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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.
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Introduction and aims: Multiple Sclerosis (MS) Centers experienced a significant disruption of their clinical activities during the first waves of COVID-19 pandemic. As part of a national multicenter survey (COVId Ms Patients SATisfaction survey - COVIMPSAT), we collected i) the opinion on quality of care (QoC) received by people with MS (pwMS) from MS Centers (MSC), and ii) data on therapeutic adherence and discontinuation, during the lockdown period (March-May 2020) in Italy. Method(s): In April-May 2021, 16 Italian MSC compiled and sent a digital (35-item) survey to their patients. Statistical analyses were performed with SPSS, version 25. Result(s): 1670 pwMS (67.3% women) completed the survey. Most of them (89.9%) were on disease-modifying therapies (DMTs). The most used DMTs were dimethyl fumarate (18.6%), ocrelizumab (14.4%) and natalizumab (13.9%). During the lockdown period, 88% did not modify their DMT regimen, while 11% reported a change in DMT intake, with a reduction in 7.8% and a drug discontinuation in only 4.2% cases. Almost 9 out of 10 pwMS (89.1%) were able to get in contact with their MSC without difficulties. Thirty-six percent of pwMS contacted their MSC for getting information about COVID-19, while 30% were directly contacted from the MSC personnel to provide information on MS and COVID-19 and preventive behaviours. More than half of the patients (63.5%) performed their check-up visits at the MSC with the same schedule as the pre-pandemic period, while 36.5% of pwMS voluntary skipped follow-up visits mainly because of fear of getting COVID-19 infection (46%) and the sensation of feeling well without an absolute/urgent need of a check-up visit (16.8%). Interestingly, although only 1.3% of pwMS underwent a teleneurology follow-up visit, 80% of patients suggested to invest more in telemedicine programs in order to expand contact channels with MSC. The overall opinion of pwMS on MSC during the pandemic period in Italy was more than positive, with 32% of pwMS declaring a significant increase in trust in their MSC. Conclusion(s): Italian pwMS judged globally well the activity, accessibility and information received by their MSC during the first wave of COVID-19 pandemic. Only 1 out of 10 pwMS underwent a change in their DMT regimen, showing a high drug adherence. Our data also demonstrate that implementing telemedicine programs would further improve the QoC of patients, particularly those with higher disability or living far from the MSC.
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Introduction: Concerns have emerged during Covid-19 pandemic about management of Disease Modifying Therapies (DMTs) in patients with Multiple Sclerosis (pwMS). In particular, Ocrelizumab (OCR)-treated pwMS faced possible delays of scheduled infusions due to disruption of MS Centers activities as well as safety worries during lockdown periods. Objective(s): To assess changes of OCR infusion schedule in Italian pwMS during the first wave of COVID-19 pandemic (observation period: February-June 2020) and to investigate predictive factors determining delaying of OCR infusions. Material(s) and Method(s): Data were extracted from the Italian MS Register database. pwMS with an OCR infusion scheduled during the observation period and at least two previous OCR infusions were selected. Demographics (age, gender), disease characteristics (MS phenotype, disease duration, Expanded Disability Status Scale score, number of previous OCR infusions) and location of MS Centers among three Italian macro-regions (North, Center, South) were tested as potential predictors for treatment delay using univariable and multivariable linear model analyses. Result(s): Five-hundred ninety-nine pwMS (343 F/256 M;411 Relapsing MS/188 Progressive MS) from 65 MS centers were included in the analysis. Mean interval between two OCR infusions was 28.1 weeks (SD 2.72) before the observation period compared to 30.8 weeks (SD 5.45) during the observation period, with a mean delay of 2.7 weeks (p <0.001). No clinico-demographic factors emerged as predictors of infusion postponement, except for location of MS centers in the North of Italy (4.7 weeks vs 1.5 in the Center and 1.6 in the South). Such a difference was confirmed in multivariate analysis (p < 0.001) adjusting for prelockdown mean OCR infusion schedule. Conclusion(s): This large registry-based study shows that OCR infusions were significantly delayed during the first wave of COVID-19 pandemic in Italy. The location of the MS Centers in Northern Italy was the only predictor of OCR infusion postponement. This geographical area corresponds to the region in Italy that was hit first and more strongly by Covid-19 pandemic. The observed delay in OCR infusions disruptions of MS centers activities due to a drastic reduction of healthcare workers availability (because of infection/quarantine and/or reallocation in Covid Units) and concerns about using an immunosuppressive DMT like OCR during a new virus pandemic with many uncertainties.
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Introduction: MS centers (MSc) activities related to OCR management were strongly and diffusely hit during the first wave of COVID-19 pandemic. Concerns were mainly related to its immunosuppressive effects and the need for in-hospital administration. Objective(s): To investigate changes in OCR schedule among Italian MS centers participating to the Italian MS Register during the first wave of COVID-19 pandemic and to identify factors determining such changes. Material(s) and Method(s): A quick online survey was sent to 65 Italian MSc in order to collect from them the following data: macro-region (North, Center, South) location, number of OCRtreated patients, modifications of OCR schedule and a list of factors potentially influencing the postponement of OCR infusions (i.e. age, co-morbidity, MS phenotype, number of previous OCR cycles, disease severity/activity, CD-20 lymphocytes count, distance to MS center, fear of infection, inclusion in a research trial, infections trend, shortage of medical/paramedical staff for reallocation/ infection). Result(s): Among 55 MSc who answered the survey, 50 (91%) declared to have suspended or extended OCR interval dosing for at least one patient. The MSc that didn't modify OCR schedule were all from the South of Italy (33% of all South MSc). Main factors influencing OCR schedule delay were advanced age/comorbidity (70%) and pandemic trend in the area (72%), while recent MS-disease activity hindered OCR schedule modifications (65%). Conclusion(s): This study shows that most Italian MSc decided either to delay or suspend OCR treatment during the first wave of COVID-19 pandemic. Advanced age and co-morbidity and no evidence of recent MS-disease activity were the most relevant patient-dependent predictors of OCR postponement. Among patient-independent factors the most relevant factor was the local trend of infections. Contrary to what expected, the shortage of medical and/or paramedical staff in MSc did not come out as relevant. The disruption of OCR schedule during the first COVID-19 pandemic wave in Italy mostly reflected the geographical distribution and the impact on the National Health System of COVID- 19 pandemic.
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Introduction: Patients with Multiple Sclerosis (pwMS) treated with Ocrelizumab (OCR) and Fingolimod (FNG) have shown a blunted humoral response to the first two doses of the BNT162b2 mRNA Covid-19 vaccine. The assessment of the safety and the humoral response to a third booster dose of the same vaccine is therefore relevant within this population. Aim(s): To investigate the safety and the humoral response to a third booster dose of the BNT162b2 mRNA Covid-19 vaccine in pwMS on OCR/FNG, comparing it with age- and sex-matched healthy controls (HCs). Method(s): Serum samples were collected from HCs and pwMS treated with OCR or FNG at the following scheduled time points: before the first of two vaccine doses (T0);8 (T1), 16 (T2), 24 (T3) weeks after the first dose;within 8 weeks before (T0b) and after (T1b) the booster dose. IgG antibodies to SARS-CoV-2 trimeric spike protein (Anti-TSP IgG) were quantified and expressed as binding antibody units (BAU)/mL. Result(s): 40 HCs and 47 pwMS (28 on OCR and 19 on FNG) were included in the study. All (100%) HCs mounted a positive (>33.8 BAU/mL) humoral response at T1 and preserved it until (T2-T3- T0b) and after (T1b) the third booster dose. At T0b only 12 (42.9%) pwMS on OCR and 6 (31.6%) on FNG were positive while, at T1b 16 (57.14%) pwMS on OCR and 16 (84.2%) on FNG, passed the threshold of positivity. Anti-TSP IgG titers in HCs were significantly higher than those of pwMS on OCR and on FNG at all time points, while no differences were found at all time points between pwMS on OCR and those on FNG. HCs showed a significant higher (relative) increase of Anti-TSP IgG levels at T1b with respect to OCR (p<.001) and FNG (p=.032) groups. The increase of Anti-TSP IgG levels in the pwMS on FNG was significantly higher than those in the OCR group (p<.001). No socio-demographic, clinical, or laboratory variables were able to predict the increase of anti-TSP IgG levels between T0b and T1b. Neither clinical relapses nor severe adverse events were reported in pwMS after each of the three doses of vaccine during the follow- up period. Conclusion(s): The administration of a third booster dose of BNT162b2 mRNA Covid-19 vaccine to OCR- and FNG-treated pwMS is able to revive the humoral response, independently of any demographic, clinical or laboratory variable, and confirms a good safety and tolerability profile, not only in terms of adverse events but also in terms of MS relapses.
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Introduction, objectives and aims: COVID-19 pandemic caused a significant disruption of clinical activities at Multiple Sclerosis (MS) Centers. As part of a national multicenter survey (COVId Ms Patients SATisfaction survey - COVIMPSAT) aimed at collecting patients' opinion regarding the quality of care and information received from MS Centers (MSC) during the pandemic, we report data about COVID-19 infections and vaccination cycle and how they were managed by the MSC. Material(s) and Method(s): In April-May 2021, 16 Italian MSC developed and sent a digital (35-item) survey by email to their patients. Statistical analyses were performed with SPSS, version 25. Result(s): 1670 people with MS (pwMS;67.3% women) completed the survey. 169 (10.1%) reported a diagnosis of COVID-19 infection: 63% were symptomatic, while 37% were not. As regards treatment for COVID-19, only 3% of the patients were hospitalized. The impact of COVID-19 infection on MS-related neurological symptoms was as follow: 69.3% of pwMS stated that the severity of their MS-related symptoms remained stable, 21.5% reported a worsening of pre-existing symptoms, 7.4% affirmed that new neurological symptoms emerged, while only 1.8% reported an improvement of MS-related symptomatology. At the time of the survey, 60.6% of pwMS were inoculated at least one dose of COVID-19 vaccine. Vaccination appointments were scheduled by: MSC staff alone (44.9%), MSC staff together with the general practitioner (17.5%), the general practitioner alone (16.1%), other Institutions (12.1%), and by the patients themselves (9.3%). At the moment of the survey 39.4% of pwMS were not vaccinated yet. The three major reasons for not being vaccinated yet were: being already on a vaccination list (40.8%), willing to be vaccinated but without an appointment (17.6%), still undecided or not willing to be vaccinated (19.3%). Conclusion(s): The results of this multicentre survey revealed a low hospitalization rate of pwMS, in line with previous studies (Moghadasi et al, 2021). In the majority of the sample, COVID-19 symptomatology did not have a significant impact on MS-related neurological symptoms. MSC promoted and facilitated vaccination procedures and scheduling, alone or in combination with the general practitioner, in more than half of pwMS.
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Introduction: MS patients affected by SARS-CoV-2 disease may present with a wide pattern of symptoms, not always suggestive of the severity of infection. A recent study has shown that main symptoms of Covid-19 can be grouped in seven different clusters. Risk and protective factors for their occurrence in MS patients has never been investigated. Objectives: To identify the most common symptoms of Covid-19 that are part of specific clusters in MS patients and evaluate all factors associated with their manifestation. Methods: As part of the MuSC-19 Italian project, all data were extracted from a dedicated web-based platform that allows researchers to evaluate the impact of Covid-19 on people affected by MS. After having tested the degree of agreement between different types of symptoms (Cohen's k), univariate and multivariate logistic regression models were applied to identify predicting factors for each group. Results: 1554 MS patients with confirmed Covid-19 and presenting at least one symptom referred to a specific cluster were analyzed. Patients presented nearly three groups of symptoms (mean: 2.8). The most common include fever/chills/rigor/fatigue/ cough (87%), followed by ageusia/anosmia (46%). Smoking habit was the most confirmed risk factor for developing a wide range of symptoms: common cold-like symptoms (OR:1.6, 95%CI:1.3- 2.1;p<0.001), joint and muscle pain (OR:1.3, 95%CI:1.1-1.7;p=0.037), gastrointestinal problems (OR:1.3, 95%CI: 1.1-1.7;p = 0.029), and loss of smell/taste (OR:1.4, 95%CI: 1.07-1.72;p=0.013). Smoking was confirmed also as risk factor for increasing the number of symptoms (OR:1.5, 95%CI:1.2-1.8;p<0.001), together with alcohol use (OR:1.25, 95%CI:1.1-1.5;p=0.021) and with assumption of anti-CD20 therapies (OR:1.7, 95%CI:1.2-2.5;p=0.004). Males have a lower risk for developing a major number of symptoms (OR:0.8, 95%CI:0.6 - 0.9;p=0.006). Finally, a lower EDSS was associated to a slight increment of symptoms, probably due to an already underlying presence of some common symptoms in most critical MS patients, which consequently were not reported (OR:0.9, 95%CI:0.8-0.9;p=0.005). Conclusions: Knowing possible risk factors and modifying some lifestyle behaviors might minimize the occurrence of Covid-19 symptoms. Anyway, further studies are needed for confirming these findings, and an additional follow up study on the presence of persistent symptoms after apparent Covid-19 resolution may help to better understand all possible risk factors.
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Introduction: Studies have pointed out that air pollution longterm exposure may play a role in the severity and prognosis of SARS-CoV-2 infections. Additionally, air pollution has been associated to MS prevalence and course. However, the role of air pollution in COVID-19 severity has never been explored specifically among MS patients. Aims: To explore the association between air pollution assessed by PM2.5 levels and COVID-19 severity among MS patients. Methods: Demographic and clinical characteristics as well as data about Covid-19 severity were extracted from an Italian webbased platform (Musc-19 project) containing clinician-reported data from 118 Italian MS centers. PM2.5 ground-level concentrations were derived from air quality model results, as provided by the 'Copernicus Atmospheric Monitoring Service' (CAMS). Ordered logistic regression models were used to assess the association between PM2.5 (continuous and in tertiles) and Covid-19 prognosis (defined on three levels as mild course, hospitalization, and intensive care unit (ICU) admission or death) while controlling for possible confounders. Results: PM2.5 concentrations were available for 1517 MS patients, of whom 1321(87%) were classified as mild Covid-19 cases, 172(11%) were hospitalized and 24(2%) were admitted to ICU or died. Higher concentrations of PM2.5 were associated with increased odds of developing a worst Covid-19 prognosis (10-unit increase in PM2.5: OR(95% CI)=1.76(1.16-2.67) p-value=0.008;3rd vs 1st tertile: OR(95% CI)=1.74(1.17-2.59) p-value=0.006). Results remained consistent when we included only the Covid-19 cases confirmed by a nasopharyngeal swab (N=1087). Conclusions: Higher concentrations of PM2.5 are associated with Covid-19 severity among MS patients. Further studies are needed to evaluate the impact of other air pollutants, but urgent measures to reduce air pollution must be surely adopted.
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Introduction: Since the worldwide launch of the SARS-CoV-2 vaccine campaign, there have been many uncertainties regarding the immune response to vaccination in patients with multiple sclerosis (pwMS), particularly those on high efficacy disease-modifying therapies (DMTs). Aim: To evaluate humoral response to NT162b2-mRNACovid- 19 vaccine in pwMS on high efficacy DMTs compared to healthy controls (HCs). Methods: We collected serum samples before the first dose and 7 days after the second dose of the NT162b2-mRNA-Covid-19 vaccine from 54 HCs and 93 pwMS on high efficacy DMTs (Ocrelizumab/OCR, Fingolimod/FNG, Natalizumab/NTZ). Exclusion criteria: history of Covid-19, baseline positive SARSCoV- 2 IgG antibodies, steroids administration within the month prior to the first dose of vaccine. Sera were tested using the LIAISONRSARS-CoV-2 TrimericSIgG assay for the detection of IgG antibodies to SARS-CoV-2 spike protein. The IgG-titers were expressed in Binding Antibody Units (BAU) with 33.8 BAU/mL as cut-off. Results: Sera of 51 HCs and 80pwMS (31 OCR, 25 FNG, 24 NTZ) were analyzed, while 3 HCs and 13 pwMS (4OCR, 5FNG, 4NTZ) were kept out due to exclusion criteria. Age, sex, and disease duration were similar across groups. Seven days after the second dose of the vaccine, SARS-CoV-2 IgG antibodies were detected in all HCs and pwMS on NTZ, in 17(54.8%) pwMS on OCR and 10(40%) pwMS on FNG. pwMS on OCR (median 59.8 BAU/mL;P25-75 4.81-598) and FNG (median 21.5;P25-75 7.49-116) showed a significant blunted response (p<0.0001, both) when compared with HCs (median 1860;P25-75 1180-4865) and NTZ patients (p<0.0001, both). pwMS on NTZ mounted a humoral response (median 3015;P25-75 1495-4905) similar to HCs (p=0.52). Interestingly, we observed a positive association between humoral response and time elapsed since the last OCR infusion (rho 0.46,p=0.001) and an inverse correlation between humoral response and treatment duration in pwMS on FTY (rho -0.57,p=0.004). No correlation was found with CD20 levels in the OCR group. Discussion: We found a clear blunted humoral response to NT162b2-mRNA-Covid-19 vaccine in pwMS treated with OCR and FNG, with a significant relationship with treatment duration in FNG-treated pwMS and time elapsed since the last infusion in the OCR-treated pwMS. Contrariwise, we found an efficient humoral response in NTZ-treated pwMS. Further data are needed to inform which strategy could optimize the response to vaccines in pwMS on OCR and FTY.
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Background and aims: In 2018 we surveyed the use of social media and digital devices among Italian neurologists. In the present study, we evaluated whether major changes had occurred in a short time-frame and indirectly assessed the impact of the Sars-COV-2 virus and the related COronaVIrus Disease 19 (COVID-19) pandemic. Methods: Online survey (September 2020 to January 2021) to collect information on attitude toward digital health of members of the Italian Society of Neurology (SIN). The outline of the survey was the same as the prior study. Results: One hundred and nine neurologists participated in the survey. Some major changes were found compared to 2018: fewer participants reported using the tablet (23% versus 43%;p < 0.001) and Facebook (18% versus 32%;p = 0.006) for professional purposes. More participants reported that social media had worsened the doctor-patient relationship, and were against a friendship with their patients in social media. There was a trend towards higher use of WhatsApp (92% versus 82%;p = 0.018), and a significant reduction in active involvement in personal websites, blogs, or online forums. Conclusions: Dramatic changes in the attitudes towards social media have occurred in Italy in a very short timeframe, probably due to the concurrent pandemic and its impact on daily practice, and the dissemination of online misinformation.
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Background and aims: Since the worldwide launch of the SARS-CoV-2 vaccine campaign, several concerns apply on the response to vaccines in people with multiple sclerosis (pwMS) particularly those on high efficacy disease modifying therapies (DMTs). We report preliminary data on humoral response to Covid-19 vaccine assessed on four pwMS treated with ocrelizumab (OCR) and compared to that measured in a sample of healthy subjects (HS) enrolled in a surveillance programme at our Clinic. Methods: We collected serum samples -at 0,14,21 days after the first dose and 7 days after the second dose of NT162b2-mRNA-Covid-19 vaccine of: i) 55 health-care workers, and ii) four relapsing MS patients on OCR, that were vaccinated with the same Covid-19 vaccine. All subjects did not have a history of Covid-19 infection. Sera were tested using the LIAISON®SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.), for the detection of IgG antibodies to SARS-CoV-2 spike protein. The IgG-titers were expressed in Binding Antibody Units (BAU). Results: Seven days after the second dose of NT162b2-mRNA-Covid-19 vaccine, all HS mounted a significant humoral response (geometric mean 2010.4 BAU/mL C.I.95%1512.7–2672), while all the four pwMS showed a very low response (range 4,9–175 BAU/mL). Conclusions: As expected and in agreement with previous data, we found a blunted humoral response to NT162b2-mRNA-vaccine in pwMS treated with OCR. Further data are urgently needed in order to confirm and expand these preliminary, yet significant results and to inform if there is any strategy to optimize the response to vaccines such as the count of circulating CD20 cells, time-elapsed since the last anti-CD20 drug administration.
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Objective: To describe the effect of disease modifying therapies (DMT) on Covid-19 severity in a large cohort of Italian patients with Covid-19 and multiple sclerosis (MS). Background: We previously presented data from a nationwide study of persons with MS with suspected or confirmed Covid-19, collected from March 2020. In June we started collecting also asymptomatic patients, when serological tests started to be routinely done. Design/Methods: This was a retrospective multi-center observational study. We defined Covid-19 severity as a 4-level variable: Level 1=asymptomatic, level 2=symptomatic without signs of pneumonia, level 3=radiologically defined pneumonia or hospitalization, level 4=intensive care unit (ICU) or death. We analysed the impact of baseline variables on this outcome by a multivariable ordinal logistic model quantifying the association by Odds Ratio (OR). Results: On October 12, we enrolled 902 MS patients, 298 (33%) with confirmed and 604 (67%) with suspected Covid-19;37 (4%) were asymptomatic. The number of ICU/deaths were 8/95 (8%) among those treated with anti-CD20 therapies (mean age=41 years), 0/84 (0%) among those treated with Interferon (mean age=47 years) and 37/723 (5%) among those treated with other drugs (mean age=43 years). Among the 37 asymptomatic patients, 7/84 (8.3%) were in Interferon, 1/95 (1.1%) was on anti-CD20 and 29/723 (4%) were on other drugs. At multivariable analysis, independent risk factors for a severe Covid-19 were age (OR=1.05, p<0.001), EDSS(OR=1.13, p=0.02), Male sex(OR=1.44, p=0.057) and DMT used: Treatment with anti-CD20 (Ocrelizumab or Rituximab) increased the risk (OR=1.99, p=0.035) and treatment with Interferon reduced the risk (OR=0.48, p=0.05) of severe Covid-19 as compared to treatment with DMF, used as the reference DMT. Conclusions: This analysis confirms on a larger population the increase of risk of severe Covid-19 of anti-CD20 therapies and highlights the protective role of Interferon. Data on asymptomatic patients are rapidly accumulating and will provide useful information about this.