NeuroImmunology

The first tremor was innocuous, akin to shivering from the cold. It seemed odd, but J. Lowe Barton, a law enforcement professional who was working on restoring a classic vehicle, didn’t pay too much attention at the time. The tremors became harder to ignore, though, as they increased in regularity over the next few weeks.

In the past decade, evidence for a fluid clearance pathway in the central nervous system known as the glymphatic system has grown. According to the glymphatic system concept, cerebrospinal fluid flows directionally through the brain and non-selectively clears the interstitium of metabolic waste. Importantly, the glymphatic system may be modulated by particular drugs such as anaesthetics, as well as by non-pharmacological factors such as sleep, and its dysfunction has been implicated in central nervous system disorders such as Alzheimer disease. Although the glymphatic system is best described in rodents, reports using multiple neuroimaging modalities indicate that a similar transport system exists in the human brain. Here, we overview the evidence for the glymphatic system and its role in disease and discuss opportunities to harness the glymphatic system therapeutically; for example, by improving the effectiveness of intrathecally delivered drugs. Evidence for a fluid clearance pathway in the central nervous system known as the glymphatic system has grown in the past decade. Nedergaard and colleagues overview the evidence for the glymphatic system and its role in disease, and discuss opportunities to harness the glymphatic system therapeutically; for example, by improving the effectiveness of intrathecally delivered drugs.

Our incomplete understanding of the causes and pathways involved in the onset and progression of multiple sclerosis (MS) limits our ability to effectively treat this complex neurological disease. Recent studies explore the role of immune cells at different stages of MS and how they interact with cells of the central nervous system (CNS). The findings presented here begin to question the exclusivity of an antigen-specific cause and highlight how seemingly distinct immune cell types can share common functions that drive disease. Innovative techniques further expose new disease-associated immune cell populations and reinforce how environmental context is critical to their phenotype and subsequent role in disease. Importantly, the differentiation of immune cells into a pathogenic state is potentially reversible through therapeutic manipulation. As such, understanding the mechanisms that provide plasticity to causal cell types is likely key to uncoupling these disease processes and may identify novel therapeutic targets that replace the need for cell ablation. This Review explores the complex roles of immune cells in the onset and progression of multiple sclerosis, describing the influence of environmental and genetic factors on immune cell phenotype and function. The authors highlight that teasing out the precise roles of different immune cell subsets at different stages of the disease will be key to effective treatment strategies.

Arachnoid granulations are poorly investigated. We show that they harbor immune cells and communicate with perisinus spaces, suggesting that granulations subser

Background There is a gap in the literature regarding genetic underpinnings of pediatric autoimmune CNS diseases. This study explored rare gene variants implicated in immune dysregulation within these disorders. Methods This was a single-center observational study of children with inflammatory CNS disorder who had genetic testing through next generation focused exome sequencing targeting 155 genes associated with innate or adaptive immunity. For in silico prediction of functional effects of single-nucleotide variants, Polymorphism Phenotyping v2, and Sorting Intolerant from Tolerant were used, and Combined Annotation Dependent Depletion (CADD) scores were calculated. Identified genes were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results Of 54 patients, 42 (77.8%) carried variant(s), among which 12 (22.2%) had 3–8 variants. Eighty-eight unique single-nucleotide variants of 55 genes were identified. The most variants were detected in UNC13D, LRBA, LYST, NOD2, DOCK8, RNASEH2A, STAT5B, and AIRE. The majority of variants (62, 70.4%) had CADD > 10. KEGG pathway analysis revealed seven genes associated with primary immunodeficiency (Benjamini 1.40E − 06), six genes with NOD-like receptor signaling (Benjamini 4.10E − 04), five genes with Inflammatory Bowel Disease (Benjamini 9.80E − 03), and five genes with NF-kappa B signaling pathway (Benjamini 1.90E − 02). Discussion We observed a high rate of identification of rare and low-frequency variants in immune regulatory genes in pediatric neuroinflammatory CNS disorders. We identified 88 unique single-nucleotide variants of 55 genes with pathway analysis revealing an enrichment of NOD2-receptor signaling, consistent with involvement of the pathway within other autoinflammatory conditions and warranting further investigation.

A higher choroid plexus volume and permeability could be useful imaging markers for cognitive impairment in patients with Alzheimer's disease