The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS,n=60) and healthy controls (n=43). Microbiome alterations in MS include increases inMethanobrevibacterandAkkermansiaand decreases inButyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances ofPrevotellaandSutterella, and decreasedSarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gutMethanobrevibacterin MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis.

Objective: To identify circulating microRNAs (miRNAs) linked to disease stage and disability in multiple sclerosis (MS). Methods: Sera from 296 participants including patients with MS, other neurologic diseases (Alzheimer disease and amyotrophic lateral sclerosis), and inflammatory diseases (rheumatoid arthritis and asthma) and healthy controls (HCs) were tested. miRNA profiles were determined using LNA (locked nucleic acid)-based quantitative PCR. Patients with MS were categorized according to disease stage and disability. In the discovery phase, 652 miRNAs were measured in sera from 26 patients with MS and 20 HCs. Following this, significant miRNAs (p < 0.05) from the discovery set were validated using quantitative PCR in 58 patients with MS, 30 HCs, and in 74 samples from other disease controls (Alzheimer disease, amyotrophic lateral sclerosis, asthma, and rheumatoid arthritis). Results: We validated 7 miRNAs that differentiate patients with MS from HCs (p < 0.05 in both the discovery and validation phase); miR-320a upregulation was the most significantly changing serum miRNA in patients with MS. We also identified 2 miRNAs linked to disease progression, with miR-27a-3p being the most significant. Ten miRNAs correlated with the Expanded Disability Status Scale of which miR.199a.5p had the strongest correlation with disability. Of the 15 unique miRNAs we identified in the different group comparisons, 12 have previously been reported to be associated with MS but not in serum. Conclusions: Our findings identify circulating serum miRNAs as potential biomarkers to diagnose and monitor disease status in MS. Classification of evidence: This study provides Class III evidence that circulating serum miRNAs can be used as biomarker for MS.

Background: Although aquaporin-4 (AQP4) is widely expressed in the human brain cortex, lesions are rare in neuromyelitis optica (NMO) spectrum disorders (NMOSD). Recently, however, several studies have demonstrated occult structural brain atrophy in NMO. Objective: This study aims to investigate magnetic resonance imaging (MRI) patterns of gray matter (GM) and white matter (WM) abnormalities in patients with NMOSD and to assess the visual pathway integrity during disease duration correlation of the retinal nerve fiber layer (RNFL) and pericalcarine cortex thickness. Methods: Twenty-one patients with NMOSD and 34 matched healthy controls underwent both high-field MRI (3T) high-resolution T1-weighted and diffusion-tensor MRI. Voxel-based morphometry, cortical analyses (Freesurfer) and diffusion-tensor imaging (DTI) analyses (TBSS-FSL) were used to investigate brain abnormalities. In addition, RNFL measurement by optic-coherence tomography (OCT) was performed. Results: We demonstrate that NMOSD is associated with GM and WM atrophy, encompassing more frequently the motor, sensory and visual pathways, and that the extent of GM atrophy correlates with disease duration. Furthermore, we demonstrate for the first time a correlation between RNFL and pericalcarine cortical thickness, with cortical atrophy evolving over the course of disease. Conclusions: Our findings indicate a role for retrograde and anterograde neurodegeneration in GM atrophy in NMOSD. However, the presence atrophy encompassing almost all lobes suggests that additional pathomechanisms might also be involved.

Multiple sclerosis (MS) involves autoimmune-related inflammatory demyelination of the central nervous system white matter and gray matter (GM).¹ The disease may transect axons and cause brain and spinal cord neuronal loss and atrophy.² Magnetic resonance imaging (MRI) is a standard tool for the diagnosis and therapeutic monitoring of MS.^3-5 Recent MRI technology allows visualization of tissue atrophy^6,7 and GM involvement^7,8 beyond the traditional focal white matter lesion assessments.⁹

The plasmacytoid dendritic cells (pDCs) express a high level of Toll-like receptor 9 (TLR-9), which recognizes viral DNA. Activated via TLR-9, pDCs also secrete large amounts of type I interferon which are involved either in stimulation or down regulation of immune response in multiple sclerosis (MS). In the present study, we determinate pDCs levels by flow cytometry in Cerebrospinal Fluid (CSF) and Peripheral Blood from MS patients in relapsing and in remitting phases of the disease, comparing with other non-inflammatory diseases (OND). We provide evidence that MS patients in relapse without any treatment have a significantly (p < 0.01) higher percentage of pDCs in CSF than do patients in remission or those with OND. No change in the percentage of pDCs was observed in the peripheral blood of any of these patients. The increase of pDCs in central nervous system during relapse may be explained either by a virus infection or a down regulatory process.