Reliability of the five times sit to stand test performed remotely by multiple sclerosis patients.

INTRODUCTION: Multiple Sclerosis, known main cause of non-traumatic neurological disability in adults, leads to changes in muscle strength, especially in the lower limbs. Assessing muscle strength in these patients is thus essential and can be achieved by the Five Times Sit to Stand Test (FTSST), commonly performed in person. Due to the COVID-19 pandemic and social distancing measured adopted, Brazilian physiotherapists turned to remote monitoring and assessment, supported by Resolution n° 516/2020, which required proving the reliability of tests. Given this scenario, this study sought to evaluate the intra- and inter-rater reliability of the Five Times Sit to Stand Test performed remotely and synchronously by multiple sclerosis patients. METHODS: A sample of 33 individuals with relapsing-remitting Multiple Sclerosis (18 women and 15 men, mean age 43.7 ± 13.4 years) were remotely and synchronously by video call. Inter-rater reliability was evaluated by analyzing FTSST execution time, in seconds, timed by two different raters on the same video call. In turn, intra-rater reliability was assessed by analyzing the execution time recorded in two different video calls made by the same rater, within a 24-28-h interval. Descriptive and inferential data analysis were performed using SPSS 20.0 software. Means and standard deviation were calculated for descriptive statistic. Intraclass correlation coefficient (ICC), with a 0.05 significance level, standard error of measurement (SEM) and minimal detectable change (MDC) were calculated for inferential analysis. RESULTS: Data analysis showed excellent ICC values and low SEM and MDC values regarding inter-rater reliability (ICC: 0.993 (0.986-0.996); p-value: <0.001; SEM: 0.6 s; MDC: 1.6 s) and intra-rater reliability (ICC: 0.962 (0.925-0.981); p-value: <0.001; SEM: 1.4 s; MDC: 3.8 s). CONCLUSION: Based on these values, FTSST performed remotely and synchronously by relapsing-remitting Multiple Sclerosis patients is reliable and can be used both by different raters, for assessment, or by the same rater, in pre- and post-test situations.

A Case of Multiple Sclerosis with Protracted Course of COVID-19.

BACKGROUND: We reported a case of multiple sclerosis (MS) with persistent symptomatic COVID-19, which was complicated by new-appearing severe pneumonia 40 days after disease onset. CASE PRESENTATION: A 38-year-old man with a history of multiple sclerosis referred to our hospital with fever, shaking chills, cough, and dyspnea. In his history, the patient had developed mild COVID-19 from 40 days ago. After 7 days of disease onset, the COVID symptoms had been subsided partially, but fatigue, myalgia, intermittent fever, and loss of taste and smell had been continued. In physical examinations, his oral temperature was 39.4 °C. He had respiratory distress, and his blood oxygen saturation on the room air was 90%. The spiral chest CT scan was performed, which revealed bilateral ground-glass and alveolar opacities in favor of COVID-19 pneumonia. The result of the RT-PCR test for SARS-COV-2 was reported positive subsequently. His current MS medication was rituximab and he had received the last dose of rituximab two months before developing COVID-19. The patient was admitted to the COVID ward and put on Remdesivir, subcutaneous interferon-beta1b, and dexamethasone. He improved gradually and was discharged from the hospital with the favorable condition after 10 days. This patient had a rare protracted disease course. We presumed that prolonged high degree fever (above 38 °C) in our patient is beyond the diagnosis of the post-COVID-19 syndrome and is more compatible with persistent infection. CONCLUSION: Although most immunocompromised patients effectively clear SARS-CoV-2 infection, this case report highlights the risk of persistent infection associated with recurrence of the disease.

Evaluating the feasibility and preliminary efficacy of a Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS): an update to the protocol for a feasibility cluster-randomised controlled trial.

BACKGROUND: Cognitive difficulties experienced by people with multiple sclerosis (MS) impact on quality of life and daily functioning, from childcare and work to social and self-care activities. The Cognitive Occupation-Based programme for people with MS (COB-MS) was developed as a holistic, individualised cognitive rehabilitation intervention to address the wide-ranging symptoms and functional difficulties that present in MS, including the ability to maintain employment, social activities, home management and self-care. The aim of the research is to evaluate the feasibility and preliminary efficacy of COB-MS for people with MS. METHODS: Due to the impacts of COVID-19, trial activities that were planned for in-person delivery were completed remotely. One hundred and twenty people with MS will be assigned to participate in either the COB-MS programme or a treatment-as-usual, wait-list control group as part of this single-blind, cluster-randomised controlled feasibility and preliminary efficacy trial of the COB-MS programme. The COB-MS group will participate in an eight-session occupational-based cognitive rehabilitation programme over 9 weeks. The COB-MS intervention was planned for in-person delivery but was delivered online by occupational therapists to small groups of people with MS. The primary outcome measure is the Goal Attainment Scaling at 12 weeks. Participants will be assessed pre-intervention, post-intervention, 12 weeks post-intervention and 6 months post-intervention. Qualitative evaluations of participants' perspectives will also be examined as part of the feasibility study. Data, due to be collected in-person, was collected online or by post. The original study design, including the statistical analysis plan, remains unchanged despite the shift to a remote trial conduct. DISCUSSION: Results will provide recommendations for a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy. TRIAL REGISTRATION: ISRCTN ISRCTN11462710 . Registered on 9 September 2019 and updated on 23 September 2020 to account for changes outlined here.

Neuro-ophthalmological Presentation of Optic Neuritis in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare demyelinating autoimmune disorder of the central nervous system. MOGAD frequently manifests with severe, bilateral, and episodes of recurrent optic neuritis (ON) and is an important differential diagnosis to multiple sclerosis and aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorders. Besides ON, the clinical manifestations of MOGAD commonly include transverse myelitis, acute disseminated encephalomyelitis, and brain stem encephalitis. In this review, we summarize the current knowledge of the neuro-ophthalmological presentation of MOGAD-ON. We describe epidemiological aspects, including the association with COVID-19 and other infections or vaccinations, clinical presentation, and imaging findings of MOGAD-ON in the acute stage and during remission. Furthermore, we report findings on prognosis, treatment response, and changes in ON-unaffected eyes. We touch upon findings on visual acuity, visual fields, and visual evoked potentials, as well as structural changes assessed with optical coherence tomography. Moreover, we explain how to differentiate MOGAD from its differential diagnoses, including other neuroinflammatory disorders (multiple sclerosis and neuromyelitis optica spectrum disorders), but also idiopathic intracranial hypertension.

Ofatumumab subcutaneous injection for the treatment of relapsing forms of multiple sclerosis.

INTRODUCTION: In recent years, different studies have highlighted the importance of B cells in the pathophysiology of multiple sclerosis (MS): they secrete cytokines to modulate the inflammatory environment, present antigens for the activation of T lymphocytes, and they secrete antibodies contributing to the destruction of the myelin sheath. Combined, these findings have lead to new possible means for treating MS. AREAS COVERED: In this review, we provide an up-to-date overview of the characteristics of ofatumumab (aka Kesimpta), and the differences between this drug and the other anti-CD20 monoclonal antibodies used to treat MS. EXPERT OPINION: The evolution of disease-modifying treatment algorithms in MS underlines the importance of starting treatment as soon as the diagnosis is defined, and with adequate 'treatment intensity.' Monoclonal antibodies and other aggressive treatments are now considered as an option at the clinical presentation of the disease, based to the prognostic profile emerging through clinical and paraclinical investigations. The recent adoption of new diagnostic criteria allows for the early diagnosis of MS. This, together with the availability of disease-modifying therapies (DMTs), such as ofatumumab, with a good efficacy/safety profile and which are easy to administer, could contribute to significant improvements in the long-term prognosis of MS.

Impact of telehealth on health care in a multiple sclerosis outpatient clinic during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has precipitated expansion of telemedicine in outpatient management of chronic diseases including multiple sclerosis (MS). Studies conducted pre-pandemic, when telehealth was an alternative to in-person consultations, represent a different setting to current practice. The aim of this study was to assess the impact of telehealth on MS outpatient care in a tertiary metropolitan hospital in Melbourne, Australia during the COVID-19 pandemic. METHOD: From March-December 2020, patients and clinicians in the MS outpatient clinic were surveyed regarding their attitudes towards telehealth. Scores on the Expanded Disability Status Scale (EDSS) from telehealth and face-to-face appointments during the study period were compared to scores from face-to-face consultations before and after this period. Medical records were reviewed to compare management decisions made during telehealth versus face-to-face consultations. Diagnoses and treatment of MS relapses were compared to 2019. RESULTS: Telehealth was used in 73% of outpatient appointments. Patient satisfaction was generally high. Patients and clinicians preferred face-to-face consultations but were willing to use telehealth longer term. Overall, there were no significant delays in identifying patients experiencing disability worsening via telehealth, but EDSS increase was recorded in more face-to-face than telehealth appointments particularly for those with lower baseline disability. Disease-modifying therapy commencement rates were similar, but symptomatic therapy initiation and investigation requests occurred more frequently in face-to-face visits. Comparable numbers of MS relapses were diagnosed and treated with corticosteroids in 2019 and 2020. CONCLUSIONS: Patient satisfaction with telehealth was high, but both clinicians and patients preferred in-person appointments. Telehealth implementation did not lead to high rates of undetected disability worsening or undiagnosed acute relapses, but telehealth-based EDSS assessment may underestimate lower scores. Treatment inertia may affect some management decisions during telehealth consultations. Telehealth will likely play a role in outpatient settings beyond the COVID-19 pandemic with further studies on its long-term impact on clinical outcomes required.

Risk factors of severe COVID-19 in people with multiple sclerosis : A systematic review and meta-analysis.

OBJECTIVES: To gather, synthesize, and meta-analyze data regarding the risk factors associated with a severe course of COVID-19 among patients with multiple sclerosis (pwMS). METHODS: MEDLINE, Embase, Scopus, and WoS were searched in May 2021. Briefly, the eligibility criteria included: 1) studies assessing COVID-19 severity among adult pwMS; 2) definitive diagnoses or high clinical suspicion of COVID-19; 3) a categorization of COVID-19 severity into at least two categories; 4) quantitative effect size and precision measurements; and 5) English language; and 6) clear effect size/precision measures. internal validity of studies was assessed using the NIH Quality Assessment Tools. A list of possible risk factors was created based on the search results and was later used in extraction, synthesis, and meta-analysis of the data. RESULTS: Thirteen studies were included in the syntheses. Outcome measures were either extracted from the papers, obtained from the primary researchers or calculated manually. The meta-analyses showed a significantly (P<0.05) increased odds of a severe COVID-19 in pwMS with all of the assessed risk factors, except smoking and most DMTs. CONCLUSION: This study facilitates evidence-based risk/benefit assessments in practice. Older men with progressive MS on anti-CD20 therapies are more at risk of an unfortunate COVID-19 outcome.

[Effective therapy in highly active pediatric multiple sclerosis]. / Magas aktivitású sclerosis multiplex hatásos kezelése gyermekkorban.

Multiple sclerosis (MS) is typically a disease of young adults. Childhood MS can be defined in patients under 18 years of age, although some authors set the limit un-der the age of 16 formerly known as "early-onset multiple sclerosis" or "juvenile multiple sclerosis", seen in 3-5% of all MS patients. Nowadays, owing to ever-evolving, better diagnostic tools and well-traced, strictly defined diagnostic criteria, childhood MS is showing an increasing incidence worldwide (0.05-2.85/100 000). MS is characterized by recurrent episodes of the central nervous system with demyelination separated in space and time. In childhood almost exclusively the relapsing-remitting (RR) type of MS occurs. Based on experience in adults, the goal in the pediatric population is also the early diagnosis, to initiate adequate DMT as soon as possible and to achieve symptom relief and good quality of life. Based on efficacy and safety studies in the adult population, inter-feron ß-1a and glatiramer acetate were first approved by the FDA and EMA for the treatment of childhood MS also. The increased relapse rate and rapid progression of childhood MS and unfavorable therapeutic response to nearly 45% of the first DMT necessitated the testing of more effective and second-line drugs in the population under 18 years of age (PARADIGMS, CONNECT). Although natalizumab was reported to be effective and well-tolerated in highly active RRMS in childhood, evidence based studies were not yet available when our patients' treatment started. In this article, we report on the successful treatment of three active RRMS patients with individually authorized off-label use of natalizumab.

Disability assessment using Google Maps.

OBJECTIVES: To evaluate the concordance between Google Maps® application (GM®) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability Status Scale (EDSS)) in people with multiple sclerosis (pwMS). MATERIALS AND METHODS: This is a cross-sectional multicenter study. AS and EDSS were calculated using GM® and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods. RESULTS: Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM® and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio [OR] = 2.8; 95% confidence interval [CI] 1.1-7.11, p = 0.03), worse fatigue (OR = 1.03; 95% CI 1.01-1.06, p = 0.01), and more severe depression (OR = 1.1; 95% CI 1.04-1.17, p = 0.002) were associated with discrepancies between GM® and routine clinical scoring. CONCLUSION: GM® could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM® should be considered for validation in further clinical studies.

GIANA allows computationally-efficient TCR clustering and multi-disease repertoire classification by isometric transformation.

Similarity in T-cell receptor (TCR) sequences implies shared antigen specificity between receptors, and could be used to discover novel therapeutic targets. However, existing methods that cluster T-cell receptor sequences by similarity are computationally inefficient, making them impractical to use on the ever-expanding datasets of the immune repertoire. Here, we developed GIANA (Geometric Isometry-based TCR AligNment Algorithm) a computationally efficient tool for this task that provides the same level of clustering specificity as TCRdist at 600 times its speed, and without sacrificing accuracy. GIANA also allows the rapid query of large reference cohorts within minutes. Using GIANA to cluster large-scale TCR datasets provides candidate disease-specific receptors, and provides a new solution to repertoire classification. Querying unseen TCR-seq samples against an existing reference differentiates samples from patients across various cohorts associated with cancer, infectious and autoimmune disease. Our results demonstrate how GIANA could be used as the basis for a TCR-based non-invasive multi-disease diagnostic platform.

Patient's point of view on the use of telemedicine in multiple sclerosis: a web-based survey.

Restrictions in the access to healthcare facilities during COVID-19 pandemic have raised the need for remote monitoring of chronic medical conditions, including multiple sclerosis (MS). In order to enable the continuity of care in these circumstances, many telemedicine applications are currently tested. While physicians' preferences are commonly investigated, data regarding the patients' point of view are still lacking. We built a 37 items web-based survey exploring patients' propensity, awareness, and opinions on telemedicine with the aim to evaluate the sustainability of this approach in MS. Analysing 613 questionnaires out of 1093 that were sent to persons with MS followed at the Multiple Sclerosis Center of Tor Vergata University, Rome, we found that more than half of respondents (54%) were open to having a televisit. Propensity toward telemedicine significantly depended on having a higher income (p = 0.037), living farther from the center (p = 0.038), using computer and tablet (p = 0.010) and using the Internet for other remote activities (p < 0.001), conversely it was not influenced by any specific disease characteristics (i.e. degree of disability). The main advantages and disadvantages of televisit reported by participants were respectively saving time (70%) and impossibility to measure physical parameters (71%). Although the majority of respondents are in favour of televisit, so far this approach is restricted to those displaying better socioeconomic conditions and higher familiarity with technology. Implications of the study are that telemedicine platforms should be better tailored to patients' demands in order to spread the use of telemedicine, to enhance usability and to increase patients' adherence.

Description and preliminary experience with Virtual Visit Assessment (ViVA) during the COVID-19 pandemic, a structured virtual management protocol for patients with multiple sclerosis.

In people with multiple sclerosis (PwMS), strict follow-up is essential. Telemedicine has the potential to overcome many of the difficulties in routine management. Herein, we present a structured protocol that can be used to remotely manage patients with MS, describing in detail the steps to be taken and exams needed at each stage. A working group was established which developed a tailored protocol that can be adapted to a variety of settings. The overall protocol consisted of 5 phases: enrolment, document sharing phase, pre-evaluation, virtual visit, and post-visit phase, which was divided into 14 individual steps. As of October 2020, 25 virtual visits have been carried out, all via Skype. The patient's caregiver was present during visits and had an active role. The average duration of the virtual visit was 24 min, and that of the pre-visit and post-visit were around 15 min each. Overall satisfaction as rated by physicians was considered high (8.0 ± 0.5). Using the system usability scale (SUS), patients also favorably rated the virtual visit (96.6 ± 6.1). In 20% of cases, the virtual visit was not sufficient to provide adequate information and an in-person clinical visit was recommended. The described protocol has the potential to provide benefits for the healthcare system as well as patients and their caregivers both during and beyond COVID-19 pandemic.

Embracing resilience in multiple sclerosis: a new perspective from COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) resulted in several psychological consequences. Past epidemiological experiences already showed the deep albeit heterogeneous psychological repercussions of pandemics. Nevertheless, little is known about COVID-19 outbreak and the possible strategies for boosting resilience in patients with chronic diseases such as Multiple Sclerosis (MS). Therefore, we designed a study aiming to assess the changes in mental distress during COVID-19 outbreak in patients with MS and to identifyfactors contributing to resilience's development.We enrolled 106 patients (69 relapsing-remitting, 20 secondary-progressive, and 17 primary-progressive) whose neuropsychological assessment before the COVID-19 pandemic (1 January 2019-1 March 2020) was available. It consisted of Brief International Cognitive Assessment for MS (BICAMS), Hospital Anxiety and Depression Scale (HADS) and patient-reported MS Neuropsychological Screening Questionnaire (MSNQ-P). All patients were re-tested during Italian lockdown through an online survey, comprehensive of sociodemographic information, HADS self-rating Scale, MSNQ-P Questionnaire and finally Connor-Davidson Resilience self-rating Scale (CD-RISC 25), in order to evaluate resilience.No significant changes in HADS and MSNQ-P scores were detected during COVID-19 pandemic in our population. Though, pre-existing lower HADS and MSNQ-P scores but not demographic, disease- and treatment-related elements were found significantly (p < 0.0001) and independently associated with a better resilience attitude.

Manifestations and impact of the COVID-19 pandemic in neuroinflammatory diseases.

OBJECTIVE: To report initial results of a planned multicenter year-long prospective study examining the risk and impact of COVID-19 among persons with neuroinflammatory disorders (NID), particularly multiple sclerosis (MS). METHODS: In April 2020, we deployed online questionnaires to individuals in their home environment to assess the prevalence and potential risk factors of suspected COVID-19 in persons with NID (PwNID) and change in their neurological care. RESULTS: Our cohort included 1115 participants (630 NID, 98% MS; 485 reference) as of 30 April 2020. 202 (18%) participants, residing in areas with high COVID-19 case prevalence, met the April 2020 CDC symptom criteria for suspected COVID-19, but only 4% of all participants received testing given testing shortages. Among all participants, those with suspected COVID-19 were younger, more racially diverse, and reported more depression and liver disease. PwNID had the same rate of suspected COVID-19 as the reference group. Early changes in disease management included telemedicine visits in 21% and treatment changes in 9% of PwNID. After adjusting for potential confounders, increasing neurological disability was associated with a greater likelihood of suspected COVID-19 (ORadj  = 1.45, 1.17-1.84). INTERPRETATIONS: Our study of real-time, patient-reported experience during the COVID-19 pandemic complements physician-reported MS case registries which capture an excess of severe cases. Overall, PwNID seem to have a risk of suspected COVID-19 similar to the reference population.

Management of central nervous system demyelinating diseases during the coronavirus disease 2019 pandemic: a practical approach.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic poses a potential threat to patients with autoimmune disorders, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Such patients are usually treated with immunomodulatory or immunosuppressive agents, which may tamper with the organism's normal response to infections. Currently, no consensus has been reached on how to manage MS and NMOSD patients during the pandemic. OBJECTIVE: To discuss strategies to manage those patients. METHODS: We focus on how to 1) reduce COVID-19 infection risk, such as social distancing, telemedicine, and wider interval between laboratory testing/imaging; 2) manage relapses, such as avoiding treatment of mild relapse and using oral steroids; 3) manage disease-modifying therapies, such as preference for drugs associated with lower infection risk (interferons, glatiramer, teriflunomide, and natalizumab) and extended-interval dosing of natalizumab, when safe; 4) individualize the chosen MS induction-therapy (anti-CD20 monoclonal antibodies, alemtuzumab, and cladribine); 5) manage NMOSD preventive therapies, including initial therapy selection and current treatment maintenance; 6) manage MS/NMOSD patients infected with COVID-19. CONCLUSIONS: In the future, real-world case series of MS/NMOSD patients infected with COVID-19 will help us define the best management strategies. For the time being, we rely on expert experience and guidance.

Remote testing of vitamin D levels across the UK MS population-A case control study.

OBJECTIVE: The association between vitamin D deficiency and multiple sclerosis (MS) is well described. We set out to use remote sampling to ascertain vitamin D status and vitamin D supplementation in a cross-sectional study of people with MS across the UK. METHODS: People with MS and matched controls were recruited from across the UK. 1768 people with MS enrolled in the study; remote sampling kits were distributed to a subgroup. Dried blood spots (DBS) were used to assess serum 25(OH)D in people with MS and controls. RESULTS: 1768 MS participants completed the questionnaire; 388 MS participants and 309 controls provided biological samples. Serum 25(OH)D was higher in MS than controls (median 71nmol/L vs 49nmol/L). A higher proportion of MS participants than controls supplemented (72% vs 26%, p<0.001); people with MS supplemented at higher vD doses than controls (median 1600 vs 600 IU/day, p<0.001). People with MS who did not supplement had lower serum 25(OH)D levels than non-supplementing controls (median 38 nmol/L vs 44 nmol/L). Participants engaged well with remote sampling. CONCLUSIONS: The UK MS population have higher serum 25(OH)D than controls, mainly as a result of vitamin D supplementation. Remote sampling is a feasible way of carrying out large studies.