IgM anti-GM2 antibodies in patients with multifocal motor neuropathy target Schwann cells and are associated with early onset.

Background: Multifocal motor neuropathy (MMN) is a rare, chronic immune-mediated polyneuropathy characterized by asymmetric distal limb weakness. An important feature of MMN is the presence of IgM antibodies against gangliosides, in particular GM1 and less often GM2. Antibodies against GM1 bind to motor neurons (MNs) and cause damage through complement activation.

A 21-bp deletion in the complement regulator CD55 promotor region is associated with multifocal motor neuropathy and its disease course.

Background And Aims: To further substantiate the role of antibody-mediated complement activation in multifocal motor neuropathy (MMN) immunopathology, we investigated the distribution of promotor polymorphisms of genes encoding the membrane-bound complement regulators CD46, CD55, and CD59 in patients with MMN and controls, and evaluated their association with disease course.

Methods: We used Sanger sequencing to genotype five common polymorphisms in the promotor regions of CD46, CD55, and CD59 in 133 patients with MMN and 380 controls. We correlated each polymorphism to clinical parameters.

Offline orbitofrontal cortex reactivation depends on recency of place-reward changes and coheres with hippocampal replay.

The orbitofrontal cortex, one of the key neocortical areas in valuation and emotion, is critical for cognitive flexibility but its role in the consolidation of recently acquired information remains unclear. Here, we demonstrate orbitofrontal offline replay in the context of a place-reward association task on a maze with varying goal locations. When switches in place-reward coupling were applied, replay was enhanced relative to sessions with stable contingencies.

OXA-48-Producing Uropathogenic Escherichia coli Sequence Type 127, the Netherlands, 2015-2022.

During 2015-2022, a genetic cluster of OXA-48-producing uropathogenic Escherichia coli sequence type 127 spread throughout the Netherlands. The 20 isolates we investigated originated mainly from urine, belonged to Clermont phylotype B2, and carried 18 genes encoding putative uropathogenicity factors. The isolates were susceptible to first-choice antimicrobial drugs for urinary tract infections.

Multifocal motor neuropathy is not associated with altered innate immune responses to endotoxin.

Objective: Antibody- and complement-mediated peripheral nerve inflammation are central in the pathogenesis of MMN. Here, we studied innate immune responses to endotoxin in patients with MMN and controls to further our understanding of MMN risk factors and disease modifiers.

Methods: We stimulated whole blood of 52 patients with MMN and 24 controls with endotoxin and collected plasma.

Spike-based coupling between single neurons and populations across rat sensory cortices, perirhinal cortex, and hippocampus.

Cortical computations require coordination of neuronal activity within and across multiple areas. We characterized spiking relationships within and between areas by quantifying coupling of single neurons to population firing patterns. Single-neuron population coupling (SNPC) was investigated using ensemble recordings from hippocampal CA1 region and somatosensory, visual, and perirhinal cortices.

Multidrug-resistant organisms in patients from Ukraine in the Netherlands, March to August 2022.

Since March 2022, there has been an emergence of multidrug-resistant organisms (MDRO) in the Netherlands in patients originating from Ukraine (58 patients, 75 isolates). For about half of these patients, recent hospitalisation in Ukraine was reported. Genomic surveillance revealed that the majority of the MDRO represent globally spread epidemic lineages and that 60% contain New Delhi metallo-β-lactamase (NDM) genes.

Anti-C2 Antibody ARGX-117 Inhibits Complement in a Disease Model for Multifocal Motor Neuropathy.

Background And Objectives: To determine the role of complement in the disease pathology of multifocal motor neuropathy (MMN), we investigated complement activation, and inhibition, on binding of MMN patient-derived immunoglobulin M (IgM) antibodies in an induced pluripotent stem cell (iPSC)-derived motor neuron (MN) model for MMN.

Methods: iPSC-derived MNs were characterized for the expression of complement receptors and membrane-bound regulators, for the binding of circulating IgM anti-GM1 from patients with MMN, and for subsequent fixation of C4 and C3 on incubation with fresh serum. The potency of ARGX-117, a novel inhibitory monoclonal antibody targeting C2, to inhibit fixation of complement was assessed.

Duplications Are Associated With Progressive Muscular Atrophy, but Not With Multifocal Motor Neuropathy and Primary Lateral Sclerosis.

Objective: To assess the association between copy number (CN) variation in the survival motor neuron () locus and multifocal motor neuropathy (MMN), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS) susceptibility and to determine the association of and CN with MMN, PMA, and PLS disease course.

Methods: In this monocenter study, we used multiplex ligation-dependent probe amplification to determine and CN in Dutch patients with MMN, PMA, and PLS and controls. We stratified clinical parameters for and CN.

High-resolution mapping identifies HLA class II associations with multifocal motor neuropathy.

Objective: To gain further insight in the immunopathology underlying multifocal motor neuropathy (MMN) by exploring the association between MMN and the human leukocyte antigen (HLA) class II DRB1, DQB1, and DQA loci in depth and by correlating associated haplotypes to detailed clinical and anti-ganglioside antibody data.

Methods: We performed high-resolution HLA-class II typing for the DRB1, DQB1, and DQA1 loci in 126 well-characterized MMN patients and assessed disease associations with haplotypes. We used a cohort of 1305 random individuals as a reference for haplotype distribution in the Dutch population.

Reconciling the object and spatial processing views of the perirhinal cortex through task-relevant unitization.

The perirhinal cortex is situated on the border between sensory association cortex and the hippocampal formation. It serves an important function as a transition area between the sensory neocortex and the medial temporal lobe. While the perirhinal cortex has traditionally been associated with object coding and the "what" pathway of the temporal lobe, current evidence suggests a broader function of the perirhinal cortex in solving feature ambiguity and processing complex stimuli.

Clinical outcomes in multifocal motor neuropathy: A combined cross-sectional and follow-up study.

Objective: To assess the clinical course of multifocal motor neuropathy (MMN) in a large cohort of patients and to identify predictive factors of a progressive disease course.

Methods: Between May 2015 and February 2016, we collected clinical data from 100 patients with MMN, of whom 60 had participated in a nationwide cross-sectional cohort study in 2007. We documented clinical characteristics using standardized questionnaires and performed a standardized neurologic examination.

Shared Learnings on the New EMA First-in-Human and Early Clinical Trial Guideline: Proceedings From a DIAlogue Session at DIA Europe 2018.

The EU is a member of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), and therefore adopts the ICH Guidelines, including the ICH M3 Guideline on Nonclinical Safety Studies. Following the 2016 incident in France with BIA 10-2474, and in light of the substantial evolvement of how early clinical development has been undertaken during the last 10 years, for example, conducting integrated (FIH) studies that include multiple parts (eg, single ascending doses, multiple ascending doses, food effect), EMA decided to update the existing 2007 FIH guideline. The key revisions to the 2007 guideline, now titled "Guideline on Strategies to Identify and Mitigate Risks for First-in-Human and Early Clinical Trials With Investigational Medicinal Products," include additional information.

Multiplexing of Information about Self and Others in Hippocampal Ensembles.

In addition to coding a subject's location in space, the hippocampus has been suggested to code social information, including the spatial position of conspecifics. "Social place cells" have been reported for tasks in which an observer mimics the behavior of a demonstrator. We examine whether rat hippocampal neurons may encode the behavior of a minirobot, but without requiring the animal to mimic it.

Biallelic variants in POLR3GL cause endosteal hyperostosis and oligodontia.

RNA polymerase III (Pol III) is an essential 17-subunit complex responsible for the transcription of small housekeeping RNAs such as transfer RNAs and 5S ribosomal RNA. Biallelic variants in four genes (POLR3A, POLR3B, and POLR1C and POLR3K) encoding Pol III subunits have previously been found in individuals with (neuro-) developmental disorders. In this report, we describe three individuals with biallelic variants in POLR3GL, a gene encoding a Pol III subunit that has not been associated with disease before.

Functional determinants of enhanced and depressed interareal information flow in nonrapid eye movement sleep between neuronal ensembles in rat cortex and hippocampus.

Compared with wakefulness, neuronal activity during nonrapid eye movement (NREM) sleep is characterized by a decreased ability to integrate information, but also by the reemergence of task-related information patterns. To investigate the mechanisms underlying these seemingly opposing phenomena, we measured directed information flow by computing transfer entropy between neuronal spiking activity in three cortical regions and the hippocampus of rats across brain states. State-dependent information flow was jointly determined by the anatomical distance between neurons and by their functional specialization.

Perirhinal firing patterns are sustained across large spatial segments of the task environment.

Spatial navigation and memory depend on the neural coding of an organism's location. Fine-grained coding of location is thought to depend on the hippocampus. Likewise, animals benefit from knowledge parsing their environment into larger spatial segments, which are relevant for task performance.

Comparative study of peripheral nerve Mri and ultrasound in multifocal motor neuropathy and amyotrophic lateral sclerosis.

Introduction: Differentiating multifocal motor neuropathy (MMN) from amyotrophic lateral sclerosis (ALS) is important, as MMN is a difficult, but treatable disorder.

Methods: We studied peripheral nerve imaging techniques in differentiating MMN from ALS by measuring the cross-sectional area (CSA) of the median and ulnar nerves in the forearms using high resolution ultrasound (HRUS) and MRI.

Results: HRUS CSA values of the median nerve in the forearm (P = 0.

Spike-Based Functional Connectivity in Cerebral Cortex and Hippocampus: Loss of Global Connectivity Is Coupled to Preservation of Local Connectivity During Non-REM Sleep.

Unlabelled: Behavioral states are commonly considered global phenomena with homogeneous neural determinants. However, recent studies indicate that behavioral states modulate spiking activity with neuron-level specificity as a function of brain area, neuronal subtype, and preceding history. Although functional connectivity also strongly depends on behavioral state at a mesoscopic level and is globally weaker in non-REM (NREM) sleep and anesthesia than wakefulness, it is unknown how neuronal communication is modulated at the cellular level.

Cell-Type and State-Dependent Synchronization among Rodent Somatosensory, Visual, Perirhinal Cortex, and Hippocampus CA1.

Beta and gamma rhythms have been hypothesized to be involved in global and local coordination of neuronal activity, respectively. Here, we investigated how cells in rodent area S1BF are entrained by rhythmic fluctuations at various frequencies within the local area and in connected areas, and how this depends on behavioral state and cell type. We performed simultaneous extracellular field and unit recordings in four connected areas of the freely moving rat (S1BF, V1M, perirhinal cortex, CA1).