Background: Diagnosis of multiple sclerosis (MS) is established on criteria according to clinical and radiological manifestation. Cerebrospinal fluid (CSF) analysis is an important part of differential diagnosis of MS and other inflammatory processes in the central nervous system (CNS). Methods: In total, 242 CSF samples were collected from patients undergoing differential MS diagnosis because of the presence of T2-hyperintensive lesions on brain MRI. The non-MS patients were subdivided into systemic inflammatory diseases with CNS involvement (SID) or cerebrovascular diseases (CVD) or other non-inflammatory diseases (NID). All samples were analyzed for the presence of oligoclonal bands and ELISA was performed for detection of: INF gamma, IL-6, neurofilaments light chain (NF-L), GFAP, CHI3L1, CXCL13, and osteopontin. Results: The level of IL-6 (p = 0.024), osteopontin (p = 0.0002), and NF-L (p = 0.002) was significantly different among groups. IL-6 (p = 0.0350) and NF-L (p = 0.0015) level was significantly higher in SID compared to NID patients. A significantly higher level of osteopontin (p = 0.00026) and NF-L (p = 0.002) in MS compared to NID population was noted. ROC analysis found weak diagnostic power for osteopontin and NFL-L. Conclusions: The classical and non-standard markers of inflammatory process and neurodegeneration do not allow for sufficient differentiation between MS and non-MS inflammatory CNS disorders. Weak diagnostic power observed for the osteopontin and NF-L needs to be further investigated.

Dementia is a growing problem of global relevance, currently affecting over 55 million people worldwide. The number of new dementia cases is still increasing, primarily due to the aging of society. Dementia is defined as a substantial decline in cognitive function, and it is inherently associated with neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, frontotemporal dementia, and vascular dementia. Of note, most patients suffering from neurodegenerative conditions, in addition to cognitive impairment, often experience various types of sleep disorders, including insomnia, rapid eye movement sleep behavior disorder, sleep-disordered breathing, and circadian rhythm disturbances. There is increasing evidence of a bidirectional interaction between sleep disturbances and mental health. Disrupted sleep may directly aggravate neuropsychiatric symptoms, like depression, anxiety, agitation, and hallucinations, and conversely, such symptoms can make sleeping more difficult. This creates a feedback loop that inevitably leads to disease progression and deterioration in quality of life. In this review, we provide an up-to-date overview of the nature and mechanisms behind sleep disorders in major neurodegenerative diseases, summarize treatment strategies for handling sleep disturbances, and discuss the clinical relevance of sleep–mental health interactions in the context of neurodegeneration-associated dementia. Neurodegeneration is a complex problem on the border between neurology and psychiatry, and it poses a challenge to the healthcare system, as it requires multidisciplinary approaches for optimal management. Understanding the connection between sleep and neuropsychiatric symptoms offers further opportunities for better symptom control, improved quality of life, and slower cognitive decline.

(1) Background: The present study aims to report the side effects of vaccination against coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) who were being treated with disease-modifying therapies (DMTs) in Poland. (2) Methods: The study included 2261 patients with MS who were being treated with DMTs, and who were vaccinated against COVID-19 in 16 Polish MS centers. The data collected were demographic information, specific MS characteristics, current DMTs, type of vaccine, side effects after vaccination, time of side-effect symptom onset and resolution, applied treatment, relapse occurrence, and incidence of COVID-19 after vaccination. The results were presented using maximum likelihood estimates of the odds ratio, t-test, Pearson’s chi-squared test, Fisher’s exact p, and logistic regression. The statistical analyses were performed using STATA 15 software. (3) Of the 2261 sampled patients, 1862 (82.4%) were vaccinated with nucleoside-modified messenger RNA (mRNA) vaccines. Mild symptoms after immunization, often after the first dose, were reported in 70.6% of individuals. Symptoms included arm pain (47.5% after the first dose and 38.7% after the second dose), fever/chills/flu-like symptoms (17.1% after the first dose and 20.5% after the second dose), and fatigue (10.3% after the first dose and 11.3% after the second dose). Only one individual presented with severe side effects (pro-thrombotic complications) after vaccination. None of the DMTs in the presented cohort were predisposed to the development of side effects. Nine patients (0.4%) had a SARS-CoV-2 infection confirmed despite vaccination. (4) Conclusions: Vaccination against SARS-CoV-2 is safe for people with MS who are being treated with DMTs. Most adverse events following vaccination are mild and the acute relapse incidence is low.

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS) mediated by autoreactive lymphocytes. The role of autoreactive lymphocytes in the CNS demyelination is well described, whereas very little is known about their role in remyelination during MS remission. In this study, we identified a new subpopulation of myelin-specific CD49d⁺CD154⁺ lymphocytes presented in the peripheral blood of MS patients during remission, that proliferated in vitro in response to myelin peptides. These lymphocytes possessed the unique ability to migrate towards maturing oligodendrocyte precursor cells (OPCs) and synthetize proinflammatory chemokines/cytokines. The co-culture of maturing OPCs with myelin-specific CD49d⁺CD154⁺ lymphocytes was characterized by the increase in proinflammatory chemokine/cytokine secretion that was not only a result of their cumulative effect of what OPCs and CD49d⁺CD154⁺ lymphocytes produced alone. Moreover, maturing OPCs exposed to exogenous myelin peptides managed to induce CD40-CD154-dependent CD49d⁺CD154⁺ lymphocyte proliferation. We confirmed, in vivo, the presence of CD49d⁺CD154⁺ cells close to maturating OPCs and remyelinating plaque during disease remission in the MS mouse model (C57Bl/6 mice immunized with MOG_35-55) by immunohistochemistry. Three weeks after an acute phase of experimental autoimmune encephalomyelitis, CD49d⁺/CD154⁺ cells were found to be co-localized with O4⁺ cells (oligodendrocyte progenitors) in the areas of remyelination identified by myelin basic protein (MBP) labelling. These data suggested that myelin-specific CD49d⁺CD154⁺ lymphocytes present in the brain can interfere with remyelination mediated by oligodendrocytes probably as a result of establishing proinflammatory environment.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the central nervous system (CNS). A clinical presentation of the disease is highly differentiated even from the earliest stages of the disease. The application of stratifying tests in clinical practice would allow for improving clinical decision-making including a proper assessment of treatment benefit/risk balance.Methods: This prospective study included patients with MS diagnosed up to 1 year before recruitment. We analyzed serum biomarkers such as CXCL13, CHI3L1, OPN, IL-6, and GFAP and neurofilament light chains (NfLs); brain MRI parameters of linear atrophy such as bicaudate ratio (BCR), third ventricle width (TVW); and information processing speed were measured using the Symbol Digit Modalities Test (SDMT) during the 2 years follow-up.Results: The study included a total of 50 patients recruited shortly after the diagnosis of MS diagnosis (median 0 months; range 0–11 months), and the mean time of observation was 28 months (SD = 4.75). We observed a statistically significant increase in the EDSS score (Wilcoxon test: Z = 3.06, p = 0.002), BCR (Wilcoxon test: Z = 4.66, p < 0.001), and TVW (Wilcoxon test: Z = 2.84, p = 0.005) after 2 years of disease. Patients who had a significantly higher baseline level of NfL suffered from a more severe disease course as per the EDSS score (Mann–Whitney U-test: U = 107, Z = −2,74, p = 0.006) and presence of relapse (Mann–Whitney U-test: U = 188, Z = −2.01, p = 0.044). In the logistic regression model, none of the parameters was a significant predictor for the achieving of no evidence of disease activity status (NEDA). In the model considering all assessed parameters, only the level of NfL had a significant impact on disease progression, measured as the increase in EDSS (logistic regression: β = 0.002, p = 0.017).Conclusion: We confirmed that NfL levels in serum are associated with more active disease. Moreover, we found that TVW at the time of diagnosis was associated with an impairment in cognitive function measured by information processing speed at the end of the 2-year observation. The inclusion of serum NfL and TVW assessment early in the disease may be a good predictor of disease progression independent of NEDA.

Multiple sclerosis (MS) is a neuroinflammatory disease where oxidative stress and DNA damage may influence disease progression. We investigated whether defects in base excision repair (BER) pathways contribute to MS by combining functional DNA repair assays, gene expression profiling, and genotype analysis. We collected peripheral blood mononuclear cells from 70 MS patients and 61 healthy controls. These cells were subjected to tert-butyl hydroperoxide (TBH)-induced oxidative stress, and comet assay kinetics were measured over a period of 60 min. Additionally, we quantified the mRNA expression of nine key BER genes and genotyped selected polymorphisms related to DNA repair capacity. Samples from MS patients exhibited significantly higher levels of TBH-induced DNA lesions and displayed a distinct repair trajectory over time, as indicated by area-under-the-curve (AUC) analyses (p < 0.001). The transcripts of MBD4 and NTHL1 were notably reduced in MS patients compared to those in the controls (p < 0.0001). A logistic regression analysis revealed an association between the specific BER-related single nucleotide polymorphisms (SNPs) rs3087404, rs4135054, and rs1052133 and ineffective DNA repair. Subset analyses of B cells, CD4⁺ cells, and CD8⁺ cells further supported the presence of altered repair kinetics in MS, even though some subsets exhibited similar baseline lesion levels. Our findings suggest that impaired oxidative DNA repair is present in MS, likely driven by functional deficits in repair kinetics and alterations in the expression of BER genes and polymorphisms. This integrated approach highlights DNA repair pathways as potential therapeutic or prognostic targets in MS.