMG-CoA reductase inhibitor, has recently been shown to reduce infarct volumes and glutamate release in a rat model of ischemic stroke, the aim of the present study was to investigate whether this neuroprotective effect may be due to a modulation of excitatory and inhibitory neurotransmitter receptors. Therefore, Wistar rats were treated six times in 4 days with pravastatin or saline and allowed to survive for 6 hours or 5 days (n =10 per time point and group), respectively. Using quantitative receptor autoradiography, ligand binding densities of [3H]MK-801, [3H]AMPA, and [3H]muscimol for labeling of NMDA, AMPA, and GABAA receptors were analyzed in sensorimotor cortices Par1 and Par2, the striatum, and the hippocampus. Statin therapy induced complex alterations of ligand binding densities in different brain regions. Labeling of NMDA receptors was significantly increased in Par2, both after 6 hours and 5 days, respectively. Within the striatum, AMPA as well as GABAA receptor binding values were significantly increased on day 5. Furthermore, a marked and significant increase of [3H]muscimol ligand binding to GABAA receptors throughout all hippocampal subfields was seen after 6 hours. This complexity could easily be unraveled when focusing on the balance between excitatory glutamate and inhibitory GABAA receptors, in which case only the increase of hippocampal [3H]muscimol ligand binding 6 hours after the first application of pravastatin was accompanied by a net shift towards inhibition. Consequently, our data suggest an additional regulatory pathway induced by statins, namely modification of the abundance of excitatory and inhibitory neurotransmitter receptors. [Copyright &y& Elsevier]

Critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) are major complications that occur in severely ill patients who require intensive care treatment. CIP and CIM affect the limb and respiratory muscles, and, as a consequence, they characteristically complicate weaning from the ventilator, increase the length of stay on the intensive care unit, and prolong physical rehabilitation. The basic pathophysiology of both disorders is complex and involves metabolic, inflammatory and bioenergetic alterations. It is unclear at present whether CIP and CIM are distinct entities, or whether they just represent different 'organ' manifestations of a common pathophysiological mechanism. This article provides an overview of the clinical and diagnostic features of CIP and CIM and discusses current pathophysiological and therapeutic concepts relating to these neuromuscular disorders. [ABSTRACT FROM AUTHOR]

Background and purpose: The effects of the coronavirus disease 2019 (COVID‐19) pandemic on telemedical care have not been described on a national level. Thus, we investigated the medical stroke treatment situation before, during, and after the first lockdown in Germany. Methods: In this nationwide, multicenter study, data from 14 telemedical networks including 31 network centers and 155 spoke hospitals covering large parts of Germany were analyzed regarding patients' characteristics, stroke type/severity, and acute stroke treatment. A survey focusing on potential shortcomings of in‐hospital and (telemedical) stroke care during the pandemic was conducted. Results: Between January 2018 and June 2020, 67,033 telemedical consultations and 38,895 telemedical stroke consultations were conducted. A significant decline of telemedical (p < 0.001) and telemedical stroke consultations (p < 0.001) during the lockdown in March/April 2020 and a reciprocal increase after relaxation of COVID‐19 measures in May/June 2020 were observed. Compared to 2018–2019, neither stroke patients' age (p = 0.38), gender (p = 0.44), nor severity of ischemic stroke (p = 0.32) differed in March/April 2020. Whereas the proportion of ischemic stroke patients for whom endovascular treatment (14.3% vs. 14.6%; p = 0.85) was recommended remained stable, there was a nonsignificant trend toward a lower proportion of recommendation of intravenous thrombolysis during the lockdown (19.0% vs. 22.1%; p = 0.052). Despite the majority of participating network centers treating patients with COVID‐19, there were no relevant shortcomings reported regarding in‐hospital stroke treatment or telemedical stroke care. Conclusions: Telemedical stroke care in Germany was able to provide full service despite the COVID‐19 pandemic, but telemedical consultations declined abruptly during the lockdown period and normalized after relaxation of COVID‐19 measures in Germany. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies have shown that inflammatory processes might play a role in epileptogenesis. Their role in ictogenesis is much less clear. The aim of this study was to investigate peri-ictal changes of the innate immune system by analyzing changes of immune cells, as well as pro- and anti-inflammatory cytokines. Methods: Patients with active epilepsy admitted for video-EEG monitoring for presurgical evaluation were included. Blood was sampled every 20 min for 5 h on 3 consecutive days until a seizure occurred. After a seizure, additional samples were drawn immediately, as well as 1 and 24 h later. To analyze the different populations of peripheral blood mononuclear cells, all samples underwent FACS for CD3, CD4, CD8, CD56, CD14, CD16, and CD19. For cytokine analysis, we used a custom bead-based multiplex immunoassay for IFN-γ, IL-1β, IL-1RA, IL-4, IL-6, IL-10, IL-12, IL-17, MCP-1, MIP-1α, and TNFα. Results: Fourteen patients with focal seizures during the sampling period were included. Natural killer (NK) cells showed a negative correlation (ρ = −0.3362, p = 0.0195) before seizure onset and an immediate increase to 1.95-fold afterward. T helper (TH) and B cells decreased by 2 and 8%, respectively, in the immediate postictal interval. Nonclassical and intermediate monocytes decreased not until 1 day after the seizures, and cytotoxic T (TC) cells showed a long-lasting postictal increase by 4%. IL-10 and MCP-1 increased significantly after seizures, and IL-12 decreased in the postictal phase. Discussion/Conclusion: Our study argues for a role of the innate immune system in the pre- and postictal phases. NK cells might be involved in preictal changes or be altered as an epiphenomenon in the immediate preictal interval. [ABSTRACT FROM AUTHOR]