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Zusammenfassung  Die durch Ultraschall beschleunigte beziehungsweise induzierte Gefäßrekanalisation, die so genannte Sonothrombolyse, stellt ein neuartiges Therapiekonzept in der Schlaganfallbehandlung dar. Verschiedene experimentelle und klinische Studien belegen die synergistischen Effekte, die sich durch gleichzeitige Behandlung mit Ultraschall und einem Fibrinolytikum erzielen lassen. Gleichzeitig könnte ein rt-PA („recombinant tissue plasmonigen activator“) -unabhängiger Einsatz zu einer Verbesserung der Prognose bei Patienten mit Kontraindikationen für eine Fibrinolytikabehandlung führen. Durch zusätzliche Gabe von Echosignalverstärkern lässt sich das thrombolytische Potenzial des Ultraschalls weiter steigern. Neben dem Wirksamkeitsnachweis kommt dem Nachweis einer ausreichenden Behandlungssicherheit bei der Entwicklung von Therapiegeräten eine zentrale Bedeutung zu. Die vorliegende Arbeit gibt eine Übersicht über den gegenwärtigen klinischen und experimentellen Stand der Entwicklung dieses Therapiekonzeptes. [ABSTRACT FROM AUTHOR]

Investigating focal cerebral ischaemia requires animal models that are relevant to human stroke. This study was designed to evaluate the influence of early reperfusion and choice of rat strains on infarct volume and oedema formation. Thirty-six Wistar and Sprague–Dawley rats were subjected to temporary middle cerebral artery occlusion (MCAO) for 90 min (groups I and II) or to permanent MCAO (groups III and IV) using the suture technique. Ischaemic lesion volume and oedema formation were quantified 24 h after MCAO using 7T-magnetic resonance imaging (MRI). Impact of rat strains: Reperfusion led to significant larger ischaemic lesion volumes in Wistar rats as compared to Sprague–Dawley rats (P<0.0005). Oedema formation was similar in both rat strains. Permanent MCAO led to significantly larger ischaemic lesion volumes in Sprague–Dawley rats (P<0.05). Oedema formation, however, was significantly more accentuated in Wistar rats (P<0.005). Impact of reperfusion: Reperfusion did not cause any changes in ischaemic lesion volume in Wistar rats. Oedema formation, however, was significantly reduced (P<0.0005). In Sprague–Dawley rats, reperfusion caused a significant reduction of ischaemic lesion volume (P<0.00005), but did not modify oedema formation. These findings emphasize the critical importance of rat strain differences in experimental stroke research. [ABSTRACT FROM AUTHOR]

Background: White matter lesions and subclinical cerebral ischemia (SCI) are described as risk factors for postoperative cognitive decline (POCD) following cardiac surgery. This report aims to investigate the effect of brain lesions on postoperative cognitive training outcomes., Methods: In a randomized, treatment-as-usual controlled trial, elderly patients scheduled for elective heart valve surgery participated. The postoperative cognitive training comprised paper-and-pencil exercises. Neuropsychological parameters were assessed preoperatively, at discharge from rehabilitation (immediately post-training), and at the 3-month follow-up. In addition, depression and anxiety (HADS) as well as health-related quality of life (SF-36) were evaluated. Brain lesions were identified using magnetic resonance imaging (training group: n = 18; control group: n = 21). Specifically, periventricular white matter lesions (PVWML) and deep white matter lesions (DWML) were assessed using T2-weighted/FLAIR sequences and categorized according to Fazekas scale. Volumetric analysis of SCI was conducted using diffusion-weighted imaging. To statistically control the impact of brain lesions on training outcomes, we employed analysis of covariance., Results: Three-month follow-up results: When controlling for the independence of SCI on training outcomes, effects were evident for global cognition (p = 0.022) and SF-36 mental component summary (p = 0.003). Considering the impact of PVWML on training outcomes, trained participants showed better values in depression (p = 0.046) and SF-36 mental component summary (p = 0.013). In a subgroup analysis for patients with PVWML the training group demonstrated superior performance for language (p = 0.037). After adjusting for DWML, training effects were noticeable in the SF-36 mental component summary (p = 0.013)., Conclusion: Patients with brain lesions may benefit from cognitive training after cardiac surgery., (Copyright © 2025 Elsevier B.V. All rights reserved.)

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).)

Cerebral sinus venous thrombosis (CSVT) is an uncommon disease that is usually treated with anticoagulation (heparin, low-molecular heparin, or vitamin K-antagonists). We compared treatment with edoxaban, an oral factor Xa-antagonist, that has not been approved in patients with CSVT, with enoxaparin, a well-established therapy, in a rat model of CSVT. Fifty male Wistar rats were randomized into 5 groups (10 animals each) and subjected to aluminum chloride (AlCl3)-induced thrombosis of the superior sagittal sinus (SSS) or sham procedure. Animals with thrombosis of the SSS were treated with edoxaban, enoxaparin, or placebo. Diagnostic workup included neurological examination, MRI imaging, MR-flow measurements of the SSS, and immunohistochemical staining. Neurological examination revealed no differences between treatment groups. Seven days after initial thrombosis, flow in the SSS was lower in the active treatment group as compared to sham-operated animals (p < 0.05). Flow in the SSS in the active treatment groups (edoxaban 1 h prior to thrombosis: 0.16 cm/s ± 0.06 cm/s; edoxaban 6 h after thrombosis: 0.13 cm/s ± 0.05 cm/s; enoxaparin: 0.13 cm/s ± 0.04 cm/s; placebo: 0.07 cm/s ± 0.02 cm/s) was higher as compared to placebo (p < 0.05), but there were no differences between the active treatment groups (p > 0.05). Immunohistochemical staining showed no differences in the actively treated animals. Edoxaban proved to be similar to enoxaparin in a model of experimental AlCl 3 -induced CSVT., (© 2023. The Author(s).)

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.)

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.)

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: 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.)

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.

Medial medullary infarction (MMI) is a vascular occlusion in the medulla oblongata leading to certain constellations of neurological symptoms and seriously affecting the patient. Effective evidence-based treatment of severe dysphagia as sole symptom of MMI has not yet been reported. This case study aims to report successful effects of evidence-based therapy based on findings of dysphagia symptoms and pathophysiology of swallowing by flexible endoscopic evaluation of swallowing (FEES) in severe isolated dysphagia after MMI. FEES was performed to evaluate swallowing pathophysiology and dysphagia symptoms in a 57-year-old male with severe dysphagia after MMI. On the basis of FEES findings, simple and high-frequent evidence-based exercises for improvement of swallowing were implemented: thermal stimulation of faucial arches, Jaw Opening Exercise, and Jaw Opening Against Resistance. After 7 weeks of high-frequent evidence-based therapy and regular FEES evaluation the patient was set on full oral diet with no evidence of aspiration risk. In a first case report of isolated dysphagia in MMI our case illustrates that high-frequent evidence-based dysphagia therapy in combination with FEES as the method to evaluate and monitor swallowing pathophysiology can lead to successful and quick rehabilitation of severely affected dysphagic patients., Competing Interests: S. Hamzic, P. Schramm, H. Khilan, T. Gerriets declared that they have no conflict of interest. M. Juenemann has received grants from German Heart Research Foundation (Deutsche Stiftung für Herzforschung) and from Kerckhoff-Foundation (Kerckhoff-Stiftung) with no relevance to the paper., (Copyright © 2021 by S. Karger AG, Basel.)

IgLON5 antibody encephalopathy is a rare but increasingly recognized disorder with a variety of clinical signs. Typical symptoms are sleep disorder, gait disturbances, signs of bulbar dysfunction and a variety of neurological symptoms like oculomotor abnormalities and movement disorders. In addition, cognitive decline can be a prominent symptom. So far, there are only a few studies that have dealt with the course and possible treatment options of IgLON5 antibody encephalopathy. In this study the clinical case of a female patient with IgLON5 antibody disease and the response to treatment is described. Here we report on the case of a 67-year-old female patient who showed cognitive deterioration, gait difficulties, and chronic obstructive sleep disorder. The diagnostic course showed a positive anti-IgLON5 serum and anti-IgLON5 IgG antibodies in cerebrospinal fluid. The patient was subsequently treated with high dosage i.v. methylprednisolone, i.v. immunoglobulins and plasmapheresis. Neuropsychological tests showed cognitive deficits in different domains, including verbal and visual memory. Both, neuropsychological deficits and antibody titer, showed an improvement after plasmapheresis. The presented case shows that IgLON5 disease can present with rapidly progressing cognitive deterioration as the prominent symptom, adding to the variety of clinical signs in this disorder. Testing for IgLON5-antibodies should be considered in patients with progressing cognitive decline, especially if accompanied by sleep disorders or neurological symptoms like oculomotor abnormalities, dysautonomia or bulbar signs., 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 © 2021 El Shazly, Juenemann, Gerriets and Tschernatsch.)

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.

Background and Purpose: Dysphagia is common in acute stroke and leads to worse overall outcome. Transesophageal echocardiography (TEE) is used in the diagnostic evaluation of stroke with regard to its etiology and is a known cause of postoperative dysphagia in cardiac surgery. The prevalence of dysphagia in acute stroke patients undergoing TEE remains unknown. The aim of the Transesophageal Echocardiography - Dysphagia Risk in Acute Stroke (TEDRAS) study was to assess the influence of TEE on swallowing among patients who have experienced acute stroke., Methods: The TEDRAS study was a prospective, blind, randomized, controlled trial that included two groups of patients with acute stroke. Simple unrestricted randomization was performed, and examiners were blinded to each other's results. Swallowing was tested using flexible endoscopic evaluation of swallowing (FEES) at three different time points in the intervention group (24 h before, immediately after and 24 h after TEE) and in the control group (FEES on three consecutive days and TEE earliest after the third FEES). Validated scales were used to assess dysphagia severity for all time points as primary outcome measures., Results: A total of 34 patients were randomized: 19 to the intervention group and 15 to the control group. The key findings of the repeated-measures between-group comparisons were significant increases in the intervention group for the following dysphagia measures: (1) secretion severity score (immediately after TEE: P < 0.001; 24 h after TEE: P < 0.001) and (2) Penetration-Aspiration Scale score for saliva (immediately after TEE: P < 0.001; 24 h after TEE: P = 0.007), for small (immediately after TEE: P = 0.009) and large liquid boli (immediately after TEE: P = 0.009; 24 h after TEE: P = 0.025)., Conclusion: The results indicate a negative influence of TEE on swallowing in acute stroke patients for at least 24 hours., (© 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

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.)

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: 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.)