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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).

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.sub.[chi]2 < 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., Author(s): Marlene Tschernatsch [sup.1] [sup.2] [sup.3], Martin Juenemann [sup.1] [sup.2], Fouad Alhaidar [sup.4], Jasmin El Shazly [sup.1], Marius Butz [sup.1] [sup.2], Marco Meyer [sup.5], Tibo Gerriets [sup.1] [sup.2] [sup.3], Markus [...]

Hypoxia 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 η2 = 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 η2 = 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide 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. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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. A multicenter observational "Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis"—TRAM study was performed in Germany, Austria, and Switzerland. 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. 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. More 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Despite clear evidence for the effectiveness of oral anticoagulation (OA) in patients with atrial fibrillation (AF), there is evidence for the underutilisation of this therapy in the secondary stroke prevention. We therefore investigate the link between the use of OA in stroke patients with AF and favourable clinical outcome following the acute event. Methods The study population was determined by identifying the overlap of two different databases: a stroke registry and claims data of a health insurance company. Baseline data originated from the registry; documented dementia and the prescriptions for OA were derived from the insurance database. Patients with AF, minor physical impairment, and evidence of more than 30 days without further hospitalisation within the subsequent 90 days after the acute event were selected for the analysis. Results 1828 patients were selected (mean age 77.6 years), 1064 patients (58.2%) were female. 827 patients (45%) received a prescription for OA. The following factors were independently associated with a prescription for oral anticoagulants: increased age (OR: 0.54, CI: 0.46-0.63; P < 0.0001), female sex (OR: 0.77, CI: 0.63-0.94; P < 0.011), worsening disability status at discharge (OR: 0.88, CI: 0.81-0.96; P < 0.006), and documented dementia (OR: 0.54, CI: 0.39-0.73; P < 0.001). Conversely, treatment in a neurological department was associated with prescription for OA (OR: 1.47, CI: 1.19-1.81; P < 0.003). Conclusions In more than half of the patients with AF who suffered a stroke OA was not prescribed. The factors associated with reluctance in prescribing anticoagulants are increasing age, female sex, treatment at a non-neurological department, worsening disability, and dementia. [ABSTRACT FROM AUTHOR]