Differences in Brain Atrophy Pattern between People with Multiple Sclerosis and Systemic Diseases with Central Nervous System Involvement Based on Two-Dimensional Linear Measures.

Conventional brain magnetic resonance imaging (MRI) in systemic diseases with central nervous system involvement (SDCNS) may imitate MRI findings of multiple sclerosis (MS). In order to better describe the MRI characteristics of these conditions, in our study we assessed brain volume parameters in MS (n = 58) and SDCNS (n = 41) patients using two-dimensional linear measurements (2DLMs): bicaudate ratio (BCR), corpus callosum index (CCI) and width of third ventricle (W3V). In SDCNS patients, all 2DLMs were affected by age (CCI p = 0.005, BCR p < 0.001, W3V p < 0.001, respectively), whereas in MS patients only BCR and W3V were (p = 0.001 and p = 0.015, respectively). Contrary to SDCNS, in the MS cohort BCR and W3V were associated with T1 lesion volume (T1LV) (p = 0.020, p = 0.009, respectively) and T2 lesion volume (T2LV) (p = 0.015, p = 0.009, respectively). CCI was associated with T1LV in the MS cohort only (p = 0.015). Moreover, BCR was significantly higher in the SDCNS group (p = 0.01) and CCI was significantly lower in MS patients (p = 0.01). The best predictive model to distinguish MS and SDCNS encompassed gender, BCR and T2LV as the explanatory variables (sensitivity 0.91; specificity 0.68; AUC 0.86). Implementation of 2DLMs in the brain MRI analysis of MS and SDCNS patients allowed for the identification of diverse patterns of local brain atrophy in these clinical conditions.

Predictive value of brain atrophy, serum biomarkers and information processing speed for early disease progression in multiple sclerosis.

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: ß = 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.

Cerebrospinal Fluid Biomarkers in Differential Diagnosis of Multiple Sclerosis and Systemic Inflammatory Diseases with Central Nervous System Involvement.

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.

Analysis of Side Effects Following Vaccination Against COVID-19 Among Individuals With Multiple Sclerosis Treated With DMTs in Poland.

Background and Objectives: Since vaccination against COVID-19 is available for over a year and the population of immunized individuals with autoimmune disorders is higher than several months before, an evaluation of safety and registered adverse events can be made. We conducted a large study of side effects following the COVID-19 vaccine among patients with multiple (MS) sclerosis treated with disease-modifying therapies (DMTs) and analyzed factors predisposing for particular adverse events. Methods: We gathered data of individuals with MS treated with DMTs from 19 Polish MS Centers, who reported at least one adverse event following COVID-19 vaccination. The information was obtained by neurologists using a questionnaire. The same questionnaire was used at all MS Centers. To assess the relevance of reported adverse events, we used Fisher's exact test, t-test, and U-Menn-Whutney test. Results: A total of 1,668 patients with MS and reports of adverse events after COVID-19 vaccination were finally included in the study. Besides one case marked as "red flag", all adverse events were classified as mild. Pain at the injection site was the most common adverse event, with a greater frequency after the first dose. Pain at the injection site was significantly more frequent after the first dose among individuals with a lower disability (EDSS ≤2). The reported adverse events following immunization did not differ over sex. According to age, pain at the injection site was more common among individuals between 30 and 40 years old, only after the first vaccination dose. None of the DMTs predisposed for particular side effects. Conclusions: According to our findings, vaccination against COVID-19 among patients with MS treated with DMTs is safe. Our study can contribute to reducing hesitancy toward vaccination among patients with MS.

Safety of Vaccines against SARS-CoV-2 among Polish Patients with Multiple Sclerosis Treated with Disease-Modifying Therapies.

(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.

Effect of Multiple Sclerosis Cerebrospinal Fluid and Oligodendroglia Cell Line Environment on Human Wharton's Jelly Mesenchymal Stem Cells Secretome.

Multiple sclerosis (MS) is a neurological disorder of autoimmune aetiology. Experimental therapies with the use of mesenchymal stem cells (MSCs) have emerged as a response to the unmet need for new treatment options. The unique immunomodulatory features of stem cells obtained from Wharton's jelly (WJ-MSCs) make them an interesting research and therapeutic model. Most WJ-MSCs transplants for multiple sclerosis use intrathecal administration. We studied the effect of cerebrospinal fluid (CSF) obtained from MS patients on the secretory activity of WJ-MSCs and broaden this observation with WJ-MSCs interactions with human oligodendroglia cell line (OLs). Analysis of the WJ-MSCs secretory activity with use of Bio-Plex Pro™ Human Cytokine confirmed significant and diverse immunomodulatory potential. Our data reveal rich WJ-MSCs secretome with markedly increased levels of IL-6, IL-8, IP-10 and MCP-1 synthesis and a favourable profile of growth factors. The addition of MS CSF to the WJ-MSCs culture caused depletion of most proteins measured, only IL-12, RANTES and GM-CSF levels were increased. Most cytokines and chemokines decreased their concentrations in WJ-MSCs co-cultured with OLs, only eotaxin and RANTES levels were slightly increased. These results emphasize the spectrum of the immunomodulatory properties of WJ-MSCs and show how those effects can be modulated depending on the transplantation milieu.

Optical Coherence Tomography in the Differential Diagnosis of Patients with Multiple Sclerosis and Patients with MRI Nonspecific White Matter Lesions.

In the differential diagnosis of nonspecific white matter lesions (NSWMLs) detected on magnetic resonance imaging (MRI), multiple sclerosis (MS) should be taken into consideration. Optical coherence tomography (OCT) is a promising tool applied in the differential diagnostic process of MS. We tested whether OCT may be useful in distinguishing between MS and NSWMLs patients. In patients with MS (n = 41) and NSWMLs (n = 19), the following OCT parameters were measured: thickness of the peripapillary Retinal Nerve Fibre Layer (pRNFL) in superior, inferior, nasal, and temporal segments; thickness of the ganglion cell-inner plexiform layer (GCIPL); thickness of macular RNFL (mRNFL); and macular volume (MV). In MS patients, GCIPL was significantly lower than in NSWMLs patients (p = 0.024). Additionally, in MS patients, mRNFL was significantly lower than in NSWMLs patients (p = 0.030). The average segmental pRNFL and MV did not differ between MS and NSWMLs patients (p > 0.05). GCIPL and macular RNFL thinning significantly influenced the risk of MS (18.6% [95% CI 2.7%, 25.3%]; 27.4% [95% CI 4.5%, 62.3%]), and reduced GCIPL thickness appeared to be the best predictor of MS. We conclude that OCT may be helpful in the differential diagnosis of MS and NSWMLs patients in real-world settings.

Speech Pathology-Specific Questionnaire for Persons with Multiple Sclerosis (SMS): adaptation, validation and preliminary assessment of the diagnostic potential.

INTRODUCTION: Speech and voice disorders are among the least well-described clinical manifestations of Multiple Sclerosis (MS) although their estimated prevalence reaches 40-50%. The aim of the present study was adaptation and validation of the Speech Pathology-Specific Questionnaire for Persons with Multiple Sclerosis (SMS) into the Polish language to be used as part of the diagnostic procedure to quantify important speech-related changes and to improve individual tailoring of therapeutic activities. MATERIAL AND METHODS: The study included a total number of 178 participants. The study group consisted of 107 patients diagnosed with Multiple Sclerosis, mean age 42.8±11.6 years and the Control Group were 71 healthy sex and age matched normophonic subjects, mean age 44.2±12.5 years with no neurological symptoms. Translated version of SMS was administered to all participants of the study. Voice Handicap Index (VHI) questionnaire was used for comparison purposes. Test-retest reproducibility, internal consistency, floor and ceiling effects, discriminant validity and construct validity of the Polish SMS were investigated. Preliminary assessment of diagnostic value of SMS was conducted on the basis of the results recorded in duration-related quartiles of the Study Group. RESULTS: High value of Intraclass Correlation Coefficient (ICC= 0 .930) obtained for the test-retest indicates a good level of reproducibility of the Polish SMS. High Cronbach's alpha (α=0.94) proves the test's good internal consistency. There were no floor and ceiling effects for the SMS test score in the Study Group and they were negligible in the Control Group. A significant difference in mean SMS total scores between patients and controls (14.22 points vs. 6.06 points) shows discriminant validity of SMS. Similar differences were observed for all the subscales of the test (in t test: p<0.001). A statistically significant correlation was found for the SMS score and its all subscales, as well as between all the subscales of the test proving good construct validity of the test. Similarly, statistically significant correlations were observed for the total score of SMS and VHI (r=.817, p <0.001) as well as between the particular subscales of SMS test and the subscales of VHI. There was a statistically significant difference in the mean total score of SMS in the distinguished quartiles of the Study Group with the highest values (20 points) recorded in the group of patients suffering from MS for over 15 years. CONCLUSION: The psychometric properties of the Polish version of Speech Pathology-Specific Questionnaire indicate that it is a valid patient-reported outcome measure suitable for the assessment of speech-language pathology aspects on the population of Multiple Sclerosis patients and can be used as an complementary diagnostic tool in clinical practice.