Tetanus and Diphtheria Toxoid-Containing Vaccine in Multiple Sclerosis Patients: A Real-World Prospective, Open-Label, Multi-Centre Study.

Age-dependent cut-offs for pathological deep gray matter and thalamic volume loss using Jacobian integration

Neurofilament light chain (NfL) is a promising biomarker for monitoring disease activity and treatment response in multiple sclerosis (MS). This meta-regression assesses the relationship between treatment effects on serum/plasma NfL (s/pNfL) and clinical and radiological endpoints in randomized controlled trials (RCTs). A systematic PubMed search identified RCTs in MS (1999-2023) with ⩾24 months' duration and s/pNfL data. Extracted outcomes included treatment effects on s/pNfL, annualized relapse rate (ARR), confirmed disability worsening (CDW), magnetic resonance imaging (MRI) new/enlarging T2 lesions, and percentage brain volume change (PBVC). We evaluated the association of treatment effect on the selected outcomes at the trial level by a meta-regression, weighted by trial size and duration. Fifteen RCTs (n = 6814) were included, nine in relapsing MS (RMS, n = 5221), and six in progressive MS (PMS, n = 1593). Treatment effects on s/pNfL showed a moderate association with treatment effects on MRI new/enlarging T2 lesions (R2 = 0.42, p = 0.01), ARR (R2= 0.33, p = 0.03) and CDW (R2= 0.30, p = 0.04), but not with PBVC. In RMS-only trials, association with ARR (R2= 0.45, p = 0.05) and CDW (R2= 0.50, p = 0.03) was more pronounced. In MS, treatment effects on s/pNfL are moderately associated with therapeutic effects on ARR, MRI new/enlarging T2 lesions, and CDW, whereas no consistent association was observed with PBVC.

Chronic stress amplifies multidimensional disease activity in multiple sclerosis patients: A year-long within-person analysis.

Peroxynitrite was hypothesized to be involved in the pathogenesis of multiple sclerosis (MS) through its various neurotoxic effects. Uric acid (UA) was shown to be a strong peroxynitrite scavenger. We analyzed cerebrospinal fluid (CSF) and serum UA concentrations in 30 MS patients and 20 controls with non-inflammatory neurological diseases (NIND) and correlated these findings with demographic and clinical characteristics of MS patients. Disease activity was assessed by brain magnetic resonance imaging (MRI) and the CSF/serum albumin quotient as an indicator of the state of blood-brain-barrier (BBB). Serum UA concentrations were found to be significantly lower in MS patients compared with controls (p=0.019). CSF UA concentrations were lower in MS patients as compared to controls, as well as in patients with active MS (clinical and/or MRI activity) in comparison to patients with inactive MS or controls, but these differences were not statistically significant. Significant correlation was found between CSF and serum UA concentrations (p=0.016) in MS patients, but not in controls; and between CSF UA concentrations and the CSF/serum albumin quotient in MS patients (p=0.043), but not in controls. Our results support the significance of UA in the pathogenesis of MS. Decreased serum UA concentrations in MS patients might be due to both intrinsically reduced antioxidant capacity and increased UA consumption in MS. CSF UA concentrations may not be a reliable marker of disease activity in MS since its concentration is dependent on leakage of UA molecules from serum through the damaged BBB and the balance between consumption/production within the central nervous system (CNS).

<h3>Objective:</h3> To describe oral hygiene habits in MS and NMOSD patients from Argentina and evaluate the oral health-related quality of life, and its possible association with IST and other relevant clinical factors. <h3>Background:</h3> Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are inflammatory diseases of the central nervous system. Most MS and NMOSD patients are on immunosuppressive treatment (IST), leading to an increased risk of infections, including those of odontogenic origin. There is scarce evidence on oral health-related quality of life in these patients. <h3>Design/Methods:</h3> A cross-sectional study was conducted using an Oral Health Impact Profile test (OHIP-14) in 202 MS, 36 NMOSD patients, and 167 controls (HC; non-MS, non-NMOSD and without any IST). We retrospectively reviewed the medical records, and demographic, clinical/paraclinical data and treatments were evaluated. Higher OHIP-14 scores are related to a poorer state of oral health. <h3>Results:</h3> A total of 405 individuals were included. NMOSD patients had a significantly worse performance in functional limitation and handicap domains of the OHIP-14 score compared with MS and HC. HC scored significantly higher in psychological discomfort than MS. No differences in the frequency of dental hygiene were found between groups. MS and NMOSD patients had worse subjective perception of their oral health and fewer odontological visits than HC within the last year. MS patients on active disease modifying treatment were independently associated with higher total OHIP-14 score (β 5.90, 95%CI 1.96–9.84, p=0.003) in our linear regression model. <h3>Conclusions:</h3> This study showed that MS and NMOSD patients may be vulnerable regarding their oral health. Using DMT in MS patients was a predictor of poor state of oral health. Patient-reported OHIP-14 scores provide comprehensive additional information in clinical practice. <b>Disclosure:</b> Veronica A. Tkachuk has nothing to disclose. Dr. Aguirre has nothing to disclose. Dr. Cao has nothing to disclose. Dr. Nadur has nothing to disclose. Dr. Isa has nothing to disclose. Mrs. Balbuena has nothing to disclose. Miss Perachino has nothing to disclose. Edgar Carnero Contentti has nothing to disclose.

Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome measures of disease activity in multiple sclerosis (MS) patients. The objective was to assess the efficacy and safety of MX in relapsing-remitting MS (RRMS), progressive relapsing MS (PRMS) and secondary progressive MS (SPMS). We searched the Cochrane MS Group Trials Register (searched April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2004), MEDLINE (Pub Med) (January 1966 to April 2005), EMBASE (January 1974 to April 2005), and reference lists of articles. We also undertook hand searching and contacting trialists and pharmaceutical companies. The trials were selected if double-blinded, placebo-controlled, randomised, irrespective of eventual additive therapy (such as steroids). Three reviewers independently selected articles for inclusion, assessed trials' quality and extracted data. Four trials involving 270 participants were included. MX was found to reduce the progression of disability at 2 years follow-up (proportion of participants with 6-months confirmed progression of disability: Odds Ratios (OR) 0.3, p = 0.05). Similar figures were found regarding the reduction in annualised relapse rate and the proportion of patients free from relapses at 1 and 2 years, as well as the number of patients with active MRI lesions at 6 months/ 1 year only. Side effects reported in the trials were more frequent in treated patients than in controls. Caution must be exercised in drawing conclusions from such data because of the heterogeneous quality and characteristics of the included trials, which are different in terms of treatment schedule and type of enrolled patients. More than half of the included patients came from a single study. Moreover, from the included trials, it was not possible to estimate the long-term efficacy and safety of MX, which may raise concerns about the risk of cardiotoxicity and therapy-related leukemias, which is increasingly reported in the literature. MX is moderately effective in reducing the disease progression and the frequency of relapses in patients affected by RR, PR and SP MS in the short-term follow-up (2 years), even if the results are based on trials heterogeneous in terms of drug dosage and inclusion criteria. No major neoplastic or symptomatic cardiotoxicity related to MX have been reported from the trials. However, longer follow-up studies are highly warranted to better explore the efficacy and safety of the drug, mainly as regards the long-term risk of therapy-related leukemias and cardiotoxicity. As a conclusion, MX has a partial efficacy, but, due to its unclear long-term safety profile, it should be used to treat patients with worsening RR and SP MS with evidence of worsening disability.

Safety Concerns for Sclerotherapy of Telangiectases, Reticular and Varicose Veins

Fibroblast growth factor-2 levels are elevated in the cerebrospinal fluid of multiple sclerosis patients

Paired serum and cerebrospinal fluid (CSF) specimens from 30 multiple sclerosis (MS) patients and 30 patients with other neurological diseases (ONDs) were analyzed for the presence of immune complexes (ICs). With each of the 4 tests used, ICs were found more frequently in sera from both MS and OND patients than in sera from healthy blood donors. IC-positivity for MS and OND patient CSF varied from 10-33% and from 10-17% in different tests. The number of IC-positive sera or CSF in MS patients did not differ significantly from those in OND patients. For both MS and OND patients, the positivity pattern for serum and CSF specimens in each IC test was essentially unique. Furthermore, because several CSF IC-positive and serum IC-negative paired specimens were found, intrathecal IC formation may be independent of IC formation in peripheral blood. The presence of ICs in serum or CSF did not correlate with the clinical status of or laboratory data on the MS patients, nor was a correlation found with the diagnosis of the OND patients. In total, these results suggest that the presence or absence of ICs in MS or OND patients may simply reflect changes in the immunological regulation of individual patients.

BackgroundNationwide surveys conducted in Japan over the past thirty years have revealed a four-fold increase in the estimated number of multiple sclerosis (MS) patients, a decrease in the age at onset, and successive increases in patients with conventional MS, which shows an involvement of multiple sites in the central nervous system, including the cerebrum and cerebellum. We aimed to clarify whether genetic and infectious backgrounds correlate to distinct disease phenotypes of MS in Japanese patients.Methodology/Principal FindingsWe analyzed HLA-DRB1 and -DPB1 alleles, and IgG antibodies specific for Helicobacter pylori, Chlamydia pneumoniae, varicella zoster virus, and Epstein-Barr virus nuclear antigen (EBNA) in 145 MS patients and 367 healthy controls (HCs). Frequencies of DRB1*0405 and DPB1*0301 were significantly higher, and DRB1*0901 and DPB1*0401 significantly lower, in MS patients as compared with HCs. MS patients with DRB1*0405 had a significantly earlier age of onset and lower Progression Index than patients without this allele. The proportion and absolute number of patients with DRB1*0405 successively increased with advancing year of birth. In MS patients without DRB1*0405, the frequency of the DRB1*1501 allele was significantly higher, while the DRB1*0901 allele was significantly lower, compared with HCs. Furthermore, DRB1*0405-negative MS patients were significantly more likely to be positive for EBNA antibodies compared with HCs.ConclusionsOur study suggests that MS patients harboring DRB1*0405, a genetic risk factor for MS in the Japanese population, have a younger age at onset and a relatively benign disease course, while DRB1*0405-negative MS patients have features similar to Western-type MS in terms of association with Epstein-Barr virus infection and DRB1*1501. The recent increase of MS in young Japanese people may be caused, in part, by an increase in DRB1*0405-positive MS patients.

Objective This study compares the nutritional status and physical activity levels of relapsing-remitting multiple sclerosis (RRMS) patients and healthy people. Method The study included 120 participants: 60 multiple sclerosis (MS) patients and 60 controls. RRMS diagnoses were made based on the 2017 McDonald criteria. The food intake frequency questionnaire was administered to the participants, their threeday food intake records were collected, their activity levels were determined, and anthropometric measurements were made. The differences between the groups were analyzed using the Mann–Whitney U test and Pearson's exact chi-squared test. Results The participants with MS (46.7%) had a significantly lower rate of shopping for their own food compared to the control group (68.3%) (p = 0.002). The MS group (3.3%) had a lower rate of intake of green leafy vegetables 5 times weekly or more frequently than the control group (20.0%) (p < 0.05); and the control group (35.0%) had a higher consumption rate of pastry more than 1 to 2 times monthly than the MS group (13.3%) (p < 0.05). The participants with MS had a higher intake of fiber, insoluble fiber, and omega 3 fatty acid than the control group (p < 0.05). Expanded Disability Status Scale (EDSS) scores indicates that a positive correlation was found between daily intake of fiber and insoluble fiber (p < 0.05). The patients with MS in the inactive group had a higher EDSS median [2.00(0.00 –5.00)] than the minimal active group [1.25(0.00 –4.00)] (p = 0.034). Conclusion With the increase in disability in MS patients, their physical activity levels decrease and it becomes difficult for them to shop on their own. In addition, the consumption frequency of green leafy vegetables, which take time to prepare and a source of fiber, is also decreasing. It has been shown that fiber intake decreases when the disability increase. Therefore, preventing the progression of disability in MS patients is very important in ensuring diversity in food consumption.

Influences of pregnancy on neuromyelitis optica spectrum disorders and multiple sclerosis

Objective: Multiple sclerosis primarily affects young adults. The prevalence is increasing worldwide, although the reason for this rise is not fully understood. The disease usually progresses with attacks. The diagnosis of disease activation is made clinically and by magnetic resonance imaging. Magnetic resonance imaging is an expensive and time-consuming examination. It is obvious that there is a need for an inexpensive and fast-resulting test that will aid in the diagnosis of active patients. Data from a complete blood count may be one of them.This study aimed to examine the association between disease activity in multiple sclerosis patients and the ratios of neutrophils to lymphocytes, platelets to lymphocytes, eosinophils to lymphocytes, and monocytes to lymphocytes. Material and Methods: One hundred and twenty patients diagnosed with multiple sclerosis and 110 healthy controls were enrolled. Demographic characteristics such as age, sex, and duration of disease, magnetic resonance lesion characteristics, and Expanded Disability Symptom Scale results were recorded. Results: The mean neutrophil-to-lymphocyte ratio in active patients was significantly higher compared to both the inactive disease group and the control group (p&amp;lt;0.001). Similarly, the mean monocyte-to-lymphocyte ratio in active patients was significantly also higher compared to the control group (p=0.002). The active and inactive patients’ platelet/lymphocyte ratio values were both significantly higher than those of the control group (p&amp;lt;0.001). Conclusion: This study suggests that the neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios are associated with the activation of multiple sclerosis. More extensive studies with larger patient populations and healthy controls are now needed to clarify the association between serum neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios and disease activity in multiple sclerosis.

T helper 17 (TH17) cells are key players in multiple sclerosis (MS), and studies in animal models demonstrated that effector TH17 cells that trigger brain autoimmunity originate in the intestine. We validate in humans the crucial role of the intestinal environment in promoting TH17 cell expansion in MS patients. We found that increased frequency of TH17 cells correlates with high disease activity and with specific alterations of the gut mucosa-associated microbiota in MS patients. By using 16S ribosomal RNA sequencing, we analyzed the microbiota isolated from small intestinal tissues and found that MS patients with high disease activity and increased intestinal TH17 cell frequency showed a higher Firmicutes/Bacteroidetes ratio, increased relative abundance of Streptococcus, and decreased Prevotella strains compared to healthy controls and MS patients with no disease activity. We demonstrated that the intestinal TH17 cell frequency is inversely related to the relative abundance of Prevotella strains in the human small intestine. Our data demonstrate that brain autoimmunity is associated with specific microbiota modifications and excessive TH17 cell expansion in the human intestine.

BackgroundWe investigated the association between chronic cerebrospinal venous insufficiency (CCSVI) and cognitive impairment (CI) in multiple sclerosis (MS). Moreover, we evaluated the association between CCSVI and other frequent self-reported MS symptoms.MethodsWe looked at the presence of CI in incident MS patients with CCVSI in a population-based cohort of Catania, Italy. All subjects were group-matched by age, sex, disease duration and EDSS score with MS patients without CCSVI, serving as controls. CI was assessed with the Brief Repeatable Battery (BRB) and the Stroop Test (ST) and it was defined by the presence of at least three impaired tests. Fatigue and depressive symptoms were assessed with Fatigue Severity Scale (FSS) and Hamilton Depressive Rating Scale (HDRS), respectively. Bladder and sexual symptoms were assessed with the respective items of the Italian version of Guy's Neurological Disability Scale (GNDS). Quality of life was evaluated with Multiple Sclerosis Quality of Life-54 Instrument (MSQOL-54).ResultsOut of 61 MS patients enrolled in the study, 27 were CCSVI positive and 34 were CCSVI negative. Of them, 43 were women (70.5%); the mean age was 43.9 ± 11.8 years; the mean disease duration was 159.7 ± 113.7 months; mean EDSS was 3.0 ± 2.6. Of them, 36 (59.0%) were classified relapsing-remitting (RR), 12 (19.7%) secondary progressive (SP), seven (11.5%) primary progressive (PP) and six (9.3%) Clinically Isolated Syndrome (CIS). Overall, CI was detected in 29/61 (47.5%) MS patients; particularly 13/27 (48.1%) in the CCSVI positive group and 16/34 (47.0%) in the CCSVI negative group. Presence of CCSVI was not significantly associated with the presence of CI (OR 1.04; 95% CI 0.37-2.87; p-value = 0.9). Not significant differences were found between the two groups regarding the other MS symptoms investigated.ConclusionsOur findings suggest a lack of association between CCSVI and CI in MS patients. Fatigue, depressive, bladder/sexual symptoms and self-reported quality of life are not associated with CCSVI.