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.

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.).

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.

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.

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.

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.

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.

The N-terminal pro-brain natriuretic peptide as a marker of mitoxantrone-induced cardiotoxicity in multiple sclerosis patients.

BACKGROUND AND PURPOSE: Mitoxantrone (MTX) has been shown to reduce progression of disability and number of clinical exacerbations in patients with progressive multiple sclerosis (MS). Prolonged administration of MTX, however, is limited by the risk of cardiotoxicity. Cardiac monitoring in MTX-treated patients includes usually measurement of left ventricular ejection fraction (LVEF) by means of echocardiography. The N-terminal pro-brain natriuretic peptide (NT-proBNP) represents a novel diagnostic tool in the assessment of heart failure. This study was aimed to evaluate the usefulness of NT-proBNP for early detection of MTX-induced cardiotoxicity in MS patients. MATERIALS AND METHODS: We measured the NT-proBNP plasma levels in 45 MS patients who completed 24-month MTX therapy and in 37 MS patients of control group. RESULTS: The median NT-proBNP plasma value was 15.12pg/mL. In 12 MTX-treated patients (27%), NT-proBNP plasma values were elevated, though this subgroup of patients neither clinical showed evidence of myocardial damage nor had the LVEF value <50%. In five patients with normal NT-proBNP, we observed LVEF decline >10%. We did not observe correlations between the NT-proBNP levels and patient age, MS duration, relapses index, Extended Disability Status Scale (EDSS), MTX single dose and the total cumulative dose of MTX. In 8 patients (22%) from control group, NT-proBNP plasma levels were also elevated. CONCLUSIONS: The results of our study confirm that MTX therapy is safe for carefully selected and closely monitored MS patients. We believe that serial evaluation of NT-proBNP levels (before, during and after MTX therapy) can identify MS patients at high risk for MTX-induced cardiotoxicity.

Multiple metastatic intracranial lesions associated with left atrial myxoma.

BACKGROUND: One of the most common cardiac tumors is myxoma. Despite its predominantly benign course, diverse cardiological, systemic as well as neurological complications have been reported. CASE REPORT: We are the first from Poland to present the case of a patient with multiple central nervous system metastases associated with the left atrial myxoma. Various diagnostic, neuroradiological and histopathological procedures were described. The patient underwent cardiac surgery. CONCLUSIONS: Follow-up studies excluded the recurrence of the heart tumor and confirmed partial resolution of brain metastases. Nevertheless, subsequent neurological assessment was advised according to the literature data and possible late relapses mainly due to cerebral emboli.

Polymorphisms of paraoxonase 1 and 2 genes and the risk of multiple sclerosis in the Polish population.

BACKGROUND AND PURPOSE: The aim of this study was to test the hypothesis that polymorphisms of the paraoxonase genes PON1 and PON2 may be associated with increased risk of developing multiple sclerosis (MS) in the Polish population. MATERIAL AND METHODS: We studied the significance of the PON gene polymorphisms C311S, A162G, Q192R and L55M in 221 patients (including 145 women) with MS and in 661 healthy controls. In the MS population, mean Expanded Disability Status Scale score was 2.92, mean age was 36.8 years, and mean disease duration was 7.7 years. PON genotyping was determined using polymerase chain reaction and restriction enzyme digestion. RESULTS: According to our results, the PON1 and PON2 genotypes distribution did not differ between the MS patients and the controls. CONCLUSIONS: The polymorphisms of the PON genes studied are not related to increased risk of MS in the Polish population.

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.

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.

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.

Sex hormone patterns in women with multiple sclerosis as related to disease activity--a pilot study.

BACKGROUND AND PURPOSE: The influence of sex hormones on immune system activity in multiple sclerosis (MS) has been suggested by clinical evidence. The aim of the study was to ana-lyse the pattern of sex hormones in MS women and to correlate the hormone pattern abnormalities to the disease course as well as to the magnetic resonance imaging (MRI) results. MATERIAL AND METHODS: We studied the serum level of the progesterone, ß-oestradiol and prolactin in 46 women with clinical definite MS aged from 19 to 65; mean disease duration was 11.80 ± 9.86 years. The evaluation of the intensity of hormonal changes was done using a scoring system (0-3). On the brain MRI, the presence of brain atrophy, of hypothalamic demyelination as well as demyelination intensity (or degree) were analysed. The evaluation of the degree of demyelination and brain atrophy was done using a scoring system (0-4). RESULTS: The main hormonal abnormalities consisted of decreased progesterone level, increased oestradiol level or both. The sex hormone pattern was abnormal in 56% of patients. Hypothalamic lesions were found on MRI in 53% of cases. The abnormal hormonal pattern correlated with intensity of MR changes (p < 0.05, Fisher's exact test), but neither with presence of hypothalamic changes nor with disease parameters (Expanded Disability Status Scale, relapse rate, disease duration). CONCLUSIONS: It is important to check the hormonal pattern in MS women because according to our results it may be related to the disease activity and probably affects the type of therapeutic intervention. This pilot study will be extended in a larger population.

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.

[Evoked potentials in multiple sclerosis: progress or stagnation?]. / Badania potencjalów wywolanych w stwardnieniu rozsianym: postep czy stagnacja?

BACKGROUND: Evoked potentials (EPs): visual (VEP), short latency somatosensory (SSEP), brainstem auditory (BAEP) and motor evoked potentials (MEP) can provide objective evidence of central nervous system (CNS) abnormalities that complement the clinical and radiological findings in establishing the diagnosis of multiple sclerosis (MS). METHODS: The EPs studies may also improve the sensitivity of MS diagnosis. RESULTS: Abnormal EPs can provide evidence for pathology to satisfy the diagnostic criteria of lesions disseminated in space in the absence of clinical findings and for a relapse in patient with new symptoms but no changes on clinical examination. Since magnetic resonance imaging (MRI) plays a critical role in the current diagnostic criteria of MS, it is important to consider the relationship between EPs and MRI. Evoked potentials provide neurophysiological information about CNS functional abnormalities, while MRI provide anatomical localisation of CNS lesions. VEPs are even more sensitive than MRI in detecting acute and old pre-chiasmatic optic nerve lesions. The revised diagnostic criteria for MS include the provision for an abnormal VEP to serve as a diagnostic factor. Rarely, patients with spinal cord pathology may have an abnormal SEP or MEP without an observed lesions on MRI. Combining multimodality evoked potentials and MRI results in the greatest diagnostic yield. CONCLUSIONS: More widespread use of multimodality EPs in combination with MRI might lead to better outcome measurement in clinical trials as well as in open therapeutic approach. Thought EPs have some limitations, they remain an important factor in the diagnosis and clinical management of MS patients.

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).