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This paper describes the self-heating effects resulting from mechanical deformation in the additively manufactured aluminium alloy AlSi7Mg0.6. The material’s self-heating effect results from irreversible changes in the material’s microstructure that are directly coupled with the inelastic deformations. These processes are highly dissipative, which is reflected in the heat generation of the material. To describe such effects, a numerical framework that combines an elasto-viscoplastic Chaboche model with the Gurson Tvergaard Needleman damage approach is analysed and thermomechanically extended. This paper characterises the sample preparation, the experimental set-up, the development of the thermomechanical approach, and the material model. A user material subroutine applies the complete material model for the finite element software Abaqus 2022. To validate the material model and the parameters, a complex tensile test is performed. In order to check the finite element model, the energy transformation ratio is included in the evaluation. The numerical analyses of the mechanical stress evolution and the self-heating behaviour demonstrate good agreement with the experimental test. In addition, the calculation shows the expected behaviour of the void volume fraction that rises from the initial value of 0.0373% to a higher value under a complex mechanical load.

Induced Pluripotent Stem Cell (iPSC) lines derived from healthy individuals are helpful and essential tools for disease modelling. Here, we described the reprogramming of skin fibroblasts obtained from a healthy 59-year-old individual without Alzheimer’s disease. The generated iPSC lines have a normal karyotype, expressed pluripotency markers, and demonstrated the ability to differentiate into the three germ layers. The iPSC lines will be used as controls to study Alzheimer’s disease mechanisms.

ABSTRACTHuman bornavirus encephalitis is an emerging disease caused by the variegated squirrel bornavirus 1 (VSBV-1) and the Borna disease virus 1 (BoDV-1). While characteristic brain magnetic resonance imaging (MRI) changes have been described for BoDV-1 encephalitis, only scarce diagnostic data in VSBV-1 encephalitis exist. We systematically analysed brain MRI scans from all known VSBV-1 encephalitis patients. Initial and follow-up scans demonstrated characteristic T2 hyperintense lesions in the limbic system and the basal ganglia, followed by the brainstem. No involvement of the cerebellar cortex was seen. Deep white matter affection occurred in a later stage of the disease. Strict symmetry of pathologic changes was seen in 62%. T2 hyperintense areas were often associated with low T1 signal intensity and with mass effect. Sinusitis in three patients on the first MRI and an early involvement of the limbic system suggest an olfactory route of VSBV-1 entry. The viral spread could occur per continuitatem to adjacent anatomical brain regions or along specific neural tracts to more distant brain regions. The number and extent of lesions did not correlate with the length of patients’ survivals. The overall pattern closely resembles that described for BoDV-1 encephalitis. The exact bornavirus species can thus not be deduced from imaging results alone, and molecular testing and serology should be performed to confirm the causative bornavirus. As VSBV-1 is likely of tropical origin, and MRI investigations are increasingly available globally, imaging techniques might be helpful to facilitate an early presumptive diagnosis of VSBV-1 encephalitis when molecular and/or serological testing is not available.

Alzheimer’s disease (AD) is a progressive neurological disorder and the most common form of dementia worldwide. Sporadic Alzheimer’s disease (sAD) cases are the main forms, over 95% of AD cases, but still poorly understood. Thereby there is a crucial need to develop in vitro models for studying this multifactorial disorder. Here, we report the reprogramming of skin fibroblasts from a 57-years-old male donor. The new generated iPSC cell line has a normal karyotype and, is pluripotent since it demonstrates the ability to differentiate in vitro into the three germ layers. This iPSC line will be used to understand pathological mechanisms of sAD.

Objective: The goal of awake craniotomy in glioma patients is sparing of cognitive function. Previous investigations suggest that patients in the postoperative state may reach their preoperative level regarding domain-based criteria. Data on significant postoperative improvement beyond the preoperative level is sparse. This article examines the prospective neuropsychological assessment of a glioma patient who underwent awake craniotomy and has shown functional improvement exceeding preoperative levels. Methods: A 34-year-old patient with high premorbid cognitive function level who underwent awake craniotomy for left frontal oligodendroglioma was neuropsychologically assessed and took part in a fMRI-examination at 3 different time points. Results: Preoperative examination revealed severe isolated impairment of working memory, long-term narrative memory in free recall and recognition, and alertness with intact language production and comprehension. After transient global aphasia in the postoperative state, the follow-up examination showed significant improvement in memory and attention exceeding the preoperative level. Conclusions: Tumor location is an important factor in terms of surgical procedures. Cognitive impairment is, however, not always associated with a specific location. Mechanical pressure of the tumor might have led to the isolated consolidation deficit which fully recovered after tumor removal. Psychological disorders should be taken into account regarding prodromal symptoms of neurooncological diseases.

Abstract Cachexia occurs in late stages of liver cirrhosis, and a low‐fat mass is potentially associated with poor outcome. This study compared different computed tomography (CT)–derived fat parameters with respect to its prognostic impact on the development of complications and death before and after liver transplantation. Between 2001 and 2014, 612 patients with liver cirrhosis without hepatocellular carcinoma listed for liver transplantation met the inclusion criteria, including abdominal CT scan (±200 days to listing). A total of 109 patients without cirrhosis served as controls. The subcutaneous fat index (SCFI), the paraspinal muscle fat index, and the visceral fat index were assessed at L3/L4 level and normalized to the height (cm2/m2). Data were collected and analyzed retrospectively. Low SCFI was associated with a higher rate of ascites and increased C‐reactive protein levels (p < 0.001). In addition, multivariate Cox regression analysis adjusting for sex, age, body mass index (BMI), and Model for End‐Stage Liver Disease showed that decreasing SCFI was also associated with an increased risk of cirrhosis‐related complications (p = 0.003) and death on the transplant wait list (p = 0.013). Increased paraspinal and visceral fat were not only positively correlated with creatinine levels (p < 0.001), BMI, and metabolic comorbidities (all p < 0.001) before transplantation, but also predictive for 1‐year mortality after transplantation. Conclusion: The distribution of body fat is a major determinant for complications and outcome in cirrhosis before and after liver transplantation.

Purpose: Cranioplasty is most commonly performed after decompressive hemicraniectomy and serves on the one hand for protection of the underlying brain tissue, on the other hand this surgery is also indicated for cosmetic reasons. In addition, patients may experience clinical improvement after this procedure, which can be explained by normalization of the CSF (Cerebrospinal fluid) and cerebral blood flow. However, this (usually underestimated) procedure is associated with one of the the highest complication rates in neurosurgery. Results: We report a case with a fatal outcome after routine cranioplasty utilizing PEEK (polyetheretherketone) implant due to a cerebrospinal fluid fistula. Conclusion: Cranioplasty after decompressive hemicraniectomy can restore aesthetics, ensures protection, and often leads to neurologic improvement in patients. However, it is one of the procedures with the highest complication rates in neurosurgery, and it should not be underestimated. The use of a drain with suction can have fatal consequences, especially when dural integrity is compromised and when there is intracranial room for considerable volume shift, e.g. after hemispheric infarction.

Background Non-ischemic cerebral enhancing (NICE) lesions have been reported as a rare complication of various neuroendovascular procedures, but information on their incidence after flow diversion is scant. It is unclear if specific devices or novel coating technologies may impact their occurrence. Methods We conducted a multicenter study on the incidence of NICE lesions after flow diverter (FD) implantation for cerebral aneurysm treatment. Results Eight centers identified 15 patients and provided detailed data. The clinical presentation ranged from asymptomatic to hemiplegia and cognitive impairment. The mean time to diagnosis after treatment was 65.1±101.5 days. Five centers disclosed information on all of their 1201 FD procedures during the inclusion period (2015-2022), during which 12 patients were diagnosed with NICE lesions in these institutions--that is, an incidence of 1%. FD coatings did not increase the incidence (6/591 patients (1%) treated with surface-modified FD vs 6/610 patients (1%) treated with bare FD; P=1.00). Significantly increased rates of 3.7% (6 cases in 161 procedures; P<0.01) and 3.3% (5 cases in 153 procedures; P<0.01) were found with stents of two specific product lines. The use of one product line was associated with a significantly lower incidence (0 cases in 499 procedures (0%); P<0.01). Conclusions Novel stent coatings are not associated with an increased incidence of NICE lesions. The incidence rate of 1% suggests that these lesions may occur more often after flow diversion than after other endovascular treatments. We found a concerning accumulation of NICE lesion cases when FDs from two product families were used. [ABSTRACT FROM AUTHOR]

Background and Purpose The Save ChildS Study demonstrated that endovascular thrombectomy (EVT) is a safe treatment option for pediatric stroke patients with large vessel occlusions (LVOs) with high recanalization rates. Our aim was to determine the long-term cost, health consequences and cost-effectiveness of EVT in this patient population. Methods In this retrospective study, a decision-analytic Markov model estimated lifetime costs and quality-adjusted life years (QALYs). Early outcome parameters were based on the entire Save ChildS Study to model the EVT group. As no randomized data exist, the Save ChildS patient subgroup with unsuccessful recanalization was used to model the standard of care group. For modeling of lifetime estimates, pediatric and adult input parameters were obtained from the current literature. The analysis was conducted in a United States setting applying healthcare and societal perspectives. Probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set to $100,000 per QALY. Results The model results yielded EVT as the dominant (cost-effective as well as cost-saving) strategy for pediatric stroke patients. The incremental effectiveness for the average age of 11.3 years at first stroke in the Save ChildS Study was determined as an additional 4.02 lifetime QALYs, with lifetime cost-savings that amounted to $169,982 from a healthcare perspective and $254,110 when applying a societal perspective. Acceptability rates for EVT were 96.60% and 96.66% for the healthcare and societal perspectives. Conclusions EVT for pediatric stroke patients with LVOs resulted in added QALY and reduced lifetime costs. Based on the available data in the Save ChildS Study, EVT is very likely to be a cost-effective treatment strategy for childhood stroke.

Studies on interferon-driven brain pathology have so far been hampered by the lack of appropriate animal models. Here the authors characterize RNASET2-deficient mice and show that neuroinflammation and brain atrophy are IFNAR1-dependent.

BackgroundCerebral vasospasm (CVS) continues to account for high morbidity and mortality in patients surviving the initial aneurysmal subarachnoid hemorrhage (SAH). Nimodipine is the only drug known to reduce delayed cerebral ischemia (DCI), but it is believed not to affect large vessel CVS. Milrinone has emerged as a promising option. Our retrospective study focused on the effectiveness of the intra-arterial application of both drugs in monotherapy and combined therapy.MethodsWe searched for patients with aneurysmal SAH, angiographically confirmed CVS, and at least one intra-arterial pharmacological angioplasty. Ten defined vessel sections on angiograms were assessed before and after vasodilator infusion. The improvement in vessel diameters was compared to the frequency of DCI-related cerebral infarction before hospital discharge and functional outcome reported as the modified Rankin Scale (mRS) score after 6 months.ResultsBetween 2014 and 2021, 132 intra-arterial interventions (144 vascular territories, 12 bilaterally) in 30 patients were analyzed for this study. The vasodilating effect of nimodipine was superior to milrinone in all intradural segments. There was no significant intergroup difference concerning outcome in mRS (p = 0.217). Only nimodipine or the combined approach could prevent DCI-related infarction (both 57.1%), not milrinone alone (87.5%). Both drugs induced a doubled vasopressor demand due to blood pressure decrease, but milrinone alone induced tachycardia.ConclusionsThe monotherapy with intra-arterial nimodipine was superior to milrinone. Nimodipine and milrinone may be used complementary in an escalation scheme with the administration of nimodipine first, complemented by milrinone in cases of severe CVS. Milrinone monotherapy is not recommended.

This paper describes the self-heating effects resulting from mechanical deformation in the additively manufactured aluminium alloy AlSi7Mg0.6. The material's self-heating effect results from irreversible changes in the material's microstructure that are directly coupled with the inelastic deformations. These processes are highly dissipative, which is reflected in the heat generation of the material. To describe such effects, a numerical framework that combines an elasto-viscoplastic Chaboche model with the Gurson Tvergaard Needleman damage approach is analysed and thermomechanically extended. This paper characterises the sample preparation, the experimental set-up, the development of the thermomechanical approach, and the material model. A user material subroutine applies the complete material model for the finite element software Abaqus 2022. To validate the material model and the parameters, a complex tensile test is performed. In order to check the finite element model, the energy transformation ratio is included in the evaluation. The numerical analyses of the mechanical stress evolution and the self-heating behaviour demonstrate good agreement with the experimental test. In addition, the calculation shows the expected behaviour of the void volume fraction that rises from the initial value of 0.0373 % to a higher value under a complex mechanical load. [ABSTRACT FROM AUTHOR]

We report on a case of a 16-year old boy with a contrast-enhancing mass on the left parietal lobe that showed complete remission after biopsy. Histological examination revealed a diffuse glioma. Due to this unusual course, an extended neurological evaluation was carried out. Cerebrospinal fluid (CSF) was analysed and electrophysiological studies were performed. There was no strong evidence for an inflammable disease and no other pathology could be identified with sufficient certainty. In the follow up cranial MRI scan 6, 12, and 18 months after surgery, complete remission of the contrast-enhancing mass and the perifocal edema persisted. Such a case has not yet been reported.

As chemically specialized forms of the extracellular matrix in the central nervous system, polyanionic perineuronal nets (PNs) contain diverse constituents, including chondroitin sulfate proteoglycans (CSPGs), hyaluronic acid, and tenascins. They are detectable by various histological approaches such as colloidal iron binding and immunohistochemical staining to reveal, for instance, the CSPGs aggrecan, neurocan, phosphacan, and versican. Moreover, biotin, peroxidase, or fluorescein conjugates of the lectins Vicia villosa agglutinin and soybean agglutinin enable the visualization of PNs. At present, the N-acetylgalactosamine-binding Wisteria floribunda agglutinin (WFA) is the most widely applied marker for PNs. Therefore, this article is largely focused on methodological aspects of WFA staining. Notably, fluorescent WFA labeling allows, after its conversion into electron-dense adducts, electron microscopic analyses. Furthermore, the usefulness of WFA conjugates for the oftentimes neglected in vivo and in vitro labeling of PNs is emphasized. Subsequently, we discuss impaired WFA-staining sites after long-lasting experiments in vitro, especially in autoptic brain samples with long postmortem delay and partial enzymatic degradation, while immunolabeling of aggrecan and CSPG link proteins under such conditions has proven more robust. In some hippocampal regions from perfusion-fixed mice, more PNs are aggrecan immunoreactive than WFA positive, whereas the retrosplenial cortex displays many WFA-binding PNs devoid of visible aggrecan immunoreactivity. Additional multiple fluorescence labeling exemplarily revealed in ischemic tissue diminished staining of WFA-binding sites and aquaporin 4 and concomitantly upregulated immunolabeling of neurofilament, light chains, and collagen IV. Finally, we briefly discuss possible future staining approaches based on nanobodies to facilitate novel technologies revealing details of net morphology.

AGO2 binds to miRNAs to repress expression of cognate target mRNAs. Here the authors report that heterozygous AGO2 mutations result in defects in neurological development and impair RNA interference.

Abstract Meningioma represents the most common primary brain tumor in adults. Recently several non-NF2 mutations in meningioma have been identified and correlated with certain pathological subtypes, locations and clinical observations. Alterations of cellular pathways due to these mutations, however, have largely remained elusive. Here we report that the Krueppel like factor 4 (KLF4)-K409Q mutation in skull base meningiomas triggers a distinct tumor phenotype. Transcriptomic analysis of 17 meningioma samples revealed that KLF4 K409Q mutated tumors harbor an upregulation of hypoxia dependent pathways. Detailed in vitro investigation further showed that the KLF4 K409Q mutation induces HIF-1α through the reduction of prolyl hydroxylase activity and causes an upregulation of downstream HIF-1α targets. Finally, we demonstrate that KLF4 K409Q mutated tumors are susceptible to mTOR inhibition by Temsirolimus. Taken together, our data link the KLF4K409Q mediated upregulation of HIF pathways to the clinical and biological characteristics of these skull base meningiomas possibly opening new therapeutic avenues for this distinct meningioma subtype.

Abstract Background Hemodynamic therapy with Flow-Diverters has become a fundamental option for treatment of cerebral aneurysms. A major obstacle of Flow-Diverters is the comparatively stiff microcatheter required for implantation. Consequentially, maneuverability is limited and primary catheterization of peripheral targets may be difficult or even futile in challenging vascular anatomies. To overcome this, a highly navigable microcatheter must be used to attain the desired vascular segment, followed by a hardly controllable exchange-maneuver via a long microwire, involving a high risk for wire-perforation. Our study aimed to investigate the value of low-profile stent-retrievers as a railway for introduction of the required microcatheter, which allows to maintain a stable endovascular position and reduce the risk for procedural vessel injury. Methods 14cases (8females, mean-age 59y) of Flow-Diverter-Implantation requiring the use of a low-profile stent-retriever were reviewed. All cases featured a challenging vascular anatomy. After micro-catheterization of the desired segment, the stent-retriever was carefully deployed as an anchor in a secure, distal location. In all cases a pREset/LITE-stent-retriever was used for introduction of the equipment required for implantation. Results In all cases the anchoring-maneuver was performed without technical complications. The stent-retrievers maintained a stable position after deployment in all situations. No potential traumatic sudden movements of the microcatheter occurred. No procedure-related perforations, dissections or vasospasms were observable during the interventions or their aftermath. Conclusions In our experience the stent-retriever-anchoring-maneuver represents a potentially essential and safe amendment for flow diverter treatment in technically challenging situations.

Background: Treatment of cerebral aneurysms using hemodynamic implants such as endosaccular flow disruptors and endoluminal flow diverters has gained significant momentum during recent years. The intended target zone of those devices is the immediate interface between aneurysm and parent vessel. The therapeutic success is based on the reduction of aneurysmal perfusion and the subsequent formation of a neointima along the surface of the implant. However, a subset of aneurysms–off-centered bifurcation aneurysms involving the origin of efferent branches and aneurysms arising from peripheral segments of small cerebral vessels–oftentimes cannot be treated via coiling or implanting a hemodynamic implant at the neck level for technical reasons. In those cases, indirect flow diversion–a flow diverter deployed in the main artery proximal to the parent vessel of the aneurysm–can be a viable treatment strategy, but clinical evidence is lacking in this regard.Materials and Methods: Five neurovascular centers contributed to this retrospective analysis of patients who were treated with indirect flow diversion. Clinical data, aneurysm characteristics, anti-platelet medication, and follow-up results, including procedural and post-procedural complications, were recorded.Results: Seventeen patients (mean age: 60.5 years, range: 35–77 years) with 17 target aneurysms (vertebrobasilar: n = 9) were treated with indirect flow diversion. The average distance between the flow-diverting stent and the aneurysm was 1.65 mm (range: 0.4–2.4 mm). In 15/17 patients (88.2%), perfusion of the aneurysm was reduced immediately after implantation. Follow-ups were available for 12 cases. Delayed opacification (OKM A3: 11.8%), reduction in size (OKM B1-3: 29.4%) and occlusion (D1: 47.1%) were observable at the latest investigation. Clinically relevant procedural complications and adverse events in the early phase and in the late subacute phase were not observed in any case.Conclusion: Our preliminary data suggest that indirect flow diversion is a safe, feasible, and effective approach to off-centered bifurcation aneurysms and distant small-vessel aneurysms. However, validation with larger studies, including long-term outcomes and optimized imaging, is warranted.

CSF protein levels are altered in neurological disorders, such as hydrocephalus of different etiologies. In this retrospective observational study, we analyzed cerebrospinal fluid (CSF) samples in hydrocephalic diseases such as aqueductal stenosis (AQS, n = 27), normal pressure hydrocephalus (NPH, n = 24), hydrocephalus communicans (commHC, n = 25) and idiopathic intracranial hypertension (IIH)/pseudotumor cerebri (PC, n = 7) in comparison with neurological patients without hydrocephalic configuration (control, n = 95). CSF was obtained through CSF diversion procedures and lumbar punction and analyzed for protein concentrations according to the institution’s laboratory standards. We found significantly decreased CSF protein levels in patients suffering from AQS (0.13 mg/dL [0.1–0.16 mg/dL] p = 2.28 × 10−8) and from PC (0.18 mg/dL [0.12–0.24 mg/dL] p = 0.01) compared with controls (0.34 mg/dL [0.33–0.35 mg/dL]). Protein levels were not altered in patients suffering from commHC and NPH compared with neurologically healthy individuals. We propose that a decrease in CSF protein levels is part of an active counterregulatory mechanism to lower CSF volume and, subsequently, intracranial pressure in specific diseases. Research regarding said mechanism and more specific proteomic research on a cellular level must still be performed to prove this hypothesis. Differences in protein levels between different diseases point to different etiologies and mechanisms in different hydrocephalic pathologies.

The regulation of surface tension (ST) by surfactants plays an important role in the human respiratory system but is largely unexplored in brain homeostasis. The aim of this study was to evaluate changes in ST in relation to surfactant proteins (SPs) in children with intraventricular hemorrhage (IVH). CSF samples from 93 patients were analyzed for ST with a force tensiometer and SP-A-D and -G with ELISA assays. Patients belonged to six groups: (i) IVH before primary intervention (PI), (ii) IVH 4–28 days after PI, (iii) IVH 44–357 days after PI, (iv) hydrocephalus, (v) sepsis and (vi) controls. We found indirect correlations and significant differences in ST and SPs (all p < 0.001; except for SP-C, p = 0.007). Post hoc analyses showed significantly decreased ST in IVH patients before PI compared with patients with hydrocephalus, sepsis or controls (p < 0.001), but it increased in IVH patients over time. All SPs were significantly elevated when comparing IVH patients before PI with controls (all p < 0.001; except for SP-C, p = 0.003). Children suffering from IVH displayed an increase in SPs and a decrease in ST as coping mechanisms to preserve CSF flow. The increase in ST over time could serve as prognostic marker for the healing process.