A multiple sclerosis training using the kinect-based MSFIT exergame. An Italian multicenter feasibility study

Introduction: Balance impairments are common in multiple sclerosis (MS). Pilates is a popular alternative method for balance performance maintenance and improvement that may reduce the rapid symptoms worsening frequently associated with physical inactivity. An Italian network of fifteen experts in MS rehabilitation developed through a User-Centered Design approach the MS-FIT exergame, a Kinect-based tool, to autonomously train balance through Pilates exercises. The MS-FIT user executes the exercises shown by a teacher's avatar and improves the performances through the feedbacks on the execution correctness. Aim(s): This study (Clinical.Trials.gov, NCT04011579) aims at evaluating the feasibility of an at-home intervention with MS-FIT. Method(s): Feasibility was investigated in terms of adherence (sessions number), usability (usability items of Tele-healthcare Satisfaction Questionnaire, u-TSQ, satisfaction (Client Satisfaction Questionnaire, CSQ-8), safety (adverse events), and physical effectiveness (Timed UP-&-GO, TUG;Timed 25-Foot Walk, T25FW;2-Minutes Walking Test, 2MWT). Result(s): Forty-five people with MS (PwMS) were enrolled and randomized into the experimental (EXP, n=23) and control (CTRL, n=22) groups. During the 6 weeks of the study, only the usual physical activities were admitted (rehabilitation excluded) and, in addition, EXP had to practice MS-FIT at least three times a week. Due to organizational consequences of COVID pandemic, 8 subjects dropped-out (EXP, n=17;CTRL, n=20). The sample analysed showed the following characteristics: gender (EXP: 6M;CTRL: 7M), age (EXP: 41.9+/-9.6y;CTRL: 43.3+/-10.5y), course (EXP: 94.4% and CTRL: 95.0% relapsing-remitting), disease duration (EXP: 9.9+/-7.2y;CTRL: 12.5+/-9.8y) and EDSS (EXP: 2.6+/-0.8;CTRL: 2.6+/-0.8). EXP highly adhered to the MS-FIT training (23.6+/-6.1 sessions);the tool was usable (u-TSQ: 3.01/4);satisfaction was medium-tohigh (CSQ-8: 25.1/32);the training with MS-FIT was safe (no adverse events). The groups did not differ in TUG, T25FW and 2MWT. An analysis separate for each group showed a significant improvement only in EXP (TUG: pre 7.5+/-1.2s, post 7.0+/-1.2s, p<0.05;T25FW: pre 6.1+/-1.5s, post 5.0+/-1.2s, p<0.01;2MWT: pre 175.4+/-51.0m, post 194.1+/-56.9m, p<0.01). Conclusion(s): MS-FIT is well-accepted and effective and could be a complement of traditional MS interventions. Based on the results and participants' feedbacks MS-FIT has been refined and is used in an ongoing randomized controlled trial.

The late onset of emotional distress in people with progressive multiple sclerosis during the COVID-19 pandemic: longitudinal findings from the CogEx study

Background: An earlier follow-up study from the CogEx rehabilitation trial showed little change in symptoms of depression, anxiety and psychological distress during the first COVID-19 lockdown compared to pre-pandemic measurements. Objective(s): Here we provide a second follow-up set of behavioral data on the CogEx sample. Method(s): Data were obtained from the CogEx study, a randomized controlled trial of exercise and cognitive rehabilitation in people with progressive MS involving 11 centres in North America and Europe. Participants completed the same COVID Impact Survey and self-report measures of depression, anxiety and MS symptoms that had been obtained during the first pandemic lockdown period. Result(s): The average time between measurements was 11.4 (SD=5.56) months. Sample size declined from 131 to 72 largely because pandemic restrictions prevented data collection from sites in Denmark and England. There were no significant differences in age, sex, EDSS, disease course and duration between those who participated in the current follow-up study (n=74) and the group that could not (n=57). One participant caught Covid in the time between assessments. Participants now took a more negative view of their mental/psychological wellbeing (p=.0001), physical wellbeing (p=.0009) and disease course (p=.005) compared to their last assessment. Depression scores increased on the HADS-depression scale (p = .01) and now exceeded the clinically significant threshold of >= 8.0 for the first time. Anxiety scores on the HADS remained unchanged. Poorer mental wellbeing was predicted by HADS depression scores (p=.012) and a secondary-progressive disease course (p=.0004). Conclusions and Relevance: A longer follow-up period revealed the later onset of clinically significant depressive symptoms on the HADS and a decline in self-perceptions of mental and physical wellbeing associated with the COVID-19 pandemic.

Effect of SARS-CoV-2 mRNA vaccination in multiple sclerosis patients treated with disease modifying therapies

Introduction: In patients with Multiple Sclerosis (pwMS) disease- modifying therapies (DMTs) are known to affect immune response to antigens and possibly to SARS-CoV2 vaccine. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. Objectives and aims: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARSCov- 2 vaccination with mRNA vaccines (BNT162b2, Pfizer/ BioNTech, Inc or mRNA-1273, Moderna Tx, Inc) to evaluate their effect on SARS-CoV-2 antibody response. Methods: A blood collection for the measure of SARS-CoV-2 antibody before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized and blinded serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche Diagnostics). Results: Preliminary data were collected on 780 pwMS (76% BNT162b2 and 24% mRNA-1273) who had pre- and 4-week post-vaccination blood assessments. 87 (11.2%) were untreated, 154 (19.7%) on ocrelizumab, 25 (3.2%) on rituximab, 85 (10.9%) on fingolimod, 25 (3.2%) on cladribine and 404 (51.7%) on other DMTs. 677 patients (86.8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariate analysis, the antibody levels of patients on ocrelizumab (178-fold decrease, p<0.001), fingolimod (26-fold decrease, p<0.001) and rituximab (17-fold decrease, p<0.001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3.5-fold higher antibody level than with the BNT162b2 vaccine (p<0.001). Interpretation: In pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3.5-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those that will be produced by studying the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS. At the time of the ECTRIMS presentation data on the full sample (about 2000 subjects) will be presented.

Is the multiple sclerosis population of the rehabilitation centers vulnerable during the COVID-19 pandemic?

Introduction: During the COVID-19 pandemic, the multidisciplinary team involved in the care of people with Multiple Sclerosis (pwMS) had to deal with many due to the vulnerability of these patients. A possible way to guarantee their management has been to use digital tools for surveillance and monitoring through remote contacts (telephone calls and e mails) to assess symptoms and needs. Aim: The aim of the study was to describe the vulnerability degree of a sample of pwMS that attend the rehabilitation centers at the beginning of the Covid-19 Pandemic. Methods: During April 1, 2020, to April 30, 2020 a multicenter observational retrospective study was conduct. The enrolment took place in five rehabilitation centers of North Italy (part of the country heavily affected by SARS-CoV-2 diffusion at the beginning of the Pandemic that followed mainly MS patients. Results: 2106 patients have been contacted, 2072 responded to the telephone interview about presence of symptoms and signs of Covid-19 infection (response rate: 98%). 99 (4.8%) subjects have been identified as Covid-19: 10 confirmed cases (tested positive for Covid-19) and 89 suspected Covid-19 symptoms. Two subjects (2.0%) were dead. There were no significant differences in gender, levels of disability (EDSS score) and use of disease modifying treatment between subjects with and those without Covid- 19. The Covid-19 patients had a younger age (53.1±10.4 vs. 56.5±12.7, p=0.06), a different distribution of MS course (16.2% vs 12.9% PP form;29.3% vs. 44.0% SP form and 54.5% vs 43.15 RR form, respectively, p=0.016) and a shorter duration of illness (12.6±10.6 vs. 17.2±11.1, p<0.001) than Covid-19 free ones. Conclusions: The MS Covid cases analyzed were younger, with lower percentages of SP form and with shorter disease duration than MS subjects Covid free. This could be explained by the higher probability to be in contact with other people and so higher probability of infection. In fact, subjects younger and with less severe form of disease have higher probability to move, work and to have social contacts. In conclusion, during the pandemic period the restriction to move are resulted the most effective indications, so it is urgent to implement use digital tools for surveillance and monitoring through remote contacts.