INTRODUCTION:Multiple Sclerosis is a disease of young females at a reproductive age.OBJECTIVE:discuss family planning in the context of providing care for women with MS.METHOD:patients with Multiple Sclerosis, female, aged between 18 and 45 years, from 01/Nov/2021 to 16/Jan/2022 participated, all of whom answered a questionnaire made available on the Google forms platform.RESULTS:A total of 233 responses were validated. Most patients discuss family planning during their medical care (61.4 %), use low-efficacy contraceptive methods (68.7 %) and do not plan to become pregnant (70.1 %). There is a high rate of use of disease-modifying treatments (88.9 %). Among those who had already become pregnant, most of them became pregnant before diagnosis and were statically younger than patients who became pregnant after diagnosis.CONCLUSION:Family planning should be discussed early on and be actively initiated by the health care professional assisting the patient and incorporated into the routine consultation. We suggest efforts should be put into ensuring a decrease in the rate of unplanned pregnancy in this population. Also, it is crucial to guarantee effective contraception in patients who express the wish not to become pregnant and are using disease-modifying treatments.

Abstract Introduction Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) which is characterized by inflammation, demyelination, axon loss and gliosis. More than 2.8 million people worldwide are affected by MS, mainly young people at reproductive age with significant lifelong repercussions. Among several MS symptoms, sexual dysfunction (SD) is one of the most neglected during routine clinical care. Objective We aimed to evaluate the prevalence of SD in female patients diagnosed with Remitting-Recurrent MS (RRMS), compared with a control group of women without comorbidity and to stratify the different causes and factors that can lead to SD. Methods This transversal analytic study was carried out by Santa Casa de São Paulo, Faculdade de Ciências Médicas, São Paulo/SP, Brazil, between November 2020 and November 2021. Our sample included 80 patients diagnosed with RRMS and 106 control group. We have collected demographic data and all participants underwent neurological examination. Questionnaires about sexual dysfunction (Multiple Sclerosis Intimacy and Sexuality Questionnaire - MSISQ-19- and Female Sexual Function Index - FSFI) and about depression and anxiety (Hospital Anxiety and Depression Scale – HADS, Beck's Depression Inventory – BDI- and Beck anxiety inventory-BAI) were applied. Baseline characteristics were reported as proportions and mean ± SD or median ± IQR as appropriate according to data distribution. The presence of SD was described according to the evaluated qualitative parameters and the association with the use of Chi-square tests or exact tests was verified and the quantitative characteristics were compared according to the presence of dysfunction with the use of t-Student tests or Mann-Whitney tests. Statistical analyses were performed using IBM-SPSS for Windows versão 20.0 Results We observed high prevalence of SD in both groups (43.4% and 38.8%, respectively, patients with RRMS and control group) according to FSFI analysis. A higher statistically prevalence (56.3%) of sexual dysfunction in patients with RRMS was observed when using the MSISQ-19 as a tool for assessing sexuality in this population, in comparison with FSFI scale (p = 0.016). The presence of anxious (53.2% to RRMS and 47.2% to control group by BAI) and depressive symptoms (37.2% to RRMS and 38.8% control group, by BDI) were statistically similar between the groups (p > 0.05). Both groups revealed high rates of anxious and depressive symptoms. There were no other statistically significant factors associated with RRMS on the prevalence of SD. Conclusions We did not find a higher prevalence of SD in MS patients when compared to the control group. Nevertheless we found a higher prevalence in both groups and the specific tool (MSISQ-19) was able to reveal that MS patients did have higher prevalence of SD. Besides that, anxious and depressive symptoms were also statistically significant in MS patients and are related to SD, so we strongly suggest that healthcare providers assess and treat these comorbidities in all RRMS patients in paralel with sexual dysfunction approach and we also suggest the use of the specific questionnaire to deal with their sexual function. Disclosure No

Introduction: Multiple sclerosis (MS) causes various cognitive symptoms. Transcranial magnetic stimulation (TMS) is a resource used for stimulation. Objectives: To evaluate the effects of TMS on the working memory of people with MS. Methods: A double-blind crossover study was carried out with 29 people diagnosed with MS (18 relapsing-remitting, 6 primary progressive and 5 secondary progressive), aged between 29 and 68 years (mean = 47.2, standard deviation [SD] = 10.9 years), 9 men (31%) and 20 women (69%), with EDSS from 0 to 6.5 (mean = 4.3 and SD = 1.85) and diagnosis time between 1 and 24 years (mean = 9.5 and SD = 6.57 years). The active group received 10 TMS interventions (primary motor cortex (Cz): 10Hz, 50 pulses per time, 30 trains, 20 seconds apart, totaling 1,500 pulses at 90% of the resting motor threshold and pre -left dorsolateral front (F3): 10 Hz, 50 pulses per train, 40 trains, 20 second interval, totaling 2,000 pulses at 110% of resting threshold) for 10 consecutive working days. The sham group received the inactive TMS and participated in the physical activities. After 30 days, there was an inversion of the active and sham groups for a new sequence of 10 days. For evaluation, an interview was conducted for data collection and the subtest Digits of the Wechsler Intelligence Scale (WAIS-III) was applied at the beginning and end of the stimulations. The chi-square test was used for statistical analysis. Results: 55.2% of people who received active TMS improved, against only 27.6% of people who received sham TMS. This difference was significant with P = 0.033. Conclusion: TMS appears to be an important resource for treating the working memory of people with MS. This result may encourage further research.

Abstract Background  People with multiple sclerosis (PwMS) show an increased risk of sexual dysfunction (SD), both in women and men. Objective  The aim of the present study was to apply the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) and evaluate our results by comparing them with those in in the literature, as well as to assess the ease of applying the scale and the engagement of the patients in discussing the topic of sexuality. Methods  We developed and applied a web-based Google form questionnaire that the respondents completed online, which included the MSISQ-19, for the assessment of sexual function. Baseline characteristics were reported as proportions and mean ± standard deviation (SD) or median ± interquartile range (IQR) as appropriate according to data distribution. Categorical variables were stratified by sex and compared with chi-squared tests. Statistical analyses were performed using STATA v. 16 (StataCorp., College Station, TX, USA). Results  Of the 621 respondents, 541 were included in the analysis. Among the patients with MS, a total of 347 (64.14%) exhibited SD. When stratified by gender, the frequencies of SD were not significantly different. Conclusion  There is a high incidence of sexual dysfunction among PwMS and we need to identify the reasons for this and implement strategies to treat and counsel our patients. The MSISQ-19 can be used to help clinicians to assess sexual functioning in a quick and easy way and give patients the possibility to address this topic and receive appropriate help and support.

Introduction: Transcranial magnetic stimulation (TMS) has good therapeutic effect and clinical application value when associated with therapeutic interventions. Objectives: To evaluate the effect of TMS combined with physiotherapy on the manual dexterity and gait of people with multiple sclerosis (MS). Methods: Participated 20 people with MS, 14 women and 6 men, aged 33 to 68 years (standard deviation 50.0) and EDSS between 0 and 6,5. The protocol consisted of 10 TMS sessions and 6 physiotherapy sessions. Participants were randomized and divided into two groups: Group I) with real stimulus, so that 10 received the TMS stimulus (primary motor cortex (Cz): 50 pulses per time, 30 trains, 20seconds of interval, totaling 1,500 pulses at 90% of resting motor threshold and left dorsolateral prefrontal cortex (F3): 10Hz, 50 pulses per train, 40 trains, 20 seconds interval, totaling 2,000 pulses at 110% of resting threshold), and Group II) sham, that received the application without TMS stimulation (10 patients). All underwent physiotherapy. The Box and Block Test and Timed up and Go Test (TUG) was applied before the combined interventions and after 60 days. Results: It was found that 90% of participants showed improvement in manual dexterity, and 10% a plateau on Box and Block Test. At the TUG, it was found 70% of improvement and 30% of decrease in performance. Conclusion: This study suggests that TMS can be incorporated into the physiotherapy in the rehabilitation of manual dexterity and gait in people with MS.

Background and Objectives Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed. Methods Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab. Results Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1-7] and 7% [95% CI 4-11]), ICU/artificial ventilation (2% [95% CI 0-4] and 4% [95% CI 2-6]), and death (1% [95% CI 0-2] and 2% [95% CI 1-4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19. Discussion Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19.

Interferon-β, a disease-modifying therapy (DMT) for MS, may be associated with less severe COVID-19 in people with MS.Among 5,568 patients (83.4% confirmed COVID-19), interferon-treated patients had lower risk of severe COVID-19 compared to untreated, but not to glatiramer-acetate, dimethyl-fumarate, or pooled other DMTs.In comparison to other DMTs, we did not find evidence of protective effects of interferon-β on the severity of COVID-19, though compared to the untreated, the course of COVID19 was milder among those on interferon-β. This study does not support the use of interferon-β as a treatment to reduce COVID-19 severity in MS.

Background and Objectives Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed. Methods Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab. Results Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1–7] and 7% [95% CI 4–11]), ICU/artificial ventilation (2% [95% CI 0–4] and 4% [95% CI 2–6]), and death (1% [95% CI 0–2] and 2% [95% CI 1–4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2–8), 3% (95% CI 1–5), and 1% (95% CI 0–3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19. Discussion Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19.

Objectives Some disease-modifying therapies (DMTs) have been associated with COVID-19 severity in people with MS. Comprehensive exploration of these relationships in large international samples is needed. Methods Clinician-reported demographic/clinical data from 27 countries were aggregated into a dataset of 5,648 patients with suspected/confirmed COVID-19. COVID-19 severity outcomes (hospitalisation, admission to ICU, requiring artificial ventilation, death) assessed using multilevel mixed-effect ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were compared to glatiramer acetate, dimethyl fumarate, pooled other DMTs, and natalizumab. Results Of 5,648 patients (83.4% confirmed COVID-19) were included. Compared to glatiramer acetate, ocrelizumab and rituximab were associated with higher probability of hospitalisation (4%(95%CI=1–7) & 7%(95%CI=4–11)), ICU/artificial ventilation (2%(95%CI=0–4) & 4%(95%CI=2–6)), and death (1%(95%CI=0–2) & 2%(95%CI=1–4)) [predicted marginal effects]. Untreated patients had 5%(95%CI=2–8), 3%(95%CI=1–5), and 1%(95%CI=0–3) higher probabilities of the three respective levels of COVID-19 severity than glatiramer acetate. Compared to pooled other DMTs and to natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. Evaluation of interferon associations with COVID-19 severity found these only apparent in comparison with the untreated but not vs individual or pooled other DMTs. All associations persisted/enhanced on restriction to confirmed COVID-19. Conclusions Analysing the largest international real-world dataset of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab) are associated with more severe course of COVID-19, while interferon-based DMTs have no intrinsic protective benefit from other treatment.

Multiple Sclerosis is an autoimmune disease with an unknown etiology. Both genetic and environmental factors are believed to trigger MS autoimmunity. Among the environmental factors, infectious agents have been extensively investigated, and the Human Endogenous Retroviruses (HERVs), especially HERV-W, are believed to be associated with MS pathogenesis. HERVs are derived from ancestral infections and comprise around 8% of the human genome. Although most HERVs are silenced, retroviral genes may be expressed with virion formation. There is extensive evidence of the relationship between HERV-W and MS, including higher levels of HERV-W expression in MS patients, HERV-W protein detection in MS plaques, and the HERV-W env protein inducing an inflammatory response in in vitro and in vivo models. Here we discuss possible links of HERVs and the pathogenesis of MS and present new data regarding the diversity of HERVs expression in samples derived from MS patients.

Background: People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods: Data from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression. Results: 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36; aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Conclusions: Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission, suggesting their use may be a risk factor for more severe COVID-19.

Abstract Background People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods Data from 12 data-sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl-fumarate, glatiramer-acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other) covariates were queried, alongside COVID-19 hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression, adjusted for age, sex, MS phenotype, and EDSS. Results 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Among suspected+confirmed/confirmed-only COVID-19, 20.9%/26.9% were hospitalised, 5.4%/7.2% were admitted to ICU, 4.1%/5.4% required artificial ventilation, and 3.2%/3.9% died. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl-fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Conclusions Despite the cross-sectional design of this study, the internal and external consistency of these results with prior studies suggests their use may be a risk factor for more severe COVID-19. Key messages Anti-CD20 DMTs may be associated with worse COVID-19 severity amongst people with multiple sclerosis.

Background: The reception and rehabilitation services for Multiple Sclerosis (MS) have been partially interrupted in most countries since the beginning of the COVID-19 pandemic. Objectives: To present the health care in neurorehabilitation promoted by the Brazilian Association of Multiple Sclerosis (ABEM) during a pandemic period by COVID-19. Methods: A Social Therapeutic Action Plan was developed to identify the needs of people with MS. Social Service call centers were made available via landline, cell phone, WhatsApp and e-mail at the beginning of the pandemic. Results: 2,975 telephone calls were made between March 23 to September 30, 2020, referrals were made and distributed as follows: art therapy = 29 (1%), physiotherapy = 2,185 (73.4%), neurology = 29 (1%), psychology = 638 (21.4%), psychiatry = 8 (0.3%), shiatsu = 86 (2.9%). Conclusions: In addition to raising awareness and encouraging people with MS not to abandon physical and mental health monitoring during the pandemic, it is extremely important to offer and provide essential services such as social and health care. The findings of this study showed the importance of the organization aimed at people with MS in the optimization and continuity of health care and access to effective interventions to promote quality of life. Diagnostic Criteria and Differential Diagnosis.

Background: As the COVID-19 pandemic continues, evidencebased clinical guidance for managing the care of people with multiple sclerosis (MS) is an ongoing concern. In recent months, data from cohorts of people with MS has indicated that certain demographic and clinical characteristics, including use of some disease- modifying therapies (DMTs), leads to worse outcomes from SARS-CoV-2 infection. The COVID-19 in MS global data sharing initiative, which now includes over 4,500 confirmed COVID- 19 cases in people with MS, gives the opportunity to corroborate previous findings with greater certainty. Methods: Clinician-reported data from 32 countries were aggregated into a dataset of 5,543 patients who had suspected or confirmed COVID-19. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes. These outcomes (hospitalisation, admission to ICU, requiring artificial ventilation, and death) were assessed in patients with suspected/ confirmed COVID-19 using multilevel mixed-effects logistic regression. All models were corrected for age, sex, EDSS, and MS type. DMTs were individually compared to glatiramer acetate (GA), as well as to pooled other DMTs and natalizumab. Results: Of 5,543 patients in the clinician-reported dataset, 909 with suspected and 4,634 with confirmed COVID-19 were included in the analysis. Previous demographic findings were confirmed: male sex, older age, progressive MS, and higher disability were associated with worse outcomes from SARS-CoV-2 infection. Use of anti-CD20 DMTs (ocrelizumab and rituximab) was associated with worse COVID-19 outcomes. Compared to GA, ocrelizumab and rituximab were associated with increased risk of hospitalisation (aOR=1.61(95%CI=1.06-2.43);aOR=2.42(95%CI=1.54-3.81) and ICU admission (aOR=3.13(95%CI=1.22-8.00);aOR=4.46 (95%CI=1.64-12.09)). Rituximab was associated with increased risk of artificial ventilation (aOR=3.57(95%CI=1.38-9.20));ocrelizumab showed a positive trend (aOR=1.86(95%CI=0.76-4.55). Rituximab showed a positive trend with increased risk of death (aOR=2.74(95%CI=0.68-11.09). Associations persisted on restriction to confirmed COVID-19 cases. Conclusions: Analysing the largest international real world dataset of people with MS who have suspected or confirmed COVID- 19 confirms previous findings that male sex, older age, progressive MS, higher disability, the use of anti-CD20 medication (ocrelizumab and rituximab) are associated with worse COVID-19 outcomes.