Analysis of seroconversion following COVID-19 vaccination among multiple sclerosis patients treated with disease-modifying therapies in Poland.

CLINICAL RATIONALE FOR THE STUDY: The rapid spread of SARS-CoV-2 throughout the world has highlighted the importance of vaccinations to control the pandemic and to protect people at risk for severe disease courses. Disease-modifying therapies (DMT) in multiple sclerosis (MS), whether immunomodulatory or immunosuppressive, may affect the immune response. Therefore, the question arose as to whether these vaccinations would be effective. AIM OF THE STUDY: We planned a study to assess the immune response to SARS-CoV-2 vaccines by type of therapy. MATERIAL AND METHODS: Participants were recruited from 14 Polish MS centres. The data was obtained by neurologists using a questionnaire. We collected data on 353 MS patients (269 females, 84 males) who received complete primary SARS-CoV-2 vaccination. All persons with MS (PwMS) were treated with disease-modifying therapies. RESULTS: 305 out of 353 PwMS (86.4%) were positive for IgG Abs against SARS-CoV-2 S domain S1 Ag after vaccination. A strong immune response was noted in 129 PwMS (36.5%). The rate of seroconversion after SARS-CoV-2 vaccination in PwMS who received immunomodulatory DMTs (interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab) was 91.5%, in PwMS receiving immune reconstruction therapy (alemtuzumab, cladribine) was 92%, and in immunosuppressive DMTs (fingolimod, ocrelizumab), the seroconversion rate was 59%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study shows that, in PwMS receiving immunomodulatory therapy, the immune response to vaccination is generally excellent. Even in immunosuppressive patients, seroconversion is satisfactory.

Sense of happiness in Polish patients with multiple sclerosis.

INTRODUCTION: Happiness is crucial to patient well-being and their acceptance of their disease. The aim of this study was to assess the sense of happiness in persons with multiple sclerosis (PwMS), compare it to the level of happiness in patients with other neurological conditions, and determine which factors affect the sense of happiness in PwMS. MATERIAL AND METHODS: Five hundred and eighty-nine PwMS and 145 control subjects (post-stroke patients with chronic pain syndromes and neuropathies) were included in the study. Due to the differences between the groups in terms of demographic variables, an adjusted group of PwMS (n = 145) was selected from the entire group of PwMS. All patients were assessed using the Oxford Happiness Questionnaire (OHQ), the Satisfaction with Life Scale (SLS), and the Family APGAR Questionnaire. Based on regression analysis, the study examined which variables affected the level of happiness in the groups. RESULTS: Analysis of the OHQ scores showed that PwMS had a lower sense of happiness compared to the control group in the overall score [113.21 (25-42) vs. 119.88 (25-49), respectively; p = 0.031] and the subscales (OHQ subscale 1 - 54.52 vs. 57.84, respectively; p = 0.027; subscale 2 - 35.61 vs. 37.67; respectively; p = 0.044). Based on linear regression analysis, life satisfaction (ß = 0.40; p < 0.001), positive orientation (ß = 0.32; p < 0.001), and primary education (ß = 0.08; p = 0.009) were the most significant predictors of a higher level of happiness in PwMS. Similar results were found in the control group. CONCLUSIONS: The sense of happiness in PwMS was lower than in patients with other conditions. The most important factors influencing happiness included life satisfaction and positive orientation. Influencing these predictors should be the aim of psychological interventions, especially in patients with a reduced sense of happiness.

Religious meaning system and life satisfaction: the mediating role of meaning in life among Polish people with multiple sclerosis.

Introduction: The complexity of the associations between religiosity and indicators of well-being suggests the presence of a mediating mechanism. Previous studies indicate that religion may influence subjective well-being because it helps to find meaning and purpose. Therefore, the aim of our study was to examine the mediating role of the presence and search dimensions of meaning in life in the relationship between religious meaning system and life satisfaction in patients with multiple sclerosis (MS). Methods: This cross-sectional study included 600 MS patients recruited from Poland who completed the Satisfaction with Life Scale (SWLS), the Religious Meaning System Questionnaire (RMS) and the Meaning in Life Questionnaire (MLQ). Model 6 of Hayes PROCESS was used to test the hypotheses. Results: The results of our research indicate that there was a significant indirect effect of religious meaning system on life satisfaction through the presence of meaning in life. The specific indirect effect of religious meaning system on life satisfaction through searching for meaning in life was not significant. Discussion: The results of our study are relevant because they show that religion as a meaning system is positively related to the presence of meaning in life, which in turn positively predicts life satisfaction. This is particularly important in the case of incurable illness, where finding meaning in life is one of the natural stages of adaptation. By incorporating these findings into mental health practice, professionals can enhance the holistic well-being of people coping with MS and contribute to a more comprehensive and effective approach to mental health care.

Complementary and alternative medicine in multiple sclerosis: a questionnaire-based study.

AIM OF THE STUDY: To assess the prevalence and characteristics of complementary and alternative medicine (CAM) use among multiple sclerosis (MS) patients in Poland. CLINICAL RATIONALE FOR THE STUDY: Multiple sclerosis (MS) is a chronic, progressive and disabling neurological disease with significant impact on quality of life. Although the efficacy and safety of complementary and alternative medicine (CAM) has not been scientifically confirmed, many patients use CAM as a complement or an alternative to conventional therapy. MATERIAL AND METHODS: Data was collected via a self-designed survey consisting of 33 questions. The questionnaire was distributed among MS patients hospitalised during 2016 in the MS Unit at the Department of Neurology, Medical University of Warsaw, Poland. The study group consisted of 75 patients (47 females, 28 males, mean age 44.6 ± 12.5 years) with clinically defined MS. RESULTS: According to the questionnaire, 48 patients (64%) had used CAM at least once. Most of the patients declared that CAM had a possible (58%) or a marked (43.7%) positive effect. 61.4% of CAM users reported reduced fatigue and 33.3% improved mood. There were significant correlations between CAM use and lower social and professional status (p < 0.04), disease progression (p < 0.03), and lack of efficacy of disease-modifying therapies (p < 0.04). There were no significant correlations between CAM usage and sex, habitation, education, marital or professional status. The most frequently used CAMs were vitamins (48%), and polyunsaturated fatty acids (36%); psychophysical methods (44%) included manual therapies (24%) and relaxation techniques (17.3%) as well as herbal medicine (29.3%). Physicians were considered to be the most reliable authority in both conventional treatment (97.3%) and CAM (67%). Complementary and alternative medicine users significantly more often discussed this issue with their doctors (56%) compared to patients who did not use alternative medicine (p < 0.05). However, 54% of patients did not inform their physician about CAM use. Responders said that physicians did not initiate discussion about it (55.9%), but 44% of patients would like to have the possibility of talking to a doctor about CAM. CONCLUSIONS AND CLINICAL IMPLICATIONS: Although CAM efficacy and safety is not confirmed, one should keep in mind that most MS patients use alternative methods, especially those individuals with a more severe phenotype. Physicians are mostly perceived as reliable authorities and therefore they should discuss this issue with patients in order to eliminate drug interactions and to improve compliance.

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.

The Big Five Personality Traits and Positive Orientation in Polish Adults with Multiple Sclerosis: The Role of Meaning in Life.

Scientific achievements concerning the direct relation between personality traits and positive orientation among patients with multiple sclerosis do not explain the role of potential mediators. In fact, some researchers argue that the traits-positivity association is much more complex than it seems to be. For this reason, we made an attempt to analyze the indirect relationship between the above-mentioned variables, including meaning in life as a mediator. In total, 618 patients with MS took part in the study. The NEO Five-Factor Inventory, the Positive Orientation Scale, and the Meaning in Life Questionnaire were used. The results showed that positive orientation/the presence of meaning/searching for meaning correlated positively with extraversion, openness to experience, agreeableness, and conscientiousness, and were negatively associated with neuroticism. Moreover, meaning in life in both its dimensions acted as a mediator in 9 of 10 models. It can be assumed that a propensity to establish interpersonal relationships (extraversion), use active imagination (openness), inspire confidence among others (agreeableness), and take responsibility (conscientiousness) can have an impact on someone's positive attitude toward oneself and the surrounding world (positive orientation) when people have meaning in life and when they are seeking it.

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.

Impact of Immunoablation and Autologous Hematopoietic Stem Cell Transplantation on Treatment Cost of Multiple Sclerosis: Real-World Nationwide Study.

OBJECTIVES: To provide real-world data on the impact of autologous hematopoietic stem cell transplantation (AHSCT) on treatment costs of patients with multiple sclerosis (MS) in Poland. METHODS: Medical data of 105 patients who underwent AHSCT in the years 2011 to 2016 were obtained from the National Health Fund (NHF) database. Treatment costs were calculated from the public payer's perspective per patient-year for the total available period as well as 12 months before and after AHSCT. The statistical analysis was performed using MATLAB 2016b. RESULTS: Mean treatment-related costs covered by the NHF per patient-year before and after the transplantation were €4314.9 and €1188.8 , respectively. The average cost of disease-modifying drugs per patient was reduced from €2497.9/year before to €65.3/year after AHSCT. CONCLUSIONS: Although the initial cost of AHSCT is high, the costs involving AHSCT and post-AHSCT treatment could, according to our analysis, pay off in 3.9 years, when compared to the costs of disease-modifying drug therapy in aggressive MS. The study provides evidence that the AHSCT can lead to significant savings in treatment costs of aggressive MS from the public payer's perspective.

Clinical course and outcome of SARS-CoV-2 infection in multiple sclerosis patients treated with disease-modifying therapies - the Polish experience.

INTRODUCTION: The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited. MATERIALS AND METHODS: This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health. RESULTS: There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used. CONCLUSIONS AND CLINICAL IMPLICATIONS: Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs.

Search for viral agents in cerebrospinal fluid in patients with multiple sclerosis using real-time PCR and metagenomics.

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disease of the central nervous system of unclear etiology, but there is some evidence that viral infections could be responsible for triggering autoimmune mechanisms against myelin. We searched for viral RNA and DNA in cerebrospinal fluid (CSF) of 34 MS patients and 13 controls using RT-PCR/PCR against common neurotropic viruses. In addition, shotgun DNA- and RNA-based metagenomics were done in 13 MS patients and 4 controls. Specific quantitative real-time RT-PCR/PCR testing revealed the presence of viral nucleic acid in seven (20.59%) MS patients and in one (7.69%) control patient. In MS patients the most frequently detected was human herpesvirus type 6 (HHV-6; 3 cases; 8.82%); followed by Epstein-Barr virus (EBV; 2 cases; 5.88%), varicella zoster virus (VZV; 1 case; 2.94%) and Enterovirus (EV; 1 case; 2.94%). The single identified virus among controls was EBV (7.69%). DNA and RNA metagenomic assays did not identify any known eukaryotic viruses even though three of the analyzed samples were low-level positive by specific quantitative real-time PCR. In conclusion, we detected the presence of Herpesviridae and occasionally Enteroviridae in CSF from patients with MS but their prevalence was not significantly higher than among controls. Metagenomic analysis seems to be less sensitive than real-time RT-PCR/PCR and it did not detect any potential viral pathogens.

The relationship between aquaporin-4 antibody status and visual tract integrity in neuromyelitis optica spectrum disorders: A visual evoked potential study.

BACKGROUND: Optic neuritis (ON) is one of the hallmark symptomatic features of neuromyelitis optica spectrum disorders (NMOSD). The majority of patients with NMOSD present highly specific autoantibodies against aquaporin-4 (AQP4). A number of studies have reported poor visual acuity outcomes in individuals with AQP4 seropositive NMOSD, but no such relationship has been found with regard to visual evoked potentials (VEP) parameters such as the amplitude and latency of the P100 component. In this paper, we aimed (i) to describe VEP responses in patients with NMOSD; (ii) to analyze those results based on a scoring system; and (iii) to investigate the association between the VEPs and AQP4 antibody status. METHODS: We retrospectively analysed the VEP responses of 40 patients with a diagnosis of NMOSD (according to the 2015 IPND criteria), including 16 with AQP4-postive status (AQP4[+]) and 24 with AQP4-negative status (AQP4[-]). In the first step, we measured the P100 peak latency and P100-N2 peak-to-peak amplitude in each patient. In the second, we converted these measures to the VEP score (0-10) using the scoring proposed by Jung et al. (2008). All recordings were performed using the same VEP device and testing protocol. RESULTS: Abnormal VEPs were recorded in 25 of 40 patients (62.6%). Of these, 17 (42.5%) had prolonged P100 latency, and 8 (20%) had no response detected in at least one eye. The patients with ON as the initial relapse symptom had significantly higher median VEP scores than those who experienced the longitudinally extensive transverse myelitis (LETM) at the disease onset (7.0 [in-terquar-tile range (IQR), 2.0-8.0] vs. 0.0 [IQR, 0.0-4.0], p<0.001). A lack of VEP response in at least one eye was detected more frequently in the AQP4[+] group than the AQP4[-] group (7/16 vs. 1/24, p<0.005). Logistic regression model controlling for age, gender, disease duration, and the type of relapse at onset showed an independent impact of AQP4[+] status (OR=35.45, p = 0.018) on the higher rate of absent VEP responses. In the entire group of patients (n = 40), those with AQP4[+] showed a small tendency towards a higher median VEP score (4.0 [IQR, 0.0-7.8] vs. 1.0 [IQR, 0.0-4.0], p = 0.304). Among individuals with abnormal responses (n = 25), the patients with AQP4[+] had significantly higher median VEP scores (7.0 [IQR, 4.0-8.5] vs. 3.0 [IQR, 1.0-7.0], p = 0.034) and more common bilateral involvement of the optic tracts (80% vs. 40%, p = 0.048) than those who were seronegative for anti-AQP4 antibody. A median regression analysis model controlling for age, gender, disease duration, type of onset, and number of relapses in last 12 months showed an independent association between the AQP4-positive status and a higher VEP score in patients with NMOSD (t = 2.882, df=2, p = 0.007). CONCLUSION: VEP study remains a useful tool in the assessment of NMOSD patients. Due to the high prevalence of absent VEPs in NMOSD patients, the scoring system appears to be more applicable for the precise analysis of VEP recordings. There is a positive association between the AQP-positive serostatus and the poorer outcome in VEP responses, especially in patients with severe impairment of the optic nerve(s).

Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system and is associated with autoantibodies to anti-aquaporin-4 (AQP4-IgG) in approximately two thirds of patients. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. The efficacy of satralizumab added to immunosuppressant treatment in patients with NMOSD is unclear. METHODS: In a phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, patients with NMOSD who were seropositive or seronegative for AQP4-IgG to receive either satralizumab, at a dose of 120 mg, or placebo, administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter, added to stable immunosuppressant treatment. The primary end point was the first protocol-defined relapse in a time-to-event analysis. Key secondary end points were the change from baseline to week 24 in the visual-analogue scale (VAS) pain score (range, 0 to 100, with higher scores indicating more pain) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (range, 0 to 52, with lower scores indicating more fatigue). Safety was also assessed. RESULTS: A total of 83 patients were enrolled, with 41 assigned to the satralizumab group and 42 to the placebo group. The median treatment duration with satralizumab in the double-blind period was 107.4 weeks. Relapse occurred in 8 patients (20%) receiving satralizumab and in 18 (43%) receiving placebo (hazard ratio, 0.38; 95% confidence interval [CI], 0.16 to 0.88). Multiple imputation for censored data resulted in hazard ratios ranging from 0.34 to 0.44 (with corresponding P values of 0.01 to 0.04). Among 55 AQP4-IgG-seropositive patients, relapse occurred in 11% of those in the satralizumab group and in 43% of those in the placebo group (hazard ratio, 0.21; 95% CI, 0.06 to 0.75); among 28 AQP4-IgG-seronegative patients, relapse occurred in 36% and 43%, respectively (hazard ratio, 0.66; 95% CI, 0.20 to 2.24). The between-group difference in the change in the mean VAS pain score was 4.08 (95% CI, -8.44 to 16.61); the between-group difference in the change in the mean FACIT-F score was -3.10 (95% CI, -8.38 to 2.18). The rates of serious adverse events and infections did not differ between groups. CONCLUSIONS: Among patients with NMOSD, satralizumab added to immunosuppressant treatment led to a lower risk of relapse than placebo but did not differ from placebo in its effect on pain or fatigue. (Funded by Chugai Pharmaceutical; ClinicalTrials.gov number, NCT02028884.).

Real-world effectiveness of fingolimod in Polish group of patients with relapsing-remitting multiple sclerosis.

OBJECTIVES: Fingolimod is indicated for the treatment of relapsing-remitting multiple sclerosis (RRMS) patients with highly aggressive disease characterized by frequent relapses and active magnetic resonance imaging. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. Fingolimod in licensed in Europe since 2011 but with a growing number of disease-modifying drugs (DMD) becoming available for RRMS, it is important to gather real-world evidence data regarding long-term effectiveness in treated patients with MS. The aim of this study was to assess fingolimod effectiveness in a real life Polish group of RRMS patients receiving fingolimod as second line treatment. PATIENTS AND METHODS: The observational study with retrospective data collection was performed at 13 sites that were asked to document eligible patients in consecutive chronological order to avoid selection bias. Demographic and clinical data from 253 adult patients with RRMS treated with fingolimod were analyzed. RESULTS: Mean treatment time with fingolimod was 42 months. Relapses reduction during 3 years treatment period was observed (2.0 v 0.2) and majority of patients were free of relapses. Mean EDSS score was stable during the time of observation. The proportion of patients who were free from any clinical disease activity, i.e. without relapses and disability progression, was over 70%. During the first and second year of observation significant reduction of new MRI lesions was observed. CONCLUSION: In the Polish group of patients with RRMS treated with fingolimod, the majority of them showed freedom from relapses, disability progression and reduction of new MRI lesions. Switching from injectable immunomodulatory drugs to fingolimod is associated with fewer relapses and lower disability progression.

Electrophysiological and clinical assessment of dysautonomia in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP): a comparative study.

CLINICAL RATIONALE FOR THE STUDY: Autonomic nervous system (ANS) involvement in different parkinsonian syndromes has been frequently discussed. It is well established in multiple system atrophy (MSA), whereas it is less evident in progressive supranuclear palsy (PSP). AIMS OF THE STUDY: The aims were to assess the presence and pattern of ANS involvement in MSA and PSP using noninvasive tests i.e. the sympathetic skin response (SSR) test and the R-R interval variation (RRIV) test; to analyse the relationship between clinical and electrophysiological abnormalities in both disorders; and to assess whether an autonomic profile might help to differentiate them. MATERIALS AND METHODS: Clinical and electrophysiological assessments of dysautonomia were performed in 59 patients with MSA (24 cases of MSA-C and 35 cases of MSA-P), these 59 cases including 31 females, mean disease duration 4.2 ± 2.7 years, mean age 60.3 ± 8.4 years, and in 37 patients with PSP (12 females, mean disease duration 4.6 ± 3.6 years, mean age 67.5 ± 6.1 years) and the results were compared to the results obtained from 23 healthy controls matched for age and sex. RESULTS: Clinical dysautonomia assessed by an Autonomic Symptoms Questionnaire was observed in 97% of the MSA patients and in 84% of the PSP patients. SSR was abnormal in 64% and RRIV was abnormal in 73% of MSA cases. In PSP cases, these figures were 78% and 81% respectively. Dysautonomia was clinically more pronounced in MSA compared to PSP (p < 0.05), whereas electrophysiological testing revealed frequently subclinical ANS damage in PSP patients. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our results point to the complementary role of electrophysiological tests in the diagnostic work-up of dysautonomia in parkinsonian syndromes.

Evaluation of reproductive health in female patients with multiple sclerosis in Polish population.

Multiple sclerosis (MS) is a chronic disease, which affects mostly women and has an early onset. Due to progress in treatment patients maintain a high quality of life for a long period and participate in all of its fields. One of them is reproductive health with all of its aspects. The aim of the study was to evaluate the reproductive health of female MS patients with regard to various features of MS. It was a cross-sectional study. The data was collected via anonymous survey distributed among patients with MS hospitalized at the Department of Neurology, Medical University of Warsaw and online. The study group consisted of 218 women diagnosed with MS. The survey consisted of demographic questions, questions assessing features of MS, reproductive health, sexual performance and psychological comorbidities, including depression and fatigue. 53.01% of MS patients declared interest in maternity. Patients interested in pregnancy were significantly younger (p < .01), often nulliparous (p < .001), had lower EDSS score (p < .006) and lower motor deficit (p < .001). History of at least one labour (p < .02) had a negative impact on the frequency of gynaecologic admissions. More advanced age (p < .003), unemployment (p < .01), at least one labour (p < .043), stronger balance problems (p < .003) and more intense motor deficit (p < .002) were related to less frequent Pap smears. Reproductive health of women with MS is similar to that of background population. Therefore, the general gynaecological care in those women should not be neglected.

Sexual dysfunction in female patients with relapsing-remitting multiple sclerosis.

INTRODUCTION: Sexual dysfunction (SD) is one of the common symptoms of multiple sclerosis (MS) and is often underdiagnosed, especially in women. Relapsing-remitting multiple sclerosis (RRMS) is the most widespread form of the disease, but the data on SD occurrence in this particular group of patients is limited. The aim of the study was to analyze the associations between demographic factors, symptoms and signs of MS, psychiatric comorbidities and SD in female patients with RRMS. MATERIAL & METHODS: A subgroup of 86 sexually active women with RRMS out of 218 total MS respondents was analyzed. Exclusion criteria included active relapse, EDSS score equal or higher than 6.5, and current pregnancy. All patients completed questionnaires including demographic data, questions about symptoms and signs of MS, Female Sexual Function Index (FSFI) for sexual performance, Patient Health Questionnaire 9 (PHQ-9) for depression, and Fatigue Severity Scale (FSS) for fatigue evaluation. RESULTS: According to FSFI, SD occurred in 21 (27.27%) of the respondents. SD occurrence was associated with depression (p < .05) and speech disturbances (p < .04). A negative effect on sexual performance was associated with depression intensity (p < .003), fatigue intensity (p < .05), more advanced age at diagnosis (p < .02), lower education level (p < .05), and smaller area of residence (p < .002). CONCLUSIONS: SD in women with RRMS is mostly associated with psychosocial parameters. Patients who are more depressed, presenting speech problems, less educated, and from smaller towns, should be considered high-risk for sexual dysfunction.

Bone metabolism and vitamin D status in patients with multiple sclerosis.

BACKGROUND: Vitamin D (VD), an important factor for bone health immobilization and immune regulation, has been shown to have low serum concentration in multiple sclerosis (MS) patients. Those patients have also multiple fracture risk factors, including progressive immobilization and long-term glucocorticoids treatment. The aim of the study was to analyze bone health (osteopenia or osteoporosis prevalence) and VD serum concentration in MS patients as well as the influence of disease activity and treatment on bone health. MATERIALS AND METHODS: The study involved 72 MS patients: 52 women and 20 men. Mean age was 40.3±10.5 yrs, mean EDSS (Expanded Disability Status Scale) 3.3±1.9. Bone health was analyzed using standard densitometry in the lumbar spine and femoral neck. Serum levels of VD, calcium, phosphate and parathormone were assessed. We compared two groups of patients with multiple sclerosis: relapsing - remitting MS (RRMS) and progressive relapsing MS (PRMS). RESULTS: Densitometry revealed osteopenia in twenty-six (36.1%) patients and osteoporosis in eleven (15.3%), no bone fractures were presented. Sixty-eight MS patients (94.4%) had lower VD serum level if compared to population referential values. Thirteen patients (18.1%) had severe VD deficiency. Densitometry parameter (T-score of the lumbar spine) worsened with EDSS increase (r=-0.43, P=0.001). There was a statistically significant negative correlation between VD concentration and EDSS score (r=-0.31; P=0.009). CONCLUSIONS: Our study indicates that patients with MS have high incidence of osteopenia and osteoporosis and vitamin D deficiency. Bone health disturbances studied by densitometry are related to the disability caused by MS.

Metagenomic Analysis of Cerebrospinal Fluid from Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of central nervous system of unknown etiology. However, some infectious agents have been suggested to play a significant role in its pathogenesis. Next-generation sequencing (NGS) and metagenomics can be employed to characterize microbiome of MS patients and to identify potential causative pathogens. In this study, 12 patients with idiopathic inflammatory demyelinating disorders (IIDD) of the central nervous system were studied: one patient had clinically isolated syndrome, one patient had recurrent optic neuritis, and ten patients had multiple sclerosis (MS). In addition, there was one patient with other non-inflammatory neurological disease. Cerebrospinal fluid (CSF) was sampled from all patients. RNA was extracted from CSF and subjected to a single-primer isothermal amplification followed by NGS and comprehensive data analysis. Altogether 441,608,474 reads were obtained and mapped using blastn. In a CSF sample from the patient with clinically isolated syndrome, 11 varicella-zoster virus reads were found. Other than that similar bacterial, fungal, parasitic, and protozoan reads were identified in all samples, indicating a common presence of contamination in metagenomics. In conclusion, we identified varicella zoster virus sequences in one out of the 12 patients with IIDD, which suggests that this virus could be occasionally related to the MS pathogenesis. A widespread bacterial contamination seems inherent to NGS and complicates the interpretation of results.