Invasive growth of brain metastases is linked to CHI3L1 release from pSTAT3-positive astrocytes.

Background: Compared to minimally invasive brain metastases (MI BrM), highly invasive (HI) lesions form abundant contacts with cells in the peritumoral brain parenchyma and are associated with poor prognosis. Reactive astrocytes (RAs) labeled by phosphorylated STAT3 (pSTAT3) have recently emerged as a promising therapeutic target for BrM. Here, we explore whether the BrM invasion pattern is influenced by pSTAT3+ RAs and may serve as a predictive biomarker for STAT3 inhibition.

Are LRRK2 p.G2019S or GBA1 variants associated with long-term outcomes of deep brain stimulation for Parkinson's disease?

Background: Deep brain stimulation (DBS) is a well-established treatment option for individuals with advanced Parkinson's disease (PD). The potential influence of the LRRK2 p.G2019S or GBA1 variants on its lasting efficacy and adverse effects should be better characterized.

The possible influence of third-order shim coils on gradient-magnet interactions: an inter-field and inter-site study.

Objective: To assess the possible influence of third-order shim coils on the behavior of the gradient field and in gradient-magnet interactions at 7 T and above.

Materials And Methods: Gradient impulse response function measurements were performed at 5 sites spanning field strengths from 7 to 11.7 T, all of them sharing the same exact whole-body gradient coil design.

Comparative analysis of methods to reduce activation signature gene expression in PBMCs.

Preserving the in vivo cell transcriptome is essential for accurate profiling, yet factors during cell isolation including time ex vivo and temperature induce artifactual gene expression, particularly in stress-responsive immune cells. In this study, we investigated two methods to mitigate ex vivo activation signature gene (ASG) expression in peripheral blood mononuclear cells (PBMCs): transcription and translation inhibitors (TTis) and cold temperatures during isolation. Comparative analysis of PBMCs isolated with TTis revealed reduced ASG expression.

Enlarged Perivascular Spaces in Infancy and Autism Diagnosis, Cerebrospinal Fluid Volume, and Later Sleep Problems.

Importance: Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume.

Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability.

Rare copy number variants (CNVs) and polygenic risk for intelligence (PRS-IQ) both confer risk for autism spectrum disorder (ASD) but have opposing effects on cognitive ability. The field has struggled to disentangle the effects of these two classes of genomic variants on cognitive ability from their effects on ASD risk, in part because previous studies did not include controls with cognitive measures. We aim to investigate the impact of these genomic variants on ASD risk while adjusting for their known effects on cognitive ability.

Pathophysiology and surgical decision-making in central cord syndrome and degenerative cervical myelopathy: correcting the somatotopic fallacy.

Our understanding of Central Cord Syndrome (CCS), a form of incomplete spinal cord injury characterized by disproportionate upper extremity weakness, is evolving. Recent advances challenge the traditional somatotopic model of corticospinal tract organization within the spinal cord, suggesting that CCS is likely a diffuse injury rather than focal lesion. Diagnostic criteria for CCS lack consensus, and varied definitions impact patient identification and treatment.

GABA receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine .

The K channel blocker 4-aminopyridine (4AP) has been extensively used to investigate the mechanisms underlying neuronal network synchronization in both and animal models of focal epilepsy. 4AP-induced effects are paralleled by an increase in both excitatory and inhibitory neurotransmitter release, but the mechanisms of action of 4AP on neuronal networks remain unclear. By employing simultaneous whole-cell patch clamp and field potential recordings from hippocampal CA3/4 pyramidal layer of acute brain slices obtained from mice (n = 30), we found that the appearance of epileptiform discharges induced by 4AP (100 μM) is consistently preceded by the transient recurrence of presumptive GABA outward currents, which are not mirrored by any field activity.

The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons.

Variants in the gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson's disease (PD). However, neither the specific variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis.

Long term effects of continuous positive airway pressure treatment of obstructive sleep apnea-hypopnea syndrome in multiple sclerosis patients.

Background: Obstructive sleep apnea-hypopnea (OSAH) is common in MS patients and is associated with fatigue. We recently published a randomized, controlled trial (RCT) of active vs sham continuous positive airway pressure (CPAP) treatment in MS patients with fatigue, poor sleep quality, and (OSAH) (Mult Scl J 2022;28:82-92). Our aim was to evaluate the long-term effects of CPAP treatment on fatigue (Fatigue Severity Scale, FSS, primary outcome) and other clinical outcomes in MS patients with OSAH.

Brain PET Imaging in Small Animals: Tracer Formulation, Data Acquisition, Image Reconstruction, and Data Analysis.

Positron emission tomography (PET) is a noninvasive functional imaging modality that involves in vivo detection of spatiotemporal changes in the binding of radioactive pharmaceuticals (a.k.a.

Brain volume increase after discontinuing natalizumab therapy: Evidence for reversible pseudoatrophy.

Background: The phenomenon of pseudoatropy after initiation of anti-inflammatory therapy is believed to be reversible, but a rebound in brain volume following cessation of highly-effective therapy has not been reported.

Objectives: To evaluate brain volume change in a treatment interruption study (RESTORE) in which relapsing-remitting multiple sclerosis (RRMS) patients were randomized to switch from natalizumab to placebo, from natalizumab to once-monthly intravenous methylprednisolone (IVMP), or to remain on natalizumab.

Methods: T2 lesion volume (T2LV), baseline normalized brain volumes, and follow-up percent brain volume changes (PBVC) were calculated.

Predicting Exercise Behavior Among Caregivers of Persons With Dementia-A Longitudinal Investigation Using an Extended Health Belief Model.

Background And Objectives: Family caregivers of persons with dementia face an elevated risk of several chronic illnesses compared to their noncaregiver counterparts. Although exercise is a strong preventive measure for several debilitating health conditions, longitudinal research guided by theoretical frameworks has not identified how behavioral determinants predict exercise among caregivers. This study aimed to investigate how intrapersonal exercise determinants contribute to caregivers' exercise participation while accounting for social-contextual factors, including perceived caregiving burden and pandemic-related distress, by employing an extended Health Belief Model.

Programs, Origins, and Niches of Immunomodulatory Myeloid Cells in Gliomas.

Gliomas are incurable malignancies notable for an immunosuppressive microenvironment with abundant myeloid cells whose immunomodulatory properties remain poorly defined. Here, utilizing scRNA-seq data for 183,062 myeloid cells from 85 human tumors, we discover that nearly all glioma-associated myeloid cells express at least one of four immunomodulatory activity programs: Scavenger Immunosuppressive, C1Q Immunosuppressive, CXCR4 Inflammatory, and IL1B Inflammatory. All four programs are present in IDH1 mutant and wild-type gliomas and are expressed in macrophages, monocytes, and microglia whether of blood or resident myeloid cell origins.

Metronidazole-induced encephalopathy in a patient with cirrhosis.

Metronidazole is a commonly used antibiotic with anaerobic bacterial, protozoal, and microaerophilic bacterial coverage. Encephalopathy and peripheral neurotoxicity are rare but known adverse events with prolonged metronidazole use, which can be difficult to distinguish from other causes of delirium in acutely ill patients. Definitive diagnosis can be made by brain magnetic resonance imaging (MRI), which often reveals symmetric bilateral hypersignal demyelination lesions typically involving the dentate nuclei, splenium of the corpus collosum, midbrain, dorsal medulla, and pons.

Introducing the Dysphagiameter: a novel patient-reported outcome measure for evaluating dysphagia in oculopharyngeal muscular dystrophy - from conceptual framework to initial development.

Oculopharyngeal muscular dystrophy (OPMD) is a rare late-onset muscle disease associated with progressive dysphagia. As there was no patient-reported outcome measure specific for the assessment of dysphagia in OPMD, the Dysphagiameter was developed. The Food and Drug Administration guidance was followed.

Bayesian workflow for the investigation of hierarchical classification models from tau-PET and structural MRI data across the Alzheimer's disease spectrum.

Background: Alzheimer's disease (AD) diagnosis in its early stages remains difficult with current diagnostic approaches. Though tau neurofibrillary tangles (NFTs) generally follow the stereotypical pattern described by the Braak staging scheme, the network degeneration hypothesis (NDH) has suggested that NFTs spread selectively along functional networks of the brain. To evaluate this, we implemented a Bayesian workflow to develop hierarchical multinomial logistic regression models with increasing levels of complexity of the brain from tau-PET and structural MRI data to investigate whether it is beneficial to incorporate network-level information into an ROI-based predictive model for the presence/absence of AD.

EEG functional connectivity in infants at elevated familial likelihood for autism spectrum disorder.

Background: Many studies have reported that autism spectrum disorder (ASD) is associated with atypical structural and functional connectivity. However, we know relatively little about the development of these differences in infancy.

Methods: We used a high-density electroencephalogram (EEG) dataset pooled from two independent infant sibling cohorts, to characterize such neurodevelopmental deviations during the first years of life.

Neuroanatomical and cognitive biomarkers of alpha-synuclein propagation in a mouse model of synucleinopathy prior to onset of motor symptoms.

Significant evidence suggests that misfolded alpha-synuclein (aSyn), a major component of Lewy bodies, propagates in a prion-like manner contributing to disease progression in Parkinson's disease (PD) and other synucleinopathies. In fact, timed inoculation of M83 hemizygous mice with recombinant human aSyn preformed fibrils (PFF) has shown symptomatic deficits after substantial spreading of pathogenic alpha-synuclein, as detected by markers for the phosphorylation of S129 of aSyn. However, whether accumulated toxicity impact human-relevant cognitive and structural neuroanatomical measures is not fully understood.

Machine learning nominates the inositol pathway and novel genes in Parkinson's disease.

There are 78 loci associated with Parkinson's disease in the most recent genome-wide association study (GWAS), yet the specific genes driving these associations are mostly unknown. Herein, we aimed to nominate the top candidate gene from each Parkinson's disease locus and identify variants and pathways potentially involved in Parkinson's disease. We trained a machine learning model to predict Parkinson's disease-associated genes from GWAS loci using genomic, transcriptomic and epigenomic data from brain tissues and dopaminergic neurons.