Newly Diagnosed IDH-Wildtype Glioblastoma and Temporal Muscle Thickness: A Multicenter Analysis

Background: Reduced temporal muscle thickness (TMT) has been discussed as a prognostic marker in IDH-wildtype glioblastoma. This retrospective multicenter study was designed to investigate whether TMT is an independent prognostic marker in newly diagnosed glioblastoma. Methods: TMT was retrospectively measured in 335 patients with newly diagnosed glioblastoma between 1 January 2014 and 31 December 2019 at the University Hospitals of Leipzig and Rostock. The cohort was dichotomized by TMT and tested for association with overall survival (OS) after 12 months by multivariate proportional hazard calculation. Results: TMT of 7.0 mm or more was associated with increased OS (46.3 ± 3.9% versus 36.6 ± 3.9%, p > 0.001). However, the sub-groups showed significant epidemiological differences. In multivariate proportional hazard calculation, patient age (HR 1.01; p = 0.004), MGMT promoter status (HR 0.76; p = 0.002), EOR (HR 0.61), adjuvant irradiation (HR 0.24) and adjuvant chemotherapy (HR 0.40; all p < 0.001) were independent prognostic markers for OS. However, KPS (HR 1.00, p = 0.31), BMI (HR 0.98, p = 0.11) and TMT (HR 1.06; p = 0.07) were not significantly associated with OS. Conclusion: TMT has not appeared as a statistically independent prognostic marker in this cohort of patients with newly diagnosed IDH-wildtype glioblastoma

Recurrence of chronic subdural hematoma due to low-grade infection

Despite the high incidence and multitudes of operative techniques, the risk factors for chronic subdural hematoma (CSDH) recurrence are still under debate and a universal consensus on the pathophysiology is lacking. We hypothesized that clinically inapparent, a low-grade infection could be responsible for CSDH recurrence. This investigation is a single-center prospective observational study including patients with recurrent CSDH. In total, 44 patients with CSDH recurrence received an intraoperative swab-based microbiological test. The intraoperative swab revealed an inapparent low-grade hematoma infection in 29% of the recurrent CSDH cases. The majority (69%) of the identified germs belonged to the staphylococcus genus. We therefore, propose a novel potential pathophysiology for CSDH recurrence

MicroRNA-335-5p suppresses voltage-gated sodium channel expression and may be a target for seizure control

There remains an urgent need for new therapies for treatment-resistant epilepsy. Sodium channel blockers are effective for seizure control in common forms of epilepsy, but loss of sodium channel function underlies some genetic forms of epilepsy. Approaches that provide bidirectional control of sodium channel expression are needed. MicroRNAs (miRNA) are small noncoding RNAs which negatively regulate gene expression. Here we show that genome-wide miRNA screening of hippocampal tissue from a rat epilepsy model, mice treated with the antiseizure medicine cannabidiol, and plasma from patients with treatment-resistant epilepsy, converge on a single target-miR-335-5p. Pathway analysis on predicted and validated miR-335-5p targets identified multiple voltage-gated sodium channels (VGSCs). Intracerebroventricular injection of antisense oligonucleotides against miR-335-5p resulted in upregulation of Scn1a, Scn2a, and Scn3a in the mouse brain and an increased action potential rising phase and greater excitability of hippocampal pyramidal neurons in brain slice recordings, consistent with VGSCs as functional targets of miR-335-5p. Blocking miR-335-5p also increased voltage-gated sodium currents and SCN1A, SCN2A, and SCN3A expression in human induced pluripotent stem cell-derived neurons. Inhibition of miR-335-5p increased susceptibility to tonic-clonic seizures in the pentylenetetrazol seizure model, whereas adeno-associated virus 9-mediated overexpression of miR-335-5p reduced seizure severity and improved survival. These studies suggest modulation of miR-335-5p may be a means to regulate VGSCs and affect neuronal excitability and seizures. Changes to miR-335-5p may reflect compensatory mechanisms to control excitability and could provide biomarker or therapeutic strategies for different types of treatment-resistant epilepsy

Frailty in cerebellar ischemic stroke—The significance of temporal muscle thickness

While comprising only 2% of all ischemic strokes, cerebellar strokes are responsible for substantial morbidity and mortality due to their subtle initial presentation and the morbidity of posterior fossa swelling. Furthermore, low temporal muscle thickness (TMT) has recently been identified as a prognostic imaging parameter to assess patient frailty and outcome. We analyzed radiological and clinical data sets of 282 patients with cerebellar ischemic stroke. Our analysis showed a significant association between low TMT, reduced NIHSS and mRS at discharge (p = 0.035, p = 0.004), and reduced mRS at 12 months (p = 0.001). TMT may be used as a prognostic imaging marker and objective tool to assess outcomes in patients with cerebellar ischemic stroke

Triplet Repeat–Derived siRNAs Enhance RNA–Mediated Toxicity in a Drosophila Model for Myotonic Dystrophy

More than 20 human neurological and neurodegenerative diseases are caused by simple DNA repeat expansions; among these, non-coding CTG repeat expansions are the basis of myotonic dystrophy (DM1). Recent work, however, has also revealed that many human genes have anti-sense transcripts, raising the possibility that human trinucleotide expansion diseases may be comprised of pathogenic activities due both to a sense expanded-repeat transcript and to an anti-sense expanded-repeat transcript. We established a Drosophila model for DM1 and tested the role of interactions between expanded CTG transcripts and expanded CAG repeat transcripts. These studies revealed dramatically enhanced toxicity in flies co-expressing CTG with CAG expanded repeats. Expression of the two transcripts led to novel pathogenesis with the generation of dcr-2 and ago2-dependent 21-nt triplet repeat-derived siRNAs. These small RNAs targeted the expression of CAG-containing genes, such as Ataxin-2 and TATA binding protein (TBP), which bear long CAG repeats in both fly and man. These findings indicate that the generation of triplet repeat-derived siRNAs may dramatically enhance toxicity in human repeat expansion diseases in which anti-sense transcription occurs

Newly Diagnosed IDH-Wildtype Glioblastoma and Temporal Muscle Thickness: A Multicenter Analysis

Background: Reduced temporal muscle thickness (TMT) has been discussed as a prognostic marker in IDH-wildtype glioblastoma. This retrospective multicenter study was designed to investigate whether TMT is an independent prognostic marker in newly diagnosed glioblastoma. Methods: TMT was retrospectively measured in 335 patients with newly diagnosed glioblastoma between 1 January 2014 and 31 December 2019 at the University Hospitals of Leipzig and Rostock. The cohort was dichotomized by TMT and tested for association with overall survival (OS) after 12 months by multivariate proportional hazard calculation. Results: TMT of 7.0 mm or more was associated with increased OS (46.3 ± 3.9% versus 36.6 ± 3.9%, p > 0.001). However, the sub-groups showed significant epidemiological differences. In multivariate proportional hazard calculation, patient age (HR 1.01; p = 0.004), MGMT promoter status (HR 0.76; p = 0.002), EOR (HR 0.61), adjuvant irradiation (HR 0.24) and adjuvant chemotherapy (HR 0.40; all p < 0.001) were independent prognostic markers for OS. However, KPS (HR 1.00, p = 0.31), BMI (HR 0.98, p = 0.11) and TMT (HR 1.06; p = 0.07) were not significantly associated with OS. Conclusion: TMT has not appeared as a statistically independent prognostic marker in this cohort of patients with newly diagnosed IDH-wildtype glioblastoma

Newly Diagnosed IDH-Wildtype Glioblastoma and Temporal Muscle Thickness: A Multicenter Analysis

Background: Reduced temporal muscle thickness (TMT) has been discussed as a prognostic marker in IDH-wildtype glioblastoma. This retrospective multicenter study was designed to investigate whether TMT is an independent prognostic marker in newly diagnosed glioblastoma. Methods: TMT was retrospectively measured in 335 patients with newly diagnosed glioblastoma between 1 January 2014 and 31 December 2019 at the University Hospitals of Leipzig and Rostock. The cohort was dichotomized by TMT and tested for association with overall survival (OS) after 12 months by multivariate proportional hazard calculation. Results: TMT of 7.0 mm or more was associated with increased OS (46.3 ± 3.9% versus 36.6 ± 3.9%, p &gt; 0.001). However, the sub-groups showed significant epidemiological differences. In multivariate proportional hazard calculation, patient age (HR 1.01; p = 0.004), MGMT promoter status (HR 0.76; p = 0.002), EOR (HR 0.61), adjuvant irradiation (HR 0.24) and adjuvant chemotherapy (HR 0.40; all p &lt; 0.001) were independent prognostic markers for OS. However, KPS (HR 1.00, p = 0.31), BMI (HR 0.98, p = 0.11) and TMT (HR 1.06; p = 0.07) were not significantly associated with OS. Conclusion: TMT has not appeared as a statistically independent prognostic marker in this cohort of patients with newly diagnosed IDH-wildtype glioblastoma

Locally Applied Valproate Enhances Survival in Rats after Neocortical Treatment with Tetanus Toxin and Cobalt Chloride

Purpose. In neocortical epilepsies not satisfactorily responsive to systemic antiepileptic drug therapy, local application of antiepileptic agents onto the epileptic focus may enhance treatment efficacy and tolerability. We describe the effects of focally applied valproate (VPA) in a newly emerging rat model of neocortical epilepsy induced by tetanus toxin (TeT) plus cobalt chloride (CoCl2). Methods. In rats, VPA () or sodium chloride (NaCl) () containing polycaprolactone (PCL) implants were applied onto the right motor cortex treated before with a triple injection of 75 ng TeT plus 15 mg CoCl2. Video-EEG monitoring was performed with intracortical depth electrodes. Results. All rats randomized to the NaCl group died within one week after surgery. In contrast, the rats treated with local VPA survived significantly longer (). In both groups, witnessed deaths occurred in the context of seizures. At least of the rats surviving the first postoperative day developed neocortical epilepsy with recurrent spontaneous seizures. Conclusions. The novel TeT/CoCl2 approach targets at a new model of neocortical epilepsy in rats and allows the investigation of local epilepsy therapy strategies. In this vehicle-controlled study, local application of VPA significantly enhanced survival in rats, possibly by focal antiepileptic or antiepileptogenic mechanisms

Newly Diagnosed IDH-Wildtype Glioblastoma and Temporal Muscle Thickness: A Multicenter Analysis

Background: Reduced temporal muscle thickness (TMT) has been discussed as a prognostic marker in IDH-wildtype glioblastoma. This retrospective multicenter study was designed to investigate whether TMT is an independent prognostic marker in newly diagnosed glioblastoma. Methods: TMT was retrospectively measured in 335 patients with newly diagnosed glioblastoma between 1 January 2014 and 31 December 2019 at the University Hospitals of Leipzig and Rostock. The cohort was dichotomized by TMT and tested for association with overall survival (OS) after 12 months by multivariate proportional hazard calculation. Results: TMT of 7.0 mm or more was associated with increased OS (46.3 ± 3.9% versus 36.6 ± 3.9%, p > 0.001). However, the sub-groups showed significant epidemiological differences. In multivariate proportional hazard calculation, patient age (HR 1.01; p = 0.004), MGMT promoter status (HR 0.76; p = 0.002), EOR (HR 0.61), adjuvant irradiation (HR 0.24) and adjuvant chemotherapy (HR 0.40; all p < 0.001) were independent prognostic markers for OS. However, KPS (HR 1.00, p = 0.31), BMI (HR 0.98, p = 0.11) and TMT (HR 1.06; p = 0.07) were not significantly associated with OS. Conclusion: TMT has not appeared as a statistically independent prognostic marker in this cohort of patients with newly diagnosed IDH-wildtype glioblastoma

Computational tissue volume reconstruction of a peripheral nerve using high-resolution light-microscopy and reconstruct.

The development of neural cuff-electrodes requires several in vivo studies and revisions of the electrode design before the electrode is completely adapted to its target nerve. It is therefore favorable to simulate many of the steps involved in this process to reduce costs and animal testing. As the restoration of motor function is one of the most interesting applications of cuff-electrodes, the position and trajectories of myelinated fibers in the simulated nerve are important. In this paper, we investigate a method for building a precise neuroanatomical model of myelinated fibers in a peripheral nerve based on images obtained using high-resolution light microscopy. This anatomical model describes the first aim of our "Virtual workbench" project to establish a method for creating realistic neural simulation models based on image datasets. The imaging, processing, segmentation and technical limitations are described, and the steps involved in the transition into a simulation model are presented. The results showed that the position and trajectories of the myelinated axons were traced and virtualized using our technique, and small nerves could be reliably modeled based on of light microscopy images using low-cost OpenSource software and standard hardware. The anatomical model will be released to the scientific community