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Background: It is important to learn more about the prevalence, severity and characteristics (i.e., which cognitive abilities are especially affected) of cognitive impairment in kidney transplant patients. Furthermore, the impact of living vs. deceased donor renal transplantation on cognitive outcome in this patient group needs further studies., Methods: Fifty-nine patients (43 men, age 55 ± 13 years) who received a deceased donor or living donor kidney transplant, completed a comprehensive neuropsychological test assessment. Neuropsychological tests explored the cognitive domains of verbal and visual memory, attention, and executive functions., Results: Fifteen percent  of the patients had mild, 25% moderate, and 15% severe cognitive impairment. The level of domain-specific cognitive deficit differed between verbal memory, attention, and executive functions (χ 2 (2) = 7.11, p = 0.029). On average, patients showed the highest deficit in executive functions, and the lowest deficit in verbal memory. Patients who received a kidney graft from a deceased donor were more likely to have a cognitive impairment than those who received a kidney graft from a living donor (OR = 3.03, 95% CI [0.99,9.32], Wald χ 2 (1)  = 3.74, p = 0.053). This effect was independent of time on dialysis as well as of creatinine levels, or creatinine clearance., Conclusions: Our results show that in kidney transplant patients with cognitive impairment, the cognitive domain of executive functions is the most affected one. This might be detrimental for quality of life. The fact that patients who received living donor kidneys seem to do better in terms of cognition than patients with deceased donor kidneys deserves more attention in future research., (© 2024. The Author(s).)

Background: Retinal artery occlusions lead to sudden, painless vision loss, affecting millions globally. Despite their significance, treatment strategies remain unestablished, contrasting with acute ischemic stroke (AIS), where IVT has proven efficacy. Similar to AIS, retinal artery occlusions demand urgent evaluation and treatment, reflecting the principle "time is retina". Even for patients with transient monocular vision loss, also known as amaurosis fugax (AF), pertinent guidelines meanwhile recommend immediate emergency assessment in a specialized facility. However, data on the clinical benefit and comparability with persistent occlusions are missing. This study aimed to compare the results of a comprehensive stroke-workup among patients with persistent retinal artery occlusions (RAO), including both central retinal (CRAO) and branch retinal artery occlusion (BRAO) and those with AF., Methods: Conducted at the University Hospital Giessen, Germany, this exploratory cross-sectional study enrolled patients with transient or permanent unilateral vision loss of non-arteritic origin. The primary outcome were differences between the two groups RAO and AF with regard to cardiovascular risk profiles and comorbidities, vascular and pharmacological interventions and clinical neurological and ophthalmological outcomes. Secondary outcome was a sub-group analysis of patients receiving IVT., Results: Out of 166 patients assessed, 76 with RAO and 40 with AF met the inclusion criteria. Both groups exhibited comparable age, gender distribution, and cardiovascular risk profiles. Notably, RAO patients did not show significantly more severe vascular comorbidities than AF patients. However, AF patients received vascular interventions more frequently. Pharmacological intervention rates were similar across groups. RAO patients had slightly worse neurological outcomes, and IVT did not yield favorable ophthalmological outcomes within any observed patients., Conclusion: The study found similar vascular burden and risk factors in patients with RAO and AF, with implications for clinical workflows. IVT for RAO may only be effective in very early treatment windows. This emphasizes the need for public awareness and collaborative protocols between ophthalmologists and neurologists to improve outcomes., (© 2024. The Author(s).)

Using ferric chloride (FeCl3) to induce experimental superior sagittal sinus (SSS) thrombosis might interfere with magnetic resonance imaging (MRI)-assisted visualization and evaluation of the thrombus, the brain parenchyma, and the quality of the occlusion. The aim of this study was to investigate whether aluminum chloride (AlCl3)-induced thrombosis of the SSS has comparable properties to those of FeCl3 without causing artifacts in MRI. SSS thrombosis was induced in 14 male Wistar rats by exposure of the SSS and subsequent topical application of a filter paper strip soaked in AlCl3 (n = 7) or FeCl3 (n = 7) over a period of 15 min. The animals with AlCl3-induced SSS thrombosis showed a constant and complete occlusion with in histological analysis large thrombi. Blood flow measurements indicated a significant reduction on the first and seventh postoperative day compared to preoperative measurements. MRI enabled visualization and subsequent evaluation of the thrombus and the surrounding parenchyma. In comparison, FeCl3-induced SSS thrombosis could not be evaluated by MRI due to artifacts caused by the paramagnetic properties and increased susceptibility of FeCl3. The occluded sinus and the surrounding area appeared hypointense. The quality of SSS occlusion by AlCl3 was comparable to that of FeCl3. AlCl3 therefore represents a significant alternative substance in experimental SSS thrombosis ideally suited for studies using MRI., (© 2024. The Author(s).)

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor protein predominantly expressed in microglia within the central nervous system (CNS). TREM2 regulates multiple microglial functions, including lipid metabolism, immune reaction, inflammation, and microglial phagocytosis. Recent studies have found that TREM2 is highly expressed in activated microglia after ischemic stroke. However, the role of TREM2 in the pathologic response after stroke remains unclear. Herein, TREM2-deficient microglia exhibit an impaired phagocytosis rate and cholesteryl ester (CE) accumulation, leading to lipid droplet formation and upregulation of Perilipin-2 (PLIN2) expression after hypoxia. Knockdown of TREM2 results in increased lipid synthesis (PLIN2, SOAT1) and decreased cholesterol clearance and lipid hydrolysis (LIPA, ApoE, ABCA1, NECH1, and NPC2), further impacting microglial phenotypes. In these lipid droplet-rich microglia, the TGF-β1/Smad2/3 signaling pathway is downregulated, driving microglia towards a pro-inflammatory phenotype. Meanwhile, in a neuron-microglia co-culture system under hypoxic conditions, we found that microglia lost their protective effect against neuronal injury and apoptosis when TREM2 was knocked down. Under in vivo conditions, TREM2 knockdown mice express lower TGF-β1 expression levels and a lower number of anti-inflammatory M2 phenotype microglia, resulting in increased cerebral infarct size, exacerbated neuronal apoptosis, and aggravated neuronal impairment. Our work suggests that TREM2 attenuates stroke-induced neuroinflammation by modulating the TGF-β1/Smad2/3 signaling pathway. TREM2 may play a direct role in the regulation of inflammation and also exert an influence on the post-ischemic inflammation and the stroke pathology progression via regulation of lipid metabolism processes. Thus, underscoring the therapeutic potential of TREM2 agonists in ischemic stroke and making TREM2 an attractive new clinical target for the treatment of ischemic stroke and other inflammation-related diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Direct oral anticoagulants (DOACs) have become widely used in clinical practice for preventing thromboembolic events. Point-of-care testing methods, particularly those based on urine samples, offer a promising approach for rapid and accurate assessment of DOAC presence. This pilot study aims to evaluate the utility of a urine-based DOAC dipstick test as a point-of-care tool for identifying DOAB presence in acute ischemic stroke (AIS) or transient ischemic attack (TIA) patients., Patients and Methods: This prospective pilot study included patients with AIS/TIA eligible for DOAC-measurement. After exclusion of 3 patients, 23 patients with DOAC-intake (DOAC group; factor-Xa-inhibitors; n  = 23) and 21 patients without DOAC-intake (control-group) remained for analyses. The urine-based DOAC dipstick test and parallel blood-based specific DOAC-level assessment were performed in all patients. Time-intervals of sampling urine/blood sampling and result of DOAC-test were recorded to analyze a potential time benefit based on dipstick evaluation., Results: The urine-based DOAC dipstick test demonstrated high sensitivity (100%) and specificity (100%), correctly identifying all patients with anticoagulatory activity due to DOAC intake (i.e., anti-Xalevel ≥30 ng/mL). Moreover, the visual readout of the test provided semiquantitative information on drug-specific anti-Xa levels, showing a sensitivity of 83% and specificity of 93% to detect anti-Xa levels ≥120 ng/mL. The dipstick test exhibited a median time-benefit of 2:25 h compared to standard blood-based DOAC-level testing., Discussion: The results of this pilot study underline the efficacy of urine-based point-of-care testing as a rapid and reliable method for assessing DOAC presence in patients with acute ischemic stroke., Conclusion: The value of this tool for clinical decision-making in stroke management needs to be established in future trials. Clinical Trial Registration : Clinicaltrails.org identifier [NCT06037200]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Doeppner, Olbricht, Maxhuni, Alhaj Omar, Sachs, Juenemann, Huttner and Gerner.)

H ypoxia triggers reactive microglial inflammation and lipid droplet (LD) accumulation under stroke conditions, although the mutual interactions between these two processes are insufficiently understood. Hence, the involvement of transforming growth factor (TGF)-β1 in inflammation and LD accumulation in cultured microglia exposed to hypoxia were analyzed herein. Primary microglia were exposed to oxygen-glucose deprivation (OGD) injury and lipopolysaccharide (LPS) stimulation. For analyzing the role of TGF-β1 patterns under such conditions, a TGF-β1 siRNA and an exogenous recombinant TGF-β1 protein were employed. Further studies applied Triacsin C, an inhibitor of LD formation, in order to directly assess the impact of LD formation on the modulation of inflammation. To assess mutual microglia-to-neuron interactions, a co-culture model of these cells was established. Upon OGD exposure, microglial TGF-β1 levels were significantly increased, whereas LPS stimulation yielded decreased levels. Elevating TGF-β1 expression proved highly effective in suppressing inflammation and reducing LD accumulation in microglia exposed to LPS. Conversely, inhibition of TGF-β1 led to the promotion of microglial cell inflammation and an increase in LD accumulation in microglia exposed to OGD. Employing the LD formation inhibitor Triacsin C, in turn, polarized microglia towards an anti-inflammatory phenotype. Such modulation of both microglial TGF-β1 and LD levels significantly affected the resistance of co-cultured neurons. This study provides novel insights by demonstrating that TGF-β1 plays a protective role against microglia-mediated neuroinflammation through the suppression of LD accumulation. These findings offer a fresh perspective on stroke treatment, suggesting the potential of targeting this pathway for therapeutic interventions.

Objectives: Postoperative cognitive decline (POCD) or decreased health-related quality of life (HQL) have been reported after cardiac surgery. A previous investigation showed beneficial effects of postoperative cognitive training on POCD and HQL 3 months after heart surgery. Here, we present the 12-month follow-up results., Methods: This bicentric, 1:1 randomised and treatment-as-usual controlled trial included elderly patients scheduled for elective heart valve surgery. The training consisted of paper-and-pencil-based exercises practising multiple cognitive functions for 36 min/day 6 days/week over a period of 3 weeks. Neuropsychological tests and questionnaires assessing HQL (36-Item Short Form Health Survey (SF-36)) and cognitive failures in daily living (Cognitive Failures Questionnaire) were performed presurgery and 12 months after training., Results: Twelve months post training, the training group (n=30) showed improvements in HQL compared with the control group (n=28), especially in role limitations due to physical health (U=-2.447, p=0.015, η 2 =0.109), role limitations due to emotional problems (U=-2.245, p=0.025, η 2 =0.092), pain (U=-1.979, p=0.049, η 2 =0.068), average of all SF-36 factors (U=-3.237, p<0.001, η 2 =0.181), health change from the past year to the present time (U=-2.091, p=0.037, η 2 =0.075), physical component summary (U=-2.803, p=0.005, η 2 =0.138), and mental component summary (U=-2.350, p=0.018, η 2 =0.095). Furthermore, the training group (n=19) showed an improvement compared with the control group (n=27) in visual recognition memory (U=-2.137, p=0.034, η 2 =0.099). POCD frequency was 22% (n=6) in the control group and 11% (n=2) in the training group (χ²(1) =1.06, p=0.440; OR=2.43, 95% CI 0.43 to 13.61)., Conclusion: In conclusion, postoperative cognitive training shows enhancing effects on HQL in cardiac surgery patients after 12 months., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Postoperative cognitive decline (POCD) after cardiosurgical interventions are well described through objective psychometric tests. However, a patient's subjective perception is essential to clinical assessment and quality of life. This study systematically evaluated patient-reported POCD between subjects undergoing coronary artery bypass grafting and heart valve replacement., Methods: This study was a multicentre, prospective questionnaire survey conducted at the cardiac surgery departments at the Kerckhoff Clinic in Bad Nauheim and the University Hospital in Giessen, Germany. We included patients undergoing elective coronary artery bypass grafting (CABG), aortic valve replacement (AVR), mitral valve replacement or reconstruction (MVR), and combined surgery (CABG + valve replacement [VR]) with extracorporeal circulation. The Hospital Anxiety and Depression Scale, the Cognitive Failures Questionnaire (CFQ) for Self-assessment (CFQ-S), and the external assessment (CFQ-foreign [F]) were completed preoperatively, as well as at 3 and 12 months postoperatively., Results: A total of 491 patients were available for analyses (CABG = 182, AVR = 134, MVR = 93, CABG + VR = 82). POCD and postoperative depression increase (PODI) were observed for each surgical procedure. (At the 3-month follow-up: CFQ-S [CABG = 7.1%, AVR = 3.7%, MVR = 9.7%, CABG + VR = 9.8%]; CFQ-F [CABG = 9.9%, AVR = 9.7%, MVR = 9.7%, CABG + VR = 15.9%]; PODI [CABG = 7.7%, AVR = 9.7%, MVR = 6.5%, CABG + VR = 8.5%]. At the 12-month follow-up: CFQ-S [CABG = 6.6%, AVR = 7.5%, MVR = 15.1%, CABG + VR = 7.3%]; CFQ-F [CABG = 7.1%, AVR = 14.9%, MVR = 10.8%, CABG + VR = 9.8%]; PODI [CABG = 10.4%, AVR = 11.2%, MVR = 6.5%, CABG + VR = 4.9%]). No significant between-group effects were observed for the CFQ-S, CFQ-F, or the Hospital Anxiety and Depression Scale., Conclusions: For clinicians, paying attention to patients' self-reported experiences of reduced cognitive function and symptoms of depression following cardiac surgery is important. Such reporting is an indication that interventions such as cognitive training or psychotherapy should be considered., (© 2023 The Authors.)

Brain injured patients often need deep sedation to prevent or treat increased intracranial pressure. The mainly used IV sedatives have side effects and/or high context-sensitive half-lives, limiting their use. Inhalative sedatives have comparatively minor side effects and a brief context-sensitive half-life. Despite the theoretical advantages, evidence in this patient group is lacking. A Germany-wide survey with 21 questions was conducted to find out how widespread the use of inhaled sedation is. An invitation for the survey was sent to 226 leaders of intensive care units (ICU) treating patients with brain injury as listed by the German Society for Neurointensive Care. Eighty-nine participants answered the questionnaire, but not all items were responded to, which resulted in different absolute counts. Most of them (88%) were university or high-level hospital ICU leaders and (67%) were leaders of specialized neuro-ICUs. Of these, 53/81 (65%) use inhalative sedation, and of the remaining 28, 17 reported interest in using this kind of sedation. Isoflurane is used by 43/53 (81%), sevoflurane by 15/53 (28%), and desflurane by 2. Hypotension and mydriasis are the most common reported side effects (25%). The presented survey showed that inhalative sedatives were used in a significant number of intensive care units in Germany to treat severely brain-injured patients.

Objective: Dysregulation of stress-reactive neuroendocrine measures, as well as subjective stress, have been found to worsen epilepsy. Transcutaneous vagus nerve stimulation (tVNS) is a relatively new treatment option for epilepsy. We were interested in its effect on the activity of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) as well as subjective stress and tiredness in patients with temporal lobe epilepsy (TLE)., Methods: Twenty patients (age 44 ± 11 years, 13 women) were enrolled in the study. They were free of seizures for more than 1 year. All took part in two sessions with 4 h of stimulation (tVNS vs. sham) in a randomized order. Saliva samples and subjective stress and tiredness levels were measured at five time points each session (before and after stimulation and three time points every hour in between). Data were analyzed using repeated measures analysis of variance as well as paired t-tests., Results: There was a dampened salivary cortisol (sCort) decrease during tVNS (time × condition effect: F [2.38, 38.15]  = 6.50, P = 0.002, partial η 2  = 0.29). Furthermore, we detected a dampened increase in salivary flow rate during tVNS (time × condition effect: F [3.28, 55.67]  = 2.82, P = 0.043, partial η 2  = 0.14). There was neither a difference in overall sCort or salivary alpha-amylase (sAA) levels nor in subjective stress or tiredness levels between conditions. sAA levels at the last measurement point were slightly higher during tVNS (t (19)  = 2.26, P = 0.035, d = 0.51), but this effect failed to reach significance when controlled for multiple comparisons., Significance: Our results partially support that tVNS influences the regulation of stress-reactive neuroendocrine systems (namely the HPA axis and ANS) in epilepsy. More research with larger samples is needed on the difference between short-term and repeated long-term stimulation., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background/objectives: Comprehensive Geriatric Care (CGC) is a specific multimodal treatment for older patients. In the current study, we aimed to investigate walking performance after CGC in medically ill patients versus those with fractures., Methods: The timed up and go test (TuG), a 5-grade scale assessment (1 = no walking impairment to 5 = no walking ability at all) for evaluating individual walking ability was performed in all patients who underwent CGC prior to and after treatment. Factors associated with improvement in walking ability were analyzed in the subgroup of patients with fractures., Results: Out of 1263 hospitalized patients, 1099 underwent CGC (median age: 83.1 years (IQR 79.0-87.8 years); 64.1% were female). Patients with fractures ( n = 300) were older than those without ( n = 799), (median 85.6 versus 82.4 years, p = 0.001). Improvement in TuG after CGC was found in 54.2% of the fracture patients compared to just 45.9% of those without fractures. In fracture group patients, TuG improved from median 5 on admission to median 3 on discharge ( p = 0.001). In fracture patients, improvement in walking ability was associated with higher Barthel index values on admission (median 45 (IQR: 35-55) versus 35 (IQR: 20-50): p = 0.001) and Tinetti assessment scores (median 9 (IQR: 4-14.25) versus 5 (IQR: 0-13); p = 0.001) and was negatively associated with the diagnosis of dementia (21.4% versus 31.5%; p = 0.058)., Conclusion: CGC improved walking ability in more than half of all patients examined. Older patients in particular might benefit from undergoing the procedure after an acute fracture. A better initial functional status favors a positive result following the treatment., Competing Interests: All authors declare they have no competing interests related to the present manuscript.

Background/objectives: Depressive symptoms (DS) may interfere with comprehensive geriatric care (CGC), the specific multimodal treatment for older patients. In view of this, the aim of the current study was to investigate the extent to which DS occur in older hospitalized patients scheduled for CGC and to analyze the associated factors. Furthermore, we aimed to investigate whether DS are relevant with respect to outcomes after CGC., Methods: For this retrospective study, all patients fulfilling the inclusion criteria were selected by reviewing case files. The main inclusion criterion was the completion of CGC within the defined period (May 2018 and May 2019) in the geriatrics department of the Diakonie Hospital Jung-Stilling Siegen (Germany). The Geriatric Depression Scale was used to asses DS in older adults scheduled for CGC (0-5, no evidence of DS; 6-15 points, DS). Scores for functional assessments (Timed Up and Go test (TuG), Barthel Index, and Tinetti Gait and Balance test) were compared prior to versus after CGC. Factors associated with the presence of DS were studied., Results: Out of the 1263 patients available for inclusion in this study, 1092 were selected for the analysis (median age: 83.1 years (IQR 79.1-87.7 years); 64.1% were female). DS (GDS > 5) were found in 302 patients (27.7%). The proportion of female patients was higher in the subgroup of patients with DS (85.5% versus 76.3%, p = 0.024). Lower rates of patients diagnosed with chronic pulmonary obstructive disease were detected in the subgroup of patients without DS (8.0% versus 14.9%, p = 0.001). Higher rates of dizziness were observed in patients with DS than in those without (9.9% versus 6.2%, p = 0.037). After CGC, TuG scores improved from a median of 4 to 3 ( p < 0.001) and Barthel Index scores improved from a median of 45 to 55 ( p < 0.001) after CGC in both patients with and without DS. In patients with DS, the Tinetti score improved from a median of 10 (IQR: 4.75-14.25) prior to CGC to 14 (IQR 8-19) after CGC ( p < 0.001). In patients without DS, the Tinetti score improved from a median of 12 (IQR: 6-7) prior to CGC to 15 (IQR 2-20) after CGC ( p < 0.001)., Conclusions: DS were detected in 27.7% of the patients selected for CGC. Although patients with DS had a poorer baseline status, we detected no difference in the degree of improvement in both groups, indicating that the performance of CGC is unaffected by the presence of DS prior to the procedure.

Background: Heart surgery is a risk factor for objectively and subjectively assessable postoperative cognitive decline (POCD), which is relevant for everyday life. The aim of this study was to investigate whether early postoperative cognitive training has an impact on health-related quality of life and cognitive failures in daily living after cardiac surgery., Methods: The study was a two-arm, randomized, controlled, outcome-blinded trial involving older patients undergoing elective heart valve surgery with extracorporeal circulation (ECC). Recruitment took place at the Departments of Cardiac Surgery of the Kerckhoff Clinic in Bad Nauheim (Germany) and the University Hospital in Giessen (Germany). The patients were randomized (1:1 ratio) to either a paper-and-pencil-based cognitive training group or a control group. We applied the Short Form Health Survey (SF-36) and the Cognitive Failures Questionnaire (CFQ) prior to surgery and 3 months after the cognitive training. Data were analyzed in a per-protocol fashion., Results: Three months after discharge from rehabilitation, the training group (n = 31) showed improvement in health-related quality of life compared to the control group (n = 29), especially in role limitations due to emotional problems (U = -2.649, p = .008, η 2  = 0.121), energy and fatigue (F[2.55] = 5.72, p = .020, η 2  = 0.062), social functioning (U = -2.137, p = .033, η 2  = 0.076), the average of all SF-36 factors (U = -2.374, p = .018, η 2  = 0.094), health change from the past year to the present time (U = -2.378, p = .017, η 2  = 0.094), and the mental component summary (U = -2.470, p = .013, η 2  = 0.102)., Conclusion: As our cognitive training has shown beneficial effects, this intervention could be a promising method to enhance health-related quality of life after cardiac surgery., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Postoperative delirium (POD) and postoperative cognitive decline (POCD) can be observed after cardiosurgical interventions. Taken together, these postoperative neurocognitive disorders (PNCDs) contribute to increased morbidity and mortality. Preoperative risk factors of PNCD, such as decreased neuropsychometric performance or decreased cognitive daily activities, can be interpreted as reduced cognitive reserve. This study aims to build up cognitive reserves to protect against the development of PNCD through preoperative, home-based, cognitive training., Methods: The planned research project is a monocentric, two-arm randomized controlled intervention study involving 100 patients undergoing elective cardiac surgery with extracorporeal circulation. Patients will be assigned to a training group or control group. The intervention involves a standardized, paper-and-pencil-based cognitive training that will be performed by the patients at home for ~40 min per day over a preoperative period of 2-3 weeks. The control group will receive neither cognitive training nor a placebo intervention. A detailed assessment of psychological functions will be performed ~2-3 weeks before the start of training, at the end of the training, during hospitalization, at discharge from the acute clinic, and 3 months after surgery. The primary objective of this study is to investigate the interventional effect of preoperative cognitive training on the incidence of POD during the stay in the acute clinic, the incidence of POCD at the time of discharge from the acute clinic, and 3 months after surgery. Secondary objectives are to determine the training effect on objective cognitive functions before the surgery and subjective cognitive functions, as well as health-related quality of life 3 months after surgery., Discussion: Should it become evident that the use of our cognitive training can both reduce the incidence of POCD and POD and improve health-related quality of life, this intervention may be integrated into a standardized prehabilitation program., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Butz, Meyer, Gerriets, Sammer, Doerr, El-Shazly, Doeppner, Choi, Schoenburg and Juenemann.)

Background and Objectives : After major heart surgery, some patients report visual hallucinations that cannot be attributed to psychosis or delirium. This study aimed to investigate the hallucination incidence in patients after coronary artery bypass grafting with (on-pump) and without (off-pump) extracorporeal circulation. Materials and Methods : A total of 184 consecutive patients listed for elective on- or off-pump coronary artery bypass grafting were prospectively enrolled into the study. Preoperative baseline investigations 24-48 h before surgery (t0) and postoperative follow-up 24-48 h (t1) and 5-6 days (t2) after surgery included cognitive testing and a clinical visual acuity test (Landolt rings). Patients reporting visual hallucinations were interviewed using a structured survey to record the type, timing, duration, and frequency of their hallucinations. All the patients received a neurological examination and cranial magnetic resonance imaging if indicated. Results : Of the patients in the sample, 155 patients underwent on-pump bypass surgery, and 29 patients received off-pump surgery. Of these, 25 patients in the on-pump group, but none in the off-pump group, reported transient visual hallucinations ( p = 0.020), which could not be attributed to stroke, delirium, psychosis, migraine, or severely impaired vision. Significant correlations were observed for the occurrence of visual hallucinations and the amount of nicotine consumption and aortic clamp/extracorporeal circulation time. Conclusions : Transient visual hallucinations occur in a noticeable proportion of patients after on-pump heart surgery. Knowledge of the phenomenon's benignity is important for patients to prevent anxiety and uncertainty and for treating physicians to avoid unnecessary medication and drug-induced delirium.

Objectives: Following cardiac surgery, postoperative cognitive decline (POCD) is a common complication that can impair the quality of life and increase mortality. The aim of this study was to investigate whether early postoperative cognitive training can decrease POCD after cardiac surgery., Methods: The study was a multi-centred, two-arm, randomized (1:1 ratio), controlled trial involving older patients undergoing elective heart valve surgery with extracorporeal circulation. Recruitment took place at the Department of Cardiac Surgery of the Kerckhoff-Clinic in Bad Nauheim (Germany) and the University-Hospital in Giessen (Germany). The patients were randomized to either a paper-and-pencil-based cognitive training group or a standard rehabilitation care control group. The cognitive training started 1 week after surgery and lasted about 3 weeks until discharge from rehabilitation. To detect POCD, neuropsychological functions were assessed prior to surgery, upon discharge from rehabilitation (primary outcome), and 3 months after discharge (secondary outcome). Data were primarily analysed in a per-protocol fashion., Results: The frequency of POCD at discharge from rehabilitation (training group, n = 37; control group, n = 44) was 50% in the control group and 19% in the training group (χ2[1] = 8.45, P = 0.004; odds ratio = 4.29, 95% confidence interval [1.56-11.80]). Three months after the cognitive training (training group, n = 33; control group, n = 34), POCD frequency was 29% in the control group and 6% in the training group (χ2[1] = 6.21, P = 0.013; odds ratio = 6.46, 95% confidence interval [1.29-32.28])., Conclusions: Since our cognitive training showed beneficial effects, it could be a promising method to prevent POCD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Association of cognitive impairment with chronic kidney disease has been reported over the last decade. Individuals show better cognitive performance after kidney transplantation than individuals on dialysis but are more likely to be affected by cognitive impairment than age-matched comparison groups. Better knowledge of the prevalence as well as course and profile of cognitive impairment is important for the design of future studies assessing the clinical impact of cognitive impairment and developing management strategies. The goal of our study is to examine the extent of cognitive impairment before and after transplantation and to derive a distinct profile of cognitive function using standard neurocognitive tests. Furthermore, we aim to assess whether transplantation per se leads to an improvement in cognitive performance., Methods: We are conducting a prospective single-center cohort study involving 100 kidney transplant individuals. Individuals who are wait-listed to receive a kidney transplantation or have already received one will be included in this study. Individuals will undergo a battery of detailed neurocognitive tests at baseline (in part before surgery), and then 3 and 12 months afterwards. Furthermore, the enrolled patients will complete a validated German version of the Cognitive Failure Questionnaire for self-assessment (s-CFQ) as well as the Hospital Anxiety and Depression Scale -Deutsche (HADS-D), a self-report screening instrument with two scales that capture anxiety and depression. In addition, a hair sample will be taken at each measurement time point for the determination of hair cortisol levels as a parameter for the cumulative hypothalamic-pituitary-adrenocortical axis activity over the previous three months. The primary outcome measure will be (a) the effect of kidney transplantation on the cognitive performance up to 12 months after transplantation and (b) the course of cognitive performance following kidney transplantation over time., Discussion: The results of our study have potentially important implications for the prevention and treatment of cognitive impairment in kidney transplant individuals. By increasing our knowledge of the neurocognitive profile and assigning the corresponding deficits, it might be possible to create an individualized training program to positively impact cognitive deficits in kidney transplant patients., (© 2022. The Author(s).)

Purpose: During an ICU stay, changes in muscles and nerves occur that is accessible via neuromuscular sonography., Methods: 17 patients recruited from the neurological and neurosurgical ICU (six women; 66 ± 3 years) and 7 healthy controls (three women, 75 ± 3 years) were included. Muscle sonography (rectus abdominis, biceps, rectus femoris and tibialis anterior muscles) using gray-scale values (GSVs), and nerve ultrasound (peroneal, tibial and sural nerves) analyzing the cross-sectional area (CSA) were performed on days 1 (t1), 3 (t2), 5 (t3), 8 (t4), and 16 (t5) after admission., Results: Time course analysis revealed that GSVs were significantly higher within the patient group for all of the investigated muscles (rectus abdominis: F = 7.536; p = 0.011; biceps: F = 14.761; p = 0.001; rectus femoris: F = 9.455; p = 0.005; tibialis anterior: F = 7.282; p = 0.012). The higher GSVs were already visible at t1 or, at the latest, at t2 (tibialis anterior muscles). CSA was enlarged in all of the investigated nerves in the patient group (peroneal nerve: F = 7.129; p = 0.014; tibial nerve: F = 28.976, p < 0.001; sural nerve: F = 13.051; p = 0.001). The changes were visible very early (tibial nerve: t1; peroneal nerve: t2). The CSA of the motor nerves showed an association with the ventilation time and days within the ICU (t1 through t4; p < 0.05)., Discussion: We detected very early changes in the muscles and nerves of ICU-patients. Nerve CSA might be a useful parameter to identify patients who are at risk for difficult weaning. Therefore our observations might be severity signs of neuromuscular suffering for the most severe patients., (© 2021. The Author(s).)

Oropharyngeal sensitivity plays a vital role in the initiation of the swallowing reflex and is thought to decline as part of the aging-process. Taste and smell functions appear to decline with age as well. The aim of our study was to generate data of oral sensitivity in healthy participants for future studies and to analyse age-related changes and their interdependence by measuring oral sensitivity, taste, and smell function. The experiment involved 30 participants younger than and 30 participants older than 60. Sensitivity threshold as a surrogate of oral sensitivity was measured at the anterior faucial pillar by electrical stimulation using commercially available pudendal electrode mounted on a gloved finger. Smell and taste were evaluated using commercially available test kits. Mean sensitivity was lower in young participants compared to older participants (1.9 ± 0.59 mA vs. 2.42 ± 1.03 mA; p = 0.021). Young participants also performed better in smell (Score 11.13 ± 0.86 vs 9.3 ± 1.93; p < 0.001) and taste examinations (Score 11.83 ± 1.86 vs 8.53 ± 3.18; p < 0.001). ANCOVA revealed a statistical association between sensitivity and smell (p = 0.08) that was moderated by age (p = 0.044). Electrical threshold testing at the anterior faucial pillar is a simple, safe, and accurate diagnostic measure of oral sensitivity. We detected a decline of oral sensitivity, taste, and smell in older adults.Trial registration: Clinicaltrials.gov, NCT03240965. Registered 7th August 2017- https://clinicaltrials.gov/ct2/show/NCT03240965 ., (© 2022. The Author(s).)

Purpose: Multiple sclerosis (MS) is the most common immune-mediated CNS disease, characterised by demyelination and progressive neurological disability. The B-cell activating factor BAFF has been described as one important factor in the pathophysiology of different autoimmune diseases., Methods: We measured BAFF levels in the serum and cerebrospinal fluid (CSF) in 50 consecutive patients with MS and 35 patients with infectious CNS disease (ID). 52 patients with other, non-inflammatory disorders (OND), served as controls., Results: BAFF-serum levels in ID patients were higher than in patients diagnosed with MS (ID 0.55 ± 0.24 ng/ml, MS 0.43 ± 0.14 ng/ml, OND 0.45 ± 0.24 ng/ml; p  = 0.09). Interestingly, MS patients had lower BAFF CSF levels compared to the controls and ID patients, and the CSF levels in the latter were elevated compared to those of the controls (MS 0.17 ± 0.11 ng/ml, OND 0.25 ± 0.14 ng/ml, ID 0.97 ± 0.78 ng/ml; p  < 0.001)., Conclusions: The ID patients' having higher absolute BAFF levels in the CSF than in the serum indicates that the increased BAFF CSF levels were caused by intrathecal synthesis rather than passive transfer via a disturbed blood-brain-barrier. The significantly decreased BAFF CSF levels in MS patients were a surprising result of our study. Although it has been reported that astrocytes in active MS lesions can express BAFF, the soluble form was not increased in the CSF of MS patients. It remains unclear whether the inflammatory features of active MS plaques are truly represented by the CSF compartment.

Background: Hereditary Transthyretin-Related Amyloidosis, a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the TTR gene, is characterized by the deposition of insoluble misfolded protein fibrils. The diagnosis, especially in non-endemic areas, is typically delayed by 4-5 years; a misdiagnosis due to clinical heterogeneity is common. The study objective was to define the prevalence of Hereditary Transthyretin-Related Amyloidosis in patients with polyneuropathy and/or cardiomyopathy of no obvious aetiology., Method: A multicenter observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis"-TRAM study was performed in Germany, Austria, and Switzerland., Results: A total of 5141 participants were recruited by 50 neurologic and 27 cardiologic specialized centres. Genetic analysis demonstrated a 1.1% Hereditary Transthyretin-Related Amyloidosis positivity rate among patients with polyneuropathy and/or cardiomyopathy of not obvious aetiology. Twenty-one various TTR variants ( TTR -positive) were identified. Body Mass Index was lower in the TTR -positive patients as an indicator for the involvement of the autonomic nervous system; the age of onset of clinical manifestations was higher in TTR -positive patients. There were no other genotype-phenotype correlations or the prevalence of specific clinical manifestations in TTR -positive patients., Conclusions: Our data support the fact that Hereditary Transthyretin-Related Amyloidosis is underdiagnosed in polyneuropathy and cardiomyopathy patients. Routine implementation of genetic testing is recommended in patients with unexplained polyneuropathy and/or cardiomyopathy to accelerate the earlier diagnosis and the time-sensitive treatment initiation.KEY MESSAGESMore than 5.000 participants with CM and/or PNP of no obvious aetiology were recruited in the observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis" TRAM study and screened for pathogenic TTR variants.The study demonstrated >1% of patients with CM and/or PNP of unclear aetiology are positive for a pathogenic TTR variant.Routine genetic testing is recommended in patients with unexplained CM and/or PNP to accelerate the initial diagnosis and timely treatment initiation.

Background: During cardiosurgical procedures that use extracorporeal circulation (ECC), a variety of neurological complications can occur, and postoperative cognitive deficits remain an unsolved problem. Among the sources of these complications are intraoperatively detectable cerebral microemboli, which mainly consist of air. This study's purpose was to assess neuroprotective effects of reducing these gaseous microemboli using a dynamic bubble trap (DBT) in patients undergoing pulmonary endarterectomy (PEA) for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH)., Methods: Patients undergoing PEA were randomly assigned to receive either a DBT (n=47) or no additional device (controls, n=46) during ECC. Neuropsychological testing was performed before and 3 months after PEA. The primary endpoint was cognitive improvement in the DBT group (n=29) compared with the control group (n=42). As secondary endpoint, ischemic brain micro-lesions were analyzed on postoperative days 6 through 10 using diffusion-weighted magnetic resonance imaging (MRI)., Results: Analysis of interaction effects revealed improved performance in visual long-term memory (P=0.008, η 2 =0.099), verbal long-term memory (P=0.030, η 2 =0.067), verbal short-term memory (P=0.014, η 2 =0.083), and attention and processing speed (P=0.043, η 2 =0.056) from pre- to post-testing in the DBT group compared to control group. In MRI, postoperative ischemic micro-lesions could only be detected in one patient; another patient suffered a severe bihemispheric embolic stroke., Conclusions: DBT positively influences memory function after PEA. This effect is most likely caused by the reduction of gaseous microemboli., Trial Registration: This study is registered in the German Clinical Trials Register, ID: DRKS00021499., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jtd-21-831). The following authors report financial activities outside the submitted work: Christoph B. Wiedenroth reports having received lecture honorary from Actelion, Bayer, BTG, MSD and Pfizer. Stefan Guth reports having received lecture honorary from Actelion, Bayer, MSD and Pfizer. The other authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

A novel wireless eight-channel electroencephalography (EEG) headset specially developed for ICUs was tested in regard of comparability with standard 10/20 EEG systems. The continuous EEG (cEEG) derivations via CerebAir EEG headset (Nihon Kohden Europe, Rosbach, Germany) and internationally standardized 10/20 reference EEGs as the diagnostic standard were performed in a mixed collective on a neurointensive care unit (neuro-ICU). The derivations were verified for comparability in detection of EEG background activity, epileptiform discharges, and seizure patterns. Fifty-two patients with vigilance reduction following serious neurological or metabolic diseases were included, and both methods were applied and further analyzed in 47. EEG background activity matched in 24 of 45 patients (53%; p = 0.126), epileptiform discharges matched in 32 (68%) patients (p = 0.162), and seizure activity matched in 98%. Overall, in 89% of the patients, cEEG detected the same or additional ICU-relevant EEG patterns. The tested wireless cEEG headset is a useful monitoring tool in patients with consciousness disorders. The present study indicates that long-term measurements with the wireless eight-channel cEEG lead to a higher seizure and epileptiform discharge detection compared to intermittent 10/20 EEG derivations in the ICU setting., (© 2020. Springer Nature B.V.)

Background: Superficial siderosis is a rare disease involving hemosiderin deposits on the surface of brain or spinal cord that are thought to cause clinical symptoms, which usually consist of cranial nerve dysfunction, cerebellar ataxia, or myelopathy. Pseudohallucinations have been described as the patient being aware of the nonreality of hallucination-like phenomena. Data on pseudohallucinations of cerebral somatic origin are sparse. We present a case of auditory and visual pseudohallucinations due to superficial siderosis. Siderosis was diagnosed using cerebrospinal fluid analysis and magnetic resonance imaging as part of the clinical routine for newly emerged psychiatric symptoms., Case Presentation: An 84-year-old white/european female presented to our hospital with no prior history of psychiatric or neurological disease and no history of trauma. She reported seeing things and hearing voices singing to her for some days. She was aware these phenomena were not real (pseudohallucinations). On examination, no relevant abnormalities were detected. Cerebrospinal fluid analysis showed elevated ferritin. Magnetic resonance imaging with susceptibility-weighted sequences revealed diffuse superficial siderosis in several parts of the brain, among other occipital and temporal gyri. The pseudohallucinations resolved with a risperidone regime. The patient was treated with rivaroxaban because of atrial fibrillation. Potentially elevating the risk of further hemorrhage, this therapy was discontinued, and an atrial appendage occlusion device was implanted., Conclusion: We report the first case of pseudohallucinations in superficial siderosis. The risk of missing this diagnosis can be reduced by applying a standardized diagnostic pathway for patients presenting with the first episode of psychiatric symptoms. Somatic and potentially treatable causes should not be missed because they might lead to unnecessary treatments, stigmatization, and legal restrictions of self-determination, especially for elderly people., (© 2021. The Author(s).)

Background: Early recanalization of an occluded vessel is associated with a better clinical outcome in acute ischemic stroke. Intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is only available in a minority of patients and often fails to reopen the occluded vessel. Mechanical recanalization is more effective in this matter but only available for selected patients when a thrombectomy centre can be reached. Therefore, sonothrombolysis might represent an alternative or complementary approach. Here, we tested microbubble-mediated sonothrombolysis (mmSTL) in a thromboembolic stroke model for middle cerebral artery occlusion (MCAO) in rats., Methods: Sixty-seven male Wistar rats underwent MCAO using an autologous full blood thrombus and were randomly assigned to four groups receiving rt-PA, mmSTL, a combination of both, or a placebo. Diagnostic workup included neurological examination, assessment of infarct size, and presence of intracerebral haemorrhage by magnetic resonance imaging (MRI) and presence of microbleedings in histological staining., Results: Neurological examination revealed no differences between the treatment groups. In all treatment groups, there was a reduction in infarct size 24 hours after MCAO as compared to the placebo (P≤0.05), but there were no differences between the active treatment groups (P>0.05) (placebo 0.75±0.10 cm 3 ; mmSTL 0.43±0.07 cm 3 ; rt-PA 0.4±0.07 cm 3 ; mmSTL + rt-PA 0.27±0.08 cm 3 ). Histological staining displayed intracerebral microbleedings in all animals. The frequency of gross bleeding detected by MRI did not differ between the groups (placebo 3; mmSTL 4; rt-PA 2; mmSTL + rt-PA 2; P>0.05) and was not associated with worse performance in clinical testing (P>0.05). There were no statistical differences in the mortality between the groups (P>0.05)., Conclusions: Our study showed the efficacy and safety of mmSTL with or without rt-PA in an embolic rat stroke model using a continuous full blood thrombus. Sonothrombolysis might be useful for patients who need to be transported to a thrombectomy centre or for those with distal vessel occlusion., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-21-75). TB reports grants from the University Medical Center Giessen and Marburg (UKGM), Germany; non-financial support from Bracco Suisse SA, Geneva, Switzerland, during the conduct of the study; non-financial support from Bayer Vital GmbH, outside the submitted work. The other authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Dysphagia is common in neurological disease. However, our understanding of swallowing and its central nervous control is limited. Sensory information plays a vital role in the initiation of the swallowing reflex and is often reduced in stroke patients. We hypothesized that the sensitivity threshold of the anterior faucial pillar could be facilitated by either electrical stimulation (ES) or taste and smell information. The sensitivity threshold was measured by ES in the anterior faucial pillar region. The measurement was repeated 5 min after baseline. Thirty minutes after baseline, the participants underwent a test for taste and smell. Immediately after the test, the ES was repeated. Thirty healthy volunteers with a mean age of 27 ± 5.1 participated in the trial. Mean sensitivity threshold at baseline was 1.9 ± 0.59 mA. The values 5 min after baseline (1.74 ± 0.56 mA, p = 0.027) and 30 min after baseline (1.67 ± 0.58 mA, p = 0.011) were significantly lower compared to the baseline, but there was no difference between the latter (p = 0.321). After 5 min, a potentially facilitating effect was found on oral sensitivity by ES of the faucial pillar area. Thirty minutes later, this effect was still present.Trial registration Clinicaltrials.gov, NCT03240965. Registered 7th August 2017- https://clinicaltrials.gov/ct2/show/NCT03240965 .

Background: We present the case of a 75-year-old female with acute embolic cerebral infarction caused by a fail-implanted venous port catheter system in the left subclavian artery., Case Presentation: A 75-year-old woman presented to our emergency room after acute onset of a right-sided hemiparesis and dysarthria. Within 2 days after admission, she developed a left-sided hemiparesis, ataxia with concordant gait disturbance and incoordination of the left upper limb. DWI-MRI showed acute multiple infarcts in both cerebral and cerebellar hemispheres. Laboratory examination, 24-h Holter electrocardiography and transthoracic echocardiography provided no pathological findings. Further examination revealed an arterially fail-implanted port catheter, placed in the left subclavian artery with its tip overlying the ascending aorta, as the source of cerebral embolism., Conclusion: This is the first case report of thromboembolic, cerebral infarction due to a misplaced venous port catheter in the subclavian artery, emphasizing the imperative need for a thorough diagnostic workup, when embolism is suspected but cannot be proven at first glance.

Purpose: Dysphagia is common in critically ill neurological patients and is associated with a high mortality and morbidity. Data on the usefulness of flexible endoscopic examination of swallowing (FEES) in neurological intensive care unit (ICU) patients are lacking, raising the need for evaluation., Method: FEES was performed in neurological intensive care patients suspected of dysphagia. We correlated findings with baseline data, disability status, pneumonia and duration of hospitalisation, as well as a need for mechanical ventilation or tracheotomy., Result: This analysis consisted of 125 patients with suspected dysphagia. Most of the patients (81; 64,8%) suffered from acute stroke. Dysphagia was diagnosed using FEES in 90 patients (72%). FEES results led to dietary modifications in 80 patients (64%). The outcome at discharge was worse in dysphagic stroke patients diagnosed by FEES as compared to non-dysphagic stroke patients ( p  = 0.009). Patients without oral diet had higher need for intubation ( p  = 0.007), tracheotomy ( p  = 0.032) and higher mortality ( p  < 0.001) in comparison to patients with at least small amounts of oral intake., Conclusion: As the clinical assessment of the patients often classified the dysphagia incorrectly, the broad use of FEES in ICU patients might help to adequately adjust patients' oral diet. This knowledge might contribute to lower mortality and morbidity.

The Functional Oral Intake Scale (FOIS) is the most frequently used scale for the evaluation of functional oral intake by dysphagia patients. FOIS was validated using data from Videofluoroscopic Swallowing Study (VFSS). Until now, a validated German version of FOIS for Flexible Endoscopic Evaluation of Swallowing (FEES) is lacking. The aim of this study was a cross-cultural validation of the German version of FOIS (FOIS-G) for FEES. The translation of the original FOIS was carried out according to the Translation, Review, Adjudication, Pretesting, Documentation (TRAPD) translation methodology. For the validation process, six experienced language therapists (SLT) retrospectively analyzed charts of 93 stroke patients. Inclusion criteria were comprised of stroke, clinical examination by an SLT within 24 h of admission, and FEES within 72 h of admission. The validity was calculated by comparison with Modified Rankin Scale (MRS), Barthel Index (BI), the Penetration-Aspiration-Scale (PAS), and a water swallow test. Spearman rank correlation of all paired raters ranged from r s  = 0.96 to r s  = 0.99, and percentage agreement ranged from 81 to 94%. The overall agreement between all raters was calculated by Fleiss kappa (0.83) (s.e. 0.02). There is a significant correlation between the BI and the MRS with the FOIS-G (r s  = 0.301, p = 0.003 for BI; r s = - 0.366, p < 0.001 for MRS), between the PAS and the FOIS-G (r s  = - 0.758, p < 0.001), as well as between the 70 ml-water-test and the FOIS-G (r s  = 0.470, p < 0.001). FOIS-G is a valid instrument for the evaluation of the functional oral intake of food and liquids in dysphagia patients.

Purpose: Patients undergoing cardiac surgery often develop delirium which increases the risk of postoperative morbidity and leads to a reduced quality of life. Retrospective studies show a higher incidence of delirium in patients with seizures. However, these studies do not systematically detect subclinical seizures, so the incidence of seizures after cardiac surgery remains speculative. The objective of this study is to determine the prevalence of electrographic seizures after elective open-chamber cardiac surgery., Methods: This prospective, blinded, monocentric, observational study investigated patients scheduled for elective open-chamber valve reconstruction or replacement. Anaesthesia, surgery and postoperative treatment were standardized and not influenced by the presented observation. After surgery, all patients arrived at the ICU, and EEG monitoring started within the first hour. EEG recording was continuously performed for up to 24 h, and the results were independently analysed by two blinded EEG board-certified neurologists., Results: 100 patients were included. Abnormal EEG patterns were present in 33% of patients, and 9% of all patients showed electrographic seizures. The main EEG activity at the beginning of each recording was suppressed or showed a burst-suppression pattern, and at the end of recording, all patients had an alpha/theta rhythm. An association between electrographic seizures and delirium was found (p χ2  < 0.01)., Conclusion: This study reveals a surprisingly high incidence of abnormal EEG patterns and electrographic seizures in patients undergoing open-chamber cardiac surgery. As electrographic seizures are associated with the incidence of delirium, this finding is a relevant phenomenon in the post-cardiac surgery ICU population.

Objective: This study was designed to investigate the indirect neuroprotective properties of recombinant human erythropoietin (rhEPO) pretreatment in a rat model of transient middle cerebral artery occlusion (MCAO)., Methods: One hundred and ten male Wistar rats were randomly assigned to four groups receiving either 5,000 IU/kg rhEPO intravenously or saline 15 minutes prior to MCAO and bilateral craniectomy or sham craniectomy. Bilateral craniectomy aimed at elimination of the space-consuming effect of postischemic edema. Diagnostic workup included neurological examination, assessment of infarct size and cerebral edema by magnetic resonance imaging, wet-dry technique, and quantification of hemispheric and local cerebral blood flow (CBF) by flat-panel volumetric computed tomography., Results: In the absence of craniectomy, EPO pretreatment led to a significant reduction in infarct volume (34.83 ± 9.84% vs. 25.28 ± 7.03%; p = 0.022) and midline shift (0.114 ± 0.023 cm vs. 0.083 ± 0.027 cm; p = 0.013). We observed a significant increase in regional CBF in cortical areas of the ischemic infarct (72.29 ± 24.00% vs. 105.53 ± 33.10%; p = 0.043) but not the whole hemispheres. Infarct size-independent parameters could not demonstrate a statistically significant reduction in cerebral edema with EPO treatment., Conclusions: Single-dose pretreatment with rhEPO 5,000 IU/kg significantly reduces ischemic lesion volume and increases local CBF in penumbral areas of ischemia 24 h after transient MCAO in rats. Data suggest indirect neuroprotection from edema and the resultant pressure-reducing and blood flow-increasing effects mediated by EPO., Competing Interests: Conflict of interest: The authors states no conflict of interest., (© 2020 Martin Juenemann et al., published by De Gruyter.)

Introduction: Successful thrombectomy improves morbidity and mortality after stroke. The present prospective, observational cohort study investigated a potential correlation between the successful restoration of tissue perfusion by mechanical thrombectomy and intact cerebrovascular autoregulation (CA)., Objective: Status of CA in patients with large vessel occlusive stroke after thrombectomy., Methods: After thrombectomy CA was measured using transcranial Doppler ultrasound. For this purpose a moving correlation index (Mxa) based on spontaneous arterial blood pressure fluctuations and corresponding cerebral blood flow velocity changes was calculated. CA impairment was defined by Mxa values more than .3., Results: Twenty patients with an acute occlusion of the middle cerebral artery or distal internal carotid artery were included. A successful recanalization of the occluded vessel via interventional thrombectomy was achieved in 10 of these patients (successful recanalization group), while in 10 patients mechanical recanalization failed or could not be applied (no recanalization group). Mean Mxa at stroke side was .58 ± .21 Table 2a in patients with successful intervention. At the unaffected hemisphere Mxa was .50 ± .20 Table 2a in successful recanalization group and .45 ± .24 Table 2b in no recanalization group without statistically significant differences. Based on the previously defined Mxa cut off more than .3, CA impairment was observable in all successful recanalized patients and in 8 of 10 patients with unsuccessful interventional treatment., Conclusions: These results suggest that brain perfusion may be affected due to impaired CA even after successful mechanical thrombectomy. Therefore, a tight blood pressure management is of great importance in post-thrombectomy stroke treatment to avoid cerebral hypo- and hyperperfusion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The occurrence of postoperative cognitive deficits, especially after heart surgery, has been demonstrated in several studies. These deficits can clearly be noticed by the patients and by their close relatives in daily life. Furthermore, postoperative cognitive deficits can decrease quality of life in social functioning and earning capacity. The aim of this study is to investigate whether early postoperative cognitive training can reduce subjective and objective postoperative cognitive deficits., Methods: The proposed study is a multicenter, two-arm, randomized controlled trial involving 144 elderly patients undergoing elective heart-valve surgery with extracorporeal circulation. Patients will be assigned to either a training group or a control group. The intervention involves paper-and-pencil-based cognitive training, which is conducted for 36 min over a period of 18 days. The training starts about 1 week after surgery and is carried out during the hospitalized rehabilitation phase. The control group will not receive cognitive training or a placebo intervention. A detailed assessment of psychological functions and health-related quality of life prior to surgery at discharge from rehabilitation and 3 and 12 months after discharge will be performed. The primary outcome of this trial is the training effect on objective cognitive functions at discharge from rehabilitation. Secondary outcomes are the training effect on objective and subjective cognitive functions (3 and 12 months after discharge), depression, health-related quality of life, and the impact of perioperative cerebral ischemia on the training effect. Perioperative cerebral ischemia will be measured with postoperative magnetic resonance imaging including diffusion-weighted sequences., Discussion: Should it be shown that our cognitive training can improve postoperative cognitive deficits and quality of life, one possibility could be to integrate this intervention into early rehabilitation. Furthermore, we hope that the investigation of perioperative ischemia by diffusion-weighted magnetic resonance imaging will improve our understanding of neurobiological factors influencing the course of postoperative cognitive plasticity., Trial Registration: German Clinical Trials Register (DRKS), DRKS00015512. Retrospectively registered on 21 September 2018.

Background: Diagnosing dysphagia in acute stroke patients is crucial, as this comorbidity determines morbidity and mortality; we therefore investigated the impact of flexible nasolaryngeal endoscopy (FEES) in acute stroke patients., Methods: The FEES investigation as performed in acute stroke patients treated at a large university hospital, allocated as a standard procedure for all patients suspected of dysphagia. We correlated our findings with baseline data, disability status, pneumonia, duration of hospitalisation, necessity for mechanical ventilation and treatment on the intensive care unit. The study was designed as a cross-sectional hospital-based registry., Results: We investigated 152 patients. The median age was 73; 94 were male. Ischemic stroke was diagnosed in 125 patients (82.2%); 27 (17.8%) suffered intracerebral haemorrhage. Oropharyngeal dysphagia was diagnosed in 72.4% of the patients, and was associated with higher stroke severity on admission (median NIHSS 11 [IQR 6-17] vs. 7 [4-12], p = .013; median mRS 5 [IQR 4-5] vs. 4 [IQR 3-5], p = .012). Short-term mortality was higher among patients diagnosed with dysphagia (7.2% vs. 0%, p = .107). FEES examinations revealed that only 30.9% of the patients had an oral diet appropriate for their swallowing abilities. A change of oral diet was associated with a better outcome at discharge (mRS; p = .006), less need of mechanical ventilation (p = .028), shorter period of hospitalisation (p = .044), and lower rates of pneumonia (p = .007) and mortality (p = .011)., Conclusion: Due to the inability of clinical assessments to detect silent aspiration, FEES might be better suited to identify stroke patients at risk and may contribute to a better functional outcome and lower rates of pneumonia and mortality. Our findings also point to a low awareness of dysphagia, even in a specialised stroke centre. FEES in acute stroke patients helps to adjust the oral diet for the vast majority of stroke patients (69.1%) based on their swallowing abilities, potentially avoiding severe complications.

Background: An association between Tako-Tsubo cardiomyopathy (TTC) and underlying malignancies has been observed, suggesting that TTC might be the consequence of paraneoplastic phenomena. This study investigates the presence of autoantibodies against cardiomyocytes as well as adrenergic (β 1 , β 2 ) and muscarinic (M2) receptors in patients with TTC., Methods and Results: Serum from 20 TTC patients and 20 controls with ischemic heart disease was obtained. Indirect immunofluorescence testing for intracellular autoantibodies against cardiomyocytes showed a homogenous distribution, as in both groups 9 of 20 sera displayed a characteristic binding pattern of antibodies including vascular walls and intracellular structures. Flow cytometry analysis revealed no difference between TTC and controls in the binding of autoantibodies to the surface antigens of cardiomyocyte HL-1 cells (p = 0.569, t-test). Flow cytometry analysis of nontransfected wild type cells (p = 0.633, t-test), M2 receptor-transfected cells (p = 0.687, t-test), β 1 receptor-transfected cells (p = 0.444, t-test) and β 2 receptor-transfected cells (p = 0.632, t-test) showed similar results for control and TTC sera. Likewise, the binding pattern of TTC patients with a history of neoplasia compared to those without or to controls did not differ significantly (p > 0.05, u-test)., Conclusion: Findings suggest that the presumed paraneoplastic etiology of TTC cannot be attributed to the formation of these antibodies., (Copyright © 2018. Published by Elsevier GmbH.)

Background: Computer-assisted planimetry is widely used in experimental stroke research to assess the size of the ischemic lesion or hemispheric volume., New Method: Only insufficient data exist on the training required to achieve sufficient reliability in planimetry. Therefore, planimetry was performed over 15 months by two blinded raters who were initially inexperienced in the method. For inter-rater reliability, the hemispheric and lesional volume of 227 male Wistar Unilever rats subjected to middle cerebral artery occlusion were determined in diffusion- and T2-weighted sequences. For the intra-rater agreement, one investigator assessed the hemispheric and lesional volume in 87 T2-weighted sequences twice within a six-week interval. The correlation was calculated using Krippendorff's alpha and Bland-Altman plots illustrated the agreement., Results: Inter-rater agreement increased during the first seven weeks and remained at high values (Krippendorff's alpha > 0.88). For intra-rater agreement, Krippendorff's alpha was 0.84 for hemispheric and 0.85 for lesional volume. The Bland-Altman plot indicated solid agreement between raters in the absence of systematic errors., Comparison With Existing Methods: Simplified geometrical models or automated methods for planimetry can be used to determine lesional volume, but both approaches are inappropriate to assess hemispheric volume., Conclusion: Computer-assisted planimetry can be an appropriate method to determine hemispheric or ischemic lesion volume in rodents but requires a sufficiently long learning period of approximately two months. Even an experienced investigator can generate data with serious variation. Inter- and intra-rater-dependent bias should be considered during the design and performance of respective studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Fibre-endoscopic evaluation of swallowing (FEES) to detect dysphagia is gaining more and more importance as a diagnostic tool. Therefore, we have investigated the impact of FEES in neurological patients in a clinical setting., Design: Cross-sectional hospital-based registry., Setting: Primary acute care in a neurological department of a German university hospital., Participants: 241patients with various neurological diseases who underwent FEES procedure., Primary and Secondary Outcome Measures: Dysphagia and related comorbidities., Results: 267 FEES were performed in 241 patients with various neurological diagnoses. Dysphagia was diagnosed in 68.9% of the patients. In only 33.1% of the patients, appropriate oral diet was chosen prior to FEES. A relevant dysphagia occurred more often in patients with structural brain lesions (83.1% vs 65.3%, P=0.001), patients with dysphagia had a longer hospitalisation (median 18 (IQR 12-30) vs 15 days (IQR 9.75-22.75), P=0.005) and had a higher mortality (8.4% vs 1.3%, P=0.041). When the oral diet was changed, we observed a lower pneumonia rate (36% vs 50%, P=0.051) and a lower mortality (3.7% vs 11.3%, P=0.043) in comparison to no change of oral diet. A restriction of oral diet was identified more often in older patients (median 75 years (IQR 66.3-82 years) vs median 72 years (IQR 60-79 years), P=0.01) and in patients with structural brain lesions (86.8% vs 73.1%, P=0.05)., Conclusion: On clinical investigation, dysphagia was misjudged for the majority of the patients. FEES might help to compensate this drawback, revising the diet regime in nearly 70% of the patients., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Continuous electroencephalography (cEEG) improves monitoring of the brain in unconscious patients, but implementation at ICU is difficult. The present investigation shows a way to introduce cEEG at an anesthesiological ICU and discusses the first experiences., Materials and Methods: The study analyzed the feasibility of cEEG, assessed the interpretable cEEG time, importance of automatic seizure detection, the incidence of seizures, the predominant background EEG activity, incidence of delirium and mortality., Results: Fifty-three cEEGs of 50 patients with a median interpretable length of 24 hours [IQR 20 to 42 hours] were recorded. One patient had status epilepticus, while 5 patients had non-convulsive seizures. Automated seizure detection recognized the status epilepticus and 3 of 10 non-convulsive seizures, however, detected 42 false positive seizures. Predominant background EEG activity was alpha (9%), theta (17%), delta (26%), burst-suppression (17%), and suppressed background activity (30%). EEG activity correlated neither with dosage of analgo-sedative drugs nor with incidence of delirium or mortality., Conclusion: Continuous electroencephalography recording is feasible and manageable. Automatic seizure detection was often false negative/positive; therefore, the interpretation of the cEEG should be supported by EEG-trained neurologists. Background EEG activity was not associated with outcome parameters, which suggests that background activity is a poor outcome predictor., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Great advances have been made in our understanding of Takotsubo syndrome in the past decade, but the aetiology of the condition remains incompletely understood. The most established theory, that catecholamine-mediated myocardial stunning is provoked by emotional or physiological stress, is supported by the presence of supraphysiological levels of plasma catecholamines in patients with Takotsubo syndrome. For this reason, the hyperexcitability of the autonomic nervous system under conditions of physical and emotional stress is often assessed in these patients. Observational studies have indicated that a predisposing influence of chronic or traumatic stress, anxiodepressive disorders, and maladaptive personality traits are linked to the pathogenesis of Takotsubo syndrome. Chronic stress can influence autonomic function through dysregulation of the hypothalamic-pituitary-adrenal axis and contribute to the development of cardiovascular disorders. In this Perspectives article, we discuss the current knowledge of the psychoneuroendocrinological and psychosocial mechanisms underlying the pathophysiology of Takotsubo syndrome.

Background: Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model., Methods: We tested BR38 and SonoVue® microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery. Rats were randomized to treatment (n = 6/group): control, rt-PA, or rt-PA+3-MHz ultrasound insonation with BR38 or SonoVue® at full or 1/3 dose. Treatment duration was 60 minutes, beginning after withdrawal of the filament, and sacrifice was immediately after treatment. Vascular volumes were evaluated with microcomputed tomography., Results: Total vascular volume of the ipsilateral hemisphere was reduced in control and rt-PA groups (p<0.05), but was not significantly different from the contralateral hemisphere in all microbubble-treated groups (p>0.1)., Conclusions: Microbubble-enhanced sonothrombolysis improves microvascular patency. This effect is not dose- or microbubble formulation-dependent suggesting a class effect of microbubbles promoting microvascular reopening. This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory.

Objectives: Postoperative cognitive decline (POCD) has a perceivable influence on daily living and is noticed more often by close relatives than by patients themselves 3 months after aortic valve replacement. This study aimed to elucidate the longitudinal course of the subjective awareness of POCD., Design: Follow-up of a prospective observational study., Setting: A single cardiothoracic center in Germany., Participants: The study included 108 patients scheduled for elective aortic valve replacement surgery and 85 close relatives of the patients., Interventions: In addition to conducting a neuropsychologic examination, the authors previously interviewed 82 patients with a Cognitive Failure Questionnaire for self-assessment (s-CFQ), and 62 relatives with the Cognitive Failure Questionnaire for others (f-CFQ) before and 3 months after surgery. Up until 12 months after surgery, the authors continuously interviewed additional patients (baseline and 3 months after surgery), thereby enlarging the original sample, and included the entire group (108 patients, 85 relatives) for the 12-month follow-up., Results: The analysis showed that relatives (p = 0.026) and patients experienced patients' cognitive decline 3 months after surgery (p = 0.009). All changes still were observed in questions related to memory and attention. After 1 year, the s-CFQ no longer differed between baseline and postoperative assessment. Mean scores in the f-CFQ still were above baseline, barely missing statistical significance (p = 0.051). In patients with "change to worse" in the f-CFQ at 1-year follow-up, declining cognitive results in nonverbal learning (p = 0.021) could be observed 3 months postoperatively. Only a decrease in 3-month f-CFQ correlated with a decline in specific neuropsychologic tests 3 months after surgery., Conclusions: Contrary to the authors' previous results, the impact of POCD on daily living functions also was recognized by the patients themselves. The long-term influence and the associations between subjective deficits and psychometric cognitive measures seemed to be assessed more reliably by close relatives., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Moyamoya syndrome is a vasculopathy characterised by progressive occlusion of the cerebral arteries resulting in the development of abnormal collateral circulation. To diagnose this syndrome, imaging of the cerebral arteries is required including CT- or MR-angiography and conventional angiography. We present a case of moyamoya disease with typical findings detected in the sonography. The diagnosis was suspected after reviewing the initial ultrasound images of the cerebral arteries with evidence for obliterated intracranial arteries and the detection of an existing collateral circulation network., Case Presentation: A 62 years old male patient presented in the hospital's emergency department with symptoms indicating a subacute cerebrovascular event. Immediate sonographic studies showed a right-sided pulsatile Doppler-signal in the common and internal carotid arteries, suggestive of distal stenoses. In addition, the transcranial examination indicated obliteration of both middle cerebral arteries. Numerous arterial vessels suggestive of leptomeningeal collateral arteries revealed a strong arterial leptomeningeal flow. At this stage of the diagnostic work-up, the collateral circulation network, characteristic of moyamoya disease, was indicated by sonography. Moyamoya syndrome was verified by conventional angiography. The aetiological work remained empty, so the diagnosis of moyamoya disease was established., Conclusion: Our case report indicates that sonography can be a useful tool for detecting the vaculopathy in moyamoya syndrome. In case routine procedures, such as the CT- or MR-angiography, with evidence for obliterated intracerebral arteries, ultrasound studies might provide important information regarding an existing collateral network in the scope of a moyamoya syndrome.

Background: Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system, which is characterized by autoantibodies directed against the water channel aquaporin-4 (AQP4). As one of the main water regulators in the central nervous system, APQ4 is supposed to be involved in the dynamics of brain edema. Cerebral edema seriously affects clinical outcome after ischemic stroke; we therefore aimed to investigate whether NMO-antibodies may exert the same functional effects as an AQP4-inhibitor in-vivo in acute ischemic stroke., Methods: Sixteen male Wistar rats were randomized into two groups twice receiving either purified NMO-IgG or immune globulin from healthy controls, 24 hours and 30 minutes before middle cerebral artery occlusion (MCAO) was performed. T2-weighted MRI was carried out 24 hours after MCAO., Results: MRI-examination showed a significant increase of infarct size in relation to the cerebral hemisphere volume with NMO-IgG treated animals (27.1% ± 11.1% vs. 14.3% ± 7.2%; p < 0.05) when corrected for the space-occupying effect of vasogenic edema formation and similar results without edema correction (34.4% ± 16.4% vs. 17.5% ± 9.3%; p < 0.05). Furthermore, T2-RT revealed a significant increase in cortical brain water content of the treatment group (19.5 ms ± 9.7 ms vs. 9.2 ms ± 5.2 ms; p < 0.05)., Conclusions: These results support the functional impact of NMO-antibodies and also offer an in-vivo-applicable animal model to investigate the properties of AQP4 in ischemic stroke.