Multiomic analyses direct hypotheses for Creutzfeldt-Jakob disease risk genes.

Prions are assemblies of misfolded prion protein that cause several fatal and transmissible neurodegenerative diseases, with the most common phenotype in humans being sporadic Creutzfeldt-Jakob disease (sCJD). Aside from variation of the prion protein itself, molecular risk factors are not well understood. Prion and prion-like mechanisms are thought to underpin common neurodegenerative disorders meaning that the elucidation of mechanisms could have broad relevance.

Hyperphosphorylated Tau and Cognition in Epilepsy.

In light of the growing interest in the bidirectional relationship between epilepsy and dementia, this review aims to provide an overview of the role of hyperphosphorylated tau (pTau) in cognition in human epilepsy. A literature search identified five relevant studies. All of them examined pTau burden in surgical biopsy specimens from patients with temporal lobe epilepsy.

Leptomeningeal Dissemination in Choroid Plexus Tumors: Magnetic Resonance Imaging Appearance and Risk Factors.

Background: Intracranial choroid plexus tumors (CPT) are rare and primarily affect young children. Leptomeningeal dissemination (LMD) has been reported not only in high-grade choroid plexus carcinoma (CPC) but also in lower histological grades; however, a systematic evaluation of CPT-specific imaging characteristics remains lacking.

Methods: We analyzed the imaging characteristics of LMD in a single-center pediatric cohort of 22 CPT patients (thirteen choroid plexus papilloma (CPP), six atypical choroid plexus papilloma (aCPP), three CPC), comparing LMD features with those of the primary tumor.

Advanced Distance-Resolved Evaluation of the Perienhancing Tumor Areas with FLAIR Hyperintensity Indicates Different ADC Profiles by Promoter Methylation Status in Glioblastoma.

Background And Purpose: Whether differences in the O-methylguanine-DNA methyltransferase () promoter methylation status of glioblastoma (GBM) are reflected in MRI markers remains largely unknown. In this work, we analyze the ADC in the perienhancing infiltration zone of GBM according to the corresponding status by using a novel distance-resolved 3D evaluation.

Materials And Methods: One hundred one patients with wild-type GBM were retrospectively analyzed.

Spatially resolved transcriptomics of benign and malignant peripheral nerve sheath tumors.

Background: Peripheral nerve sheath tumors (PNSTs) encompass entities with different cellular differentiation and degrees of malignancy. Spatial heterogeneity complicates diagnosis and grading of PNSTs in some cases. In malignant PNST (MPNST) for example, single cell sequencing data has shown dissimilar differentiation states of tumor cells.

The clinical and molecular landscape of diffuse hemispheric glioma, H3 G34-mutant.

Background: Diffuse hemispheric glioma, histone 3 (H3) G34-mutant, has been newly defined in the 2021 WHO classification of central nervous system tumors. Here we sought to define the prognostic roles of clinical, neuroimaging, pathological, and molecular features of these tumors.

Methods: We retrospectively assembled a cohort of 114 patients (median age 22 years) with diffuse hemispheric glioma, H3 G34-mutant, CNS WHO grade 4 and profiled the imaging, histological and molecular landscape of their tumors.

The Value of Multidisciplinary Neuro-oncological Tumor Boards to Increase the Accuracy of FET PET for Identifying Brain Tumor Relapse.

Purpose: Especially in Europe, amino acid PET is increasingly integrated into multidisciplinary neuro-oncological tumor boards (MNTBs) to overcome diagnostic uncertainties such as treatment-related changes. We evaluated the accuracy of MNTB decisions that included the O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET information compared with FET PET results alone to differentiate tumor relapse from treatment-related changes.

Patients And Methods: In a single academic center, we retrospectively evaluated 180 MNTB decisions of 151 patients with CNS WHO grade 3 or 4 gliomas (n = 122) or brain metastases (n = 29) presenting equivocal MRI findings following anticancer treatment.

Tissue concepts: Supervised foundation models in computational pathology.

Due to the increasing workload of pathologists, the need for automation to support diagnostic tasks and quantitative biomarker evaluation is becoming more and more apparent. Foundation models have the potential to improve generalizability within and across centers and serve as starting points for data efficient development of specialized yet robust AI models. However, the training of foundation models themselves is usually very expensive in terms of data, computation, and time.

A distinct hypothalamus-habenula circuit governs risk preference.

Appropriate risk evaluation is essential for survival in complex, uncertain environments. Confronted with choosing between certain (safe) and uncertain (risky) options, animals show strong preference for either option consistently across extended time periods. How such risk preference is encoded in the brain remains elusive.

Prognostic factors for overall survival in elderly patients with glioblastoma: Analysis of the pooled NOA-08 and Nordic trials with the CCTG-EORTC (CE.6) trial.

Background: The majority of patients diagnosed with glioblastoma are >60 years. Three randomized trials addressed the roles of radiotherapy (RT) and temozolomide (TMZ) for elderly patients. NORDIC and NOA-08 compared RT versus TMZ, while CE.

Ironing out differences in attenuation and blooming artifact in acute stroke thrombi.

This study aims to improve our understanding of acute ischemic stroke clot imaging by integrating CT attenuation information with MRI susceptibility signal of thrombi. For this proof-of-principle experimental study, fifty-seven clot analogs were produced using ovine venous blood with a broad histological spectrum. Each clot analog was analyzed to determine its RBC content and chemical composition, including water, Fe III, sodium, pH, and pO2.

Computational Methods for Data Integration and Imputation of Missing Values in Omics Datasets.

Molecular profiling of different omic-modalities (e.g., DNA methylomics, transcriptomics, proteomics) in biological systems represents the basis for research and clinical decision-making.

Dysregulation of Myelination in Focal Cortical Dysplasia Type II of the Human Frontal Lobe.

Focal cortical dysplasias (FCDs) are local malformations of the human neocortex and a leading cause of intractable epilepsy. FCDs are classified into different subtypes including FCD IIa and IIb, characterized by a blurred gray-white matter boundary or a transmantle sign indicating abnormal white matter myelination. Recently, we have shown that myelination is also compromised in the gray matter of FCD IIa of the temporal lobe.

VGLL-fusions define a new class of intraparenchymal CNS schwannoma.

Background: Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the CNS. They are not classified as a separate tumor type in the 2021 WHO classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly.

Impact of molecular classification on prognosis in children and adolescents with spinal ependymoma: Results from the HIT-MED database.

Background: Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. This study aims to evaluate the prognostic impact of molecular typing on pediatric spinal cord ependymomas.

Methods: Eighty-three patients with spinal ependymomas ≤22 years registered in the HIT-MED database (German brain tumor registry for children, adolescents, and adults with medulloblastoma, ependymoma, pineoblastoma, and CNS-primitive neuroectodermal tumors) between 1992 and 2022 were included.

Visual quality of life in NMOSD and MOGAD: profiles, dynamics and associations with ageing and vision.

Objective: In this multicentric study, we were interested in the vision-related quality of life and its association with visual impairment in neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in comparison to multiple sclerosis (MS) and healthy controls.

Methods: We analysed extracted data from the German NEMOS registry including National Eye Institute Visual Function Questionnaire (NEI-VFQ) scores, high and low contrast visual acuity (HCVA, LCVA), visually evoked potentials (VEP) and the scores for the expanded disability status scale (EDSS) and other neurological tests which assessed their disease-related impairment. The mean follow-up time of our patients was 1.

Assessing hand motor function in chronic immune-mediated neuropathies: a proof-of-concept study using a data glove.

Background: Chronic immune-mediated neuropathies are clinically heterogeneous and require regular, objective, and multidimensional monitoring to individualize treatment. However, established outcome measures are insufficient regarding measurement quality criteria (e.g.

Extrasinusoidal macrophages are a distinct subset of immunologically active dural macrophages.

Although macrophages in the meningeal compartments of the central nervous system (CNS) have been comprehensively characterized under steady state, studying their contribution to physiological and pathological processes has been hindered by the lack of specific targeting tools in vivo. Recent findings have shown that the dural sinus and its adjacent lymphatic vessels act as a neuroimmune interface. However, the cellular and functional heterogeneity of extrasinusoidal dural macrophages outside this immune hub is not fully understood.

Challenging granulomatous differential diagnosis of CNS lesions in a 75-year-old patient with indolent lymphoma.

We report here on a patient with concomitant indolent lymphoma who showed a rapid progressive deterioration of his general condition and emerging neurological symptoms. The combination of severe B symptoms with hypermetabolic involvement of the adrenal glands and multiple central nervous system (CNS) lesions initially suggested a malignant disease. However, when the patient presented to us with biopsy results from one of the CNS lesions, the biopsy revealed granulomatous inflammation but no evidence of malignancy.

Small molecule protein assembly modulators with pan-cancer therapeutic efficacy.

Two structurally unrelated small molecule chemotypes, represented by compounds PAV-617 and PAV-951, with antiviral activity in cell culture against Mpox virus (formerly known as monkeypox virus) and human immunodeficiency virus (HIV) respectively, were studied for anti-cancer efficacy. Each exhibited apparent pan-cancer cytotoxicity with reasonable pharmacokinetics. Non-toxicity is demonstrated in a non-cancer cell line and in mice at doses achieving drug exposure at active concentrations.

Abatacept Induces Long-Term Reconstitution of the B-Cell Niche in a Patient With CTLA-4 Haploinsufficiency: A Case Report.

Objectives: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency is a rare genetic condition characterized by development of immune cytopenia, hypogammaglobulinemia, and/or lymphoproliferative disorder, as well as multiple autoimmunity. Treatment with abatacept was shown to alleviate autoimmune conditions, yet its long-lasting impact on bone marrow function remains undetermined.

Methods: We here present the case of a now 39-year-old woman with CTLA-4 haploinsufficiency with predominant CNS affection, yet multiorgan autoimmunity and lymphopenia.

Optimization of antiviral dosing in Herpesviridae encephalitis: a promising approach to improve outcome?

Background: Despite established antiviral therapy for herpes simplex virus, varicella zoster and cytomegalovirus encephalitis, the outcome remains poor.

Objectives: To assess pharmacokinetic (PK) and pharmacodynamic (PD) data of antiviral drugs in the central nervous system (CNS) to optimize the treatment of Herpesviridae encephalitis.

Sources: PUBMED search 1950 to September 2024, terms (1) "encephalitis" and ("HSV" or "VZV" or "CMV") or (2) cerebrospinal and ("(val)acyclovir" or "(val)ganciclovir" or "foscarnet" or "cidofovir").

Human Genetic GLUT1 Deficiency Results in Impaired T Cellular IFN-γ Production.

GLUT1 deficiency prevents glucose uptake in T cells resulting in lower intracellular ATP generation and IFNy production.