The cerebral biomarkers, neurofilament light chain (NfL), amyloid-β, tau, and neuron specific enolase (NSE) reflect a wide spectrum of neurological damage in the brain and spinal cord. With this study, we aimed to assess whether these biomarkers hold any potential diagnostic value for the three most common canine neurological diseases. Canines suffering from meningoencephalitis of unknown origin (MUO), brain tumors, and selected non-infectious myelopathies were included. For each diagnosis, we analyzed these biomarkers in the cerebrospinal fluid collected via cranial puncture from the cisterna magna. Elevated levels of CSF tau, NfL, and NSE were observed in MUO, with all three biomarkers being intercorrelated. Tau and NSE were increased while amyloid-β was decreased in dogs suffering from tumors. In contrast, no biomarker changes were observed in dogs with myelopathies. Covariates such as age, sex, or castration had minimal impact. CSF biomarkers may reflect molecular changes related to MUO and tumors, but not to non-infectious myelopathies. The combination of NfL, tau, and NSE may represent useful biomarkers for MUO as they reflect the same pathology and are not influenced by age.

• Keywords
• Cerebral biomarkers, Meningoencephalitis, Myelopathies, Tumors,
• MeSH
• Amyloid beta-Peptides cerebrospinal fluid   MeSH
• Biomarkers * cerebrospinal fluid   MeSH
• Phosphopyruvate Hydratase cerebrospinal fluid   MeSH
• Meningoencephalitis cerebrospinal fluid   veterinary   diagnosis   MeSH
• Brain Neoplasms cerebrospinal fluid   veterinary   MeSH
• Nervous System Diseases cerebrospinal fluid   veterinary   diagnosis   MeSH
• Dog Diseases * cerebrospinal fluid   diagnosis   MeSH
• Neurofilament Proteins * cerebrospinal fluid   MeSH
• tau Proteins * cerebrospinal fluid   MeSH
• Dogs MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Dogs MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amyloid beta-Peptides MeSH
• Biomarkers * MeSH
• Phosphopyruvate Hydratase MeSH
• neurofilament protein L MeSH Browser
• Neurofilament Proteins * MeSH
• tau Proteins * MeSH

AIM: The aim of this study was to identify whether NfL and CXCL13 cerebrospinal fluid (CSF) concentrations at diagnostic lumbar puncture can predict the course of multiple sclerosis (MS) in terms of relapses, higher expanded disability status scale (EDSS) and magnetic resonance imaging (MRI) activity. METHODS: We conducted a single-centre prospective observational cohort study at the MS center, University Hospital Ostrava, Czech Republic. CSF NfL (cNfL) and CXCL13 concentrations were examined (ELISA method) in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) at the time of diagnostic lumbar puncture. RESULTS: A total of 44 patients with CIS or early RRMS were enrolled, 31 (70.5%) of whom were women. The median age at the time of CSF sampling was 31.21 years (IQR 25.43-39.32), and the follow-up period was 54.6 months (IQR 44.03-59.48). In the simple and multiple logistic regression models, CXCL13 levels did not predict relapses, MRI activity or EDSS > 2.5. Similarly, cNfL concentrations did not predict relapses or MRI activity in either model. In the multiple regression, higher cNfL levels were associated with reaching EDSS > 2.5 (odds ratio [OR] 1.002, 95% confidence interval [CI] 1.000 to 1.003). CONCLUSIONS: Our data did not confirm cNfL and/or CXCL13 CSF levels were predictive factors for disease activity such as relapses and MRI activity at the time of diagnostic lumbar puncture in patients with RRMS. While cNfL CSF levels predicted higher disability only after adjustment for other known risk factors, elevated CSF CXCL13 did not predict higher disability at all.

• Keywords
• CXCL13, biomarkers, clinical course, multiple sclerosis, neurofilament light chain,
• MeSH
• Biomarkers cerebrospinal fluid   MeSH
• Chemokine CXCL13 MeSH
• Adult MeSH
• Intermediate Filaments MeSH
• Humans MeSH
• Disease Progression MeSH
• Prospective Studies MeSH
• Recurrence MeSH
• Multiple Sclerosis, Relapsing-Remitting * diagnostic imaging   cerebrospinal fluid   MeSH
• Multiple Sclerosis * diagnosis   cerebrospinal fluid   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Names of Substances
• Biomarkers MeSH
• Chemokine CXCL13 MeSH
• CXCL13 protein, human MeSH Browser

BACKGROUND: Neurofilament light (NfL) levels reflect inflammatory disease activity in multiple sclerosis (MS), but it is less clear if NfL also can serve as a biomarker for MS progression in treated patients without relapses and focal lesion accrual. In addition, it has not been well established if clinically effective treatment re-establishes an age and sex pattern for cerebrospinal fluid NfL (cNfL) as seen in controls, and to what degree levels are affected by disability level and magnetic resonance imaging (MRI) atrophy metrics. METHODS: We included subjects for whom cNfL levels had been determined as per clinical routine or in clinical research, classified as healthy controls (HCs, n = 89), MS-free disease controls (DCs, n = 251), untreated MS patients (uMS; n = 296), relapse-free treated MS patients (tMS; n = 78), and ProTEct-MS clinical trial participants (pMS; n = 41). RESULTS: Using linear regression, we found a positive association between cNfL and age, as well as lower concentrations among women, in all groups, except for uMS patients. In contrast, disability level in the entire MS cohort, or T1 and T2 lesion volumes, brain parenchymal fraction, thalamic fraction, and cortical thickness in the pMS trial cohort, did not correlate with cNfL concentrations. Furthermore, the cNfL levels in tMS and pMS groups did not differ. CONCLUSIONS: In participants with MS lacking signs of inflammatory disease activity, disease modulatory therapy reinstates an age and sex cNfL pattern similar to that of control subjects. No significant association was found between cNfL levels and clinical worsening, disability level, or MRI metrics.

• Keywords
• biomarker, brain atrophy, disease-modifying therapies, multiple sclerosis, neurofilament light chain, progressive multiple sclerosis, relapsing-remitting multiple sclerosis,
• MeSH
• Biomarkers cerebrospinal fluid   MeSH
• Demography MeSH
• Intermediate Filaments pathology   MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Multiple Sclerosis, Relapsing-Remitting * MeSH
• Multiple Sclerosis * diagnostic imaging   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH

The composition of microbiota and the gut-brain axis is increasingly considered a factor in the development of various pathological conditions. The etiology of multiple sclerosis (MS), a chronic autoimmune disease affecting the CNS, is complex and interactions within the gut-brain axis may be relevant in the development and the course of MS. In this article, we focus on the relationship between gut microbiota and the pathophysiology of MS. We review the contribution of germ-free mouse studies to our understanding of MS pathology and its implications for treatment strategies to modulate the microbiome in MS. This summary highlights the need for a better understanding of the role of the microbiota in patients' responses to disease-modifying drugs in MS and disease activity overall.

• Keywords
• disease-modifying drugs, gut-brain axis, microbiome, multiple sclerosis,
• MeSH
• Humans MeSH
• Microbiota * MeSH
• Mice MeSH
• Brain-Gut Axis MeSH
• Multiple Sclerosis * MeSH
• Gastrointestinal Microbiome * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH