Displaying One Session

LB Poster Sat, Sep 26, 2020
Session Type
LB Poster
Date
Sat, Sep 26, 2020
COVID-19 Poster Presentation

P0293 - Attenuation of antibody response to SARS-CoV-2 in a patient on ocrelizumab. (ID 413)

Speakers
Authors
Presentation Number
P0293
Presentation Topic
COVID-19

Abstract

Background

As the world faces the spread and aftermath of the novel coronavirus disease (COVID-19), we are expectantly looking forward to vaccine. Ocrelizumab (OCR), which is a monoclonal antibody directed against peripheral CD20+ B cells, is approved in multiple countries for both RRMS and PPMS. There has been concern about differential effects on immunoglobulin production for ocrelizumab based on the rituximab literature. Rituximab decreased serum antibody levels compared to methotrexate in the pivotal trial for rheumatoid arthritis. In the VELOCE trial for ocrelizumab, humoral responses were attenuated but patients were still able to mount an immune response to vaccines.

Objectives

To describe a patient with MS on OCR with COVID-19 who subsequently tested negative on the immunoassay for antibodies against SARS-CoV-2.

Methods

A chart review was undertaken of the patient’s chart. In addition, a literature search was undertaken to review pertinent studies and abstracts.

Results

A 48-year-old female on OCR (last dose 1/24/2020) presented to a drive up COVID-19 testing site with two days of fever, upper respiratory symptoms, and malaise on March 30, 2020. She tested positive for the antigen to SARS-CoV-2. She was prescribed hydroxychloroquine and azithromycin by her primary care physician, but withheld the hydroxychloroquine due to concern about side effects. Due to worsening shortness of breath, one week later she presented to the emergency room and was admitted for supportive care. Chest x-ray showed left upper lobe and left lung base pneumonia. She was started on ceftriaxone and hydroxychloroquine. IL-6 was elevated at 7 pg/ml, lymphocytes were normal at 1000/ul. IgG was 538 mg/dl, IgM was <25 mg/dl, and IgA was 161 mg/dl. She did not require oxygen and was discharged 3 days later after clinical improvement. She had a prolonged symptomatic period, requiring over 3 weeks from onset to recover from her shortness of breath and fever and 7 weeks to recover from her malaise. In early June 2020, she sought antibody testing and tested negative for SARS-CoV-2 IgG with the Abbott immunoassay. She had a second specimen tested several days later and it also tested negative with the same immunoassay.

Conclusions

This patient illustrates a growing concern about the immunogenicity of SARS-CoV-2 in patients on OCR. On the one hand, one could argue that perhaps she had a false negative result. However, a study found the Abbott IgG immunoassay to be 100% sensitive and 99.9% specific. On the other hand, this could represent an example of an attenuation of humoral response in response to OCR. The question is whether exposure to a future vaccine will also result in an attenuation of humoral response. However, as seen in the VELOCE trial, patients were still able to mount an immune response to vaccines despite the attenuated humoral response. Further studies should be conducted and a database should be formed regarding the humoral response to SARS-CoV-2.

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Biosensors Poster Presentation

LB1144 - How does Coronavirus Disease 2019 (COVID-19) “Sheltering in Place” Affect Ambulatory Activity in People with Multiple Sclerosis? (ID 327)

Speakers
Presentation Number
LB1144
Presentation Topic
Biosensors

Abstract

Background

People with neurological conditions that impair mobility such as multiple sclerosis (MS) have low levels of physical activity, with walking their primary form of exercise. When the San Francisco Bay Area shelter-in-place order was announced in mid-March 2020 to flatten the curve of SARS-CoV-2 infections, the abrupt closure of gyms, fitness studios, and malls greatly limited options for safe exercise. We leveraged an ongoing study utilizing wearable technology, to understand the impact of the pandemic and the shelter-in-place policy on physical activity in people with MS (PwMS) at-risk for neurological worsening.

Objectives

To test the hypothesis that the average daily step count (STEPS) in people with MS would decrease due to the COVID-19 shelter-in-place order.

Methods

Average daily step count (STEPS) was measured from a large UCSF MS Center cohort of PwMS using a wrist-worn accelerometer (Fitbit Flex2) as previously detailed. STEPS before and after the shelter-in-place were available for 42 participants. Amount, type and frequency of exercise, as well as fatigue (Modified Fatigue Index; MFIS-5) and mental health (Mental Health Inventory; MHI-5) were assessed via questionnaire. The UCSF Institutional Review Board approved the study protocol. Descriptive statistics and pre-post comparisons using Wilcoxon Signed-rank were performed, and figures generated, using R studio.

Results

A decrease in STEPS was observed during the week (p =0.024), and month (p=0.048) after versus before the shelter-in-place order in 42 participants with valid STEPS data during this time period. Individual data showed marked decreased in STEPS the week immediately post shelter-in-place, yet some recovered to near pre shelter-in-place levels. As a group, this rebound was not significant. No significant difference comparing 2019 and 2020 similar epoch STEPS data was observed for these participants.

Conclusions

The data supported the hypothesis that physical activity would be reduced in people with MS due to the COVID-19 activated shelter-in-place. Overall prolongation of reduced activity is troubling, particularly in a population where low activity is already pervasive due to detrimental secondary effects of inactivity. These observations were made possible by the use of remote activity monitoring and aligns with broader efforts to use wearables to track and promote physical activity, augment telehealth, and improve telerehabilitation across populations with chronic neurological disorders.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

LB1145 - The 2020 COVID-19 pandemic and multiple sclerosis: Health behavior and lifestyle impacts in >1,000 people with MS  (ID 402)

Speakers
Presentation Number
LB1145
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

The first case of COVID-19 was reported in the United States on January 19th, 2020. By June 2020, >1.8 million people had been reported infected and >100,000 had died. Due to the COVID-19 pandemic, many MS physicians and patient advocacy organizations have recommended delaying or modifying treatment dosages for patients on high efficacy disease modifying therapies (DMTs). The wider impact of COVID-19 on people with MS (PwMS) has not been well characterized.

Objectives

To determine how PwMS navigated the initial phase of the COVID-19 pandemic with an emphasis on changes in health behavior, access to MS care, and employment.

Methods

A cross-sectional survey of adult PwMS was performed online, using the iConquerMS™ platform, between April 3 and April 30, 2020.

Results

The response rate was 20%. 1,019 PwMS responded completely (average age: 54.2 years, range: 20-81; 79% female; 88% from the USA). 64% had relapsing remitting MS; 22% had secondary progressive MS; and 12% had primary progressive MS. The most frequent comorbidities were: depression (41%), hypertension (26%), and asthma (12%). 748 (73%) used a DMT in the last year, primarily higher-efficacy therapies: ocrelizumab (n=238), dimethyl fumarate (n=85), fingolimod (n=80).

Women were more worried than men about COVID-19 (p=0.001); non-white-identifying PwMS believed it was a greater danger to their health than white-identifying PwMS (p=0.002). 10% (n=98) made changes to their DMT regimen because of COVID-19, most commonly delaying at least one dose (n=65). 26% of those who made changes reported doing so without the input of their neurologist or physician

11% had difficulties and delays accessing DMTs, most commonly ocrelizumab (n=42). 18% had difficulties in non-MS related medical procedures. 64% (n=650) canceled or postponed medical visits and 37% (n=382) had telemedicine visits due to COVID-19.

4% (n=43) of PwMS were tested for SARS-CoV-2: 7 were positive (5 female; age range:29-64 years). Their DMTs were dimethyl fumarate (n=2), ocrelizumab (n=1), rituximab (n=1), and an unstated clinical trial drug (n=1). 128 PwMS (13%) wanted to be tested but were not; 395 (39%) knew somebody exposed to SARS-CoV-2 and 38 (4%) were aware of a personal exposure.

37% (n=374) experienced employment changes, most commonly working from home (n=194) and having work hours reduced (n=65). 32 PwMS lost their jobs.

Conclusions

Although most PwMS expressed worry about COVID-19, only 4% were tested for SARS-CoV-2 and 1% tested positive. Due to COVID-19, PwMS are experiencing changes to their care that could impact their long-term health.

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Disease Modifying Therapies – Risk Management Poster Presentation

LB1146 - Covid19 on U.S. and Canadian Neurologists’ Therapeutic Approach to Multiple Sclerosis: A Survey of Knowledge, Attitudes, and Practices (ID 403)

Speakers
Presentation Number
LB1146
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

There have been >1.8 million cases of Sars-CoV-2 (Covid19) in the USA. and >100,000 deaths reported as of June 2020. Immunosuppression is reported as a risk factor for developing Covid19. Amidst this pandemic and declared national emergency in the USA, with a parallel response in Canada, neuroimmunologists are making important decisions and adjudicating complex situations of risk for their patients living with MS. No synthesized study of North American neuroimmunologists’ perceptions has been conducted.

Objectives

To report the experiences, opinions, and decision-making of U.S. and Canadian neuroimmunologists as they relate to the treatment of patients with multiple sclerosis (MS) during the Covid19 pandemic of 2020.

Methods

A new survey instrument was designed and distributed electronically. Invitations were sent via a known panel of MS neurologists and to publicly available e-mail addresses of MS-focused U.S. and Canadian neurologists, April 14-May 3, 2020. Inclusion criteria included treating at least 10 MS patients in the prior 6 months.

Results

243 respondents (average 197 MS patients seen in the prior 6 months (i.e. pre-Covid19); average practice duration 16 years; 92% USA, 8% Canada; 5% rural, 17% small city, 38% large city, 40% highly urbanized) met our inclusion criteria.

MS patient volume dropped by 79% on average (from 53 to 11 patients per month) during the time of Covid19. 23% of neurologists were aware of patients self-discontinuing a DMT due to fear of Covid19 with 43% estimated to be doing so against medical advice. 65% of respondents reported deferring >=1 doses of a disease modifying therapy (DMT) (49%), changing the dosing interval (34%), changing to home infusions (20%), switching a DMT (9%), and discontinuing DMTs altogether (8%) due to Covid19. Changes in DMT administration were most common among the higher-efficacy therapies alemtuzumab, cladribine, ocrelizumab, rituximab, and natalizumab; however, 35% of neurologists reported making no changes to DMT prescribing.

98% of respondents expressed worry about their patients contracting Covid19 and 78% expressed the same degree of worry about themselves. >50% reported believing that high-efficacy DMTs prolong viral shedding of SARS-CoV-2 and that B-cell therapies might prevent protective vaccine effects. Accelerated pace of telemedicine was identified as a major shift in practice.

Conclusions

Reported prescribing changes and practice disruptions due to Covid19 may be temporary but are likely to have a long-lasting influence on MS patients and their care.

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Epidemiology Poster Presentation

LB1147 - Multivitamin, Vitamin C and Vitamin D Pills Self-Medication in Multiple Sclerosis Patients in Montenegro During COVID-19 Pandemic (ID 428)

Speakers
Presentation Number
LB1147
Presentation Topic
Epidemiology

Abstract

Background

The recent COVID-19 pandemic has shaken all countries of the world, and especially their health systems. In the days of fear and uncertainty, many chronic patients, including patients with multiple sclerosis (MS), began to use vitamin supplements in order to strengthen immunity and protect against the new SARS-Cov2 virus.

Objectives

The aim of our study was to determine how the COVID-19 epidemic in Montenegro, a small Balkan country with 631.219 inhabitants, affected the intake of vitamin preparations in patients with MS.

Methods

The research was conducted through an online-generated questionnaire during the days with the highest number of virus cases in Montenegro.

Results

In total, we received 101 responses (response rate was 77.7%). The sample was composed of 25 male (24.7%) and 76 female (75.3%) patients with mean age of 39.4±8.7 years. In our group, 40 patients (39.6%), due to the COVID-19 epidemic, started taking vitamin C preparations, and among them there were statistically more males, and it was noticed that as the age of patients and the duration of the disease increased the frequency of taking vitamin C preparations is also growing. The largest number of our respondents (78, ie 77.2%) used vitamin D supplements during the epidemic, but the largest number of them (73, ie 72.3%) used it even before the epidemic outbreak. The group that does not use vitamin D preparations is statistically younger than the population that uses them. Regarding multivitamin preparations, due to the epidemic of the new virus 33 of our respondents (32.7%) started using them, and among them there are statistically more males, as well as those living in the regions of Montenegro that were affected by the COVID-19 epidemic. The group that does not use multivitamin preparations is less afraid for the further course of their disease and believes that there is a lower risk of getting SARS-Cov2 virus.

Conclusions

The recent COVID-19 epidemic has influenced MS patients from Montenegro to intensify their intake of vitamin preparations in order to strengthen immunity and prevent SARS-Cov2 infection.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

LB1148 - Neuromyelitis optica (NMO) practice and prescribing changes in the setting of Covid19: A survey of neurologists (ID 441)

Speakers
Presentation Number
LB1148
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

The Sars-CoV-2 (Covid19) pandemic has caused >100,000 deaths in the USA and has the potential to disrupt the care of NMO patients to a great extent. A unified and thorough set of guidelines for NMO management across countries has yet to be established.

Objectives

To document the prescribing and treatment patterns of North American neurologists with expertise in NMO patient care during the Covid19 pandemic.

Methods

We created a new survey instrument to query the practices, decision-making, and perspectives of a group of neuroimmunology-focused neurologists who actively care for patients with NMO in the USA or Canada. Survey responses included rating of statements for agreement, open-ended questions, multiple choice, and estimates of current practices in gradient forms. The survey was circulated from April 14, 2020 to May 4, 2020.

Results

192 neurologists met our inclusion criteria and were most often from academic hospitals (51%), followed by single specialty groups (21%). The volume of in-person NMO visits declined from 4 NMO patients per typical month pre-Covid19 to <1 patient in the prior month (approximately April 2020). More than half of neurologists indicated NMO patients were delaying their scheduled MRIs (57%), two-thirds indicated patients were delaying clinical visits (67%) and roughly half indicated patients were delaying laboratory testing (52%) due to fear of contracting Covid19. Seventeen percent of neurologists have deferred one or more doses of NMO patients’ immunosuppressive drug, 16% changed the dosing interval, and 15% switched health facility-based infusions to home-based infusions. Roughly half of all neurologists were uncomfortable with prescribing tocilizumab (48%), though 19% of neurologists anticipated using tocilizumab more often for their NMO patients given its current investigation as a treatment for Covid19.

Conclusions

The prescribing patterns and treatment decisions of NMO care providers during the Covid19 pandemic indicate a need for evidence-based, comprehensive guidelines for treating NMO patients amid healthcare crises moving forward.

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Observational Studies Poster Presentation

LB1149 - Perceptions of risk and adherence to care in MS patients during the COVID-19 pandemic: a cross-sectional study (ID 825)

Speakers
Presentation Number
LB1149
Presentation Topic
Observational Studies

Abstract

Background

The COVID-19 pandemic has raised concerns for increased risk of infection in patients with multiple sclerosis (MS) and disrupted their routine MS care.

Objectives

The aim of this study is to characterize the extent of MS patients’ perceptions of risk and adherence to care during the pandemic.

Methods

A survey was emailed to patients from a large MS center in New York City during the local peak of the pandemic to assess perceptions of infection risk and adherence to MS care including appointments, laboratory studies, MRIs, and taking disease-modifying therapies (DMT).

Results

529 patients from the MS center responded to the survey during two-weeks in April 2020. Patients collectively showed concern about becoming infected with COVID-19 (88%) and perceived a higher infection risk because of having MS (70%) and taking DMTs (68%). Patients frequently postponed appointments (41%), laboratory studies (46%), and MRIs (41%). Noncompliance with DMTs was less common (13%). Decisions to alter usual recommendations for care were made by the patient more often than by the provider regarding adherence to appointments (68%), laboratory studies (70%), MRI (67%), and DMTs (65%). Degree of concern for infection was associated with adherence to appointments (p=0.020) and laboratory studies (p=0.016) but not with adherence to MRI and DMTs. Thirty-five patients reported being tested for COVID-19, of whom fourteen reported a positive test.

Conclusions

Patients with MS were highly concerned about becoming infected during the local peak of the COVID-19 pandemic. Behaviors that deviated from originally recommended MS care were common and often self-initiated, but patients were overall compliant with continuing DMTs.

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Disease Modifying Therapies – Risk Management Poster Presentation

LB1150 - Multiple sclerosis during COVID-19 pandemic  in Santiago, Chile (ID 932)

Speakers
Presentation Number
LB1150
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Although non-pharmaceutical measures have been able to reduce the instantaneous reproduction number (R) of SARS-CoV-2 to less than 1 in some countries, the easing of control measures and the absence of herd immunity against coronavirus disease 2019 (COVID-19) may accumulate cases resulting in a substantial increase in R, leading to a second wave. This causes a decision-making problem for immunosuppressed patients due to disease modifying treatment as neither aggressive countermeasures nor treatment deferment can be indefinitely lengthened. In patients with multiple sclerosis (pwMS) expert recommendations consider safe to start or continue interferons β, glatiramer acetate, fingolimod and natalizumab. In relation with lymphodepleting drugs (e.g., alemtuzumab, ocrelizumab), the recommendations are less straightforward. In the real clinical practice, for instance, neurologists have stopped or postponing re-doses of alemtuzumab. However, emerging case reports suggest that lymphodepleting drugs may be safe during the COVID-19 pandemic.

Objectives

To report our initial experience on fifty-two pwMS from one clinical centre during COVID-19 pandemic in Santiago, Chile.

Methods

This is a prospectively-followed cohort (from February to mid-July 2020) of 52 pwMS at the University of Chile Hospital. pwMS treated with alemtuzumab were included if they have had infusions within 12 months prior to or during the COVID-19 pandemic.

Results

The mean age was 34 years (SD ±11), 69% were women, mean disease duration was 3 years and mean EDSS 1.6. 85% pwMS (45/52) have followed a preventine quarantine. 19 pwMS receiving fingolimod, 11 interferons, 4 glatiramer acetate (GA) and 3 natalizumab continued their treatments without changes. Ocrelizumab treatment (n: 6) was postponed in three patients while it continued in three other patients with severe disease. The last infusions of alemtuzumab (n: 9) took place at the end of February when two patients with severe disease received their second cycle. Alemtuzumab re-dosings were postponed in two patients. COVID-19 diagnosis was confirmed by RT-PCR in five patients, 10% of this cohort: two treated with GA, one with fingolimod and two with alemtuzumab. All pwMS with COVID-19 were a contact of a confirmed case of COVID-19. Two patients -one on fingolimod and one on GA- required hospitalization, but not intensive care, for mild pneumonia. Both patients on alemtuzumab had severe depletion of circulating T lymphocytes, but mild COVID-19 disease.

Conclusions

Lymphodepleting DMTs seem to be safe during the COVID-19 pandemic with self-limiting infections. The decision to start, continue or stop treatment with a given DMT should be strongly influenced by whether pwMS do follow recommendations or not to prevent exposure to the virus.

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Clinical Trials Poster Presentation

LB1151 - Clinical outcomes in patients with COVID-19 infection during phase IV studies of cladribine tablets for treatment of multiple sclerosis (ID 947)

Speakers
Presentation Number
LB1151
Presentation Topic
Clinical Trials

Abstract

Background

The COVID-19 pandemic has become a significant concern for patients (pts) with multiple sclerosis (MS) and their healthcare providers, prompting various guidelines on the appropriate use of disease-modifying drugs (DMDs) such as cladribine tablets.

Objectives

We report on clinical outcomes in pts who developed COVID-19 infection during two ongoing Phase IV studies of cladribine tablets (CLARIFY-MS [NCT03369665] and MAGNIFY-MS [NCT03364036]). Post-approval cases of COVID-19 infection are reported elsewhere.

Methods

CLARIFY-MS is investigating the impact of cladribine tablets on health-related quality of life in pts with highly active relapsing MS, while MAGNIFY-MS aims to determine the onset of action of cladribine tablets in such pts. Both studies utilize an open-label, single-arm, multicenter design, in which pts are treated with cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years). Some 680 pts are continuing in both studies. Cases of suspected COVID-19 infection were identified from adverse event reports and reviewed in terms of patient baseline characteristics, comorbidity, disease/treatment history (including most recent Extended Disability Status Scale [EDSS] score before COVID-19), and timing of cladribine tablets dosing/lymphocyte counts in relation to COVID-19 severity and outcomes.

Results

Three cases of suspected COVID-19 infection were identified (CLARIFY-MS, n=2; MAGNIFY-MS, n=1). Patient #1 (21-year history of MS; most recent EDSS score, 4.5; concomitant cardiovascular disease/asthma; prior DMD use) developed severe COVID-19 infection (confirmed) necessitating hospitalization but recovered and was discharged with residual cough/fatigue. Patient #2 (2-year history of MS; most recent EDSS score, 2; previous deep vein thrombosis during pregnancy; no prior DMDs) was also hospitalized for severe COVID-19 symptoms (not confirmed) but self-discharged and was recovering with chest tightness, fatigue, and neuropathic pain under self-isolation. The remaining patient (7-year history of MS; most recent EDSS score, 1; prior use of interferon β-1a) experienced mild symptoms of COVID-19 infection (confirmed); hospitalization was not required and the patient recovered under self-isolation. None of the pts required mechanical ventilation or died.

Conclusions

All 3 pts who developed COVID-19 infection during two ongoing Phase IV studies of cladribine tablets recovered or were recovering, and none required mechanical ventilation.

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Observational Studies Poster Presentation

LB1152 - COVID-19 and lockdown in patients with multiple sclerosis: a descriptive study of prevalence and emotional impact (ID 954)

Speakers
Presentation Number
LB1152
Presentation Topic
Observational Studies

Abstract

Background

The SARS-Cov2 produced a world-wide health-pandemia situation where people must stay home. People with multiple sclerosis (MS) were considered one of high-risk infection population groups due to their immunological status. This situation may increase the risk of emotional unbalance and produced a high uncertainty for MS patients.

Objectives

To describe medical, demographical and emotional characteristics of a sample from our own MS Unit in a tertiary Hospital in Madrid during lockdown.

Methods

In one month we consecutively interviewed 138 MS patients, collecting information about their demographic characteristics (age, gender, years of education, house-company), their MS (physical disability, treatment, years with MS), the SARS-Cov2 (if they had it, someone living with him, the type of lockdown, protection method used outdoors) and their emotional status (previously to SARS-Cov2, compare to before, about their quality of live (QoL), coping strategies, depression and anxiety). We applied standardized questionnaires for QoL, disability related to health condition and emotion.

Results

The majority of participants were woman (69,9%) middle age (42,8) and high education (71% university), with a low disability (EDSS mode=1) after 10,3 years with MS and under treatment (97%). Smokers as frequent comorbidity (23,9%), they lived with company at home (87%) and they followed lockdown completely (61,6%), using mainly face-mask and gel as outdoors protection. Emotional situation during lockdown was described as “worse than before” in 46,4% but some patients reported feeling better (15,2%). Self-reported health was rated as 67,1 over 100 with a high EQ-5D index (M=0,73) and they were not depressed (M=4,8; SD=3,7) neither anxious (M=6,7; SD= 4,3). Infected-MS patients (only 8 cases) showed significantly higher depression (p=0,039) and lower rating in health (p=0,012) in EQ-5D than non-infected patients, using equivalent coping-strategies and rating similar physical independence.

Conclusions

Despite the immunological special status of MS patients, we found that the prevalence of SARS-Cov2 was really low, as stated in the literature. Our patients were quite responsible with lockdown rules and almost half of them confessed that lockdown affected their emotional status to the worse even though they were not infected. Interestingly, those who reported a positive lockdown indicated that not commuting, slowing down and teleworking improved their QoL significantly.

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Disease Modifying Therapies – Risk Management Poster Presentation

LB1154 - COVID-19 in cladribine-treated patients with relapsing-remitting multiple sclerosis: a monocentric experience (ID 1085)

Speakers
Presentation Number
LB1154
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Cladribine significantly reduces disease activity and disability progression in relapsing-remitting multiple sclerosis (RRMS) through a selective but transient depletion of lymphocyte subsets. The SARS-COV-2 outbreak has raised several concerns regarding cladribine use for RRMS patients.

Objectives

To evaluate the prevalence and clinical features of COVID-19 disease among cladribine-treated relapsing-remitting MS patients.

Methods

Fifty-six RRMS patients treated with cladribine in our centre (female=39; mean age=33.8 years [y]; median Expanded Disability Status Scale [EDSS]=1.5, disease duration [DD]=5.2 y, treatment duration=1.15 y) were asked if they had developed manifestations suggestive of SARS-COV-2 infection up to June 30th 2020. Their detailed characteristics were collected.

Results

At June 30th 2020, nasal/pharyngeal swabs have been found positive in 0.94% of the Lombardy population. Since the pandemic start, 2/56 (3.6%) cladribine-treated RRMS complained a symptomatology suggestive of COVID-19 disease, with a prevalence similar to that of the whole MS population of our centre (84/2950, 2.8%). The first patient was a 30-year-old male with RRMS (DD=1.2 y, EDSS=1.5) and no comorbidities. He started cladribine on January 10th 2020. One week later, he developed fever (<37.5°), ageusia, cough, fatigue, sputum production, sore throat, nasal congestion, shortness of breath without desaturation and conjunctivitis.

The second patient is a 39-year-old female with RRMS (DD=13.2 y, EDSS=3.5), and no comorbidities. She started cladribine on February 13th 2020 and underwent the second week of the first treatment course from March 5th 2020. On March 30th, she developed fever (<37.8°), anosmia, ageusia, cough, fatigue, and bone/joint pain. Serology for SARS-COV-2 was positive in May 2020. For both patients, blood examinations performed before and after COVID-19 disease were within normal limits. Both patients were telephone-monitored at home and completely recovered within 15 days.

Conclusions

Only a minority of cladribine-treated RRMS patients developed a mild and self-limiting COVID-19 disease. In our cohort, this occurred in two RRMS patients within a few weeks from treatment course and the possible nadir of selective immunosuppression. Both patients recovered completely. Cladribine administration seems to be safe also in the setting of the COVID-19 pandemic.

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Epidemiology Poster Presentation

LB1155 - Vitamin D levels in the UK MS population and COVID-19 susceptibility (ID 1116)

Abstract

Background

Despite the well-described association between vitamin D and MS, little is known about current behaviours surrounding vitamin D and the corresponding vitamin D status in this group at a population level across the UK. During the COVID-19 pandemic, interest in the role that vitamin D might play in reducing susceptibility to and severity of COVID-19 has come to the foreground.

Objectives

To determine the vitamin D status of the UK MS population, understand the factors that influence it, and examine how vitamin D supplementation affects the risk of COVID-19.

Methods

A cohort study using the UK MS Register was performed. Self-reported data surrounding vitamin D and remotely collected biological samples were collected. 1768 people with MS (pwMS) completed a questionnaire regarding vitamin D-influencing behaviours; dried blood spots were collected from 388 of these pwMS and 309 matched controls, and serum 25(OH)D was measured. Subsequently, 592 participants from this MS cohort prospectively completed questionnaires evaluating symptoms suggestive of COVID-19.

Results

Marked differences were observed between supplementation behaviours with pwMS more likely to take supplements (72% vs 26% controls, p<0.001), and at higher doses (median 1600 IU/day vs 600 IU/day in controls, p<0.001). Serum levels of 25(OH)D were higher in pwMS than controls (71nmol/L, IQR 48 vs 49nmol/L, IQR 27, 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, IQR 35 vs 44 nmol/L, IQR 21, p<0.001). 71% of those self-diagnosed with COVID-19 reported taking vitamin D vs 72% without COVID-19. Median dose for those with COVID-19 was reported as 1000 IU/day vs 2000 IU/day in those without (p=0.682).

Conclusions

pwMS living in the UK are more likely to have adequate levels of vitamin D than controls, and is driven by the higher rate and dose of supplementation across this population. This has implications on the design and interpretation of any future clinical trials with vitamin D in this population. In addition, we found no evidence that vitamin D supplementation had an impact on susceptibility to COVID-19 in this population.

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Rehabilitation and Comprehensive Care Poster Presentation

LB1156 - Physical activity behavior in people with multiple sclerosis during the COVID-19 pandemic in Israel: Results of an online survey (ID 1152)

Speakers
Presentation Number
LB1156
Presentation Topic
Rehabilitation and Comprehensive Care

Abstract

Background

Multiple sclerosis (MS) itself and first-line disease modifying therapies do not increase the risk of contracting COVID-19. However, home isolation is likely to result in a significant decrease in participation in leisure time physical activities and an increase in sedentary behavior. This avoidance behavior might be harmful for essential functions such as mobility, cognition, and physical fitness, resulting in a reduced quality of life in people with MS (PwMS), exceeding the typical impact of the disease.

Objectives

Provide data related to the impact of COVID-19 epidemic on physical activity (PA) behavior and fitness level in an Israeli cohort of PwMS.

Methods

During the 30-day period of May 15th and June 15th, 2020 an online survey questionnaire related to physical activity was distributed via e-mail and common social websites to ~500 PwMS. Descriptive information including age, gender, disease duration, and use of walking support was collected to characterize the population. Specifically, participants were asked to report on whether, and to what extent, the pandemic conditions had altered their PA behavior. Participants were asked to report the frequency per week they took part in PA sessions, and the duration and the type of activity they were engaged in. In addition, participants were asked to rate their level of physical fitness compared to the period prior to the COVID-19 pandemic.

Results

One hundred thirteen PwMS completed the online survey, 74 were females with a mean age of 43.0 (S.D.=12.9) years. In the majority of responders (42.5%) disease duration was short, between 1-5 years, and 88.5% were not using any walking support. PA behavior during the pandemic demonstrated that 16.8% who were engaged in PA before the COVID-19 pandemic stopped practicing, 33.6% reduced their PA, 20.4% continued as before, and 18.6% increased their PA. Aerobic exercises were the main type of PA performed by 58.4% of patients. As for the patient’s self-reported fitness level, 31.9% reported that their fitness level had decreased during the pandemic, 60.2% felt no change, and 8% reported an improvement.

Conclusions

Our findings serve as a call of action for all professionals involved in MS management to address PA behavior in PwMS during the COVID-19 epidemic.

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Internet and Social Media Poster Presentation

LB1157 - Experiences of Latin American MS and/or NMOSD experts in practice during the COVID-19 pandemic: focus in Telemedicine. (ID 1198)

Speakers
Presentation Number
LB1157
Presentation Topic
Internet and Social Media

Abstract

Background

Different scientific associations have elaborated recommendations about MS and/or NMOSD patients care and management during COVID-19 pandemic. They advised to take extra care to minimize their exposure to the virus and use alternatives to face-to-face medical appointments. This has prompted a transition of conventional care to telemedicine (TM) as quickly as possible. There is no data regarding current patient’s follow-up neither TM usage among MS and/or NMOSD Latin American experts.

Objectives

To investigate experiences from Latin American MS and/or NMOSD experts on follow-up of their patients focusing on TM management.

Methods

A cross-sectional study was performed. 141 MS and/or NMOSD experts from Argentina (AR), Chile (CH), Colombia (CO) and Brazil (BR) were invited to answer an anonymous, voluntary web-based survey. The survey was sent via email (3 July 2020) to potential respondents and was available online for only one week to avoid bias regarding epidemic change in our region.

Results

A total of 129 (91.48 %) experts completed the survey (56 from AR, 33 BR, 30 CH, and 10 CO), age 41.23 ±10.20, 43.4% works at public hospital. Regarding medical appointments (virtual or face-to-face), it decreased on a 50% during the pandemic era (14.78 ±16.71 and 7.43 ±9.68 patients/week before and during the COVID-19 pandemic respectively). Only 19.4% had experience in TM previous COVID-19 pandemic (26.8% AR, 0% BR, 23.3% CH, and 30% CO), while 79.8% are currently using TM (89.3% AR, 75.8% BR, 60% CH, and 100% CO). Most of them using video call (52.3%). Using TM, 44.1% of the experts were able to carry out neurological examination, 85.6% believe be able to identify a relapse, 48.6% use Patient Determined Disease Steps (PDDS) and 38.7% continue using the conventional Expanded Disability Status Scale (EDSS). On the other hand, 83.7% continue face-to-face medical appointment, the most frequent causes were: first time appointment (91.8%), therapeutic failure (94.%) and management of a relapse (97.3%) and only 20% for the routine appointment. To decrease virus exposure, only 40% perform a complete and thorough neurological evaluation, most of them avoid funduscopy.

Conclusions

Considering the vertiginous speed of the spread of COVID-19 in Latin American, results from our survey demonstrate preparedness and responsiveness among Latin American MS and/or NMOSD experts. Despite scarce prior TM experience, most experts were able to use TM as a new tool for monitoring their patients.

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Neuropsychology and Cognition Poster Presentation

LB1158 - COVID-19 pandemic and mental distress in Multiple Sclerosis: implications for clinical management (ID 1300)

Abstract

Background

in multiple sclerosis (MS), disease-related factors and dysfunctional coping might favour the development of mental distress induced by COVID-19 containment measures.

Objectives

to explore the relationship between mental distress, disability and coping strategies in the Italian MS population under lockdown.

Methods

Structural equation modeling (SEM) was applied to information collected via web-survey to identify modifiable factors that could account for mental distress. Information about the following domains was collected: (1) socio-demographic features; (2) general and MS related health status; (3) changes in lifestyle; (4) COVID-19 infection and risk perception; (5) physical disability assessed via the Patient-Determined Disease Steps (PDDS) scale and the Upper Extremity Function – Short Form (UEF) from the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system; (6) cognitive function investigated using the Cognition Function– Short Form from the Neuro-QoL. Abstract reasoning, logical thinking and, in part, sustained attention, were measured using six Raven-like matrices; (7) mental distress: four domains from the Neuro-QoL were explored. Specifically, sleep disturbances, anxiety feelings, depressive symptoms, emotional dyscontrol; (8) coping strategies: individual response to lockdown was assessed using 18 items from the COPE-NVI-25, evaluating five independent coping strategies: avoidance (AV), social support (SS), positive attitude (PA), problem solving (PS) and turning to religion (TR).

Results

845 subjects (497 MS and 348 controls) were included in the study. MS patients showed higher scores than controls for depression (p=0.005), but not for anxiety, emotional dyscontrol or sleep disturbances. The SEM explained 74% of the variance observed in depression score. Within the model, three latent factors were characterized from measured variables: motor disability and cognitive dysfunction contributed to disability (β=0.509 and β=0.836, p<0.001); positive attitude and exercise contributed to active attitude (β=0.386 and β=0.297, p<0.001); avoidance, social support and watching TV contributed to passive attitude (β=0.301, β=0.243 and β=0.212, p<0.001). As per the relationship between latent factors and their influence on depression, disability contributed to passive attitude (β=0.855, p<0.001) while both passive and active attitude significantly influenced depression (β=0.729 and β=-0.456, p<0.001).

Conclusions

As practical implication of our model, favoring exercise would enhance active attitude and its positive impact on mental well-being while, at the same time, reducing the negative impact of disability on depression, representing a valuable tool for the long term management of COVID-19 related mental distress in MS.

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Clinical Outcome Measures Poster Presentation

LB1159 - The Effect of COVID-19 Pandemic on Treatment Adherence of People with Multiple Sclerosis (ID 1305)

Speakers
Presentation Number
LB1159
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Decreased adherence to disease modifying treatment has been shown to be associated with an increase in relapse frequency in people with multiple sclerosis (pwMS). Coronavirus disease 2019 (COVID-19) has changed the functioning of health systems and has seriously affected patients' lifestyles and the way health professionals work. However, there has been no study investigating the effects of Covid-19 pandemic on treatment adherence of pwMS.

Objectives

This study aims to investigate the effect of the Covid-19 pandemic on treatment adherence of pwMS receiving oral and injectable DMT's.

Methods

The study was conducted using an online survey form. Individuals who were followed up with the diagnosis of MS and registered to iMed database in the MS unit of Erciyes University Medical Faculty were invited to participate to the study. PwMS were asked to assess the treatment adherence before and during the Covid-19 pandemic with the Turkish Version of Multiple Sclerosis Treatment Adherence Questionnaire (MS-TAQ) which has been found as valid and reliable tool in Turkey.

Results

448 pwMS who met the inclusion criteria were invited to participate the study. 221 answered the questionnaire. 9 had incomplete or doubtful data and 8 was not receiving any DMT. 204 were enrolled to the study. 37 pwMS were receiving monoclonal antibody therefore they were excluded from treatment adherence analysis. 167 pwMS were eligible for further analysis. PwMS were predominantly females (68.3%). Mean age was 32.97±8.60 years. Median disease duration was 4 (0.1-25) years. 155 pwMS (92.8%) were defined as adherent and 12 (7.2%) were defined as non-adherent before the pandemic and 152 pwMS (91.0%) were defined as adherent and 15 (9.0%) were defined as non-adherent during the pandemic. Additionally, two pwMS, one receiving teriflunomide and the other receiving glatiramer acetate, reported having had the Covid-19 infection. During the pandemic period, 52 participants (31,3%) missed at least one dose during one month in the pandemic period, while 43 participants (25,7%) missed at least one drug dose in the last month before pandemic (p= 0,022). Treatment adherence status and the number of missed dose were not statistically different before and during pandemic (p=0.959). The barriers affecting treatment adherence did not reveal any statistically significant difference before and during the pandemic.

Conclusions

In this study, the effect of the Covid-19 pandemic on the treatment adherence of pwMS was evaluated for the first time. The results of our study showed that the pandemic only slightly affected treatment adherence of pwMS in Turkey. Multinational studies on individuals with MS will be able to provide more detailed information about the treatment adherence.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

LB1160 - Multiple Sclerosis patients and Health Care accessibility during COVID-19 Pandemic (ID 1368)

Speakers
Presentation Number
LB1160
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Multiple Sclerosis (MS) is a chronic disease that requires frequent medical follow-up. COVID-19 pandemic may have changed the way patients accessed Health Care facilities including laboratory and imaging exams as well as urgent or routine medical appointments.

Objectives

To assess differences in health care accessibility from a patient perspective since the announcement of the state of emergency, due to COVID-19 pandemic, by the Portuguese government.

Methods

We performed an online questionnaire-based study; 485 adult patients followed in our tertiary centre with the diagnosis of MS were invited to answer the survey that was accessible from April to June 2020.

Results

We included 195 valid questionnaires from 195 patients. Fifty-four percent had a university degree (53.8%) and approximately half of the patients were professionally active. Most of the patients (69.7%) did not experience any symptom related to MS. Fifty-nine patients (30.3%) had new possible MS- related symptoms of whom 37 (62%) sought health care services: 47% had an appointment with their neurologist through a phone call, 22% contacted the MS nurse, 17% contacted the general practitioner, 8% were seen at the MS clinic (by other neurologist) and 6% at the emergency department. About a third of patients (30.6%) who did not seek a health care appointment admitted that would do it otherwise in a non-pandemic context. Regarding scheduled exams, 37 patients (19%) did not perform a scheduled blood collection and 23 (11.8%) did not perform scheduled imaging, mostly due to medical advice (46% and 44% respectively) or due to patient fear (31% and 19%). Eighteen patients (9.2%) stopped their prescribed medication of which 14 did so on their own volition. Thirteen patients were tested for COVID-19, two were positive. More than half the patients (55.9%) considered that teleconsultation was adequate and were satisfied with the information and recommendations provided (59.5%).

Conclusions

We conclude that COVID-19 pandemic markedly impacted Health Care access to MS patients and may change the way MS clinics evaluate and follow their patients as telemedicine emerges as a valuable tool.

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Internet and Social Media Poster Presentation

LB1161 - Teleneurology for MS care at two large academic centers before and during the-COVID-19 pandemic (ID 1394)

Speakers
Presentation Number
LB1161
Presentation Topic
Internet and Social Media

Abstract

Background

Teleneurology has the potential to improve patient access to specialized multiple sclerosis (MS) centers. MS patients face multiple barriers to receiving in-clinic care including physical limitations, driving restrictions, and financial limitations. The COVID-19 pandemic further highlighted the need to re-evaluate healthcare delivery models.

Objectives

To describe the teleneurology populations at two large MS centers (Cleveland Clinic (CC) and University of California, San Francisco (UCSF)) and the changes that occurred in teleneurology use before and during the COVID-19 pandemic.

Methods

In this cross-sectional study we identified all teleneurology visits conducted at our two centers between 01-2019 and 04-2020. We compared group demographics, visit characteristics, and MS disease characteristics using T-tests and chi-squared tests for normally distributed variables and Kruskal-Wallis test for non-parametric variables.

Results

2268 patients completed 2579 teleneurology visits during the study period across the two sites (mean age 48.3±12.3 years, 72.9% female); 78.1% had an MS diagnosis. Among MS patients, age and sex were similar (p>0.1 for each) but a greater proportion of patients seen at UCSF were non-white (74.8% vs 87% white, p=<0.001), had RRMS (78.7% vs 74.5%, p=.015), were on infusible DMTs (45.5% vs 35.2%, p=<0.001), walked independently (78.4% vs 72.7% p=<0.001), and lived closer to the Center (50.0 vs 57.2 miles, p=<0.005). CC had a higher proportion of advanced practice providers (APP) conducting visits (62.3% vs 2.6%, p=<0.001) and new patient visits (15.4% vs 4.0% p=<0.001). The post-COVID population (patients seen after March 15) across both sites had a higher proportion of African Americans (12.7% vs 5.0%, p=<0.001) and shorter driving distance (35.6 vs 130 miles, p=<0.001) compared to the pre-COVID population. The populations pre- and post-COVID did not differ on sex, current DMT, disease course, or disability level.

Conclusions

Teleneurology visits at baseline reflected the organizational and teleneurology reimbursement patterns across our Centers. Following precautionary measures and expanded reimbursement for telemedicine associated with the COVID-19 pandemic, we significantly increased utilization of specialized MS teleneurology care for local and African American patients. These findings illustrate the potential for societal factors to rapidly change disparities in technology adoption and access to specialized MS care.

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Disease Modifying Therapies – Risk Management Poster Presentation

LB1162 - Rapid transfer of knowledge for multiple sclerosis clinical care during COVID-19: ECHO MS (ID 1423)

Speakers
Presentation Number
LB1162
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Healthcare providers caring for people with multiple sclerosis (MS) have had significant concerns about the intersection of MS and COVID-19. As a result, there has been an urgency to understand and share information about how to best provide MS clinical care during COVID-19. The Project ECHO model is well-suited for this challenge, as it provides a uniquely efficient and effective approach to sharing information in real-time using real cases.

Objectives

We report on the translation of the Project ECHO model for the rapid sharing of knowledge among MS clinical providers during COVID-19.

Methods

The ECHO MS COVID-19 Response Clinic was a videoconference-based education and case consultation program offered to providers in the U.S. who care for individuals with MS. The Response Clinic was offered as four sessions, each delivered by three regional hubs. Data were collected on participation and the self-reported impact of the program.

Results

A total of 132 unique providers participated in the Response Clinic, which consisted of 11 didactic modules and 43 case consultations. Participant providers overwhelmingly indicated that the program improved their knowledge, attitude, and skills for providing healthcare for people with MS during the COVID-19 pandemic.

Conclusions

The Project ECHO model was successfully adapted to serve the needs of the MS community during COVID-19, suggesting the program could be continued or could be expanded to other disease areas for a similar purpose. More research is needed to objectively measure the impact of the program on patient outcomes.

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Epidemiology Poster Presentation

LB1164 - "Awareness of Covid-19 in patients with MS in Saudi Arabia" (ID 1440)

Speakers
Authors
Presentation Number
LB1164
Presentation Topic
Epidemiology

Abstract

Background

Coronavirus disease 2019 (Covid-19) was first introduced in December 2019 and has since taken the world by storm becoming a global pandemic as of March 2020. As the pandemic is still ongoing, a lot of uncertainty circles around the risk of the Covid-19 infection and outcome in patients with multiple sclerosis (MS). The decision of treatment discontinuation, switching or timing of therapy could serve as a source of anxiety for these patients in particular. Patients with MS could face some difficulties accessing routine health care services either due to unavailability or as a result of fear for contracting the infection if they go. This vulnerable group is at considerable risk because of insufficient health communication7.

Objectives

First of all, to determine the level of knowledge of the COVID-19 pandemic in patients with MS. Thereafter, to evaluate the extent of the impact that MS has had on their attitude regarding their clinical condition and daily living. Finally, to look at the impact of the pandemic on the healthcare and practice related to patients with MS.

Methods

A descriptive study to evaluate COVID-19 pandemic and MS with the theme of the study focused on knowledge, awareness, and attitude in patients with MS. An electronic google form was sent to the participants who include patients diagnosed with MS for at least one year. The survey was designed by the authors to cover issues related to Covid-19 pandemic in patients with MS. The survey questions were based on emerging COVID-19 reports, clinical experience, in addition to incorporating patients enquires during the pandemic. Reliability of the questionnaire was conducted by measuring internal consistency in a pilot sample (30 participants).

Results

A total of 176 patients with MS responded to the questionnaire. A vast majority of the participants were female (n= 122,69%) with a mean age of 32 (SD: 9.2) years. The majority of participants had RRMS (n=168, 95.5%). Overall patients had good knowledge and attitude towards the pandemic in more than 80% of the participants. However, this did not correlate well with impact on health care r=0.06. With 46% being anxious about taking their medication and 32% of the participants having missed their appointments because they wanted to avoid any possible source of contracting the infection. It is worth noting that 15% of the respondents mentioned they had a relapse and did not go to the hospital because of the pandemic.

Conclusions

In conclusion, patients with MS had a good understanding of the COVID-19 pandemic, with the vast majority of patients following health precautions to mitigate their infection risk. The pandemic has a significant impact on the care of patients with MS. Since it is still unsure when this pandemic will come to an end, the adoption of telemedicine, probability of home infusion options and giving more time to address patient queries are the best ways to minimize the impact of the pandemic on this ‘at risk’ group of the society.

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Disease Modifying Therapies – Risk Management Poster Presentation

LB1165 - COVID-19 in cladribine-treated patients with Multiple Sclerosis (ID 1470)

Speakers
Presentation Number
LB1165
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

The emergence of a new coronavirus (COVID-19) and the subsequent pandemic present a unique challenge to neurologists managing patients with multiple sclerosis (MS). Preliminary reports do not support an increased risk of severe outcome associated with disease modifying therapies (DMTs) but real-world evidence is lacking.

Objectives

To describe our experience in 14 patients with MS who have been affected by SARS-CoV-2 (with a clinical, RT-PCR, or serological diagnosis) and who were being treated with cladribine in Spain.

Methods

We conducted a consecutive clinical series study including cases occurred in Spain since January 31, 2020 when the first COVID-19 patient was detected in Spain until the end of June 2020.

Results

Patients were mostly female (64%), with an average age of 40.1 (± 12.0) years and a disease duration of 9.7 (± 8.9) years. Median EDSS was 1 (IQR 0–2.5), and the average time on treatment with cladribine was 7.7 (±5.77) months. Two patients had grade 1 lymphopenia, five patients had grade 2 lymphopenia, one patient had grade 3 lymphopenia and six patients were in normal range. Only 1 patient required hospitalization. None required ICU care, or intubation. 93% of the patients improved without any specific treatment. 2 patients (14%) were asymptomatic, 11 (79%) were mild and 1 (7%) was moderate. All recovered without sequelae. 7 of the patients (50%) had a serology test done that showed presence of anti-viral antibodies of IgG and IgM type in all cases.

In our series the patients had a favorable evolution, and all recovered. Factors that could have influenced those results could be the age of the patients, the lack of other risk factors and the mechanism of action of cladribine. It is known that the limited activity of cladribine on cells of the innate immune system and its relatively minor impact on CD8 T cells and plasma cells may have implications for maintained protection from bacterial and viral infections. Importantly, cladribine CD4+ T cell and B cells depletion is partial and transient. The short-term dosing regimen of oral cladribine, potentially reduces depleting effects on the innate immune system.

Conclusions

From this limited number of patients our observations suggest that cladribine treatment does not appear to worsen COVID-19 disease prognosis. MS is a debilitating disease and discontinuing effective treatments might have adverse consequences, benefit/risk assessment is crucial in the current context. Our patients treated with cladribine had an adequate resolution of COVID-19 and mounted an immune response, however more studies are necessary to confirm and extend our preliminary findings.

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Epidemiology Poster Presentation

LB1166 - Risk and outcomes of COVID-19 in patients with multiple sclerosis in Madrid Spain  (ID 1480)

Abstract

Background

Infections are an important cause of hospitalization in patients with MS. Data on outcomes of COVID-19 in patients with MS are limited

Objectives

To quantify the risks of infection, hospitalization, admission to intensive care and death due to SARS-CoV-2 infection among patients with MS relative to the general population, and to identify factors associated with risk of hospitalization

Methods

A regional registry was created to collect data on incidence, hospitalization rates, intensive care unit (ICU) admission and death in patients with MS and COVID-19. National government outcomes and seroprevalence data were used for comparison.

Results

Two-hundred nineteen patients with MS were included in the registry, 51 of whom were hospitalized. The infection incidence rate (IR) was lower in patients with MS than the general population (adjusted IR ratio 0.78; 95% confidence interval: 0.70–0.80), but hospitalization rates were higher (adjusted relative risk 6.52 [6.13–7.04]). Disease severity was generally low, with only one ICU admission and five deaths. Males with MS had higher incidence rates and risk of hospitalization than females. No association was found between the use of any disease-modifying therapy (DMT) and hospitalization risk.

Conclusions

Patients with MS do not appear to have greater risks of SARS-CoV-2 infection or severe COVID-19 outcomes compared with the general population. The decision to start or continue DMT should be based on a careful risk-benefit assessment.

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Disease Modifying Therapies – Risk Management Poster Presentation

LB1167 - Reported Covid19 symptoms in patients on oral Disease Modifying Treatmentss (DMTs) at a single centre (ID 1493)

Presentation Number
LB1167
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

There is concern amongst the MS community regarding increased risk of COVID-19 infection in patients on Disease Modifying Therapies (DMTs). Guidance from the Association of British Neurologists (ABN) recommends to continue most oral DMTs during the pandemic.

Objectives

To identify number of patients on oral DMTs in a single centre who reported COVID-19 symptoms. To identify how this compares to national infection rate, whether there was a link to lymphocyte counts prior to infection and how many patients stopped or interrupted treatment.

Methods

Patients on oral DMTs (dimethyl fumarate (DMF), teriflunomide (TF) & fingolimod (FING)) were identified through a local database. The pharmacy team called these patients to advise on DMT monitoringduring the pandemic. Patients were also asked if they had experienced any symptoms of COVID-19 infection, had been tested, or had stopped treatment . Recent lymphocyte counts were obtained.

Results

501 patients on oral DMTs were identified (14 on TF, 169 on FING, 318 on DMF). 50% of these were contacted. (DMF=174, FING=71, TF=10). The average age of those on treatment was 45, average EDSS 2.2, and average time on DMT 3.7 years. Of those asked 90% (229) reported that they had not exprienced COVID-19 symptoms. 10% (26) reported that they had experienced COVID-19 symptoms (3 on TF, 8 on FING, 15 on DMF). According to a recent study by the UK Office of National statistics, of those individuals providing blood samples in the UK, 7% tested positive for antibodies to COVID-19. Of those who reported symptoms the last recorded lymphocyte counts were all within accepted ranges, with a mean of 1.2 (TF 2.0, DMF 1.5, FING 0.4). One patient taking DMF died due to COVID-19. Further data will be presented on the average lymphocyte counts in those who did not report symptoms, number of patients who went on to be tested for COVID-19 and the number who stopped or interrupted treatment.

Conclusions

Results present real world data on COVID-19 infection in patients on oral DMTs for MS and how these relate to lymphocyte count and infections rates in general population.

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Prognostic Factors Poster Presentation

LB1168 - COVID-19 in MS patients: susceptibility and severity risk factors (ID 1524)

Abstract

Background

In the present pandemic, gathering information regarding Multiple Sclerosis (MS) patients with COVID-19 is needed.

Objectives

To investigate the incidence of COVID-19 in a Barcelona cohort of MS patients, to describe the characteristics of MS patients with COVID-19, and to identify risk factors for susceptibility and severity.

Methods

Retrospective cohort study of adult MS patients included from February to May 2020. COVID-19 and non-affected cases were identified through a COVID-19 mail survey and clinical visits. Demographic, clinical, MS characteristics, and laboratory data (lymphocyte and CD19+ count, immunoglobulins, and vitamin D) were obtained. Serological SARS-CoV-2 testing was performed in all suspected cases. We examined the relationship between the previously mentioned variables with COVID-19 susceptibility and severity.

Results

Out of the 2903 surveys sent, a total of 875 were answered. 117 (13.37%) patients were excluded for not meeting inclusion criteria. 48 out of 758 were suspected COVID-19 and the remaining were classified as non-COVID-19. The estimated incidence was 6.3%. 45 additional suspected COVID-19 cases were detected in clinical visits. In the multivariate analysis, COVID-19 susceptibility was associated with being younger (OR 0.54, IC95% 0.34-0.87,p<0.01), having had contact with a confirmed case (OR 193.20, IC95% 55.34-674.43,p<0.01), living in Barcelona (OR 2.35, IC95% 1.08-5.09, p=0.03) and a longer MS disease duration (OR 1.43, IC95% 1.10-1.85,p<0.01). In patients treated with an anti-CD20 therapy, COVID-19 susceptibility increased with treatment duration (OR 3.36, IC95% 1.42-7.96, p<0.01). 19 (20.43%) of the 93 COVID-19 cases were hospitalized, 9(9.68%) presented a severe course and 2(2.15%) of them died. In the univariate analysis, older patients with comorbidities, a progressive and longer MS duration, and without disease-modifying therapies, presented a more severe disease although these results were not observed in the multivariate analysis. Out of the 79 (84.9%) with serological test, 45.6% had generated antibodies and 17.6% in patients receiving anti-CD20. No relation of lymphopenia, vitamin D, or immunoglobulins levels with COVID-19 susceptibility or severity was found.

Conclusions

MS patients present similar incidence, risk factors, and outcomes for COVID-19 than the general population. Patients treated with an anti-CD20 therapy for a longer period of time might be in a higher risk of COVID-19 and of generating lower antibody response.

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Neuropsychology and Cognition Poster Presentation

LB1169 - Psychological consequences of COVID-19 pandemic in Italian MS patients: a surprising resilience  (ID 1668)

Speakers
Presentation Number
LB1169
Presentation Topic
Neuropsychology and Cognition

Abstract

Background

Italy was strongly hit by COVID-19 pandemic, therefore the Italian Government decreed urgent measures promoting social distancing in order to limit the spread of the virus. In fact, since March 11th, all not indispensable work, social, sporting, retail and recreational activities were suspended or, where possible, converted to the so-called smart-working. Fear of getting sick from COVID-19, government’s lockdown and the imposed social distancing might have an impact on anxiety, depression and quality of life (QoL) in people with Multiple Sclerosis (pwMS).

Objectives

The aim of our study was to investigate anxiety, depression and QoL changes in pwMS during SARS-CoV-2 outbreak and lockdown in Italy.

Methods

Sixty-seven pwMS with a previous (less than 6 months) neuropsychological evaluation before SARS-CoV-2 outbreak (T0) were re-evaluated at the time of the outbreak and lockdown in Italy (T1). They underwent a clinical and neurological evaluation (at T0) and completed the State-Trait Anxiety Inventory (STAI-Y1), the Beck Depression Inventory second edition (BDI-II), and Multiple Sclerosis Quality of Life-54 (MsQoL-54) at T0 and T1. Bonferroni correction for multiple comparisons was applied.

Results

BDI-II and STAI-Y1 scores did not change between T0 and T1, whereas the satisfaction on sexual function subscale of MsQoL-54 was significantly higher at T1 (p<0.001).

Conclusions

Despite the tight Italian lockdown due to the COVID-19 pandemic and the fear of getting sick, we did not observe a relevant negative impact on anxiety, depression and QoL of our sample of pwMS. Contrariwise, we were even able to detect some positive effects on specific aspects of QoL, such as sexual satisfaction.

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COVID-19 Poster Presentation

LB1170 - Use of IVIG in three immunosuppressed patients hospitalized with COVID-19 (ID 1673)

Speakers
Presentation Number
LB1170
Presentation Topic
COVID-19

Abstract

Background

The use of intravenous immunoglobulin (IVIG) in patients with severe COVID-19 is currently under investigation. Preliminary data report shorter length of stay and reduced use of mechanical ventilation in patients receiving IVIG. Little is known about the safety and effectiveness of IVIG in an immunosuppressed population with COVID-19.

Objectives

We will describe the use of IVIG in hospitalized patients with neuroinflammatory diseases on chronic immunotherapy presenting with SARS-CoV-2 infection.

Methods

Data was collected prospectively through direct inpatient care as well as follow up via outpatient visits and telephone calls.

Results

We treated three patients admitted to our hospital with IVIG. Patient 1 is a 30-year-old man with antibody-positive neuromyelitis optica (NMO) treated with rituximab 650mg every 3 months with undetectable CD19+ B lymphocytes who presented with multifocal pneumonia and mild hypoxia. His absolute lymphocyte count (ALC) was 600/mm3 on admission. Patient 2 is a 54-year-old woman with CNS vasculitis treated with mycophenolate mofetil 2g daily and one dose of Rituximab 1g five months prior who presented with fever, cough and pneumonia. ALC was 600/mm3. Patient 3 is a 56-year-old woman with antibody-positive NMO, autoimmune hepatitis and autoimmune myositis on mycophenolate mofetil 2.5g daily who presented with hypoxemia requiring high-flow nasal cannula. ALC was 700/mm3. Immunotherapy was held on admission for all patients. They were given 0.4g/kg IVIG (Gammagard) daily for 5 days and prophylactic enoxaparin. IVIG was initiated on days 5, 4 and 3; patients were discharged on days 16, 10 and 17, respectively. The first patient was diagnosed with COVID-19 clinically with later positive antibody testing to SARS-CoV2; the second two were diagnosed via SARS-CoV2 RT-PCR. All patients made a complete recovery without relapse of neuroinflammatory disease.

Conclusions

All three patients had grade II lymphopenia on admission, which is known to be a marker of poor prognosis in COVID-19. None of our patients required intubation nor had side effects from IVIG. The use of IVIG may have prevented relapse provoked by viral illness as well as hastened recovery. Mechanisms of IVIG effect on coronavirus may be governed by sialosides on IgG serving as decoy receptors for the virus or IgG binding to sialosides on the viral surface and preventing viral attachment and fusion. IVIG may prevent an excessive inflammatory response by minimizing the release of pro-inflammatory cytokines and chemokines. Clinicians should carefully consider the risk and benefits when administering IVIG to a patient with SARS-CoV2. Finally, research on how lymphopenia affects outcomes of COVID-19 infection in immunosuppressed patients is warranted.

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Neuropsychology and Cognition Poster Presentation

LB1171 - Embracing resilience in Multiple Sclerosis: a new perspective from COVID-19 pandemic. (ID 1742)

Speakers
Presentation Number
LB1171
Presentation Topic
Neuropsychology and Cognition

Abstract

Background

Coronavirus Disease 2019 (COVID-19), a severe acute respiratory syndrome due to Coronavirus 2 (SARS-CoV-2) infection, determined cross-sectional social and emotive consequences, representing an unprecedented social experiment. Past epidemiological experiences and recent studies dealing with COVID-19 pandemic and healthy population already showed the deep albeit heterogeneous psychological repercussions of pandemics. Nevertheless, little is known about the relationship between COVID-19 outbreak and patients with chronic diseases, Multiple Sclerosis (MS) in particular, and about the possible strategies for boosting resilience, a well-known protective and buffering instrument helping in facing the challenges of life.

Objectives

To assess the changes in mental distress during COVID-19 outbreak in patients with MS (pw-MS) and to identify predictive factors that could help in developing resilience and facing COVID-19 pandemic.

Methods

We enrolled 106 pw-MS (69 relapsing-remitting, 20 secondary-progressive and 17 primary-progressive) who had undergone neuropsychological assessment before outbreak (between January the 1st 2019 and March the 1st 2020): patients were previously tested with 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 asked to fulfill an online survey comprehensive of sociodemographic information (e.g. marital and employment status), HADS self-rating Scale, MSNQ-P Questionnaire and finally Connor-Davidson Resilience self-rating Scale (CD-RISC 25), in order to evaluate resilience. Statistical analyses (repeated-measures ANCOVA) were performed using SPSS 23.

Results

Even if no significant changes in HADS and MSNQ-P scores were detected during COVID-19 pandemic in our population, pre-existing lower HADS and MSNQ-P scores were found to be significantly (p<0.0001) and independently associated with a better resilience attitude; conversely, no demographic, disease- and treatment-related elements resulted predictive neither of anxiety, depression and perceived cognitive status nor of better resilient behaviour

Conclusions

Our study confirms the fundamental role of anxiety diagnosis and of neuropsychological evaluation in pw-MS, outlining its compelling role in predicting a resilient and positive response in case of pervasive commitment and the necessity of a comprehensive care for pw-MS.

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Internet and Social Media Poster Presentation

LB1172 - MS and COVID-19: A Webinar Series for Healthcare Providers (ID 1746)

Speakers
Presentation Number
LB1172
Presentation Topic
Internet and Social Media

Abstract

Background

Background: MS is a complex disease that requires a well- educated workforce. The COVID-19 pandemic added to that complexity- from the lack of knowledge of viral behavior, to the possible impact of disease modifying therapy on the susceptibility of contracting COVID-19, to the prognosis of MS patients with COVID-19. To help meet the educational needs of MS healthcare professionals during the unprecedented pandemic, the National MS Society (NMSS) and the Consortium of MS Centers (CMSC) collaborated to develop a professional educational program to provide emerging, evidence-based information on MS and COVID-19.

Objectives

Objectives: Participants will 1) have easy access to emerging, evidence-based content on COVID-19 and the impact on people living with MS, 2) gain knowledge about MS and COVID-19.

Methods

Methods: An educational program entitled MS and COVID-19: A Webinar for Healthcare Providers was initiated on March 19, 2020. The series has consisted of 1-hour webinars (six as of July 1) on topics identified by healthcare providers including: overview of COVID-19; infection risk for people living with MS; impact of disease modifying therapies on infection and prognosis of MS patients; and outcomes from the COViMS data registry. Each webinar included a 50-minute town-hall style presentation based upon questions submitted by webinar registrants followed by a 10-minute facilitated question and answer session. Participants had the option to attend a live webinar or view a recorded presentation. Following the live webinars, all registrants were sent a link to the webinar recording and a program evaluation survey.

Results

Results: As of July 1, 2020, 4,763 healthcare providers attended the live or recorded webinars and 273 responded to the program evaluation survey which included topic specific and non-topic related survey questions. Survey results indicated 78% of respondents reported improved knowledge of COVID-19 and 73% reported improved confidence in discussing COVID-19 with their MS patients. Additionally, 72% reported they planned to make a change in their practice as a result of webinar participation and 86% would recommend the National MS Society to a colleague.

Conclusions

Conclusions: The MS and COVID-19 webinar series is an important collaborative effort between the NMSS and CMSC, engaging a wide variety of healthcare providers including pioneers in specialized MS care, and introduced the MS community to providers and researchers at the forefront of COVID research and care. The series provided healthcare providers with timely, free, and easily accessible professional education in a time of crisis. Survey results indicate that the webinar provided much needed information on COVID-19 and its impact on patients living with MS to participants.

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Disease Modifying Therapies – Mechanism of Action Poster Presentation

LB1174 - Patient and healthcare professional perspectives of immune dynamics and MS disease-modifying therapies mode of action throughout COVID-19 pandemic   (ID 1766)

Speakers
Presentation Number
LB1174
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

Disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) modulate or deplete immune cells, including T and B cells. Healthcare professionals (HCPs) and patients consider many factors when selecting a DMT in a shared decision model, including efficacy, frequency/route of administration and safety. Patient understanding of mechanisms of action (MoA), and DMT effects on the dynamics and function of the immune system may be challenging to understand and further influenced by the COVID-19 pandemic, including risk interpretation and administration preferences.

Objectives

To assess the involvement of patients in MS treatment selection and the importance for patient understanding of MoA using a patient narrative approach, and to design a preliminary qualitative survey to inform future studies.

Methods

A preliminary qualitative survey was developed to explore factors most important to patients when considering DMTs, including patient understanding of immunological aspects of MS, MoAs, preferences regarding route of administration and provision of MS clinical information. Perspectives were sought from HCPs and patients on how this dialog has changed during the COVID-19 pandemic. The survey was distributed by email to 3 patients and 1 caregiver.

Results

Results are based on survey results and email correspondence from two adults with RMS, and an adolescent with pediatric MS and her caregiver. Overall, respondents felt they understood the general role of the immune system in MS and the role of DMTs but had poorer understanding of B and T cell functions and the impact of DMTs and their MoAs. Safety and efficacy were equally the most important variables when considering a new DMT. Face-to-face discussions between patients and HCPs were preferred to noninteractive materials; HCP authors (3 neurologists and 1 MS physician assistant) agreed that more face-to-face clinic time for dialog is needed. Patient independence was a key factor in preferences for methods of administration. Respondents reported an increase in MoA conversations in light of COVID-19.

Conclusions

While safety and efficacy are important in patients’ considerations of DMTs, there is a clear need to increase understanding of MoAs when starting or switching DMTs; immunological knowledge has become increasingly important during the COVID-19 pandemic. The preliminary qualitative survey can be used to inform future studies of what is needed to improve communication on DMT MoAs.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

LB1175 - Multiple Sclerosis patients and disease management during COVID-19 Pandemics (ID 1785)

Speakers
Presentation Number
LB1175
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Multiple Sclerosis (MS) is a chronic disease that encompasses lifelong symptoms and both physical and psychological disability. The COVID-19 pandemic may have changed the way patients accessed Health Care facilities, with an impact on their perceived health status and psychological well-being.

Objectives

To evaluate physical disability and psychosocial well-being since the announcement of the state of emergency, due to COVID-19 pandemic, by the Portuguese government.

Methods

We performed an online questionnaire-based study; 485 adult patients followed in our tertiary centre with the diagnosis of MS were invited to answer the survey that was accessible from April to June 2020. We analysed data regarding disability (self-reported EDSS), mental status, fatigue and sleep through scales validated for the Portuguese population: suffering thermometer, Depression Anxiety Stress Scales-21 (DASS-21) (answered when suffering thermometer scored more than 5), Modified Fatigue Impact Scale (MFIS-21) and Satisfaction Alerteness Timing Efficiency Duration (SATED) sleep scale.

Results

We included 195 valid questionnaires from 195 patients. Fifty-four percent had a university degree (53.8%) and approximately half of the patients were professionally active. Self-reported EDSS presented a positive correlation with last EDSS measured by the neurologist (p<0.01, R2=0.68). Median (IQR) DASS-21 was 18 (12-25), MFIS-21 was 31 (17-49) and SATED 20 (16-24). Emotional suffering was equal or greater than 5/10 in 31% during the state of emergency and in 53% at the time of survey response. A third of patients reported lower quality of sleep due to COVID-19 and higher fatigue. A quarter of patients reported more pain and 30% reported more spasticity.

Patients who had a self-reported EDSS worse than the last EDSS measured by the neurologist had significantly worse performance in MFIS (p<.001) and SATED (p=.007), while no differences were observed for DASS-21 (p=.36). Patients who said that were feeling worse since COVID-19 pandemics also had worse performance in MFIS-21 (p<.001) and SATED (p=.028), while this was not observed for DASS-21 (p=0.26).

Conclusions

We conclude that the COVID-19 pandemic impacted the physical and psychological well-being of MS patients. Patients who felt more disabled scored significantly higher in fatigue and sleep quality measures. In-person follow-up is needed to confirm the patient-reported disability worsening.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

LB1176 - Anxiety affects the general well-being of people with MS during the COVID-19 pandemic more than the infection itself (ID 1893)

Speakers
Presentation Number
LB1176
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Anxiety and depression are more common in people with multiple sclerosis (pwMS) compared to people without MS. The unpredictable nature of the COVID-19 pandemic has caused widespread distress, but it is unknown if it would affect pwMS disproportionately.

Objectives

To evaluate the impact of the COVID-19 pandemic on the mood and well-being of pwMS in the UK and compare it to that of controls.

Methods

The UK MS Register has been collecting Hospital Anxiety and Depression Scale (HADS) data of pwMS since 2011. In the mood and well-being UKMSR COVID-19 study, we asked pwMS (n=5240) and controls (n=376) to answer questions on General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) for depression and Revised Impact of Event Scale (IES-R) for post-traumatic stress disorder (PTSD) in addition to changes in their lifestyle and well-being during the COVID-19 outbreak.

Results

The HADS score of pwMS (n=2225) during the COVID-19 outbreak had not changed compared to the year before (mean difference 0.004, 95%CI -0.11−0.12, p=0.952 for anxiety and mean difference 0.05, 95%CI -0.05−0.15, p=0.283 for depression). The rate of anxiety (GAD-7>5) in male pwMS (37.2%) was more than controls (24.3%) (p=0.032) but was similar in female pwMS and controls. More male pwMS had moderate to severe depression (PHQ-9>9) compared to controls (28.5.4% vs 12.2%, p=0.003), but again, the rate was similar in females. More pwMS who had COVID-19, experienced anxiety or PTSD (IES-R>32) compared to those without the infection (54% vs 44%, p=0.018; 30.5% vs 22.5%, p=0.024, respectively). The rate of depression was similar in pwMS with or without symptoms of the disease. Anxiety, compared to the actual infection, was more strongly associated with subjective worsening of general health (57.1% vs 37.3%, with anxiety or COVID-19 respectively, p=0.008) or MS symptoms (61% vs 31.3%, p<0.001).

A high proportion of both pwMS and controls did not experience any change in the quality of their relationships. However, more pwMS reported worsening of their relationships compared to controls (21.4% vs 16.7%, p<0.001). The change in loneliness was similar between the two groups with 4 in 10 pwMS and controls feeling lonelier during the outbreak.

Conclusions

Anxiety during the COVID-19 pandemic is having a more profound effect on the general well-being of most patients compared to the infection itself.

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Imaging Late Breaking Abstracts

LB1177 - PAMRINO: International MRI and clinical data repository for neuromyelitis optica spectrum disorder (ID 469)

Abstract

Background

Neuromyelitis optica spectrum disorders (NMOSD) encompasses a group of rare inflammatory diseases which primarily target the optic nerves, spinal cord, and brain. Typically, magnetic resonance imaging (MRI) data from single-center studies comprise 20-50 patients, limiting statistical power for outcomes research. Using retrospective data from the PArallel MRI in NmOsd (PAMRINO) study, a novel prospective NMOSD image repository (NMOsDIR) representing multiple international sites was coordinated by Charité-Universitätsmedizin Berlin and the Medical Image Analysis Center (Basel).

Objectives

The PAMRINO study aimed to investigate and analyze retrospective MRIs collected from NMOSD-specialized centers, potentially for the evaluation of disease-related brain and spinal cord changes. NMOsDIR serves as an international imaging research resource (comprising standardized retinal optical coherence tomography and MRI scans) and clinical data hub for prospective studies in NMOSD. Linking imaging and clinical data, as well as enabling analysis pipelines for each modality, will facilitate multi-centered studies using sufficient data and statistical power to advance outcomes research in this rare disease.

Methods

For clinical data collection in PAMRINO, a Research Electronic Data Capture (REDCap) platform was used, where participating centers entered data relevant for NMOSD patient monitoring. An image database (XNAT) was established for image uploads. This large collection of MRI data is currently being analyzed in a joint international effort of NMOSD clinical neuroradiologists and scientists.

Results

Brain, spinal cord, and optic nerve MRI scans with associated clinical data were collected from 514 NMOSD patients and 56 healthy controls from 17 international centers. Roughly 20,000 individual MRI scans from patients and healthy controls were collected. Of these, 78% had T1-weighted cerebral MRIs (55% with 3D scans), 80% had T2-weighted cerebral MRIs (54% with 3D scans), 86% had T2-weighted spinal cord MRIs (55% with 3D scans), and 35% had optic nerve MRIs.

Conclusions

We successfully established PAMRINO, an international collaborative retrospective MRI and clinical data repository. The knowledge gained during this process provided important new insights, where the initial analysis of the dataset has underscored the large degree of heterogeneity in image and clinical data collection in NMOSD-specialized centers. Thus, calling for more standardized methods of data acquisition and imaging analysis, as not to limit research opportunities. The new longitudinal, prospective NMOsDIR will help us to answer many pressing - yet open - questions regarding patients seropositive for aquaporin-4-IgG+, myelin oligodendrocyte glycoprotein-IgG+ and other autoimmune-related diseases. In turn, such a strategy will strengthen future capabilities in research, diagnosis, monitoring and improving NMOSD patient care.

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Biomarkers and Bioinformatics Late Breaking Abstracts

LB1178 - Monitoring of blood neurofilaments improves stratification of disease activity in multiple sclerosis (ID 1322)

Speakers
Presentation Number
LB1178
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

The concept of no evidence of disease activity-3 (absence of brain MRI and clinical disease activity; NEDA-3) in multiple sclerosis (MS) reflects disease activity with limited sensitivity. The added value of neurofilament light chain levels in serum (sNfL) to NEDA-3 has not yet been investigated.

Objectives

To assess whether sNfL allows to identify among patients with and without NEDA-3 status those at higher risk of future disease activity and accelerated brain volume loss.

Methods

We analyzed 369 samples from 155 early relapsing-remitting MS patients (SET study). sNfL levels and brain MRI scans were evaluated annually. The comparison of subgroups defined by high or low sNfL (>90th or <90th percentile of healthy controls of the same age) and NEDA-3 status was performed by generalized estimating equation models. Changes in global and regional brain volumes were calculated on three-dimensional T1-weighted scans.

Results

Patients with disease activity (EDA-3) in the preceding year and high sNfL, compared to those with low sNfL, had: a) higher odds of EDA-3 in the following year (87% versus 58%; OR 4.39, 95%-CI:2.18, 8.94; p<0.001), b) greater whole brain volume loss during the following year (0.39%, 95%-CI:-0.63, -0.16; p<0.001) and c) greater whole brain volume loss (0.61%, 95%-CI:-0.66, -0.17; p<0.001) during the preceding year. Accordingly, NEDA-3 patients with high sNfL showed a trend for a return of disease activity (EDA-3) in the following year compared with those with low sNfL (57% versus 31%).

Conclusions

High sNfL levels are associated with increased future risk of disease activity and accelerated brain volume loss. Adding of sNfL improves the prognostic value of the NEDA-3 concept.

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Prognostic Factors Late Breaking Abstracts

LB1179 - Predictors of Disease Modifying Treatment Failure Amongst Neuromyelitis Optica Spectrum Disorder Patients, Stratified by Antibody Serostatus (ID 1947)

Speakers
Presentation Number
LB1179
Presentation Topic
Prognostic Factors

Abstract

Background

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare autoimmune disease characterized by demyelination and axonal injury of the central nervous system. Serologic classification for aquaporin-4 immunoglobulin G (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) can be useful and have been associated with diverse outcomes.

Objectives

To characterize NMOSD stratified by antibody serostatus (AQP4-IgG antibody positive, MOG-IgG antibody negative, and APQ4-IgG/MOG-IgG double negative) and evaluate predictors of disability outcomes.

Methods

This was a retrospective, single center study of 75 patients meeting NMOSD 2015 criteria who are seen and followed at a single center. AQP4-IgG and MOG-IgG antibodies were tested. The relationship between antibody status (AQP4-IgG+, MOG-IgG+) and double seronegative (DNeg) and DMT failure and Expanded Disability Status Scale (EDSS) was tested using multivariate linear regression (adjusted for age of onset, sex, race/ethnicity). DMT failure was defined as having to switch due to breakthrough disease on current DMT.

Results

Most were female (76.7%), Hispanic (62.7%), with a median age of onset of 39.0 (SD±13.9) and disease duration of 8.0 (SD±7.5). More than 2/3 (69%) were on rituximab. Presentation with optic neuritis or myelitis varied by seropositive types (P-value<0.05). APQ4-IgG+ presented more likely with optic neuritis (44.5%) while DNeg were more likely to present with myelitis (87%). Disability also differed significantly between the groups (p-value<0.05). About 40% of AQP4IgG+ and DNeg patients had EDSS>=4 while all MOG-IgG patients had EDSS<4. Greater odds of DMT failure was observed with being MOG-IgG+ (OR 2.9 95% CI 0.86-10.22) compared to AQP4-IgG+. After controlling for age, sex, age at onset and DMT failure, MOG-IgG+ patients had lower disability (mean EDSS:1.6, p-value<0.01) compared to AQP4-IgG+ and DNeg patients (mean EDSS:3.6).

Conclusions

In this predominant Hispanic sample of NMOSD, we confirm that MOG-IgG+ serostatus is an important biomarker of treatment failure. Treatment approaches specific to NMOSD MOG-IgG+ are warranted.

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COVID-19 Late Breaking Abstracts

LB1181 - COVID-19 Outcomes among patients with Multiple Sclerosis: Experience from RWJBH Multiple Sclerosis Comprehensive Care Center (ID 1965)

Speakers
Presentation Number
LB1181
Presentation Topic
COVID-19

Abstract

Background

COVID-19 is a pandemic caused by the novel coronavirus, SARS-CoV-2. Disease-modifying therapies (DMTs) used to treat Multiple Sclerosis (MS) act primarily by altering the immune system. While many DMTs have well understood mechanisms of action, the consequences of immunomodulation in the setting of exposure to a novel viral pathogen were largely unknown until recently.

Objectives

Analyze clinical outcomes and risk of treatment with DMTs among patients with MS and related disorders who contracted COVID-19.

Methods

From March 10to July 1st, 2020, patients with MS and related disorders at RWJBH MS Comprehensive Care Center (MSCCC) with laboratory-confirmed COVID-19 were identified. The diagnosis was established through the nurse triage telephone line, telehealth visits with physicians, and review of medical records with subsequent clinical follow up.

Results

We identified 25 patients (13 with relapsing MS; 11 with progressive MS; and 1 with Neuromyelitis Optica Spectrum Disorder (NMOSD)) with laboratory-confirmed COVID19, either polymerase chain reaction (PCR) or serologic testing for SARS-CoV-2 antibodies. Of the entire cohort, 23 (92%) were on DMTs, with the majority on either anti-CD20 monoclonal therapies 10/25 (40%) or dimethyl fumarate 7/25 (28%). A total of 21 (84%) are fully recovered or recovering; 1 (4%) never developed symptoms; 8 (32%) required hospitalization; and 3 (12%) are deceased. Among those hospitalized, 5/8 (62.5%) were on anti-CD20 therapies. While the majority of our sample of MS patients had relapsing MS 13/24 (54.2%), the majority of hospitalized patients had progressive MS 5/8 (62.5.8%). Among the cohort, 9/25 (36%) were tested for anti-SARS-CoV-2 antibodies, 8/9 (88.9%) had detectable antibodies while 1/9 (11.1%) did not, likely as a consequence of peripheral B lymphocyte depletion.

Conclusions

Although nearly all patients at our MS center who contracted COVID-19 were on DMTs, most did not require hospitalization. According to June 2020 data from the Centers for Disease Control and Prevention (CDC), 14% of patients with COVID-19 in the US required hospitalization, and 5% died. While the proportion of patients on DMT requiring hospitalization was higher than that reported for the general population, the mortality rate was similar.

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COVID-19 Late Breaking Abstracts

LB1182 - Multiple Sclerosis and the psychological impact of COVID-19  (ID 1969)

Presentation Number
LB1182
Presentation Topic
COVID-19

Abstract

Background

Heightened anxiety is often reported during a pandemic and this has featured widely during the recent COVID-19 pandemic. People with MS are known to experience higher levels of anxiety than any other population and pandemic situations could potentially heighten this experience due to factors such as interrupted treatment and impact on relationships crucial to effective MS care. Recent research examining the impact of COVID-19 on psychological wellbeing in people with MS noted the contrary to be the case, that no changes were experienced on the most part, and that some people even experienced improved wellbeing.

Objectives

This study sought to examine the overall impact of the COVID-19 pandemic on people with MS and to better understand the patient perspective.

Methods

A global sample of 300 people with MS were surveyed online during the COVID-19 key lockdown period between the months of April to June 2020. Participants were asked to indicate whether the main impact of the COVID-19 situation had been positive, negative or neutral for them. They were also asked to explain the thinking behind their response. A thematic analysis was carried out on this data.

Results

Overall, across all MS participants, the most commonly reported experience related to worries and anxiety. Nevertheless, the majority of people in the sample reported a neutral impact of the COVID-19 pandemic. This was followed by a negative impact being reported, and a positive impact was the least commonly reported. Where participants cited a positive impact, their explanation centred around finding some benefit in the situation. This was lacking for those who reported a negative impact, and an over-riding sense of anxiety and worry for themselves or others prevailed. Of those who reported a neutral impact, some indicated there was no real change in their current situation, and others cited a mixture of both positive and negative factors.

Conclusions

While the COVID-19 pandemic generated worrying and anxious thoughts in MS patients, there was still considerable variability in the overall perceived impact, suggesting that coping strategies might be particularly relevant.

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Neuro-Ophthalmology Late Breaking Abstracts

LB1183 - Utilizing Optical Coherence Tomography to Assess the Gender Role on Retinal Structures in Patients with Early MS (ID 1973)

Speakers
Presentation Number
LB1183
Presentation Topic
Neuro-Ophthalmology

Abstract

Background

Optical Coherence Tomography (OCT) is a fast, non-invasive tool utilized to quantify retinal thickness and volume. It is thought that men experience a more aggressive course of MS than women with faster accumulation of disability.

Objectives

To compare the gender influence on retinal volumes and thickness of patients in the early stages of multiple sclerosis (MS).

Methods

Sixty patients in the early stages of MS (≤3 years since symptom onset) underwent OCT exams and were included in this single-center, retrospective, cross-sectional analysis. Patients were divided into 2 groups: 22 men (mean age±SD: 39.95±10.95; mean disease duration±SD: 0.98±1.15) and 38 women (mean age±SD: 38.21±11.52; mean disease duration±SD: 1.45±0.97). All OCT scans were performed to quantify peripapillary retinal nerve fiber layer (pRNFL) thickness. The pRNFL was then separated into four quadrants: superior (S), inferior (I), nasal (N), and temporal (T). Fully automated, intra-retinal segmentation was performed to measure the volume of the macula: total macular (TMV), retinal nerve fiber (RNFL), ganglion cell + inner plexiform (GCIP), and photoreceptor (PR). A multiple analysis of covariance (MANCOVA) with gender as the independent variable and OCT parameters as dependent variables was used to analyze our data. Age and disease duration were included as covariates (SPSS v26).

Results

TMV and PR retinal volumes were found to be statistically lower in women than men (p=0.042 and 0.008 respectively). RNFL volume was trending lower in women than men, but did not reach significance (p=0.090). There was no significance noted in the other retinal volumes or thickness between the two groups.

Conclusions

Our results indicate there may be more prominent retinal volume loss in women than men in the early stages of MS. OCT should be utilized as a surrogate tool to monitor early disease progression, especially in the female population. Future longitudinal studies with larger samples should be conducted to confirm these findings.

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Machine Learning/Network Science Late Breaking Abstracts

LB1184 - Molecular models of multiple sclerosis severity identify heterogeneity of pathogenic mechanisms (ID 1974)

Speakers
Presentation Number
LB1184
Presentation Topic
Machine Learning/Network Science

Abstract

Background

New drug development and clinical management of patients with chronic, polygenic diseases, such as Multiple Sclerosis (MS), are suboptimal due to our inability to measure putative pathogenic processes contributing to destruction of the central nervous system (CNS). While blood is an excellent source of biomarkers used in clinical practice for management of e.g., cardiovascular disease, cerebrospinal fluid (CSF) represents a biological fluid that bring us as close to the CNS tissue in living patients as possible. Therefore, CNS-specific biomarkers in CSF could provide an insight into pathogenic mechanisms underlying disease expression in patients, its temporal distribution, intra-individual heterogeneity, and ultimately lead to precision medicine-based polypharmacy regimens.

Objectives

We sought to determine if CSF biomarkers can be aggregated to predict future rates of MS progression and provide molecular insight into mechanisms of CNS destruction and repair.

Methods

Using DNA-based SOMAscan technology we blindly measured 1,305 CSF biomarkers in longitudinal CSF samples of untreated MS patients divided into training (N=129) and validation (N=64) cohorts. We used machine learning algorithms in the training cohort to generate models of MS severity while the independent validation cohort samples were used to assess the predictive power of the models.

Results

CSF biomarker-based random forest models, validated in an independent longitudinal cohort, were able to predict reliably future rates of disability progression in MS patients. We were able to rule out the hypothesis that neuro-degenerative aspects of MS represent “accelerated aging” and instead defined, on a molecular level, mechanisms that correlate with how fast MS patients lose central nervous system (CNS) tissue, reflected by volumetric brain imaging and by clinical disability outcomes.

Conclusions

Cluster analysis of identified biomarkers revealed intra-individual molecular heterogeneity of disease mechanisms that include both CNS- and immune-related pathways and may represent novel targets for drug development and personalized treatments that would inhibit MS progression.

Acknowledgments: The research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID).

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Observational Studies Late Breaking Abstracts

LB1185 - Real-world experience with Ocrelizumab in the German NeuroTransData Registry (ID 1978)

Speakers
Presentation Number
LB1185
Presentation Topic
Observational Studies

Abstract

Background

Ocrelizumab (OCR) is approved for the treatment of relapsing and primary progressive forms of multiple sclerosis (MS).

Objectives

In a real-world setting, to describe 1) baseline characteristics of patients with MS treated with OCR, 2) treatment pathway across lines of therapy up to initiation of OCR, and 3) initial clinical experience.

Methods

This analysis included adult patients with MS from the German NeuroTransData (NTD) Registry, a network of 66 neurology outpatient services across Germany. Patients were treated with OCR between January 2018 and January 2020. Descriptive statistics were used to analyze baseline patient characteristics recorded within 3 months prior to or at time of OCR initiation. Occurrence of relapse was analyzed in relapse-remitting MS (RRMS) patients with ≥3 months follow-up data from OCR initiation.

Results

As of January 2020, the NTD registry included 439 patients treated with OCR, including 352 patients with RRMS, 35 with relapsing secondary progressive MS (rSPMS), and 52 with primary progressive MS (PPMS). Median age at OCR initiation varied from 41.7 years, 54.5 years, to 52.5 years in patients with RRMS, rSPMS, and PPMS, respectively. Most RRMS and rSPMS patients were female (64.8% and 54.3%) compared to PPMS patients (46.2%). Median disease duration from symptom onset up to OCR initiation was longer in rSPMS patients (14.9 years) than in RRMS (10.8 years) and PPMS (5.7 years). Median EDSS at OCR start was 2.5, 6.0, and 4.0 in the RRMS, rSPMS, and PPMS cohorts, respectively. OCR was initiated as first disease modifying therapy (DMT) therapy in 12.2%, 11.4%, and 71.2% of RRMS, rSPMS, and PPMS patients, respectively. 258 RRMS patients directly switched from another DMT, primarily from fingolimod (23.3%) and natalizumab (19.8%). 319 patients with RRMS had ≥3 months follow-up during OCR exposure; of these, 283 remained relapse free (88.7%; 95% CI 84.9, 91.8) within a median follow-up time of 1 year (Q1-Q3, 0.6-1.3 years). Annualized relapse rate was 0.13 (95 % CI 0.09, 0.16).

Conclusions

In this German outpatient real world cohort, RRMS and rSPMS patients treated with OCR, on average had a disease duration ≥10 years and already reached a moderate to severe disability status. Most patients received previous DMT and OCR was initiated most frequently as second line treatment. Although PPMS patients showed a shorter disease duration, the disability status was relatively severe. Only about one third of patients received previous DMT.

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Neuroprotection, Regeneration and/or Remyelination Late Breaking Abstracts

LB1186 - Investigating fractalkine as a potential remyelination therapy in the cuprizone MS mouse model (ID 1983)

Presentation Number
LB1186
Presentation Topic
Neuroprotection, Regeneration and/or Remyelination

Abstract

Background

We have previously discovered that a certain type of neurons, inhibitory interneurons, secrete cytokine fractalkine (FKN), which regulates oligodendrocyte formation from embryonic cortical oligodendrocyte precursor cells (OPCs) during brain development (Voronova et al. 2017 Neuron).

Objectives

Here, we aimed to analyze whether administration of exogenous FKN after demyelination injury may engage OPCs to enhance remyelination in the adult mouse brain.

Methods

We utilized single-cell RNA fluorescent in situ hybridization (RNA scope) to detect FKN receptor CX3CR1 expression in demyelinated murine brain. We also injected FKN directly conjugated to fluorophore Alexa-647 (FKN-647) to identify which cell types bind FKN in vivo. We then infused FKN into the lateral ventricle of cuprizone-demyelinated brains to test the effect of exogenous FKN infusion on remyelination. To determine the mechanism of FKN-mediated remyelination, murine primary microglia-free OPCs or isolated microglia were incubated in the presence of vehicle-control or FKN and analyzed for differences in proliferation, differentiation, survival, migration, and/or phagocytosis. Finally, to determine if FKN signalling is necessary for oligodendrocyte genesis, microglia-free OPCs were incubated in the presence of FKN or CX3CR1 function blocking antibodies.

Results

We show that FKN receptor Cx3cr1 mRNA is expressed in OPCs in the adult demyelinated brain, in addition to microglia; moreover, FKN-647 injected into the lateral ventricle of the adult murine brain diffuses into the tissue and binds OPCs and microglia. Our initial data suggest FKN infusion into cuprizone demyelinated brains may increase formation of new oligodendrocytes in vivo in both male and female brains. Microglia-free OPC culture experiments demonstrate FKN signalling is sufficient for OPC migration and survival and necessary for oligodendrocyte differentiation. Finally, exogenous FKN may increase myelin debris phagocytosis by both OPCs and microglia. We are currently investigating how FKN affects microglia-OPC cell-to-cell communication during remyelination.

Conclusions

Our studies address the exciting possibility of remyelination therapies in MS using the candidate therapeutic FKN, and reveal FKN may directly regulate OPC function for enhanced remyelination in a demyelinated brain.

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Prognostic Factors Late Breaking Abstracts

LB1187 - Evaluation of multiple sclerosis progression with clinic parameters in Tomsk Region, Russian Federation (ID 1986)

Speakers
Presentation Number
LB1187
Presentation Topic
Prognostic Factors

Abstract

Background

Progression of multiple sclerosis (MS) is a low modified process. An effective way to prevent MS progression is to choose an appropriate disease modified treatment (DMT), but there is no evidence-based approach to using non-drug methods. Mostly it is connected with high life quality in MS patients, which approve the ability to change twenty- or thirty- years prognosis for MS patients. In that way, the investigation of MS progression becomes is a scientific and clinical trend.

Objectives

The study aims to evaluate MS progression in different duration and disease activity with the use of clinic parameters.

Methods

In this observational study, 13 MS patients (female n=8, male n=5) with a relapse-remitting course (RRMS) participated. The average age was 33±5 [21-44] years, and the MS duration median was 4,7 (2,8; 6,9). Participants were evaluated with Montreal Cognitive Assessment (MoCa); the median was 26 (22; 26). Also, MS duration, age of MS debut, the annual average frequency of relapses, rate of progression (score of expanded disability status (EDSS)/ MS duration), annual average cognitive loss (level of deficit in MoCa/ MS duration). Spearman coefficient was used for statistical analysis of correlation.

Results

There were found statistical significant correlation between rate of MS progression and disease duration (p=0,001; k=-0,809), number of relapses (p<0,001; k=-0,827). A positive correlation was found between the MS progression rate and annual average rate of cognitive loss (p=0,011; 0,676).

Conclusions

The results show that the rate of MS progression decreases due to an increase in the MS duration and the number of relapses. At the moment of this study, seven patients have taken DMT. It influences the results because an increase in MS duration will lead to an increased chance of DMT taking. It is interesting to note that the linear correlation between the rate of MS progression and annual average cognitive loss was found in patients with the MS duration ranging from one year. In that way, the rate of cognitive loss correlates with the rate of MS progression and are existing at the early stages of RRMS. The theory of «cognitive reserve» and «brain reserve» can help understand the probability of cognitive and motor deficit management by non-drug measures for modifiable risk factors.

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COVID-19 Late Breaking Abstracts

LB1188 - Epidemiology of COVID-19 among persons with neuroimmunological disorders at the Columbia University MS Center in New York City (ID 1987)

Speakers
Presentation Number
LB1188
Presentation Topic
COVID-19

Abstract

Background

The 2019 coronavirus (COVID19) is a novel infectious entity that has incited a global pandemic. Most infected patients experience mild to moderate upper respiratory symptoms but up to 20% have severe pulmonary and multisystem organ involvement. Few studies have assessed the risk for severe COVID19 infection among persons with multiple sclerosis (MS) or other neuroimmunological disorders, many of whom are treated with disease-modifying therapy (DMT).

Objectives

To describe the baseline clinico-sociodemographic characteristics and recent COVID19 epidemiology of patients managed at our center.

Methods

The electronic medical record was queried for patients evaluated at our center with at least two clinical visits within the past 2 years from censure date 1 March 2020. Variables of interest were collected from 1 March to 31 July 2020, and descriptive statistics were obtained.

Results

717 patients were included in the study, comprising 90.7% MS, 5.6% neuromyelitis optica spectrum disorder (NMOSD), 2.0% autoimmune encephalitis (AE), and 1.7% other neuroinflammatory. Median age was 43 (range 14-80), and 69.5% were women. The most commonly reported race and ethnic identities were 14.8% Black, 50.9% Caucasian, and 16.2% Hispanic. The most frequent DMT regimens were anti-CD20 therapy (38.5% ocrelizumab [OCV], 19.8% rituximab [RTX]), dimethyl fumarate (9.8%), and no DMT (8.9%). We found a 9.9% (n=71) report rate of symptoms suspicious for COVID19 of whom 37% (n=26) had confirmatory viral PCR testing. Two subgroups were compared: COVID19 asymptomatic (n=79) and COVID19 symptomatic PCR confirmed. PCR confirmed cases had statistically significant higher rates of Black race (26.9%, p=0.000), Hispanic ethnicity (26.9%, p=0.042), and multiple medical co-morbidities (42%, p=0.002). Most COVID19 symptomatic patients were managed at home (86%). Serious COVID19 infection necessitating hospitalization occurred rarely in patients treated on glatiramer acetate (1), natalizumab (1), OCV (3), or RTX (5). Of those hospitalized (n=10), 4 were admitted to ICU and 5 died (3 MS, 1 NMOSD, 1 AE).

Conclusions

Among a diverse population of patients with neuroimmunological disorders on various DMT regimens residing in one of the epicenters of the COVID19 pandemic, our retrospective observational study found lower rates of hospitalization and mortality compared to the general population of New York City. Significantly higher rates of Black and Hispanic patients tested positive for COVID19 compared to a subgroup who denied symptoms.

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Imaging Late Breaking Abstracts

LB1189 - Diagnostic Value of  DWI-MRI for Detecting Acute Plaqes in  Relapse Phase of  Multiple Sclerosis (ID 1988)

Speakers
Presentation Number
LB1189
Presentation Topic
Imaging

Abstract

Background

The 2010 revision of McDonald Criteria for multiple sclerosis (MS) diagnosis have established that dissemination in time (DIT) can be demonstrated by simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing plaques on a single magnetic resonance imaging (MRI). Since gadolinium contrast agents have some contraindications, Diffusion-Weighted Imaging (DWI) can confirm diffusion alterations in active inflammatory plaques in these patients.

Objectives

The purpose of this study was to investigate whether DWI can be an alternative to the contrast-enhanced T1-weighted imaging for demonstrating DIT in MS.

Methods

We recruited 30 definite MS patients with acute relapse according to 2010 revision of the McDonald Criteria and evaluated their brain MRI via DWI‚ contrast-enhanced T1-weighted imaging and FLAIR sequences. Asymptomatic plaques were defined as either hyperintense or non-hyperintense on DWI and enhancing or non-enhancing on T1GAD-MRI. The statistical indices for prediction of plaque enhancement in T1 GAD-MRI via DWI-MRI were calculated.

Results

Thirty patients with 925 demyelinating plaque that were hyperintense in FLAIR-MRI and more than 3mm in size were enrolled. The diffusion hyperintensity and plaque enhancement were significantly correlated. The sensitivity‚ specificity ‚ positive predictive value‚ negative predictive value and accuracy were 69.66%‚99.76%‚96.88%‚96.86% and 96.86% respectively.

Conclusions

Hyperintense DWI findings do not necessarily overlap with contrast enhancements in T1 GAD-MRI, so cause many false positive results. Although T1 GAD-MRI may not be replaced by DWI to demonstrate DIT criteria due to low sensitivity, DWI may surrogate as a screening imaging sequence whenever the use of T1GAD-MRI be a concern.

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COVID-19 Late Breaking Abstracts

LB1190 - The Emotional Impact of the COVID-19 Pandemic on Individuals with Progressive Multiple Sclerosis. (ID 1989)

Abstract

Background

Pre-existing chronic illness is associated with increased psychiatric distress due to the spread of COVID-19, specifically increased stress, anxiety and depression. This potentially placed individuals with MS in a uniquely vulnerable position to experience greater psychiatric symptomatology.

Objectives

To examine the impact of the COVID-19 pandemic on emotional symptomatology and quality of life in individuals with Progressive Multiple Sclerosis (PMS).

Methods

Data were obtained during a randomized clinical trial on rehabilitation taking place at 11 centers in North America and Europe (The CogEx Trial, ClinicalTrials.gov Identifier: NCT03679468). Participants included 131 individuals with PMS. Study procedures were interrupted in accordance with governmental restrictions as COVID-19 spread. During study closure, a COVID Impact Survey was administered via telephone or email to all participants, along with patient report outcome (PRO) measures of depressive and anxiety symptoms, quality of life and MS symptomatology that were previously administered pre-pandemic.

Results

The time between baseline PRO completion and lockdown survey completion varied (M=9.5 months, SD=4.1 months). 4% of respondents reported COVID-19 infection. No significant changes were noted in anxiety, quality of life, or the impact of MS symptomatology on daily life from baseline to lockdown. While total HADS depression scores increased significantly at follow up, this did not translate into more participants scoring above the HADS threshold for clinically significant depression. No significant relationships were noted between disease duration, processing speed ability or EDSS and changes in symptoms of depression or anxiety.

Most participants reported impact of the virus on their psychological well-being, with little impact on financial well-being. Perceived impact of the pandemic on physical and psychological well-being correlated significantly with the impact of MS symptomatology on daily life, as well as changes in depression.

Conclusions

Overall, in a sample confined exclusively to people with chronic progressive MS, little clinically significant change was noted in symptoms of depression or anxiety or quality of life during the pandemic lockdown.

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Patient-Reported Outcomes and Quality of Life Late Breaking Abstracts

LB1191 - Validation of the Italian version of the Multiple sclerosis intimacy and sexuality questionnaire-19 (ID 1991)

Speakers
Presentation Number
LB1191
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

People with Multiple sclerosis (MS) may experience sexual dysfunction throughout the disease course. Prevalence for sexual dysfunction in MS ranges from 70 to 90 %, higher than in healthy controls (about 50%). Clinicians do not always ask for sexual dysfunction both for the limited timeframe for clinical assessment and the intimate nature of the subject. Hence, the use of self-reported questionnaires would be useful in clinical practice. However, validated scales to assess sexual dysfunction in MS for Italian patients are lacking.

Objectives

We aimed at validating Multiple Sclerosis Intimacy and Sexuality Questionnaire (MSISQ-19) for Italian MS patients.

Methods

We included both male and female MS patients. Each patient completed the Italian translation of the MSISQ-19, the Beck Depression Inventory (BDI-II), the Modified Fatigue Impact Scale (MFIS), the State-Trait Anxiety Inventory (STAI-Y) questionnaire, the International Consultation on Incontinence Questionnaire Lower Urinary Tract Symptoms Quality of Life Module (ICIQ-LUTSqol), the Female Sexual Function Index (FSFI, for female) and the International Index of Erectile Function (IIEF for male). Construct validity for the Italian version of the MSISQ-19 was explored by the exploratory factor analysis and the Cronbach’s alpha coefficient. Test-retest stability and concurrent internal and external validity was examined by Pearson’ correlation coefficients.

Results

We enrolled 369 MS patients (323 female). Mean MSISQ-19 total score was 37.2 ± 15.2 (range 18 - 89) with a sexual dysfunction prevalence of 59% in male MS patients and 41% in female MS patients. Cronbach’s alpha was 0.92 for the MSISQ-19. MSISQ-19 test and retest total scores correlated between each other (r=0.48, p=0.01). MSISQ-19 total score also correlated with primary, secondary and tertiary subscales (p<0.001), with the EDSS (r=0.19, p<0.001) and all other neuropsychological scales.

Conclusions

The Italian Version of the MSISQ-19 showed satisfactory internal consistency and reliability with moderately adequate test-retest reproducibility, suggesting that the Italian MSISQ-19 questionnaire provides a valuable measure of sexual dysfunction in the Italian population.

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Comorbidities Late Breaking Abstracts

LB1193 - The Framingham cardiovascular risk score and 5-year progression of multiple sclerosis (ID 2012)

Speakers
Presentation Number
LB1193
Presentation Topic
Comorbidities

Abstract

Background

Cardiovascular risk factors and comorbidities can affect the prognosis of multiple sclerosis (MS). The Framingham risk score is an algorithm that can estimate the 10-year risk of developing macrovascular disease.

Objectives

To evaluate possible association between the Framingham risk score at baseline, and MS relapses, disability and disease-modifying therapy choices over 5-year follow-up.

Methods

This is a retrospective cohort study including 251 MS subjects. At baseline, we calculated the Framingham risk score considering the following variables: age, sex, diabetes, smoking, systolic blood pressure, and body mass index. MS outcomes including relapses, disability and treatments were collected over 5 years. Cox proportional regression models were employed to estimate hazard ratios (HR).

Results

1-point increase in the Framingham risk score was associated with 31% higher risk of relapse (HR=1.31; 95%CI=1.03, 1.68), 19% higher risk of reaching of EDSS 6.0 (HR=1.19; 95%CI=1.05, 3.01), and 62% higher risk of disease modifying treatment escalation (HR=1.62; 95%CI=1.22, 3.01).

Conclusions

Higher cardiovascular risk was associated with higher risk of relapses, disability, and treatment escalation in MS. Early identification, correction and treatment of cardiovascular comorbidities should be carefully considered within MS management.

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Biostatistical Methods Late Breaking Abstracts

LB1194 - Analysis of count data in MS clinical trials (ID 2013)

Speakers
Authors
Presentation Number
LB1194
Presentation Topic
Biostatistical Methods

Abstract

Background

Count outcomes are common in clinical studies of multiple sclerosis (MS), but the methods for the analysis of count outcomes are not commonly discussed in introductory statistics courses.

Objectives

To introduce commonly used statistical approaches for clinical studies of MS with a focus on the similarities and differences between the approaches.

Methods

For this session, data was simulated to mimic two recent MS clinical trials. The first dataset was simulated to mimic a phase III clinical trial with the number of relapses as the outcome. The second dataset was simulated to mimic a phase II clinical trial with the number of new gadolinium enhancing lesions on a brain MRI as the outcome.

Results

When the goal is to analyze the number of new relapses, a commonly used approach is Poisson regression. This approach estimates the rate ratio and easily accommodates different follow-up intervals for each subject by including an offset in the model. This approach is related to a comparison of incidence rates and the analysis of recurrent events using survival analysis. When the goal is to analyze the number of new lesions, Poisson regression is usually not appropriate because the mean and variance of the number of new lesions are often quite different due to a small number of subjects having a large number of new lesions. This leads to highly skewed data. To analyze this outcome, Poisson regression with robust standard errors or negative binomial regression are preferred because these approaches accommodate overdispersion. Results from the statistical software package Stata will be shown to demonstrate the commands described in the session.

Conclusions

Count outcomes are common in MS clinical studies, and specific analysis approaches are used for these outcomes. Many of the analysis approaches used for count outcomes are related, but each approach makes different assumptions so the best approach will depend on the outcome of the study.

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Rehabilitation and Comprehensive Care Late Breaking Abstracts

LB1195 - Changes in Mobility and Brain Connectivity following over-ground Robotic Exoskeleton Rehabilitation in Persons with MS (ID 2020)

Speakers
Presentation Number
LB1195
Presentation Topic
Rehabilitation and Comprehensive Care

Abstract

Background

Multiple Sclerosis (MS) has an estimated prevalence of 337-362 per 100,000 people[1] and is characterized as an autoimmune disease that causes axonal degradation, leading to mobility and cognitive impairments. While physical rehabilitation has been identified as one of the best methods for restoring function in MS[2], it can be challenging to implement in individuals with severe impaired mobility. One approach is the use of a novel assistive device such as a wearable Robotic exoskeletons (RE). REs have been increasingly used to provide gait rehabilitation for persons with mobility disorders (e.g. spinal cord injury and stroke) [3-7], and more recently for persons with MS[8, 9]. The current study examines potential improvements in mobility, cognitive processing speed, as well as resting-state (RS) functional connectivity of the brain in persons with MS through the use of RE.

Objectives

To determine if gait training using RE improves mobility, cognition, and brain RS functional connectivity in persons with MS.

Methods

Four persons with relapsing-remitting MS (RRMS) participated in this randomized pilot prospective study. Two MS patients received eight 1-hour RE training sessions (Ekso-GT, Ekso Bionics, Berkley, CA, USA) administered by a licensed physical therapist; the other two participants received eight 1-hour Conventional Gait Therapy (CGT) sessions. The 8-seesion interventions occurred over a four week period (2 sessions/week). The Six Minute Walk Test (6MWT), Symbol Digit Modalities Test (SDMT), and RS functional MRI (fMRI) of the brain, acquired using a Siemens Skyra 3 Tesla MRI scanner were assessed at baseline and after the 4-week intervention. A seed-based RS functional connectivity analysis approach was used, with seeds placed in the motor and ventromedial prefrontal cortices (vmPFC).

Results

The RE group improved by 21% in walking distance in the 6MWT while the CGT group showed essentially no change (a 2% decrease in the distance). The RE group also showed improvements in SDMT performance (ZRE = 0.95; ZCGT = - 0.78), as well as improvements in functional connectivity in the motor cortex (ZRE = 0.8; ZCGT = - 0.08) and in the vmPFC (ZRE = 0.8; ZCGT = -0.003).

Conclusions

Improvements in mobility, cognitive processing speed, and resting state functional connectivity in the motor cortex and in the vmPFC were observed for participants in the RE gait training group but not in the CGT group. These pilot results suggest that gait training using RE can be an effective therapy for improving walking ability, cognitive function, and brain connectivity in resting-state networks in persons with MS. Data analysis of a larger sample is underway to confirm the findings.

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Neuroprotection, Regeneration and/or Remyelination Late Breaking Abstracts

LB1196 - Enhancing myelin repair in MS preclinical models by modulating the cholesterol biosynthesis pathway (ID 2021)

Speakers
Presentation Number
LB1196
Presentation Topic
Neuroprotection, Regeneration and/or Remyelination

Abstract

Background

Enhancing remyelination in MS is the next frontier in therapeutic approaches to stop disease progression and improve neurological disabilities. However, an efficacious remyelination therapy is yet to be developed. One approach to enhance myelin repair which has been extensively demonstrated in response to a variety of stimuli, hinges on pharmacological stimulation of CNS resident oligodendrocyte progenitor cells (OPC), to mature into myelinating oligodendrocytes.

Objectives

Our goal is to develop an efficacious remyelination therapy to be administered conjunctive with existent immunomodulators.

Methods

In this pathway, we have determined a major role for the sterol isomerase Emopamil Binding Protein (EBP), which converts 8,9 into 7,8-unsaturated sterols, an essential step in cholesterol biosynthesis. Sterol accumulation can be measured by mass spectrometry in cultured OPCs and in CNS tissue from rodents treated with EBP inhibitors.

Results

Treatment of cultured OPCs with EBP inhibitors dramatically increased maturation as a consequence of elevated sterol accumulation. In vivo, we observed a robust accumulation of intermediate sterols in mouse brains within hours of peripheral administration of EBP inhibitors. Moreover, EBP inhibition significantly enhanced myelin repair after demyelination caused by focal injections of lysolecithin in the mouse spinal cord and in a chronic de/remyelination animal model.

Conclusions

Extensive preclinical validation supports EBP as viable target for a remyelination therapy in MS. Identification of novel, selective and safe small molecule inhibitors of EBP is undergoing with several advanced chemical series showing high efficacy in vitro and in pharmacodynamic assays.

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Imaging Late Breaking Abstracts

LB1197 - Myelin water imaging provides evidence for unique anatomical-functional relationships between myelin damage and different cognitive domains in MS (ID 2022)

Abstract

Background

Background: An improved understanding of the impact of demyelination on multiple sclerosis (MS) related cognitive impairment is crucial for targeting and testing therapies with the potential to slow cognitive decline. Demyelination can be assessed using myelin water imaging, a quantitative magnetic resonance imaging (MRI) technique that measures signal from water in the myelin bilayers, providing a specific measure of myelin (myelin water fraction, MWF).

Objectives

Objective: To determine if there is an anatomical-functional relationship between myelin content and location with cognitive performance.

Methods

Methods: 76 MS participants (mean (SD) age:50.4y(10.6y), 51F) underwent T2 relaxation imaging to calculate MWF maps and cognitive testing (Symbol Digit Modalities Test (SDMT); Selective Reminding Test (SRT); Controlled Oral Word Association Test (COWAT); Brief Visuospatial Memory Test-Revised (BVMT-R)). Nonparametric permutation testing with FSL Randomise was used to determine which white matter (WM) MWF voxels were associated with cognitive test performance for each test (p<0.01, after multiple comparisons correction), creating test-specific maps of associated WM areas. Pearson ́s correlations assessed relationships between mean MWF in the cognitive test-specific WM areas and respective test scores. MS patients were categorized into cognitively impaired, mildly impaired and cognitively preserved groups based on published norms. Kruskal Wallis ANOVA with post hoc pairwise comparisons investigated mean MWF differences between cognitive groups.

Results

Results: MWF in several WM areas was significantly associated with SDMT, SRT and BVMT-R scores but not the COWAT. All tests found voxels within the corona radiata, posterior thalamic radiation and parts of the corpus callosum significant. Unique WM areas were the inferior longitudinal fasciculus and anterior cingulum for SDMT and the retrolenticular part of the internal capsule for the BVMT-R. Mean MWF in the test-specific WM areas correlated significantly with performance on the SDMT (r=0.58, p= 4.11 x 10-8), SRT (r=0.56, p= 4.14 x 10-7) and BVMT-R (r=0.56, p= 1.0 x 10-6). Mean MWF in the test-specific WM areas was significantly lower in the cognitively impaired group relative to the cognitively preserved group (p<0.01).

Conclusions

Conclusions: There is an anatomical-functional relationship between myelin damage and cognitive performance in MS with unique WM patterns for different cognitive domains.

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COVID-19 Late Breaking Abstracts

LB1199 - Marked increase of CSF sampling induced vasovagal response secondary to COVID-19 pandemic (ID 2030)

Speakers
Authors
Presentation Number
LB1199
Presentation Topic
COVID-19

Abstract

Background

According to 2017 McDonald criteria, CSF analysis is useful for the diagnosis of multiple sclerosis. Incidence of vasovagal response after spinal anesthesia, a similar procedure to spinal tap, is estimated around 4-5 % in the published literature[i].

Since the implementation of new sanitary measures for COVID-19 pandemic (mask for patient and medical staff, face shield for the staff), the author suspected an increase in vasovagal response occurring in patients during spinal tap procedure.

[i] Vahabi S, Slavash B, Badiozaman R. The incidence of vasovagal response in spinal anesthesia during surgery. J Anest & Inten Care Med. 2018; 5(1).

Objectives

Under an unchanged practice setting of the author, the objective is to compare the occurrence of vasovagal response in association with CSF sampling since the beginning of the COVID-19 pandemic in March 2020 in comparison with the previous year.

Methods

The author is working in an out-of-hospital private neurology clinic. CSF sampling are done within the clinic by the author using the same technical procedure for the last 3 years, using the sitting position for the vast majority. The patients' reactions to the procedure have been systematically documented in their chart. In a retrospective analysis, the author's patients undergoing a CSF examination since the beginning of the pandemic (2020-03-16) were compared to the ones from the previous year, specifically examining the occurrence of vasovagal response.

Results

From 2020-03-23 to 2020-07-16, 15 patients (18-72 years, mean 46.4y) were sampled for CSF, 60% for multiple sclerosis suspicion. In the previous year, from 2019-03-01 to 2020-02-12, 26 patients (26-82 years, mean 50.2y) were sampled, 46.2% for multiple sclerosis suspicion.

9 (46.7%) patients experienced a vasovagal response during the COVID-19 pandemic compared to 2 (7.7%) patients in the previous year (p = 0.003). One patient having recurrent vasovagal response during the procedure had to be referred for fluoroscopy, a situation that rarely occurs in the author's practice. As for confounding factors, there were more cardiovascular issues identified in the pre-pandemic cohort.

Conclusions

A marked increase of vasovagal response after CSF sampling is observed since the beginning of the pandemic, in comparison to expected occurrence from previous year. Anxiety related to COVID-19 & the mask use (doctor or patient) are suspected factors in this increase. A study supports these findings; 47% of medical students that experienced syncope in operating theatre reported that wearing a surgical mask was a contributory factor[i].

Favoring a lateral decubitus position and particular COVID-19 reassurance have been implemented in the author's practice in order to decrease the occurrence of this unpleasant reaction. Follow-up is ongoing.

[i] Jamjoom A, Nikkar-Esfahani A, Fitzgerald J. Operating theatre related syncope in medical students : a cross sectional study. BMC Med Educ. 2009; 9 : 14.

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Clinical Trials Late Breaking Abstracts

LB1200 - The SUNLIGHT Study: A telehealth intervention to address mental health in persons with MS during COVID-19  (ID 2034)

Speakers
Presentation Number
LB1200
Presentation Topic
Clinical Trials

Abstract

Background

The arrival of the Covid-19 pandemic in the United States brought a heightened level of anxiety to the general population. Individuals with chronic diseases such as multiple sclerosis (MS) were expected to be particularly affected. To address mental health needs safely and immediately, we conducted a trial of a group-based telehealth treatment of professional online support groups to reduce anxiety in persons with MS, the SUNLIGHT study.

Objectives

To determine feasibility and initial efficacy of a pilot trial of online structured, moderated professional support groups to reduce anxiety in persons with MS during the US outbreak of Covid-19. Trial was registered at clinicaltrials.gov (NCT04379661).

Methods

All procedures were conducted remotely. Thirty-two patients with MS were recruited in March-April 2020 at an MS Center in New York City. Consent was obtained via eConsent. 21 received active treatment: 1 hour/week online structured group therapy; 11 served as an inactive control group (i.e., treatment as usual, TAU). Baseline measures were collected from all participants: anxiety (Stait-Trait Anxiety Inventory, primary efficacy outcome), stress (Perceived Stress Scale), distress (Impact of Event Scale), mood (Patient Health Questionnaire), loneliness (UCLA Loneliness Scale), self-efficacy (General Self-Efficacy Scale), quality of life (Functional Assessment of Multiple Sclerosis).

Results

Sample was diverse: 83% female; 23.3% Hispanic / Latino, 10% Black, 3.3% Asian; age range: 24-72 years; disease duration: .25 -38 years. 30% Major Depressive Disorder, 30% anxiety disorder. At baseline, 36.6% had an anxiety attack within past 4 weeks.

Feasibility: Completion and adherence for treatment group were high; 80.9% completed the intervention; average adherence was 75%.

Efficacy results: Anxiety decreased in the treatment group after 12-weeks (STAI mean change = -2.7 points; p=.09).

Qualitative results: 100% responded YES to 'did you find the SUNLIGHT study to be worth your time,' and 'would you recommend SUNLIGHT study to a friend with MS;' 95% responded YES to 'if it were possible to continue your participation in the SUNLIGHT study, would you choose to do so;' 53% responded YES to 'do you think participation in the SUNLIGHT study contributed to a decrease in any of your MS symptoms?'

Conclusions

Telehealth provides an acceptable, accessible, safe vehicle for delivering mental health treatment to chronic disease populations during Covid-19. High adherence and completion, and initial evidence showing reduced anxiety bolster professional support groups as a promising treatment option for individuals with MS. Low cost, high return solutions such as online support groups should be further explored in future large-scale trials. Rigorous clinical trail evidence is needed to elevate the priority given to telehealth behavioral treatments.

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COVID-19 Late Breaking Abstracts

LB1201 - SARS-CoV-2 associated Neuromyelitis optica (ID 2036)

Speakers
Presentation Number
LB1201
Presentation Topic
COVID-19

Abstract

Background

SARS-CoV-2 has been shown to cause numerous neurologic sequelae, including meningoencephalitis, ischemic or hemorrhagic stroke, and acute disseminated encephalomyelitis. Following respiratory symptoms, acute transverse myelitis has also been reported. Neuromyelitis Optica (NMO) is a rare, inflammatory demyelinating disease of the central nervous system (CNS), predominantly affecting the optic nerves and spinal cord. We report a case of NMO occurring in a patient who initially presented with acute meningoencephalitis of unknown etiology and, shortly thereafter, was found to be SARS-CoV-2 antibody positive.

Objectives

NMO is a rare demyelinating disorder of the CNS. Some studies of NMO have suggested a triggering role for infectious agents, but the primary immunizing event remains poorly understood. Here we describe a case of NMO presenting in a SARS-CoV-2 antibody positive patient after an initial hospitalization for meningoencephalitis of unknown etiology.

Methods

The case report was compiled using outside hospital and Thomas Jefferson University Hospital electronic medical record data. Figures were obtained through PACS and formatted in Microsoft Powerpoint.

Results

NMO is diagnosed by the presence of at least 1 of 6 core clinical characteristics and detection of AQP4-IgG. The core clinical characteristics implicate 6 CNS regions including optic nerve, spinal cord, area postrema of the dorsal medulla, brainstem, diencephalon, or cerebrum. Our patient had 2 core clinical characteristics including spinal cord lesion spanning greater than 3 segments and area postrema syndrome due to dorsal medullary lesion. Furthermore, his serum AQP4-IgG was positive. He developed these symptoms after becoming seropositive for SARS-CoV-2 antibodies with a positive nasopharyngeal swab test.

Conclusions

This is the first case report about NMO potentially triggered by SARS-CoV-2 infection. While causality remains difficult to prove, the temporal relationship between SARS-CoV-2 infection and NMO attack is compelling for parainfectious phenomenon.

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Imaging Late Breaking Abstracts

LB1202 - The effects of obesity on retinal structures in African American and Caucasian relapsing remitting multiple sclerosis patients (ID 2043)

Speakers
Presentation Number
LB1202
Presentation Topic
Imaging

Abstract

Background

It has been investigated that obesity may impact RRMS disease severity. It has been well established that retinal layers thin over time in RRMS, and that AA patients tend to experience a more aggressive disease course than CA patients. Optical coherence tomography was utilized to quantify retinal thickness and volume.

Objectives

To assess the effect of obesity on retinal structures between African American (AA) and Caucasian (CA) patients with Relapsing Remitting Multiple Sclerosis (RRMS).

Methods

One hundred thirty-six RRMS patients were included in this single-center retrospective study and split into two groups: 67 obese (BMI≥30, 40 AA, 27 CA, mean BMI±SD: 36.7±5.8) and 69 non-obese (BMI˂30, 23 AA, 46 CA, mean BMI±SD: 24.0±3.1). An OCT was performed to quantify the peripapillary retinal nerve fiber layer (pRNFL) thickness and volumetric macular scans. The pRNFL was segmented into quadrant thickness: superior (S), inferior (I), temporal (T), and nasal (N). Automated intra-retinal segmentation was performed to obtain the following macular volumes: total macular (TMV), papillomacular bundle (PMB), retinal nerve fiber (RNFL), ganglion cell + inner plexiform (GCIP), inner nuclear (INL), outer plexiform (OPL), and outer nuclear (ONL) layers. A generalized linear model with OCT parameters as dependent variables and BMI grouping as the independent variable was used for analysis with age and disease duration as covariates (SPSS v26).

Results

There was a significant direct correlation between obesity and thickness in the T quadrant of the pRNFL (p=0.044), and also the INL (p=0.034) and RNFL (p=0.009) volumes across all patients. AA patients in the obese group had significantly lower measures of T (p=0.033), N (p=0.044), TMV (p=0.003), RNFL (p=0.013), OPL (p=0.050), ONL (p=0.026), and GCIP (p=0.038) compared to obese CA patients. Among non-obese patients, the ONL was significantly lower in AA compared to CA patients (p<0.001).

Conclusions

Our data suggests a correlation between obesity and increased retinal thinning, specifically in the T region of the pRNFL, and the INL and RNFL volumes. While obesity affects retinal integrity in all patients, our data also suggests the impact is more prominent in AA patients than CA patients. Further investigations should be conducted regarding the impact of other health factors on RRMS across racial groups to better understand how to monitor disease course in patients of different backgrounds.

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COVID-19 Late Breaking Abstracts

LB1203 - Neuromyelitis optica spectrum disorders (NMOSD) attack triggered by COVID-19 infection (A case report) (ID 2044)

Speakers
Presentation Number
LB1203
Presentation Topic
COVID-19

Abstract

Background

Neurological presentations of SARS-CoV-2 infection (COVID-19) are now increasingly reported, however some specific presentations as well as the neurological para or post infectious sequels are still under recognized. Here, we report a patient with acute bilateral diminution of vision and acute diencephalic syndrome wiith clinical and imaging findings consistent with NMOSD, 2 weeks following a COVID-19 infection.

Objectives

We would report a case of female patient with COVID-19 who had clinical and radiological disease consistent with NMOSD 2 weeks after her COVID-19 infection

Methods

A 56 years old female patient who was completely healthy without any previous history of neurologic disease except past history of left temporal meningioma which removed surgically successfuly 12 years ago. The patient had developed fever (up to 39 C), associated with respiratory symptoms, easy fatigability, anorexia and generalized body aches. Her Blood picture showed lymphopenia with normal other labs, CT chest showed bilateral ground glass appearance highly suggestive of Covid -19 infection. SARS-CoV-2 PCR sample from nasopharyngeal swab was positive. Patient recieved treatment for her COVID-19 infection at her home according to the treatment protocl. Her fever as her other symptoms gradually improved within 2 weeks. At the end of 2 weeks,the patient presented to the emergency department with acute bilateral loss of vision, lethargy and disorientation.Her tvital signs were within normal refrences, Oxygen saturation was 95% and the patient metabolic profile was within normal range. Neurological examination showed disorientation to time, place and person. All extremities moved spontaneously equal with normal tone, intact deep tendon reflexes and positive planter response. Brain MRI showed abnormal signal intensity seen involving diencephalic, medial thalamic, optic chiasm, optic tracts and radiation, being hyper intense inT2W1 and FLAIR, no DW restriction, no perilesional edema or mass effect. According to examination and imaging findings, NMOSD diagnosis was postulated. Methylprednisolone 1 g IV daily was administered for the presumed acute demyelinating event. Later on patient developed bradycardia (50 b/min), became shocked, uncorrected hypothermia (35 c). At the end she developed central diabetes insipidus complicated by hypernatremia (160 mmol/L).A follow up MRI with contrast was done and showed no significant changes from baseline MRI with partial enhancement of the chiasm and diencephalic region. Patient developed 2 attacks of generalised tonic clonic convulsions, aspirated, arrested respiratory, mechanicaly ventilated and died few hours later.

Results

The diagnosis of the patient as NMOSD was established according to patient clinical scenario and radiological findings.

Conclusions

NMOSD could be a possible complication to COVID-19 infection, In addition to its previously known neurologic complications

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COVID-19 Late Breaking Abstracts

LB1205 - Covid-19 Infection in Patients with Multiple Sclerosis: an observational study by The New York COVID-19 Neuro-Immunology Consortium (NYCNIC) (ID 2054)

Abstract

Background

New York became one of the first epicenters of the COVID-19 pandemic in the United States and many neurologists were faced with the unprecedented challenge of providing medical advice to patients with multiple sclerosis (MS) without the support of evidence-based scientific data. Large collaborative studies are needed to determine whether MS itself, or associated disease-modifying therapies (DMT), increase the risk of acquiring COVID-19 or worsen its course.

Objectives

We aim to characterize the patterns of COVID-19 infection in patients with MS and to identify risk factors for severe infection.

Methods

Demographics, MS and COVID-19 clinical features were collected on patients currently followed at 5 large MS Centers in New York City and the tri state area (MSSM, Columbia, Northwell, NYU, and Neurological Associates Of Long Island). Patients with MS or related disorders, who self-identified as diagnosed with COVID-19 by a healthcare provider (based on characteristic symptoms, radiographic findings and/or positive COVID-19 PCR/serology when available) were included. The severity of COVID-19 infection was measured by a 4-point ordinal scale (home care, hospitalization, ICU, death). Univariate and multivariate logistic regression models were used to assess associations of demographic variables with hospitalization.

Results

Our cohort included 349 patients with median age of 45 (range 13-76), 70.8% female, 25.3% African-American, 23.7% Hispanic. Mean disease duration was 11.5y [SD 9.1]. The prevalence of DMT use was 87.2%, and 80.2% were ambulatory without assistance. Forty-eight (14.2%) patients were hospitalized, and 13 (3.9%) patients died. Multivariate logistic regression models showed associations between EDSS ≥6 (OR 3.9 [95% CI, 1.7-8.8]), obesity (OR 2.4 [95% CI, 1.1-4.9]) and age (OR per 10 year increase: 1.5 [95% CI, 1.1-2.2]) with hospitalization for COVID-19. There were no significant associations between race, ethnicity, comorbidities (cardiac, pulmonary or diabetes), smoking status, or specific DMT and severe COVID-19 infection requiring hospitalization.

Conclusions

Age, obesity, and higher EDSS independently predicted severe COVID -19 infection necessitating hospitalization. This is in agreement with COVID -19 outcome predictors in the general population and other MS cohorts. Older patients with limited mobility should be counseled to maintain increased vigilance during the ongoing pandemic.

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COVID-19 Late Breaking Abstracts

LB1206 - Sars-Cov-2 infection releated inflammatory and demyelinating disease; a brief case series (ID 2055)

Speakers
Presentation Number
LB1206
Presentation Topic
COVID-19

Abstract

Background

Coronavirus disease 2019 (COVID-19) is typically manifested by fever and respiratory symptoms caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although SARS-CoV-2 is a respiratory infection agent, various neurological syndromes have been reported with central and peripheral nervous system involvement, which may be associated with COVID-19. Most recently, a case diagnosed with multiple sclerosis (MS) after an optic neuritis (ON) attack associated with COVID-19 infection has been published.

Objectives

In this case series we would like to to discuss the posibility of COVID-19-associated inflammatory / demyelinating disease.

Methods

We present 3 new cases admitted to our clinic with various neurological findings that all cases were affected by COVID-19. Imaging studies have shown that inflammatory / demyelinizing lesions appeared in different areas of the central nervous system which were accepted as an atypical demyelinating spectrum associated with SARS-CoV-2.

Results

Case 1

A 28-year-old man presented with left hemiparesia. Brain magnetic resonance imaging (MRI) showed hyperintense lesions adjacent to the lateral ventricles on T2-weighting with diffusion restriction and contrast enhancement. Chest CT scan was compatible with viral pneumonia and nasopharyngeal swab with a realtime polymerase chain reaction (RT-PCR) test resulted positively for SARS-CoV-2. After management of the infection, intravenous methylprednisolone (IVMP) treatment was given to the patient and neurological deficits were fully recovered.

Case 2

An 18-year-old woman presented with severe acute visual loss in the left eye and retrobulbar ON was diagnosed. Brain and cervical spine MRI showed multiple demyelinating lesions without gadolinium enhancement. SARS-CoV-2 PCR analysis of nasopharyngeal swab and immunological testing for IgG was negative whereas she was positive for IgM, compatible for a possible active infection. She was started on IVMP and despite completion to 10 days, recovery was only achieved by 70%.

Case 3

A 48-year-old man presented with right hemiparesia. He was hospitalized with the diagnosis of Covid-19 10 days ago. Brain MRI showed T2- FLAIR hyperintense lesions in the supratentorial area and posterior fossa with diffusion restriction and contrast enhancement. Control MRI after 2 months revealed that the lesions significantly regressed spontanously and complete recovery was observed in neurological deficits.

Conclusions

With increasing experience, it has been understood that the SARS-CoV-2 also has a neurotropic effect. These 3 cases suggest that the virus plays a role in the clinical onset of the inflammatory / demyelinating disease. The responsible mechanism here is probably not as a result of direct infectious effect of the virus rather a trigger role in autoimmune processes like other viral agents. Further long-term studies relating to the pathophysiology of COVID-19 is warranted.

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Pathogenesis – Immunology Late Breaking Abstracts

LB1207 - Elevated levels of serum CD5 antigen-like protein distinguish secondary progressive multiple sclerosis from other disease subtypes (ID 2058)

Speakers
Presentation Number
LB1207
Presentation Topic
Pathogenesis – Immunology

Abstract

Background

Limiting MS progression requires characterization of the pathological processes that distinguish disease subtypes that progress from those that do not. CD5 antigen-like (CD5L) protein is predominantly macrophage-secreted with roles in modulating inflammation, lipid metabolism, and inhibiting cell apoptosis. Previous studies have found serum CD5L levels tend to decrease with age in healthy individuals yet are elevated in inflammatory conditions including chronic infections, psoriatic arthritis, and systemic lupus erythematosus.

Objectives

To compare serum CD5L levels in healthy controls (HC) to individuals with relapsing remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), and clinically isolated syndrome (CIS).

Methods

The study cohort included 35 HC, 20 CIS, and 83 clinically definite MS (CDMS: 33 RRMS, 30 SPMS, 20 PPMS) participants recruited at the University of British Columbia MS clinic. Serum CD5L levels were assessed with a commercial enzyme-linked immunosorbent assay. Correlation, univariate and multivariate linear regression analyses were used to determine the relationship between CD5L levels and age, sex, disease duration (DD), and expanded disability status scale (EDSS).

Results

Compared to HC (median [IQR], 4.2 [2.8-6.3] μg/ml), SPMS had elevated serum CD5L (7.0 [4.6-8.5] μg/ml, p=0.0006). There were no differences between HC and RRMS (4.8 [3.5-5.8] μg/ml) or PPMS (4.3 [3.3-5.8] μg/ml), and CIS tended to have higher CD5L (5.1 [4.0-7.5] μg/ml, p=0.45). PPMS CD5L levels were low compared to SPMS (p=0.02), but this was not due to differences in age between subtypes. CD5L levels tended to correlate negatively with age in HC (p=0.06), but not in RRMS, SPMS, and PPMS. In contrast, CD5L levels correlated positively with age in the CIS group (p=0.03). Multivariate (p=0.009) and univariate (p=0.002) analyses showed increased CD5L in CDMS was associated with longer DD rather than differences in age, sex, or EDSS. Univariate analysis showed the pattern of increased CD5L in CDMS with longer DD seems to be driven mostly by SPMS (p=0.16).

Conclusions

Our studies suggest that CD5L titers could reflect differences underlying neurological mechanisms in PPMS and SPMS. The positive relationship between CD5L and DD in SPMS points to a distinct and chronic peripheral inflammatory profile compared to other subtypes. Further studies are needed to characterize the processes driving CD5L expression in MS and its potential utility as a biomarker of MS progression.

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Imaging Late Breaking Abstracts

LB1208 - Linking structural and functional brain alterations in relapsing-remitting MS (ID 2063)

Speakers
Presentation Number
LB1208
Presentation Topic
Imaging

Abstract

Background

MRI studies have consistently shown structural and functional alterations in the brain of patients with MS. However, pathogenic mechanisms of MS are “multidimensional”, reflecting complex events and thus requiring multivariate analysis methods. A complementary knowledge of such events and their clinical relevance is currently lacking in MS.

Objectives

To investigate “hidden” covarying structural-functional pathogenic patterns in MS patients compared to normal controls (NC).

Methods

We applied linked independent component analysis, a type of fusion approach, to images of grey matter (GM) density, fractional anisotropy (FA) and resting-state functional MRI. We assessed 100 relapsing-remitting MS patients (age: 39.7±10.5 years, 60 female, disease duration: 9.4±6.9 years; median EDSS=1.5, cognitive impairment [CI]: 30%) and 43 demographically-matched NC.

Results

Out of 20 linked structural-functional patterns across study population, only one showed significant group difference, with a loading coefficient across MRI modalities lower in MS than NC (-0.29±1.05 vs 0.69±0.34, corrected-p <0.004), which was already present at very early disease stage and was particularly low in the MS subgroups with larger white matter (WM) lesion volume (LV, >3.5 cm3), higher EDSS (>1.5), CI occurrence and longer disease duration (>5 years). The contribution of each modality to the significant linked covarying pattern was 41% for GM density, 42% for WM FA and 17% for network-functional connectivity (FC). The contribution of FC increased in the MS group with increasing LV, EDSS, CI and disease duration.

Conclusions

These findings suggest that in MS patients with mild disability common pathogenic mechanisms are characterized by a prevalent structural damage equally affecting WM and GM and, to a lesser degree, by concurrent widespread alteration of short-range FC. Such mechanism is already present since the early MS stage and becomes more pronounced with increasing focal pathology and disease severity.

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Neuropsychology and Cognition Late Breaking Abstracts

LB1209 - A tablet-based videogame for capturing slowing processing speed in multiple sclerosis patients: a pilot study (ID 2064)

Speakers
Presentation Number
LB1209
Presentation Topic
Neuropsychology and Cognition

Abstract

Background

Slowing information processing speed (IPS) is a biomarker of neuronal damage in patients with MS (pwMS). Computerized tools allow testing different cognitive load conditions that might reveal initial IPS inefficiencies before the appearance of formal cognitive impairment (CI) as assessed with paper-and-pencil neuropsychological tests.

Objectives

To further explore the feasibility of computerizes tools, we developed a tablet-based videogame for quickly and efficiently measuring IPS in pwMS without formal CI with the aim to assess its specificity and sensitivity in testing IPS in different cognitive load conditions in pwMS as compared to healthy controls (HC).

Methods

Forty-five pwMS (age:36.8±9.3; edu:13.9±3.1; F=33) without CI and 20 matched HC (age:34.4±12.3; edu:17.5±2.5; F=7) underwent 3 videogame levels of increasing cognitive load. Reaction times (RTs) and accuracy were recorded and subjected to mixed-repeated ANOVAs. PwMS also underwent neuropsychological tests of IPS, attention, executive functioning (EF), and memory; correlation analyses between RTs of each level and the neuropsychological tests were performed.

Results

Significant differences between pwMS and HC were found as a function of increasing cognitive load conditions, on both RTs (p<.001) and accuracy (p<.001), with pwMS being on average significantly slower (p=.003) and less accurate (p=.004) than HC. Significant correlations between RTs of each level and composite score of IPS-attention (level 1: p=.006; level 2: p=.009; level 3: p=.002) and EF (level 1: p=.03; level 2: p=.002; level 3: p=.002), but not memory (all ps>.12), were found.

Conclusions

Measuring IPS efficiency in pwMS with computerized tools (i.e., videogame) could be useful in both screening and monitoring disease progression and response to therapies within a telemedicine perspective. The inverse relationship between increasing cognitive load and slowing IPS efficiency might be related either to over-recruitment or dysfunction of neural networks (i.e., neural plasticity) which may induce cognitive inefficiency even before the appearance of formal CI.

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Neuropsychology and Cognition Late Breaking Abstracts

LB1210 - Cerebrospinal fluid inflammatory profile of cognitive dysfunction in newly diagnosed multiple sclerosis patients (ID 2066)

Speakers
Presentation Number
LB1210
Presentation Topic
Neuropsychology and Cognition

Abstract

Background

Increased cerebrospinal fluid (CSF) expression of proinflammatory cytokines (IFNG, TNF, IL2, and IL22) and molecules related to sustained B-cell activity and lymphoid-neogenesis (CXCL13, CXCL10, LTa, IL6, and IL10) was found associated to increase cortical grey matter (GM) pathology and more active and severe disease outcome either in naive MS patients or in post-mortem MS cases. Cognitive impairment (CI) is one of the main features of GM damage in MS and can be early observed in newly diagnosed MS patients.

Objectives

To investigate whether a potential link between CSF inflammatory profile and CI exists in newly diagnosed MS patients.

Methods

Sixty-nine, treatment-naïve MS patients (54 F, age=37.3±11.6 ys; education=14.4±3.5 years) underwent an extended battery of neuropsychological tests (median time between LP and neuropsychological assessment: 1 month) and the protein analysis of the levels of 57 inflammatory mediators by using customized immune-assay multiplex Bio-Plex X200. MS patients were classified into three groups (Cognitively Normal: CN; mild CI: mCI; severe CI: sCI) according to the number of neuropsychological tests below the cut-off (5th percentile).

Results

Increased CSF levels of CXCL13 were detected in sCI (mean=29.6pg/ml±SD=59.3) compared to both CN (5.5±9.6) and mCI (6.7±6.3) patients. Furthermore, in mCI compared to CN patients were found higher levels of CHI3L1 (mCI: 5431.7±31942.7; CN: 32743.6±18050.9), CX3CL1 (mCI: 550.7±402.2; CN: 311.7±146.1), IL8 (mCI: 116.5±128.6; CN: 43.1±30.5), CCL3 (mCI: 8.8±7.7; CN: 4.7±2.7), CCL19 (mCI: 164.5±117.0; CN: 83.8±93.4), sTNFr2 (mCI: 1017.9±761.3; CN: 550.1±366.6), and CCL8 (mCI: 590.4±1097.6; CN: 97.4±194.5). Finally, in sCI compared to CN patients were found higher levels of IL22 (sCI: 46.5±43.7; CN: 17.1±15.2), IL35 (sCI: 330.0±214.2; CN: 192.1±133.2), IL12 (sCI: 31.0±37.1; CN: 9.6±11.9), and LIGHT (sCI: 291.3±519.3; CN: 61.6±100.1). In particular, significant correlations were found between the cytokines-chemokines and tests of memory, attention/executive functions, and information processing speed. No significant difference in the CSF Nf-L level was found among the three groups (p=.96).

Conclusions

The presence of CI might be reflected by increased CSF levels of inflammatory mediators. In particular, we found a specific molecular pattern discriminating CN (innate immunity) from mCI and sCI (B-cell chemotaxis and activity). These results demonstrate, for the first time, that specific intrathecal inflammatory milieu might possibly contribute to the MS-related cognitive impairment since the early phases of MS disease.

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Clinical Trials Late Breaking Abstracts

LB1211 - Histaminergic basis of fatigue in Multiple Sclerosis (ID 2069)

Speakers
Presentation Number
LB1211
Presentation Topic
Clinical Trials

Abstract

Background

The histaminergic tuberomammillary system through its varied connections control the circadian rhythm and regulate wakefulness and sleep, satiety and hunger, memory and learning, as well as energy and tiredness. Blocking brain histamine receptors lead to tiredness and sleep. In this study we examined if raising brain histamine levels can improve fatigue in severely fatigued patients with multiple sclerosis.

Objectives

To validate the concept that raising brain histamine will alleviate fatigue in severely fatigued patients with multiple sclerosis

Methods

A strategy was developed to raise brain histamine by loading patients with l-histidine, the precursor for histamine. Conversion systemically from l-histidine to histamine was blocked using histidine decarboxylase inhibitor, lodosyn, which has no access to the brain across the blood brain barrier.All subjects received a fixed dose lodosyn, 50 mg po bid. Three groups of l-histidine loading wereundertaken. Group-1 received 250 mg po bid, Group-2 500 mg po bid and group 3, 1 gm po bid. Pharmacokinetic (PK) and pharmacodynamic (PD) studies were conducted to measure blood and CSF l-histidine and histamine levels before and during treatment. Response to treatment was gauged using the visualanalogue fatigue scale (VAFS), Fatigue severity scale (FSS) and the modified fatigue impact scales (MFIS). To be considered a responder, patients had to improve in all three scales and show at least a 20% improvement from their mean screening/baseline MFIS scores.

Results

A dose-based response to improvement of fatigue was observed anywhere from 30% to 88% in MFIS scores with the least responders in Group 1 and most in Group 3. Improvement was noted in all three domains of the MFIS; the physical, cognitive and psychosocial. Improvement in the cognitive domain was associated with subjects reporting improved attention, concentration and improvement of the“brain fog”. Responders reported an overall sense of well being while others reported no change.

Conclusions

This proof -of-concept study has identified a population of MS patients with fatigue that respond to treatment using elevation of brain histamine. This novel approach opens up a new avenue to identify drugs that raise brain histamine as a mechanism of treatment of fatigue in MS and possibly other disorders with fatigue where histamine may play a pivotal role in the pathogenesis of this common and severely disabling symptom. Additionally this treatment could also provide an approach to help cognitive impairment in multiple sclerosis since raising brain histamine can facilitate also the enhanced release of a number of neurotransmitters including acetylcholine, implicated in the pathogenesis of cognitive impairment in various disorders including multiple sclerosis.

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Comorbidities Late Breaking Abstracts

LB1212 - Evaluating Multiple Sclerosis patients for gluten sensitivity – worthwhile or not? (ID 2071)

Speakers
Presentation Number
LB1212
Presentation Topic
Comorbidities

Abstract

Background

MS is a T- cell mediated CNS autoimmune disease of likely multifactorial etiology. Although gluten has been suggested to play a role in MS, it is not standard medical practice to evaluate for gluten sensitivity in MS patients.

Objectives

The aim of this review is to consider current evidence of gluten’s role in MS, and to explore if the evaluation of MS patients for gluten sensitivity should be incorporated into patient care plans.

Methods

A literature search was conducted in PubMed, Embase, Google Scholar and Ovid Medline. Studies on gluten’s role in MS, other CNS autoimmune diseases and T-cell mediated autoimmune diseases were included. Studies on effects of other diets on MS as well as studies exploring methods of evaluating non-celiac gluten sensitivity were also included.

Results

The positive effects of gluten-free diets (GFD) on MS was noted, even though the serological evidence for gluten-sensitivity markers in MS patients was inconsistent. However, existing studies used only celiac gluten sensitivity markers in the serologic evaluation, and did not include non-celiac gluten sensitivity markers. Positive effects of GFD on other CNS autoimmune diseases and other T-cell mediated autoimmune diseases were noted in select case studies. Other diets were also shown to have some positive impact on Quality of Life (QOL) measures in MS patients, although evidence is not strongly convergent.

Conclusions

Although GFD intervention studies show positive trends in health outcomes for MS patients, gluten’s role in MS needs to be further explored. Non-celiac gluten sensitivity evaluation using PBL miRNA expression, in addition to using current markers of celiac gluten-sensitivity, may be beneficial. Excluding celiac MS patients from GFD intervention studies, as well as using miRNA expression of PBL, have been suggested as directions for future research. Since distinct diets have been shown to improve MS in the peer reviewed literature, the shared aspect of mindful eating may be an operative component. In conclusion, using PBL miRNA expression laboratory evaluation for non-celiac gluten sensitivity, as well as recommending a food diary to promote mindful eating, can be considered by physicians who treat MS patients.

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Machine Learning/Network Science Late Breaking Abstracts

LB1213 - Attention-based deep learning identifies a new microstructural diffusion MRI contrast sensitive to focal pathology and related to patient disability (ID 2074)

Speakers
Presentation Number
LB1213
Presentation Topic
Machine Learning/Network Science

Abstract

Background

Microstructural biophysical models reconstructed from advanced diffusion MRI (dMRI) data provide quantitative measures (qMs), which inform about the brain tissue microenvironment, based on different assumptions.

Objectives

To compare the sensitivity of available qMs to focal pathology in multiple sclerosis (MS), and to explore which qMs– or combinations of qMs – are best correlated with patients disability.

Methods

dMRI (1.8 mm isotropic resolution, 149 directions, b-values were 0, 700, 1000, 2000, 3000 s/mm2) was acquired from 67 relapsing-remitting and 33 progressive MS patients (median EDSS: 2.5). The qMs for the isotropic and intra-axonal compartments were derived from the following available models: Ball and Stick, NODDI, SMT-NODDI, MCMDI, NODDIDA, DIAMOND, Microstructure Bayesian approach (MB) and microstructure fingerprinting. In total, 13 qMs were included and subject-wise normalized within brain tissue (nqMs).

To identify the nqMs sensitive to focal pathology, an attention-based convolutional neural network (aCNN) was built to (a) classify randomly sampled WM lesion and perilesional WM patches and (b) generate attention weights (AWs) representing the relative importance of the qMs in the classification. Twenty patients were randomly selected in the test dataset (709 lesion patches and 746 perilesional WM patches), and the rest were in the cross-validation (CV) dataset (2925 lesion patches and 3176 perilesional WM patches). The performance metric was the area under the receiver operating characteristic curve (AUC). Because of the correlation between the nqMs, which may influence the relative AWs, we performed 10-fold CV and selected the nqMS that most contributed to the classification.

To assess which nqMS – or combination of nqMS was best correlated with EDSS, we used Spearman’s correlation coefficient (ρ) with two-sided 20000 permutation tests and followed by Bonferroni correction.

Results

The test AUC was 0.911 indicating the aCNN learned the right AWs to differentiate lesions and perilesional WM. The most discriminating nqMs included isotropic and intra-axonal compartments from MB, the neural density index (NDI) from the NODDI and the intra-axonal compartment from MCMDI.

The sum of isotropic and intra-axonal compartments of the MB (sMB) showed the strongest correlation with EDSS (ρ=-0.40,corr. p<0.0001) followed by the sum of sMB and NDI (ρ=-0.30,corr. p<0.05), and the sum of sMB and intra-axonal compartment from MCMDI (ρ=-0.32,corr. p<0.05). None of the selected nqMs as a single measure and their other combinations correlated with EDSS.

Conclusions

By performing aCNN-aided selection of the openly available WM quantitative measures, we have identified the measures most sensitive to MS focal pathology; furthermore, we have derived a new contrast that – by combining the measures of isotropic and intracellular diffusion – strongly correlated with patients’ disability.

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COVID-19 Late Breaking Abstracts

LB1214 -  Antiviral activity of Interferon beta-1b to SARS-CoV-2 infection (ID 2078)

Speakers
Presentation Number
LB1214
Presentation Topic
COVID-19

Abstract

Background

SARS-CoV-2, is a new coronavirus (CoV), which is spreading all over the world, since it was identified in a group of people with pneumonia of an unknown cause at Wuhan, province of Hubei, China. At the present time, it is working hard in a vaccine development and in the searching of medical treatments with the purpose of improving the prognosis of those cases that get the infection. Nowadays, neurologists treating patients with Multiple Sclerosis (MS) face the uncertainty of the impact that this new disease may generate.

Objectives

To assess whether interferons can play a protective or therapeutically important role in patients infected with SARS-CoV-2

Methods

Recently we have seen the case of a 68 years of age patient with a diagnosis of Relapsing Remitting Multiple Sclerosis (RRMS) under Interferon beta-1b treatment since the illness diagnosis has been received 8 years ago. She shows history of hypertension with the pharmacological treatment and resides at a geriatric together with other 20 people (all of them older than 65 five years old) and 4 nurses for her assistance. Since the preventive social isolation was ruled in Argentina, residents at the geriatrics do not receive their family visits and at the situation of a medical examination, this was accomplished with the protection protocols. During the month of July of this year, a male resident of the same institution experienced fever and cough (48 hours before he had been discharged from a hospital), so he was transferred to another hospital and a swab (oropharyngeal and nasal) was carried out suspecting CoV, resulting the same positive.

Results

It was decided to swab the 25 people that reside at the geriatric. From the 4 nurses 2 were positive and from the 20 older adults’ residents, 19 obtained a positive result except the patient under MS diagnosis in treatment with Interferon beta-1b. All of them were hospitalize because of age and comorbidities, 4 died and 16 are still hospitalized. They are stable but a second swab resulted positive (at the month of August). Our patient has never developed fever nor any other symptomatology, her breathing rate and oxygen saturation were always normal.

Conclusions

We can conclude that nowadays, the Interferon beta-1b still is a good option for the treatment of MS patients, especially during this difficult pandemic period and time will tell us if additionally this molecule may fulfill a role of therapeutic importance in patients infected with SARS-CoV-2.

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Neuromyelitis Optica and Anti-MOG Disease Late Breaking Abstracts

LB1215 - "Clinical course, Safety of Low-dose Rituximab for Vietnameses Patients with Neuromyelitis Optica Spectrum Disorder" (ID 2079)

Speakers
Authors
Presentation Number
LB1215
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis Optica Spectrum Disorders (NMOSD) is a severe autoimmune disease, predominantly affects optic nerves and spinal cord. In Viet Nam, NMOSDs cases are rarely reported. The monoclonal anti-CD20 B-cell antibody Rituximab (RX) is the most effective off-label therapeutic option for NMOSD. For Vietnamese patients with NMOSD, RX is not covered by insurance; therefore, most patients can not afford the standard dose.

Objectives

To evaluate the clinical, MRI characteristics, disease impact; safety, efficiency of low-dose rituximab treatment in 8 Vietnamese patients.

Methods

We performed a prospective cohort study of 8 patients with NMOSD confirmed by presence of antibody Anti Aquaporine 4 (AQP4) IgG. All patients were infused with RX 100 mg once per week for 3 consecutive weeks, and infused three times at 4-week intervals from the last infusion at Ha Noi Medical University Hospital.

Results

8 patients with relapsing NMOSD were included, all patients were females with mean age at onset of 46 ( 26 to 64). At time of onset, long extensive myelitis transverse (LEMT) occured in 6/8. Optic neuritis occured in 1/8. Postrema syndrome revealed the diagnostic in 1/8. The mean annualised relapse rate was 1.18. Concomitant systemic lupus erythematous was found in 1/8 patients. The Expanded Disability Status Scale Score (EDSS) 3.0 and 6.0 was reached respectively 6/8 and 2/8 patients. Brain white matter lesions appeared in 3/8 subjects. Spinal cord MRI showed lesions extending across 3 or more segments in all 8/8 subjects. One or more CSF abnormalities were found at least once in 4/8 patients, pleocytosis in 4/8, oligoclonal bands were negative in all patient, high protein level in 3/8 patient. Low-dose Rituximab was well tolerated even after up to 5 consecutive treatment courses. None of 8 patients has had the new attack on treatment with low-dose Rituximab.

Conclusions

NMOSD has a poor prognosis in most cases. Compared with multiple sclerosis, NMOSD patients have a higher age at onset, females are more frequently affected and the course is more severe. Serum AQP4 antibody supports the probability of NMOSD. Low-dose Rituximab is effective in NMOSD and has an acceptable safety profile.

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Biomarkers and Bioinformatics Late Breaking Abstracts

LB1216 - Cortical and deep grey matter volume loss is specifically linked to cerebrospinal fluid inflammation in early multiple sclerosis. (ID 2081)

Speakers
Presentation Number
LB1216
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Several neuropathological and imaging studies demonstrated that cortical and deep grey matter damage follows a ‘surface in’ gradient, suggesting the possibility that soluble inflammatory factors released in the cerebrospinal fluid (CSF) might play a pathogenetic role.

Objectives

To verify whether soluble factors released from meningeal and CSF inflammation are considered the most probably triggers of superficial grey matter damage.

Methods

We evaluated the association, at diagnosis, between, among 110 relapsing remitting naïve MS patients, who underwent blinded clinical, CSF and 3T-MRI evaluations at time of diagnosis. The CSF protein levels of 32 inflammatory mediators were correlated, by using multivariate regression analysis, with the volume loss in hippocampus, insula, cerebellum and thalamus.

Results

Significant correlations were found between: hippocampus volume loss and the CSF protein levels of CXCL13 (β=-5.65x10-3;p<0.0001), CXCL10 (β=-1.46x10-4;p<0.05) and sCD163 (β=-3.20x10-6; p<0.0001); thalamic volume loss and the CSF protein levels of CXCL13 (β=-12.5;p<0.0001), sTNF-R1 (β=-6.00x10-2; p<0.05), sCD163 (β=-1.33x10-2; p<0.0001) and fibrinogen (β=-31.48; p<0.05); cerebellum volume loss and the CSF protein levels of sCD163 (β=-6.78x10-2; p<0.001) and chitinase-3-like1(β=-3.20x10-2;p<0.05); finally, insula volume loss and the CSF protein levels of CXCL13 (β=-5.92x10-3; p<0.001), CCL20 (β=-1.14x10-1; p<0.001) and osteopontin (β=1.71x10-6; p<0.05).

Conclusions

At time of diagnosis, elevated CSF levels of the mayor B-cell chemoattractant molecule CXCL13 is substantially linked to grey matter atrophy in all the deep and cortical grey matter examined areas. In addition, elevated levels of markers of glia activity, such as sCD163, osteopontin, chitinase-3-like1 and sTNFR1 have also a key role in grey matter volume loss. These data represent the first demonstration of a direct link between intrathecal CSF inflammatory myelin and the surface in grey matter damage since early disease stages.

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Neuro-Ophthalmology Late Breaking Abstracts

LB1217 - Macular pigment concentration and distribution in multiple sclerosis (ID 2084)

Speakers
Presentation Number
LB1217
Presentation Topic
Neuro-Ophthalmology

Abstract

Background

Oxidative stress is implicated in inflammation and neurodegeneration in multiple sclerosis (MS). Similar to the brain, the retina is susceptible to reactive oxygen species (ROS). Macular pigment (MP), consisting primarily of the carotenoids lutein (L) and zeaxanthin (Z) blocks deleterious blue light, and provides anti-oxidant protection. To date, there has been a paucity of study of MP in MS.

Objectives

To examine MP concentration and distribution in MS eyes relative to healthy control (HC) eyes using macular pigment optical density (MPOD) imaging.

Methods

In this cross-sectional study, 27 MS patients (47 eyes) and 19 HCs (37 eyes) underwent MPOD imaging on a Spectralis (Heidelberg) device. MP absorbs blue light, but allows the free passage of green light. MPOD imaging involves the subtraction of blue from green wavelength auto-fluorescence macular scans, providing the optical density (OD) of MP. Radii of interest for MPOD were 0°, 0.23°, 0.51°, 0.98° and 1.99° degrees of eccentricity from the fovea, as well as peak, and half-peak MPOD locations. Study participants completed dietary L & Z screening questionnaires. Mixed effects linear regression models were used in analyses.

Results

Mean MPOD at 0° was 0.52 density units (d.u.) (SD 0.14) in MS and 0.63 d.u. (SD 0.18) in HC eyes (difference: -0.10 d.u., CI: -0.18 - -0.01, p=0.027). The median MPOD peak location eccentricity was 0.08° (IQR: 0 - 0.12) in MS and 0.04° (IQR: 0 - 0.08) in HC eyes (difference: 0.10°, CI: 0.01 - 0.20, p=0.031). Mean MPOD at the peak location was -0.09 d.u. lower in MS eyes relative to HC eyes (CI: -0.18 - -0.01, p=0.04). In addition, the half-peak MPOD location, similar to the MPOD peak location, was situated further from the fovea in MS eyes relative to HC eyes (difference: 0.28°, CI: 0.10 - 0.47, p=0.002). Analyses adjusted for age, body mass index, sex, and L & Z dietary scores, showed similar differences for MPOD at 0° eccentricity, and at the peak MPOD location, between MS and HC eyes.

Conclusions

Our findings suggest MP concentrations are reduced in MS eyes, with peak and half-peak MPOD locations shifted further from the fovea than in HC eyes. Increases in ROS consuming antioxidant MPs, and/or dysfunction in proteins transferring carotenoids to the fovea, among other reasons, may help explain reductions in MPOD in MS eyes. Our preliminary finding warrant further study, in larger, prospective MS cohorts, including determination of their clinical relevance.

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COVID-19 Late Breaking Abstracts

LB1218 - Impact of COVID-19 on MS patients’ access to care and neurologists’ treatment practices worldwide: results from the ECTRIMS survey (ID 2086)

Speakers
Presentation Number
LB1218
Presentation Topic
COVID-19

Abstract

Background

Restrictions imposed by the National and local authorities to mitigate the spread of Coronavirus disease-19 (COVID-19) posed unique challenges in the access to care and management of people with multiple sclerosis (PwMS).

Objectives

To collect data about the impact of the COVID-19 emergency on access to care for PwMS and analyze influence on treatment practices of MS neurologists worldwide.

Methods

Between March and July 2020 the European Committee for Treatment and Research in MS (ECTRIMS) promoted an online survey among Council members and MS specialists worldwide, covering five major areas: general information; MS patient access to care; management of relapses and visits; use of disease modifying therapy (DMT); experience with COVID-19 MS patients.

Results

Three-hundred-sixty neurologists (46% females, median age 48 years) from 52 countries (Europe 68%; Central/South America 17%; North America 10%, others 5%) completed the survey. Seventy-five percent worked within a specialized MS centre, 42% followed > 1000 patients. Ninety-eight percent of respondents reported COVID-19 pandemic had a negative impact on patients’ care. Routine MS clinical activities were suspended in 63% of cases and only urgent visits were guaranteed. Telemedicine services (mainly calls, video-calls, messaging) were provided by 90% of respondents: only in 20% of cases telemedicine was already in use in the practice. Forty-five percent revealed changes in relapse treatment: dosage and/or duration reduction 30%; treatment offered only for severe relapses 36%; treatment delivered at home 28%. As for DMT, 98% of respondents felt no modification was needed for interferons and glatiramer; 48-60% deemed no change was needed for dimethyl fumarate, teriflunomide, fingolimod and siponimod, while nearly 25% considered switching/suspending these agents based on lymphopenia. On the other hand, for natalizumab 31% applied an extended-dose regimen, for cladribine and alemtuzumab 42-52% considered postponing treatment in any case as the best choice. For anti-CD20 monoclonal antibodies, postponing treatment in any case (32%) or based on the patient immunophenotype (25%) were the preferred options. Sixty-one percent of respondents had at least one patient affected by COVID-19, 27% had at least one patient with severe infection; 70% of severe cases were on DMT. Finally, 11% of respondents reported at least one COVID-19 related death and 36% of fatal cases were on DMT.

Conclusions

While analysis of geographic differences is ongoing, the survey highlighted that COVID-19 pandemic is having a major impact on MS care worldwide. Telemedicine has a great potential to mitigate issues and needs to be potentiated/implemented de novo at most centres. As for DMT, major changes regarded cladribine, alemtuzumab and anti-CD20. Collecting standardized, reliable data on the potential impact of DMT on COVID-19 in PwMS is urgently needed to inform appropriate treatment decisions.

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Biomarkers and Bioinformatics Late Breaking Abstracts

LB1219 - Normal serum NFL levels: a proposal of cut-off strategy definition for the clinical practice (ID 2090)

Speakers
Presentation Number
LB1219
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Serum Neurofilament light (sNFL) protein is the most promising marker of disease activity and treatment response in Multiple Sclerosis (MS). To implement sNFL in clinical practice, the definition of normal widely accepted values represents a crucial step still to be addressed. Clinically applicable cut-off values need to take into account age dependency; in addition, recent evidences suggest that physical parameters as body mass index (BMI) and blood volume (BV) might influence sNFL levels.

Objectives

The present study aims to address these crucial needs, describing sNFL levels in healthy population, their inter-individual variability in a short-term follow-up and defining reference cut-off values. The final objective is to define a strategy to allow implementation of sNFL in clinical practice.

Methods

We measured sNFL by single molecule array (Simoa) assay (NF-light advantage Kit, Quanterix) in 79 healthy individuals to define reference cut-off values. Age, BMI and BV were correlated with sNFL levels. In addition, sNFL were evaluated after a short-term follow-up time (median 67 days) to assess intra-individual variability: consecutive blood samples were tested in a subset of 27 participants (n=2-4 sample for each individual) and the coefficient of variation (CV) for NFL levels of each participant was evaluated.
sNFL were also tested in 23 naïve MS patients both at diagnostic time and immediately before treatment (median 76 days after) to evaluate the variability of sNFL in patients and the applicability of obtained cut-off values.

Results

1) Our data confirmed a strong correlation between sNFL levels and age. We found a negative correlation between sNFL levels and BV. 2) Short-term follow-up NFL assessments showed an overall intra-individual stability in sNFL levels in healthy population (median CV 15%). 3) We defined specific age decade-related cut-off values. 4) In naïve MS patients, sNFL levels were higher than control values; a high variability between diagnostic time and the beginning of treatment (median CV 39%) was shown. Cut-off values were applied in MS patients to discriminate high from normal sNFL levels: at diagnostic time, 57% of MS patients showed high sNFL levels, while at treatment start, 70% of patients demonstrated normal NFL values.

Conclusions

The present study suggests a strategy to define clinical applicable cut-offs to exploit sNFL as a personalised medicine tool in MS: specific cut-off values were calculated for each age decade. sNFL levels demonstrated an overall intra-individual stability in healthy participants in the short-term: this is relevant for a biomarker of disease activity and treatment response that, if successful, will be serially assessed during patients follow-up.

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Biomarkers and Bioinformatics Late Breaking Abstracts

LB1220 - Real-life experience with sNFL in Multiple Sclerosis patients, as monitoring and treatment decision biomarker   (ID 2091)

Speakers
Presentation Number
LB1220
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Neurofilament light chain (NFL) are the most promising biomarkers to investigate clinical activity and treatment efficacy in multiple sclerosis (MS), for which, to date, clinical examination and magnetic resonance imaging (MRI) are the only tools available for diagnosis and monitoring. NFL are released upon axonal damage in the cerebrospinal fluid and, in low concentration, in serum (sNFL). Whilst correlation between NFL and clinical outcomes is established, their implementation in clinical practice is still to be addressed.

Objectives

The aim of the present real-life cross-sectional study is to describe sNFL in a large cohort of MS patients as additional measure of disease activity and treatment efficacy.

Methods

We measured sNF-L by single molecule array (Simoa) assay (NF-light advantage kit, Quanterix) in 79 healthy participants and in 961 MS patients (n=1130 samples). sNFL were cross-sectionally evaluated in 830 relapsing remitting (RR), 53 primary progressive (PP) and 78 secondary progressive (SP) MS patients at different disease stages including diagnostic time, immediately before treatment, and during treatment with the main disease modifying treatments (DMTs): Interferon-beta, Glatiramer acetate, DimethylFumarate, Teriflunomide, Natalizumab, Alemtuzumab, Fingolimod, anti-CD20 . Clinical assessment was performed to evaluate correlations between sNFL, MRI and relapses.

Results

1) We established clinically applicable cut-off values for each age decade testing healthy individuals, later used to interpret sNFL levels in individual MS patients. 2) Progressive MS patients showed higher sNF-L levels and a greater prevalence of high sNFL levels (32% in PPMS and 26% in SPMS) relative to RRMS patients (16%), with respect to the previously determined cut-off values. 3) Patients experiencing MRI and/or clinical activity close to NFL dosage (+/-60 days) showed higher levels than stable patients; according to cut-off values, high NFL levels were observed in a substantial percentage of MRI active patients (72%) and clinically active patients (75%). 4) All DMTs notably lower sNF-L in RRMS patients treated for more than 12 months relative to untreated patients; though, 12% of treated patients still demonstrated high NFL levels.

Conclusions

This study provides a real-life picture of sNFL in a large cohort of MS patients. Cut-off values specific for age decade were applied to discriminate patients samples in different contexts, showing correlation with disease subtype, clinical activity and DMTs efficacy. Our study shows that clinically applicable cut-offs can enable the implementation of sNFL in everyday clinical practice in individual patients, demonstrating its potential as monitoring and treatment decision biomarker.

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Biomarkers and Bioinformatics Late Breaking Abstracts

LB1221 - Applicability of sNFL in Multiple Sclerosis as additional measure in clinical practice and implications in NEDA-3 evaluation.   (ID 2092)

Speakers
Presentation Number
LB1221
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Despite the increased availability of efficient therapeutic options, early and effective intervention is still mandatory for successful clinical management in Multiple Sclerosis (MS). Speaking of which, a composite measure of disease status termed "no evidence of disease activity" (NEDA) has been proposed as target for treatment in MS. However, this definition needs to be implemented with biological measures for a more personalized medicine. Serum Neurofilament light chain (sNfL) represents the most promising biomarker of disease activity and treatment efficacy in MS, reflecting axonal damage in the central nervous system. To date, sNFL correlation with clinical outcomes is well established in group analysis, yet, its implementation for individual patients is still to be addressed.

Objectives

The aim of the present real-life study is to investigate sNFL as additional measure of treatment efficacy in NEDA-3 patients.

Methods

We measured sNF-L by single molecule array (Simoa) assay (NF-light advantage kit, Quanterix) in 79 healthy participants and in 582 cross-sectionally enrolled RRMS patients, including 61 naive patients, and 521 patients treated with first- or second line therapies, demonstrating NEDA-3 status (no relapses, no disability progression, no MRI activity) during at least 12 months.

Results

1) We established clinically applicable cut-off values for each age decade testing healthy individuals, later used to interpret sNF-L levels in MS patients. 2) In MS patients, treatments notably lower sNF-L relative to untreated patients. 3) According to cut-off values, 53/521 (10%) NEDA-3 patients still demonstrate high NFL levels. These patients were distinguished in different categories: a) patients showing borderline sNFL values; b) patients with concomitant pathologies; c) patients experiencing chronic ongoing fatigability (not classifiable as disability progression); d) patients with a very active disease history; e) patients with conceivable inflammation not detectable by RMN or clinics. 4) The percentage of NEDA-3 patients with high NFL lowers with the extension of NEDA-3 status duration (down to 5% in patients with NEDA-3 status longer than 8 years).

Conclusions

The present cross-sectional study identified a subgroup of NEDA-3 patients showing high sNFL levels. High pathological sNFL levels, reflecting axonal damage, suggest the presence of chronic disease activity or subclinical transitory active inflammation not detectable by RMN or clinics in NEDA-3 patients. The establishment of simple applicable cut-off values allows sNFL applicability in everyday clinical practice. In particular, sNFL could represent an additional measure to be included in NEDA assessment for monitoring therapeutic response in individual MS patients.

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COVID-19 Late Breaking Abstracts

LB1222 - Outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders (ID 2095)

Abstract

Background

Outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown.

Objectives

The objective was to describe the clinical characteristics and outcomes of COVID-19 in patients with neuromyelitis optica and associated disorders and to identify the factors associated with COVID-19 severity.

Methods

We conducted a multi-center, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020 and June 30th, 2020. Main outcome was COVID-19 severity score assessed on a 7-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death).

Results

Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower EDSS score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]).

Conclusions

COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19, however we recommend to maintain preventive measures to limit the risk of contamination with SARS-CoV-2 in this immunocompromised population.

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COVID-19 Late Breaking Abstracts

LB1223 - Telehealth: another tool in the toolkit to provide usual care to people with Multiple Sclerosis during the COVID-19 pandemic. (ID 2097)

Speakers
Presentation Number
LB1223
Presentation Topic
COVID-19

Abstract

Background

On 11 March 2020 the Director-General of the World Health Organisation (WHO) announced that the number of cases and spread of coronavirus (COVID-19) characterised it as a pandemic. Evidence from prior epidemics and pandemics has demonstrated that neglect of ‘usual care’ can be an unintended consequence of prioritising an emergency response. The Australian Government introduced an expansion of subsidised telehealth consultations on March 14, 2020 in response to the pandemic. While a number of studies have examined health system responses and the experiences of clinicians in relation to the provision of routine health care during epidemics and pandemics, few have elicited the experiences of people with chronic health conditions in terms of their access to usual health care during these times.

Objectives

Our aim was to examine the experiences of people with Multiple Sclerosis (MS) in accessing health care during the COVID-19 pandemic in the Australian Capital Territory, Australia.

Methods

We adopted a qualitative methodological approach involving semi-structured interviews (n=8) and conducted a thematic analysis of interview transcripts. A purposive sample of participants aged over 18 years, with a clinical diagnosis of MS, and living in the Australian Capital Territory were recruited. Interviews were conducted between June 2020 and July 2020 via Zoom or telephone, recorded, and transcribed. Interviews lasted between 30 and 90 minutes. Data collection continued until saturation was reached.

Results

Key themes were: Assessing personal risk, Postponing usual care, and New ways of accessing care. Participants with MS were aware their condition made them more vulnerable to contracting COVID-19 and put measures in place to reduce social contact and, in some cases, usual care was postponed or not sought. Telehealth consultations were recognised as having benefits such as improved access, convenience, and being contactless. Limitations included an inability to read body language over the telephone, seeming less personal, and that some regular tests and observations cannot be completed remotely. Video consultations were favoured over telephone consultations. Face to face consultations remained the gold standard, however, most participants planned to incorporate them as part of their health care routine in the future.

Conclusions

Telehealth consultations have a place in providing usual care for people with MS. They offer convenience and greater access to health care professionals enabling a safer contactless option during the pandemic.

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Pathogenesis – Role of Glia Late Breaking Abstracts

LB1224 - Thalamic and whole brain atrophy are linked with white matter microglial activation: A [F-18]PBR06-PET study in multiple sclerosis  (ID 2099)

Speakers
Presentation Number
LB1224
Presentation Topic
Pathogenesis – Role of Glia

Abstract

Background

Thalamic and whole brain atrophy have been extensively studied as biomarkers of neurodegeneration in multiple sclerosis but their mechanism is not clear. [F-18]PBR06-Positron Emission Tomography (PET) is a novel molecular imaging technique to assess microglial activation.

Objectives

To determine the relationship of thalamic and whole brain atrophy with white matter (WM) microglial activation in multiple sclerosis.

Methods

22 individuals (13 MS, including 8 relapsing-remitting and 5 secondary progressive, and 9 healthy control (HC)) subjects underwent 3T MRI and [F-18]PBR06-PET. Individualized z-score maps of WM microglial activation were generated by voxel-by-voxel comparison between each subject's PET SUVR images and a control dataset. Glial activity load on PET in WM (“GALP-WM”) was calculated as the sum of voxel-by-voxel z-scores ≥4 in the WM subjects and its logarithmic transformation (“ln-GALP”) was also obtained. "Z-max" score was calculated as the highest z-score in the WM matter averaged over surrounding 5 voxels. SIENAX and FSL-FIRST pipelines determined normalized brain parenchymal volume (BPV) and thalamic volumes (Th-V) respectively. A p-value <0.05 was considered statistically significant.

Results

Th-V and BPV were lower in MS vs. HC (19.7±2.2 vs. 22.4±1.6 ml, 1376.6±81.3 vs. 1475.1±70.9 ml, both p<0.01). GALP-WM, Z-max and ln-GALP were higher in MS vs. HC (18757.9±13646 vs. 7580.5±12216, 13.2±2.9 vs. 8.3±4.1, and 9.5±0.92 vs. 7.4±1.9, all p<0.05). Th-V and BPV were inversely correlated with WM microglial activation, represented by GALP-WM, Z-max and ln-GALP (r=-0.62, -0.66 and -0.62, all p<0.01 for Th-V and r=-0.68, -0.643 and -0.678, all p<0.01 for BPV) that remained significant after adjustment for age (all p<0.05).

Conclusions

Thalamic and whole brain atrophy are linked with white matter microglial activation in MS, representing a link between neuroinflammation and neurodegeneration across central nervous system compartments. Further investigation of the “GALP” method as a novel, individualized approach for evaluating glial activity in MS is warranted. Prospective longitudinal studies to determine the impact of therapeutically targeting microglial activation on neurodegeneration in MS patients are urgently needed.

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COVID-19 Late Breaking Abstracts

LB1225 - Acute disseminated encephalomyelitis in a pediatric patient in the setting of SARS-CoV2 with histopathology (ID 2104)

Speakers
Presentation Number
LB1225
Presentation Topic
COVID-19

Abstract

Background

Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating syndrome of the central nervous system (CNS) usually following a febrile illness. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is predominantly a respiratory infection with rare direct neurologic involvement. Although neurological symptoms are increasingly reported, it is unclear if these represent a para-infectious or post-infectious manifestation of SARS-CoV-2. We report the first case to our knowledge of pediatric ADEM associated with SARS-CoV-2.

Objectives

We present a case of a 5 year-old boy with ADEM in the setting of SARS-CoV with histopathology showing meningoencephalitis.

Methods

Case report featuring clinical presentation, laboratory, neuroimaging, and histopathology results, and medical decision-making, treatment, and clinical course.

Results

A 5-year-old previously healthy Hispanic boy presented with 3 weeks of headache, right eye blurry vision, and vomiting. Infectious work-up was negative except for SARS-CoV-2 RNA PCR. MRI brain demonstrated multifocal lesions with intense enhancement and diffusion restriction, most prominent in the right frontal lobe, basal ganglia, and cerebellum with vasogenic edema and punctate foci of hemorrhage as well as bilateral swelling of optic nerves and optic chiasm. MRI spine revealed longitudinally extensive myelitis with an intensely enhancing, expansile intramedullary lesion from T1 to T3.

Differential diagnosis included infectious and inflammatory etiologies leading to a brain biopsy which showed foci of lymphohistiocytic perivascular inflammation (predominantly CD3+ T-cells and CD68+ histiocytes, with rare CD20+ B-cells) consistent with meningoencephalitis. There were features suggestive of, but not definitive for demyelination, including occasional macrophages with staining indicating ingestion of myelin breakdown products. No definite viral inclusions were identified by light or electron microscopy.

Neurology was consulted, noting that he was very irritable with decreased upper extremity movements. Based on his clinical syndrome and imaging, ADEM was suspected and started on high dose IV methylprednisolone. Cerebrospinal fluid showed 9 nucleated cells/mm3 (97% lymphocytes), 44 mg/dL protein, 77 mg/dL glucose, enterovirus and herpes simplex virus PCR negative. Due to brain, optic nerve, and spinal cord involvement, MOG related ADEM is suspected (test pending) and PLEX was also initiated.

Conclusions

We report the first case to our knowledge of ADEM in a child in the setting of SARS-CoV2 with histopathology showing meningoencephalitis. Based on his brain, optic nerve, and spinal cord involvement, MOG antibody disease is suspected, presumably triggered by SARS-CoV2 infection rather than resulting from SARS-CoV2 infection itself. Additional studies are needed to further characterize the direct and indirect neurological sequelae of SARS-CoV2.

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COVID-19 Late Breaking Abstracts

LB1226 - Use and safety of interferon beta-1b during the COVID-19 outbreak: current data from a pharmacovigilance safety database (ID 2105)

Speakers
Presentation Number
LB1226
Presentation Topic
COVID-19

Abstract

Background

Since the first report of coronavirus disease (COVID-19) in late 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease quickly became a pandemic with a variety of clinical presentations, including death.

The risk of COVID-19 for patients with multiple sclerosis (MS) receiving interferon beta-1b (IFN β-1b) has been unclear.

In the absence of specific antiviral agents, IFN β has been suggested as a potential therapeutic option for COVID-19 based on its immunomodulatory and antiviral properties. In preclinical studies, IFN β has shown antiviral activities against coronavirus in Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome, but currently there is no clinical data supporting its therapeutic use in COVID-19 patients.

Objectives

The objective of our study is to review the current safety data on IFN β-1b in MS and non-MS patients impacted by COVID-19.

Methods

Retrospective data on IFN β-1b case reports with mention of COVID-19 were extracted from Bayer’s pharmacovigilance (PV) database through July 29, 2020.

Results

A total of 109 cases mentioned COVID-19, which included 75 MS patients (68.8%) and 34 non-MS patients (31.2%) who received IFN β-1b.

Of the 75 MS patients, 23 (30.7%) were diagnosed with COVID-19 (median 49 years; range 27-65 years). No relevant drug-related adverse events (AE) were reported. Two patients (2.7% of 75, 8.7% of 23; ages 42 and 49 years) died due to COVID-19. The 52 patients (69.3%) with no evidence of COVID-19 reported being negatively impacted with depression, anxiety, and difficulty accessing medical care for MS exacerbations and other health conditions.

Of the 34 non-MS patients who received IFN β-1b for experimental COVID-19 treatment, AEs were reported in 19 (55.8%). The most frequently reported AEs were associated with hepatic impairment such as hepatitis, mixed liver injury, hyperbilirubinemia, and increased hepatic enzyme. These events are appropriately reflected in the reference safety information. In almost all cases, IFN β-1b was concomitantly used with other antiviral drugs. Seven patients (20.6%) died due to COVID-19 (median 71 years; range 64-79 years) but IFN β-1b use was not implicated. Five patients (14.7%) reported non-approved route of administration (sublingual), however no AEs were associated with this method.

Conclusions

Our study revealed a small portion of MS patients using IFN β-1b who became infected with SARS-CoV-2 or developed COVID-19.

Although underreporting is a known limitation of PV data, our findings are in accordance with the published low incidence of COVID-19 in IFN β-treated MS population. Future serum anti-SARS-CoV-2 antibody tests may determine the number of asymptomatic COVID-19 IFN-b-1b-treated MS patients.

AEs reported in IFN β-1b-treated COVID-19 patients are consistent with the established safety profile. No new safety concerns were observed in MS or non-MS COVID-19 patients treated with IFN β-1b.

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Clinical Trials Late Breaking Abstracts

LB1227 - Glatiramer Acetate Depot (extended-release) phase IIa study in patients with Primary Progressive Multiple Sclerosis: safety and efficacy snapshot (ID 2106)

Abstract

Background

PPMS is characterized by worsening neurologic function (accumulation of disability) from the onset of symptoms, without early relapses or remissions. GA long-acting injection (GA Depot) consists of extended-release microspheres containing GA, administered intramuscularly (IM) once every 28 days. Results of GA Depot phase IIa for three years in relapsing remitting MS suggest that GA Depot is safe, tolerable and efficacious. The IM administration route together with the slow release formulation may result in a noted effect on PPMS patients as well.

Objectives

To assess the safety and efficacy snapshot data of GA Depot treatment (for up to 112 weeks) in the eleven primary progressive MS (PPMS) subjects enrolled out of the 24 planned.

Methods

Eligibility criteria included: age 18-65 years, subjects diagnosed with PPMS with signs of rapid disease progression (rate of ≥ 1 point increase / year on EDSS score) in the year prior to screening, EDSS score of ≥2.0 and ≤ 6.5 at baseline. Patients are receiving GA Depot IM at a dose of 40 mg every 28 days. Safety is assessed by analysis of adverse events, CBC and blood chemistry. Efficacy is assessed by EDSS, 9HPT, T25FW tests, as well as by MRI analysis.

Results

AEs were mainly mild. Most common AEs included injection site reactions and general weakness. No unexpected AEs were reported. Two SAEs were reported (one related and one not related to study drug). EDSS score remained stable for all patients and no 12 weeks confirmed disability progression (CDP) was detected. Mean 9HPT score and T25FW remained stable. MRI analysis (compared to baseline) revealed findings in three out of the 11 patients’ population.

Conclusions

These interim snapshot data suggest that GA Depot is possibly a safe and effective treatment for patients with PPMS, as demonstrated by stable mean EDSS, mean 9HPT and mean T25FW data, which encourage us to continue this on-going investigation.

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Clinical Trials Late Breaking Abstracts

LB1228 - Glatiramer Acetate Depot (Extended-Release) Phase IIa Study in Patients with RRMS: Safety, Tolerability and Efficacy Four-Years Analysis (ID 2107)

Abstract

Background

Multiple sclerosis is a chronic disease, requiring lifelong therapy. While several DMTs have been approved, improvement of treatment adherence remains an unmet need. Glatiramer acetate (GA) long-acting injection (GA Depot) consists of extended-release microspheres containing GA, administered intramuscularly once every 28 days. Results of GA Depot phase IIa one-year core study and three years extension period in relapsing remitting MS (RRMS) suggest that GA Depot is safe, tolerable and efficacious.

Objectives

Assess the safety, tolerability and efficacy by NEDA-3, defined as: no relapses, no 12-week confirmed disability progression, no new T2 lesions and no gadolinium-enhancing lesions on MRI after three years of treatment with GA Depot in the subpopulation of 10 RRMS patients who completed the core study and continued through three years of the study extension.

Methods

Eligibility criteria included: age 18-70 years, diagnosis of RRMS and treatment with Copaxone® for ≥12 months prior to enrollment. Patients received monthly GA Depot at doses of 80mg or 40mg in the core study and 40mg in the study extension.

Results

Adverse events (AEs) mainly included mild injection site reactions. No unexpected AEs were reported. The number of AEs was significantly reduced during the extension study compared to the core study, and during the fourth extension year compared to the first two years of the study. No systemic immediate post-injection reactions were detected. Patients received all injections as per protocol. Data analyzed by intention to treat population (mITT) (n=10): Mean EDSS score after four years showed no change compared to baseline. No Relapses or MRI activity was noted during that period. Four years NEDA-3 was achieved by 90% of the per protocol population.

Conclusions

Encouraging results of the GA Depot four-year study support its long-term safety, tolerability, and efficacy in this study cohort. It further supports the assumption of GA Depot’s potential to improve MS treatment by significantly reducing frequency of injections, increasing adherence and providing a therapeutic benefit.

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Clinical Trials Late Breaking Abstracts

LB1229 - CLASSIC-MS: Long-term efficacy and real-world treatment patterns for patients receiving cladribine tablets - interim data with 8–14 years follow-up (ID 2108)

Speakers
Presentation Number
LB1229
Presentation Topic
Clinical Trials

Abstract

Background

CLARITY, CLARITY Extension, and ORACLE-MS have previously demonstrated the efficacy of cladribine tablets (CT; cumulative dose 3.5 mg/kg over 2 years). CLASSIC-MS (NCT03961204) seeks to explore the long-term efficacy and durability of effect of CT beyond the 2 annual treatment cycles in patients (pts) enrolled to these parent trials, with the aim of informing future treatment approaches.

Objectives

To present interim data on long-term efficacy and durability of effect of CT and real-world treatment patterns in CLASSIC-MS.

Methods

CLASSIC-MS is an exploratory, low-interventional, multicenter, ambispective, Phase IV study of pts with multiple sclerosis (MS), or those with a first clinical demyelinating event, previously enrolled into Phase III parent trials, and who had received ≥1 course of CT or placebo. The primary objective is long-term mobility (no wheelchair use/bedridden; EDSS <7 in the 3 months prior to first visit in CLASSIC-MS). The main secondary objective is long-term disability status (EDSS <6 any time since last parent study dose [LPSD]). Further objectives seek to assess differences in clinical and magnetic resonance imaging characteristics in long-term responders vs non-responders, with long-term responder status defined as: (A) not requiring further disease-modifying drug (DMD) treatment until ≥4 years after LPSD, or (B) no evidence of disease reactivation based on clinical outcomes in the 4 years following LPSD. Analyses are descriptive.

Results

The interim population comprised 147 pts (61% female; 88% exposed to CT in parent studies; mean EDSS 3.3±2.1 at baseline of CLASSIC-MS [vs. 2.6±1.2 at baseline of parent studies]). Median time since LPSD was 10 (range 8–14) years. The proportion of pts not using a wheelchair/bedridden in the 3 months prior to CLASSIC-MS was 94.6% (139/147) and the proportion of pts with no need of ambulatory device at any time since LPSD was 83.7% (EDSS <6; 123/147). Overall, 73.5% of pts (108/147) were long-term responders by definition A and 45.6% by definition B. In addition, 63.3% of pts (93/147) received no subsequent DMD treatment after LPSD, and 59.1% of pts maintained active employment.

Conclusions

Interim data from CLASSIC-MS, with a median of 10 years’ follow-up, suggests sustained efficacy of CT following 2 annual treatment cycles, with a substantial proportion of pts requiring no further treatment with DMDs or assistive ambulatory device.

CLARITY: NCT00213135; CLARITY Extension: NCT00641537; ORACLE: NCT00725985

Funding: This study was sponsored by Merck KGaA, Darmstadt, Germany.

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COVID-19 Late Breaking Abstracts

LB1230 - Longitudinally Extensive Transverse Myelitis in association with COVID-19 (ID 2109)

Speakers
Presentation Number
LB1230
Presentation Topic
COVID-19

Abstract

Background

Background: Since the beginning of Coronavirus disease 2019 (COVID-19) pandemic, several neurological associations have been described in literature including Transverse Myelitis. Longitudinally Extensive Transverse Myelitis (LETM) is largely known in association with Neuromyelitis Optica Spectrum Disorders (NMOSD) but can be seen with many other inflammatory, infectious, malignant and metabolic causes.

Objectives

Objectives: We hereby report our experience with 3 patients who suffered from LETM preceded by COVID-19 infection. The clinical presentation and outcome as well as the laboratory data is being discussed.

Methods

Methods: We collected the data from 3 patients who were diagnosed to have COVID-related LETM between the period from March 2020 to July 2020. We describe the clinical and laboratory data of these patienst in detail.

Results

Results: There were 3 patients seen from March 2020 to July 2020 who suffered from COVID-19 related post-infectious LETM. They were males from different backgrounds with age ranging from 32 to 52 years. Two of them presented with sensory symptoms and unstable gait, other presented with pure motor syndrome. We investigated the patients for other possible infectious/autoimmune etiologies in detail. All had positive COVID-19 PCR and developed myelitis-related symptoms in variable phase of post-infective period, ranging from 4 days to 4 weeks. NMO- antibodies were absent in all. Associated lab investigations revealed positive Lupus anticoagulant and low Protein S in one patent who developed myelitis within first week of infection and subsequently developed pulmonary embolism. Two patients had CSF results which showed slight increments in protein and leukocytes. Magnetic Resonance Imaging results long segment involvement of cervical and dorsal at different levels, with variable contrast enhancement. One had concomitant involvement of brain. They were all treated as acute post-infectious myelitis as per the general consensus with IV pulse steroid therapy, Methylprednisolone 1 gm daily for 5 days. All showed remarkable recovery and were discharged with minimal neurological symptoms, if at all.

Conclusions

Our findings suggest that despite being a potential cause of longitudinally extensive transverse myelitis, COVID-19 carries a good prognosis if treated in time, with pulse steroid therapy as in our case.

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COVID-19 Late Breaking Abstracts

LB1231 - Demographic and Clinical Profile of Pediatric patients with Multiple Sclerosis infected with SARS-Cov2 (ID 2111)

Abstract

Background

COVID-19, the disease caused by SARS CoV2, causes severe respiratory disease, and rarely multisystem inflammatory syndrome, in some pediatric patients. Little is known about the disease course among patients with pediatric-onset multiple sclerosis.

Objectives

To describe the demographic and clinical characteristics of a subgroup of pediatric-onset multiple sclerosis (POMS) patients infected with SARS CoV2.

Methods

The Network of Pediatric Multiple Sclerosis Centers (NPMSC), a consortium of 10 US pediatric multiple sclerosis (MS) centers contributes clinical information about POMS patients and demyelinating disorders to a centralized database, the Pediatric Demyelinating Disease Database (PeMSDD), to facilitate research for this rare disorder. In addition to collecting clinical data on clinical course, comorbidities, disease modifying therapy use, and functional status, the NPMSC developed a screening questionnaire to administer to patients during standard of care visits to further evaluate their COVID- 19 status. Additionally POMS patients with confirmed or highly suspected COVID-19, will be assessed for risk factors including smoking use, recent glucocorticoid use, comorbidities; clinical presentation, including symptoms, radiological and laboratory data; COVID-19 treatments and outcomes. POMS patients will also complete the COViMS (COVID-19 Infections in MS & Related Diseases) database, a joint effort of the US National MS Society and the Consortium of MS Centers to capture information on outcomes of people with MS and other central nervous system (CNS) demyelinating diseases (Neuromyelitis Optica Spectrum Disease, or MOG antibody disease) who have developed COVID-19. Together with data collected from the PeMSDD, we will present comprehensive data on the POMS patient experience with COVID-19 and compare it to POMS patients without known or suspected COVID-19.

Results

Data collection continues. Results available by the meeting due date will describe the demographics, risk factors, treatments and outcomes of POMS with COVID-19.

Conclusions

Conclusions will be drawn pending results of data analysis. We anticipate reporting on demographic data, risk factors, outcomes and any associations with disease modifying therapy.

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COVID-19 Late Breaking Abstracts

LB1232 - Managing Multiple sclerosis patients diagnosed with COVID-19 infection; into the field of unknown (ID 2112)

Speakers
Presentation Number
LB1232
Presentation Topic
COVID-19

Abstract

Background

Treatments that have been proven to positively change the natural course of Multiple sclerosis (MS) and are widely used in the clinical practice are defined as immunosuppressant or immunomodulatory treatments. Oral, subcutaneous or infusion therapies is based on selective modulation or suppression of certain cells, cell subtypes or interleukins of the immune system. İt's accepted that they increase susceptibility to infections at certain rates. The Covid-19 outbreak, which has been declared a global pandemic, has affected large populations in many countries since January 2020. It is a matter of curiosity about how the patients with MS and those under immunomodulatory treatment, will be affected in this pandemic.

Objectives

We aim to detect the patients with COVID-19 diagnosis among the patients who are followed up with MS diagnosis, whether under immunomodulatory treatment or not and to evaluate how the disease process develops, how the diagnosis of MS and the preventive treatment used affect the disease process.

Methods

The patients who are followed up with the diagnosis of demyelinating disease/MS in our Multiple Sclerosis and Demyelinating Disorders outpatient clinic of the Department of Neurology of the Istanbul Bagcilar Training and Research Hospital were included in this study. Patients were contacted via phone or e-mail or were evaluated in the outpatient and inpatient clinics. A questionnaire was conducted about contact with a person who had a positive test result for COVID-19, symptoms of COVID-19, application to a health care facility, possible/definitive diagnosis of COVID-19, and treatment. Thus, patients diagnosed with COVID-19 were identified, and their clinical features and their treatment were summarized.

Results

We are informed that 9 of our patients were diagnosed with COVID-19. While 6 patients were under preventive treatment, 2 patients were followed without treatment and one patient was diagnosed with MS and COVID-19 simultaneously. All of the patients developed mild symptoms associated with COVID-19 and were treated under quarantine under home conditions. Clinical findings of seven patients were found to be compatible with general viral infection findings such as fever, headache, muscle and joint pain. In addition, chest pain and cough complaints compatible with pneumonia were observed in 2 patients. Covid-19 was confirmed by PCR, and preventive treatment of patients was suspended. Covid-19 treatment was started in accordance with the protocol used in our country. No complication related to COVID-19 infection was observed in any patient. After the control tests, the preventive treatment of the patients was resumed. It was determined that most of the patients had other patients in the family.

Conclusions

Based on the information obtained, the measures that can be taken to ensure the continuity of follow-up and treatment of the patients under pandemic conditions are discussed.

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Observational Studies Late Breaking Abstracts

LB1233 - Blood brain barrier permeability and high dose corticosteroids for MS relapses: a pilot study (ID 2113)

Speakers
Presentation Number
LB1233
Presentation Topic
Observational Studies

Abstract

Background

High dose corticosteroids (HDC) are standard of care for MS relapses. There is scant literature regarding whether relapse localization or timing of HDC affects relapse recovery or blood brain barrier (BBB) recovery.

Objectives

1) To gather data on BBB recovery after HDC treatment using a novel CT technique measuring BBB permeability; and 2) to better understand BBB recovery and examine the clinical correlates associated with BBB recovery after HDC relapse treatment.

Methods

Consecutive persons with MS diagnosed with a relapse requiring HDC treatment were approached. Subjects were excluded if they received HDC in the last 30 days/had started HDC, had an allergy to iodine/CT contrast, had eGFR < 35 mL/min or were diabetic, or if the relapse localized to the optic nerve. Subjects underwent a CT with contrast on days 0 (before HDC), and days 2, 4, and 6 after starting HDC. CT studies were analyzed to generate functional maps of blood flow, blood volume and BBB permeability. Clinical evaluations (EDSS) occurred at relapse, and 4, 12, or 24 weeks after HDC. Planned recruitment was 26 subjects; early termination occurred due to the COVID19 pandemic.

Results

Sixteen subjects agreed to participate; one subject did not to take HDC and was removed. At the time of this abstract, CT data on 2 subjects had not yet been analyzed. All subjects had relapsing MS, with a mean age of 33.1 (+/- 8.3) years. Nine (69.2%) were female; median EDSS was 3.0 (2.0-5.0) at relapse assessment. Mean number of days between symptom onset and HDC was 8.9 (SD 6.5). Relapses clinically localized to the brain (3), posterior fossa (4) or cervical spinal cord (6). Six (46.0%) of subjects demonstrated an improvement in BBB permeability early (responders), while 5 (38.5%) responded slowly and 2 (15.4) did not respond to HDC. There was no significant difference between responders vs non-responders in terms of age, gender, days between onset and HDC, or relapse localization. There was no significant difference between recovery (EDSS) at 4, 12, or 24 weeks between responders vs non-responders.

Conclusions

We did not show any difference between BBB permeability in responders vs non responders (or slow responders) after HDC treatment in terms or relapse recovery. Also, there were no predictors regarding responders vs non-responders. This study may have been underpowered due to early termination. The finding that some subjects’ BBB permeability did not respond at all to HDC warrants further exploration.

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COVID-19 Late Breaking Abstracts

LB1234 - COVID-19 infections in NMOSD and MOGAD: a population based study (ID 2114)

Speakers
Presentation Number
LB1234
Presentation Topic
COVID-19

Abstract

Background

SARS-COV-2 pandemic poses an imminent threat to humanity and in particular in those people suffering chronic diseases. Immune-mediated disease, as NMOSD and MOGAD, could be at a higher risk of severe forms of COVID-19 both for the disease itself and for immunosuppressive treatments.

Objectives

To evaluate the prevalence and severity of COVID-19 infection in the NMOSD/MOGAD population in Italy and evaluate possibily risk factors for disease outcomes.

Methods

The MS Study Group of the Italian Neurological Society has set up a proactive programme to provide information about COVID-19 in NMOSD/MOGAD patients, using a semistructured survey.

Results

569 NMOSD/MOGAD patients from 40 Italian MS Centres have been censored for COVID-19.

68% (387/569) of the patients were treated with rituximab, 16% (91/569) with azathioprine, 4.4% (25/569) with tocilizumab, 5.4% (31/569) with other therapies and 6.2% (35/569) were untreated or without information.

8/569 patients (1.4%) were diagnosed having confirmed or highly suspected COVID-19: positive rhino-pharyngeal swabs for SARS-CoV-2 were found in 4 out of 6 tested patients.

At the time of data collection, 6 patients recovered, 1 was still hospitalised and, unfortunately, 1 died. Hospitalisation was required for 3 patients.

5/8 (68%) patients were treated with rituximab. There was no evidence of any difference of such a percentage with the one of the overall population (OR=0.78, 95%CI=0.18-3.31, p=0.74).

COVID-19 infection was classified mild in 5, severe in 2 and critical in 1. The main experienced symptoms were fever, cough, fatigue and shortness of breath. 5/8 patients experienced CNS symptoms as headache (3), dizziness (1), anosmia (1) and delirium (1).

Conclusions

1) the prevalence of COVID-19 infection appears low in NMOSD/MOGAD patients (1.9%) with a mortality rate similar to that of the general italian population (12.5% vs 14.3%);

2) no other risk factors for severe course of COVID-19 than those already known emerge;

3) the baseline use of biologics, and in particular anti-CD20 monoclonal antibodies, is not associated with a higher risk of COVID-19 infection and apparently not with worse COVID-19 outcomes

Even if preliminary, these findings suggest a cautious optimism in the care of these autoimmune conditions during the pandemic phase.

The MS Study Group: M Inglese, A Di Sapio, D Vecchio, P Cavalla, A Protti, M Radaelli, S Malagu', A Gajofatto, D Landi, G Marfia, MP Amato, A Lugaresi, C Scandellari, S Bonavita, P Perini, F Rinaldi, D Centonze, S Di Lemme, P Immovilli, U Aguglia, M Zaffaroni, S Montepietra, L Moiola, M Filippi, MT Ferro', M Salvetti, MC Buscarinu, F Granella, M Dotta, M Mirabella, M Lucchini, G De Luca, C Tortorella, C Gasperini, G Maniscalco, D Ferraro, E Cocco, R Bergamaschi, M Ulivelli, P Valentino, M Falcini, L Brambilla, G Lus, M De Riz, M Trojano, P Ragonese, A Bertolotto

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COVID-19 Late Breaking Abstracts

LB1235 - Frequency of SARS-CoV-2 antibodies and COVID-19 severity in a cohort of Italian multiple sclerosis patients on DMTs inhibiting immune cell trafficking (ID 2116)

Speakers
Presentation Number
LB1235
Presentation Topic
COVID-19

Abstract

Background

Coronavirus disease 2019 (COVID-19) pandemic is provoking major concerns among physicians and people living with Multiple Sclerosis (pwMS) undergoing disease modifying treatments (DMT). As per today, we do not know what is the impact of SARS-CoV-2 on pwMS and undergoing treatment with DMTs inhibiting immune cell trafficking that are natalizumab (NTZ) and fingolimod (FTY), and vice versa what may be the effects of these drugs on the infection and related disease.

Objectives

To investigate the frequency of SARS-CoV-2 antibodies and to report COVID-19 severity in pwMS on NTZ and FTY affiliated to the MS Centre of IRCCS Mondino, Pavia, Lombardy, Italy.

Methods

Roche SARS-CoV-2 IgG assay (Elecsys®) was used to test serum samples from 106 pwMS (51 treated with NTZ and 55 with FTY). COVID-19 severity was assessed via a 7-point ordinal scale.

Results

Among our cohort of pwMS on NTZ or FTY, the frequency of antibody anti-SARS-CoV-2 was 15%.
Half of seropositive cases were asymptomatic; and half of symptomatic seropositive cases were pauci symptomatic. About 35% of our cohort of pwMS reported COVID-19 symptoms, none of them required hospitalization or die due COVID-19.

Conclusions

Despite we found a high frequency of SARS-CoV-2 antibodies in our cohort of pwMS, half of seropositive cases were asymptomatic. None of symptomatic cases had a severe COVID-19 course. DMTs inhibiting immune cell trafficking seem to be safe in our cohort of pwMS and may be considered as a therapeutical option for highly active MS during COVID-19 pandemic.

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Genetics and Epigenetics Late Breaking Abstracts

LB1236 - The role of ten eleven translocase 2 (TET2) in the regulation of autoimmune demyelinating disease (ID 2117)

Speakers
Authors
Presentation Number
LB1236
Presentation Topic
Genetics and Epigenetics

Abstract

Background

Ten-Eleven Translocase 2 (TET2) is a Fe(III)-, α-ketoglutarate-dependent enzyme that catalyzes the oxidation of methylated cytosine to 5’-hydroxymethyl cytosine (5hmC). 5hmC is a stable epigenetic mark that can either activate or repress gene expression in a cell- and loci-dependent manner. Recently Tet-2 was identified as a genetic susceptibility locus in MS. TET2 loss-of-function mutations are abundant in a variety of cancers characterized by aberrant myeloid proliferation, differentiation, and activation. Since myeloid cells play a critical role in the pathogenesis of Multiple sclerosis (MS) and the animal model experimental autoimmune encephalitis (EAE), we hypothesized that Tet-2 reduction or inactivation in myeloid cells promotes susceptibility to autoimmune demyelinating disease.

Objectives

To measure the expression of Tet2 and 5hmC in CNS-infiltrating myeloid cells during the development of adoptively transferred EAE, and to assess the impact of Tet2 deficiency on the clinical course.

Methods

EAE was induced via adoptive transfer of Th17-polarized, myelin oligodendrocyte glycoprotein (MOG)-specific CD4+ T cells in WT and Tet2+/- mice. CNS mononuclear cells and splenocytes were analyzed via flow cytometry and transcriptomics.

Results

Tet2, 5hmC content, and markers of Tet2 activity, were reduced in CNS-infiltrating monocytes, macrophages and monocyte derived dendritic cells at the peak of EAE compared with their splenic counterparts. Tet2+/- mice experienced an exacerbated clinical course of Th17-mediated EAE compared to Tet2+/+ mice. The increase in disease severity was associated with hyperactivation of CNS myeloid cells. Ongoing studies in our laboratory are examining the effects of a myeloid-specific TET2 deletion on neuroinflammation and CNS damage during EAE using a Cre/lox genetic system.

Conclusions

Our data suggest that downregulation of TET2 expression and activity during EAE enhances neuroinflammation, CNS damage and neurological disability. This study elucidates a novel mechanism of myeloid cell regulation during CNS autoimmune disease. Disease modifying therapies that prevent Tet2 downregulation in myeloid cells may be beneficial in individuals with MS and related disorders who do not respond to lymphocyte targeting agents.

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Disease Modifying Therapies – Mechanism of Action Late Breaking Abstracts

LB1237 - An Antigen-Specific Microparticle Formulation Therapeutically Treats a Mouse Model of Multiple Sclerosis (ID 2121)

Speakers
Presentation Number
LB1237
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

Experimental autoimmune encephalomyelitis (EAE) is a mouse model commonly used to study MS in vivo. We show that an antigen-specific microparticle (MP) system that delivers the autoantigen myelin oligodendrocyte glycoprotein (MOG35-55) along with granulocyte-macrophage colony-stimulating factor (GM-CSF), transforming growth factor beta-1 (TGF-β1), and vitamin D3 (VD3) can alleviate disease in B6 mice suffering from primary progressive EAE. GM-CSF serves as a recruitment chemokine to localize dendritic cells (DCs) to the injection site, while TGF-β1 and VD3 serve as tolerogenic factors to elicit a suppressive phenotype while autoantigen is presented.

Objectives

The objective of this study is to determine the efficacy and the mechanism of the dMP MOG35-55 treatment through the evaluation of clinical scores, immune cell phenotype, myelin differences, and response to opportunistic infection.

Methods

The VD3-loaded MPs and antigen-loadedMPs were fabricated to be phagocytized (1 µm), while TGF-β1-loaded MPs and GM-CSF-loaded MPs were fabricated to be non-phagocytosable (30-50 μm) allowing the release of factors extracellularly. These poly(lactic-co-glycolic acid) MPs were fabricated based on standard solvent evaporation techniques based on hydrophobicity. In vivo experiments: At the onset or peak of disease, a cocktail of VD3, TGF-β1, GM-CSF, and either OVA323-339 (irrelevant antigen) or MOG35-55 microparticles were injected subcutaneously in the middle of the back, with a 2nd injection 3 days later. Additionally, mice were challenged with a listeria monocytogenes infection following dMP treatment to test the antigen-specificity of this treatment. Of note, this experiment was conducted in non EAE induced mice.

Results

dMP MOG35-55 treatment was able to halt EAE at onset and reverse disease at peak. Flow cytometry showed dMP MOG35-55 treatment decreases MHC II expression compared to treatment with dMP OVA323-339 with both treatment at the onset and the peak of disease. Additionally, there were fewer CD8 T-cells, fewer cells expressing GM-CSF, and tbet in dMP MOG35-55 treated mice. Luxol fast blue staining for myelin sheath shows mice treated with dMP MOG35-55 had less demyelination in the lumbar spinal cord. Additionally, infected mice could clear the infection in a time consistent with health controls despite reaching the peak of infection faster.

Conclusions

In this study, we show that the dMP MOG35-55 formulation can halt or reverse EAE in an antigen-specific manner. The lack of demyelination and physical impairment can in part be attributed to a reduction in activated DCs and fewer cytotoxic T-cells in the CNS of dMP MOG35-55 treated mice compared to dMP OVA323-339 treated mice. A future direction will be to expand on CNS cell profiling using histological analysis.

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Neuromyelitis Optica and Anti-MOG Disease Late Breaking Abstracts

LB1238 - Myelin Oligodendrocyte Glycoprotein-antibody positive transverse myelitis presenting as acute flaccid paralysis in a child with enterovirus infection (ID 2123)

Speakers
Presentation Number
LB1238
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Acute transverse myelitis is an immune-mediated disorder targeting the spinal cord and manifests with weakness, sensory deficits, and loss of bowel and bladder control. It can occur as a part of a serologically-defined neuroimmunological syndrome or as monophasic post-infectious illness. While these conditions generally respond well to immunotherapies, direct infections of the spinal cord (e.g. enterovirus related acute flaccid myelitis [AFM]) fare poorly and theoretically could be negatively impacted by immunosuppressive treatments. The clinical and radiological overlap in these conditions poses challenges to acute management of a child presenting with acute flaccid limb weakness.

Objectives

We report a child who presented with subacute onset of flaccid paraplegia, anesthesia, and urinary retention with positive nasopharyngeal swab for enterovirus/rhinovirus (EV/RV), who was found to be positive for MOG antibodies.

Methods

Case report detailing the clinical presentation, laboratory findings, neuroimaging results, clinical decision-making, treatment, and hospitalization course.

Results

A 4-year-old previously healthy Hispanic boy presented with back pain and lower extremity weakness and numbness in July 2020. The symptoms evolved over several hours the previous evening and were preceded by an upper respiratory infection 2 weeks prior. His exam was notable for flaccid paralysis, areflexia, and anesthesia of his lower extremities and urinary retention.

Pertinent laboratory findings included nasopharyngeal swab detection of EV/RV, CSF with 222 WBCs/mm3, glucose 59 mg/dL, protein 171 mg/dL, elevated IgG index of 0.87, and negative CSF enterovirus PCR. Spine MRI demonstrated a longitudinally extensive transverse myelitis largely restricted to the gray matter. Brain MRI showed T2 hyperintense lesion in the right pons and left occipital white matter.

Given his profound leg weakness and potential in benefitting from empirically treating an immune-mediated myelitis, he received IV methylprednisolone and plasma exchange. Serum MOG autoantibody later returned positive (1:100). He regained volitional bladder function and had antigravity lower extremity movements following these treatments.

Conclusions

The case highlights the diagnostic challenges of a child presenting with acute flaccid weakness of unclear etiology. Our patient had demographic (age, seasonality), exam (flaccid, areflexic limbs), and laboratory features (enterovirus/rhinovirus positive on nasal swab) which combined were highly suggestive AFM. However, the presence of a supratentorial brain lesion and concern for an immune-mediated myelitis led to administration of immunotherapies prior to knowledge of his serological results. More efforts are needed to better define the unique characteristics associated with these syndromes to provide diagnostic and treatment guidelines.

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Neuromyelitis Optica and Anti-MOG Disease Late Breaking Abstracts

LB1239 - Pharmacodynamic modeling and exposure-response assessment of inebilizumab in subjects with neuromyelitis optica spectrum disorders (ID 2124)

Speakers
Presentation Number
LB1239
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis optica spectrum disorders (NMOSD) is an autoantibody-mediated, B cell-driven disease. Compared to CD20, CD19 is expressed on a wider range of the B cell lineage, from pro-B to plasmablasts and some plasma cells. Inebilizumab is a humanized, affinity-optimized, afucosylated IgG1κ monoclonal antibody that binds to CD19 resulting in effective depletion of B cells.

Objectives

To conduct population modeling of B cell response following inebilizumab treatment in adult subjects with NMOSD, and to assess the impact of drug exposure to outcome.

Methods

In a double-blind, placebo-controlled study (NCT02200770), adult NMOSD patients were randomized in a 3:1 ratio to receive intravenous infusions of either inebilizumab (300 mg) or placebo on Days 1 and 15 of a randomized-controlled period (RCP, 197 days) and every 6 months thereafter during the open label period. A hematopoietic transit model was developed to describe the depletion of circulating CD20+ B cell by inebilizumab. Furthermore, the relationships between inebilizumab pharmacokinetic (PK) exposure and the primary efficacy endpoint (Adjudication Committee (AC)-determined NMOSD attack) and key secondary efficacy endpoints were evaluated.

Results

Treatment with inebilizumab led to rapid, profound, and sustained depletion of circulating B cells in NMOSD patients. The pharmacodynamic effect of inebilizumab was exerted by joint effects of reducing influx from pro-B cells and accelerating CD20+ B cell depletion in the blood. At the 300 mg dose, there was no apparent relationship between efficacy (reduction in disease attack risk, worsening from baseline in Expanded Disability Status Scale, cumulative total active MRI lesions, and number of NMOSD-related in-patient hospitalizations) with PK exposure. Subjects with low, medium and high PK exposure had a similar hazard ratio of AC-determined NMOSD attack for inebilizumab.

Conclusions

The pharmacodynamic modeling and exposure-response analyses of primary and key secondary endpoints confirmed effective depletion of B cells is achieved with 300 mg dose administered as an IV infusion on Day 1 and Day 15 and every 6 months thereafter. The PK variability between patients had no apparent effect on the hazard ratio for NMOSD attack.

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Diagnostic Criteria and Differential Diagnosis Late Breaking Abstracts

LB1240 - A kappa free light chain index of 6.6 represents an alternative to positive oligoclonal bands in the 2017 McDonald criteria (ID 2125)

Abstract

Background

Oligoclonal bands (OB) are part of the 2017 McDonald criteria but their determination is rater-dependent. Kappa free light chains (KFLC) are determined quantitatively and could be an alternative to OB, but a vendor-specific index cut-off is needed.

Objectives

To compare the proportion of patients with clinically isolated syndromes (CIS) and positive OB and a KFLC index equal or greater than 6.6 (KFLC-6.6, Leurs CE Mult Scler 2020) or 10.61 (KFLC-10.61, Gaetani L J Neuroimmunol 2020). To compare the diagnostic properties of OB, KFLC-6.6 and KFLC-10.61 for 2nd attack and 2017 MRI dissemination in space (DIS) and time (DIT).

Methods

MRIs were obtained 3-5 months after the CIS, at 1 year and every 5 years. OB were determined by isoelectric focusing combined with immunoblotting. We selected 228 patients with sufficient data to assess DIS and DIT, OB determination and enough remnant frozen samples to measure KFLC by turbidimetry (Optilite, The Binding Site). We compared the proportion of patients with positive OB, KFLC-6.6 and KFLC-10.61 and the 3-year diagnostic properties for the following outcomes: 2nd attack (n=179) and MRI DIS and DIT (n=192).

Results

Of all patients, 146 (64.0%) had OB, 147 (65.5%) KFLC-6.6 and 137 (60.1%) KFLC-10.61. In total, 130 (57.0%) had OB and KFLC-6.6, 16 (7.0%) only OB, 17 (7.5%) only KFLC-6.6 and 65 (28.5%) had neither. As for OB and KFLC-10.61, 122 (53.5%) had both, 24 (10.5%) only OB, 15 (6.6%) only KFLC-10.61 and 67 (29.4%) had neither. At baseline, the criteria were fulfilled by patients with OB, KFLC-6.6 and KFLC-10.61 as follows: DIS 109/135 (80.7%), 114 (84.4%) and 106 (78.5%); DIT 70/87 (80.5%), 78 (89.7%) and 74 (85.1%); DIS plus DIT 64/78 (81.2), 71 (91.0%) and 67 (85.9); DIS plus OB 109 (100.0%), 101 (92.7%) and 94 (86.2); and McDonald 111/130 (85.4%), 113 (86.9%) and 106 (81.5%). The diagnostic properties of OB, KFLC-6.6 and KFLC-10.61 for 2nd attack were sensitivity 77.8, 85.6 and 78.0; specificity 44.9, 48.3 and 51.7; and accuracy 61.5, 67.0 and 65.4. Results for MRI DIS plus DIT were sensitivity 81.8, 87.9 and 82.6; specificity 66.7, 70.0 and 73.3; and accuracy 77.1, 82.3 and 79.7.

Conclusions

KFLC-10.61 had the greatest specificity and KFLC-6.6 the best overall diagnostic properties. The results were probably due to the higher proportion of positive KFLC patients with DIT compared to those with positive OB, suggesting KFLC-6.6 could be used as an alternative to OB in the McDonald criteria.

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COVID-19 Late Breaking Abstracts

LB1241 - Incidence and clinical outcome of COVID-19 in a cohort of 11.560 Brazilian patients with Multiple Sclerosis (ID 2127)

Abstract

Background

Little information is available regarding the incidence and clinical outcome of the SARS-CoV-2 infection in patients with multiple sclerosis (pwMS).

Objectives

To determine incidence and severity of COVID-19 among pwMS, and to describe the impact of COVID-19 on MS clinical features.

Methods

This observational study was prospectively performed on a cohort of 11.560 Brazilian pwMS from 47 MS referral centers that registered patients with flu-like symptoms at the REDONE.br platform, from March 13th to June 4th 2020. Inclusion criteria were: i) MS diagnosis according to revised McDonald criteria and ii) clinical symptoms compatible with COVID-19 (cough, fever and asthenia). It was considered COVID-19 confirmed cases those with positive serological or SARS-CoV-2 polymerase chain reaction (PCR) test. Disease severity was classified as mild (home treatment), moderate (hospitalization) and critical (intensive care unit admission). Data related to demographic profile, comorbidity, COVID-19 symptoms, MS treatment and relapse were collected. Univariate and multi-variable regression logistic analysis were performed to identify the variables associated with a higher severity risk in COVID-19 patients.

Results

The incidence of COVID-19 for pwMS patients was 27.7/10.000 patients and for the general Brazilian population was 29.2/10.000 inhabitants at the same time interval (Risk Ratio [RR] 0.92, Confidence Interval (CI) 0.65-1.31, P=0.64). A total of 94 patients (82% female), aged 40 ±10.25 years, presenting 9.9±8.6 years of MS disease duration, developed COVID-19, 66% of them were classified as probable and 34% as confirmed cases by RT-PCR or antibody testing. Most pwMS presented mild (87%) COVID-19 form, that did not require hospitalization, whereas the remaining patients exhibited moderate (11%) and critical (2%) forms. Among critical patients, two developed sepsis and one pwMS (also diagnosed with cancer) died. Eighty (85%) patients maintained MS disease modifying treatment (DMT) during COVID-19 pandemic, and 14 (15%) patients were not in use of any DMT. New neurological manifestations included headache (54%) and anosmia or ageusia (46%). Thirteen (14%) patients evolved with worsening of previous MS symptoms, and a single case had MS relapse five days after infection. Age over 50 years (P=0.024), hypertension (P=0.036) and chronic pulmonary disease (P=0.021) were associated with COVID-19 severity at the univariate analysis. Applying multi-variable analyses, age over 50 years (P=0.010, OR 3.922, 95%CI 1.383-11.121) and the presence of more than one comorbidity (P=0.011; OR 37.329; 95%CI 2.279-611.445) were associated with unfavorable COVID-19 outcome.

Conclusions

Incidence of COVID-19 in Brazilian pwMS was not different from that observed for the general Brazilian population. Most pwMS exhibited mild COVID-19, despite the maintenance of MS treatment. There was MS relapse in only one patient.

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COVID-19 Late Breaking Abstracts

LB1242 - COViMS Registry: Clinical Characterization of SARS-CoV-2 Infected Multiple Sclerosis Patients in North America (ID 2128)

Speakers
Presentation Number
LB1242
Presentation Topic
COVID-19

Abstract

Background

Emergence of SARS CoV-2 causing COVID-19 provoked the need to gather information on the overall outcomes and potential risks associated with morbidity and mortality in multiple sclerosis (MS) patients with COVID-19 infections. The COViMS registry was initiated as a rapid and efficient means to collect this data from North American health care providers.

Objectives

To describe the spectrum of outcomes in SARS CoV-2 infected North American MS patients and to ascertain characteristics associated with severe COVID-19 outcomes.

Methods

The COViMS registry requested that MS, neuromyelitis optica (NMO), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), and radiographically isolated syndrome (RIS) patients with SARS-CoV-2 infection be reported after the outcome was reasonably certain. Data were de-identified and cross-sectional. Effort was made to harmonize with other international registries for COVID-19. Poor clinical outcomes assessed were: mortality, mortality and/or admission to the intensive care unit (ICU), and mortality, ICU admission and/or hospitalization. Associations between patient characteristics and these outcomes were evaluated using multivariable logistic regression. Covariates included sex, age, race, smoking, MS clinical course (relapsing, progressive), MS disease duration, ambulation (fully ambulatory, walks with assistance, non-ambulatory), individual comorbidities (cardiovascular disease, cerebrovascular disease, chronic kidney disease, chronic lung disease, diabetes, hypertension, morbid obesity), and disease modifying therapy (DMT) use.

Results

As of Aug 3, 2020, 764 patients from over 140 different practices were reported; 734 MS, 21 NMO, 4 MOGAD, and 5 RIS. MS patients were 73.4% female (73.4%), 65.2% Caucasian, with mean (SD) age of 48.2 (±13.5) years. Mean disease duration was 13.8 (±9.9) years. 70.9% were fully ambulatory. Ocrelizumab and dimethyl fumarate (DMF) were the top two DMTs used. Most (77.1%) were laboratory confirmed for SARS-CoV-2. Of MS cases, 6.1% died, 13.8% were admitted to the ICU and/or died, and 31.2% were either hospitalized, admitted to the ICU or died. Older age, non-ambulatory status and cardiovascular disease were associated with increased risk of poor outcomes. No specific DMT was associated with increased odds of mortality and mortality and/or ICU admission. Anti-CD20 DMT use showed an increased odds of mortality, ICU admission and/or hospitalization compared to DMF (OR: 2.53 95%CI [1.17, 5.50]).

Conclusions

The data provide reassurance that the MS registry population aligns with reported COVID-19 outcomes in the general North American population. While reported deaths are few, no clear association between a specific therapy and mortality has been seen after adjustment for age, sex, ambulatory status and comorbidities. Data collection continues.

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Pediatric MS Late Breaking Abstracts

LB1243 - Disease modifying treatment changes in pediatric onset multiple sclerosis patients over the past 10 years. A single center retrospective study. (ID 2129)

Speakers
Presentation Number
LB1243
Presentation Topic
Pediatric MS

Abstract

Background

Disease modifying treatments (DMT) in multiple sclerosis (MS) have evolved significantly over the past decade. The expansion of treatment choices provides more options to patients and providers with regards to delivery methods and relapse rate control, however, this also poses new challenges secondary to their side effect profiles. The debate is ongoing in subject to induction versus escalation therapy. The prior proposes initiation of treatments with lower efficacy (lower risk profile) then switching to higher efficacy as needed, whereas the latter recommends immediate higher efficacy treatment. The guidelines to this subject are even less clear in pediatric onset multiple sclerosis patients (POMS).

Objectives

To examine trends of DMT use in POMS patients at a tertiary care center (Baylor College of Medicine/Texas Children’s Hospital) over the past ten years.

Methods

Retrospective chart review via SlicerDicer software was performed looking for POMS patients. Of the initial 239 patients, 124 patients met the following inclusion criteria: diagnosis of MS <18 years of age, ages 0-21 and use of DMT. Data collected: demographics, DMTs used, magnetic resonance imaging findings, expanded disability score status and clinical relapses. Disease progression was defined as the development of new lesions on MRI or a clinical relapse. DMT: injectables-glatiramer acetate, interferons; per os (PO)-fingolimod, dimethyl fumarate, teriflunomide; infusion-rituximab, natalizumab, ocrelizumab.

Results

Of the 124 POMS patients, 41.1% were male and 58.8% were female, with mean age of diagnosis at 15 years (standard deviation +/- 3). 60 patients (48.4%) transitioned DMT during follow up, while 64 (51.6%) remained on their initial medication. Of those who transitioned DMT, 17 switched more than once (totaling 85 switches). 45 switches were due to disease progression (52.9%), whilst 40 were due to side effects and/or noncompliance (47.1%). Of the patients switching DMT due to disease progression, 60% were on injectables, 37.8% on PO and 2.2% on infusions. For those who never switched DMT, 39.7% were on injectables, 33.3% on infusions, and 27% were on PO. 95.45% of patients started on infusions never switched, however 54.84% on PO and 35.71% on injectables switched their DMT. In 2011, 20 patients were on injectables, 14 on PO and 2 on infusions. Whereas in 2020, only 6 patients were on injectables, 8 on PO and 29 on infusions, demonstrating an upward trend in use of infusions. Annual relapse rate (AAR) between 2011-2020 regardless of DMT was 0.13 with a median of 0. The AAR for injectables, orals and infusions were 0.13, 0.17 and 0.026, respectively.

Conclusions

At this tertiary care institution, nearly half of patients with POMS have changed DMT either due to disease progression or side effects. Those on infusion therapies were seen to be more likely to remain on their treatment, have lower ARR and less disease progression compared to other treatment options.

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COVID-19 Late Breaking Abstracts

LB1244 - Manifestations and Impact of the COVID-19 Pandemic in Neuroinflammatory Diseases (ID 2130)

Abstract

Background

We have limited understanding of the risks and impact of COVID-19 in neuroinflammatory diseases (NID) of the central nervous system, particularly among patients receiving disease modifying therapies (DMTs).

Objectives

To report initial results of a planned multi-center year-long prospective study examining the risk and impact of COVID-19 among persons with NID.

Methods

In April 2020, we deployed online questionnaires to individuals in their home environment to assess the prevalence and potential risk factors of COVID-19 symptoms in persons with and without NID.

Results

Our cohort included 1,115 participants (630 NID, 98% MS; 485 reference) as of April 30, 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. Persons with NID 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 persons with NID. 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).

Conclusions

Our study of real-time, patient-reported experience during the COVID-19 pandemic complements physician-reported MS case registries that capture an excess of severe cases. Overall, persons with NID seem to have a risk of suspected COVID-19 similar to the reference population.

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Biomarkers and Bioinformatics Late Breaking Abstracts

LB1245 - BB-CRESM: a structured institutional biobank for quality research in Multiple Sclerosis. (ID 2131)

Speakers
Presentation Number
LB1245
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Biobanks have recently become an important tool in clinical research. The availability of biological samples collected and stored following strict quality standards is crucial in biomedical and translational research in Multiple Sclerosis (MS), to better understand disease pathogenesis, identify biomarkers of diagnosis, prognosis and treatment response.

The Regional Reference Multiple Sclerosis Center (CRESM) at the S. Luigi Gonzaga Hospital provides comprehensive care for more than 2000 MS patients. It has been operational since 2013 in transforming the reserve of biological samples into a structured biobank.

Objectives

To describe the establishment of a structured MS biobank starting from a collection of biological samples and the process for providing scientists with biological samples and associated data.

Methods

According to guidelines by the “Biobanking and Biomolecular Resources and Research Infrastructure” (BBMRI), the steps for the BB-CRESM establishment were: Institutional commitment; Biobank management and staffing; Development of procedures to address ethical, legal, and social issues, according to the General Data Protection Regulation, in collaboration with a bioethicist.

All technical procedures were included into Standard Operating Procedures manual.

Results

BB-CRESM is a structural part of the Piedmont Regional Health Service. The General Director of San Luigi Hospital approved its Regulation, selected the BB-CRESM director and the members of the Scientific Committee.

BB-CRESM is a non-profit organization supported by the Italian Multiple Sclerosis Foundation.

Specific protocols regulate the timing and modalities of biological sample collection, ensuring privacy of subjects.

A detailed description of the biobank is in-person explained to each patient or healthy subject with the help of a leaflet; following which the informed consent is obtained. The Ethical Committee approved both the leaflet and the informed consent model.

Scientists can apply to the director of BB-CRESM specifying number, types and quantity of required samples and data. The samples can be distributed if a) they are used for a research project approved by an Ethic Committee; b) the research project is approved by the Scientific Committee; c) the scientist signs the Material Transfer Agreement; d) scientist agrees to share crude data with BB-CRESM e) scientist contributes to BB-CRESM collection and shipment expenses.

Since 2013, more than 1000 participants (healthy controls and MS patients) have enrolled in the BB-CRESM; over 20000 tubes of biological material (cerebrospinal fluid, serum, plasma, PBMCs, RNA and DNA) have been collected and stored.

Conclusions

BB-CRESM collects, stores and distributes biological samples along with associated data ensuring quality of collection and bio-banking according to BBMRI.

MS researchers can contact BB-CRESM at biobanca.cresm@sanluigi.piemonte.it.

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Imaging Late Breaking Abstracts

LB1246 - Future implementation of automated analysis tools for Multiple Sclerosis on conventional magnetic resonance imaging. (ID 2132)

Speakers
Presentation Number
LB1246
Presentation Topic
Imaging

Abstract

Background

Magnetic resonance imaging (MRI) is imperative for the detection and characterization of Multiple Sclerosis (MS) lesions in the central nervous system. The revised McDonald's criteria of 2017 involve brain and spinal cord MRI lesions with respect to dissemination in time and space to aid in establishing the diagnosis. Furthermore, MRI is the principal tool of tracking brain and spinal cord changes and monitoring treatment effects and disease progression. Manual evaluation of multiple evolving MS lesions and particularly estimation of brain atrophy is difficult due to the time-consuming nature of longitudinal assessment, the complexity of brain volume estimation, and is subject to significant inter-observer variability.

Objectives

This study aims to survey current commercial and freeware automated tools for lesion identification and brain volume monitoring. We evaluate the feasibility and identify barriers in the adoption of computerized tools in the clinical setting.

Methods

A literature search was performed in PubMed, and Google Scholar databases and publications on automated image evaluation tools in multiple sclerosis were identified and reviewed. Findings in other neurologic populations supplemented limited evidence on reliability and validity.

Results

We evaluated various existing automated software packages suitable and specifically developed for the multiple sclerosis population, including SepINRIA, Icobrain, DeepMedic, and others. We confirmed the benefits of image analysis automation. We describe differences between available software models, their advantages and disadvantages. Notably, we identify challenges faced by existing software implementations representing an obstacle to their wide adoption, such as hardware requirements, price of purchase and maintenance, absence of a gold standard, and uncertainty of healthcare benefits.

Conclusions

After exploring the barriers, we propose solutions to integrating automated image analysis into routine practice through the development of a quality assurance and decision support system.

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COVID-19 Late Breaking Abstracts

LB1247 - Clinical features of COVID-19 in patients with neuromyelitis optica spectrum disorders  (ID 2133)

Abstract

Background

Brazil is currently considered one of the main epicenters of the coronavirus disease 2019 (COVID-19). There are many concerns related to neuromyelitis optica spectrum disorders (NMOSD) patients. In addition to the older age of onset, higher disability and the higher rate of hospitalization compared to MS, many of the commonly used preventive therapies for NMOSD are cell depleting immunosuppressants with increased risk of viral and bacterial infections.

Objectives

To describe the frequency and clinical characteristics of COVID-19 in neuromyelitis optica spectrum disorder (NMOSD) patients in Brazil.

Methods

The Brazilian Study Group NMOSD of the Brazilian Academy of Neurology has set up the registration of COVID-19 cases in NMOSD patients, using a designed web-based case report form, encompassing neuroimmunology centers and individual neurologists across the country. Data collected between March 19thand July 31th 2020 were uploaded at the REDONE.br platform. Inclusion criteria were: (i) NMOSD diagnosis according to 2015 International Panel; (ii) confirmed SARS-Cov-2 infection (RT-PCR or serology) or clinical suspicion of COVID-19 diagnosed according to CDC/CSTE case definition. Demographic data, NMOSD clinical characteristics pre and post infection, comorbidities, immunosuppressive treatment, COVID-19 clinical features and severity were described.

Results

Among the 2,061 NMOSD patients inscribed at the REDONE.br platform, 34 patients (29 women) aged 37.1 years (range 8-77), with disease onset at 31.2 years (range 4-69) and disease duration of 5.9 years (range 0.2-20.5), developed COVID-19 (18 confirmed and 16 probable cases). Most patients exhibiting mild disease was treated at home (76.5%) and 4 patients needed treatment at intensive care units (severe cases); one patient died. Four patients had NMOSD relapse during the infection; one with partial recovery.

Conclusions

The clinical features of COVID-19 in NMOSD patients were described, stressing the combination of comorbidities and immunosuppression. Mild COVID-19 was the main presentation. Collaborative studies using shared NMOSD data are needed to suitably define factors related to COVID-19 outcome.

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Symptom Management Late Breaking Abstracts

LB1248 - Proof-of-concept trial of a novel dietary supplement, Multicafe®, for fatigue in multiple sclerosis (ID 2134)

Abstract

Background

Fatigue is a prevalent and disabling symptom of multiple sclerosis (MS). Inflammation and oxidative stress may play a role in the pathophysiology of fatigue. While a few pharmacological and behavioral interventions may be helpful, there remains an unmet need for more effective and affordable options. Multicafe® is a novel dietary supplement composed of coffee, guarana, selenium and L-carnitine, that showed anti-inflammatory and antioxidant effects in preclinical studies.

Objectives

We aimed to investigate the safety of Multicafe®. Secondarily, we aimed to assess the effect of Multicafe® as well as the influence of daytime sleepiness, cognitive processing speed, and walking time on fatigue.

Methods

This was a proof-of-concept, double-blind, controlled trial. Adult patients with relapsing or progressive MS, EDSS up to 5.5 and clinically relevant fatigue were randomized to an oral daily dose of either Multicafe® or placebo, as an add-on therapy, for 12 weeks. The primary endpoint was the Modified Fatigue Impact Scale (MFIS), with a reduction of 10 or more points from the baseline (responders). Secondary endpoints included the Epworth Sleepiness Scale, Symbol Digit Modalities Test (SDMT), and Timed 25-Foot Walk (T25FW).

Results

Among the total of 30 patients recruited, 16 received Multicafe® and 14 received placebo for 12 weeks. Female preponderance was lower (69% vs 93%) and MFIS score at baseline was slightly higher (55.8 vs 48.4) in the Multicafe® arm, with other demographic and clinical features similar between groups. Two patients in each group experienced mild, self-limited gastrointestinal symptoms. No other adverse events were considered related to Multicafe®. There were no serious or unexpected adverse events. Mean reduction in the MFIS score at 12 weeks was greater in the Multicafe® arm compared to placebo (-26% vs -7%); similarly, the proportion of responders was higher with Multicafe® (57% vs 40%). The patients who had greater reduction in the MFIS were younger and had a trend towards lower EDSS scores at baseline. The MFIS scores correlated with the Epworth scale and the T25FW, but not with the SDMT.

Conclusions

Multicafe® was safe and well-tolerated in MS. Our preliminary data suggest a possible benefit in reducing MS-related fatigue, especially in younger patients with lower disability. Future efficacy study may confirm the clinical benefit of this dietary supplement for fatigue in MS.

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COVID-19 Late Breaking Abstracts

LB1249 - Types of pharmaceutical intervention in patients with Multiple sclerosis (MS): A fine line between immunosuppressive and risk of COVID-19 infection (ID 2135)

Speakers
Presentation Number
LB1249
Presentation Topic
COVID-19

Abstract

Background

COVID-19, as an infectious respiratory disease, was identified in December 2019, which quickly spread around the world and developed to a pandemic. COVID-19 mainly affects people with underlying medical conditions and older individuals. Based on the reports of Iran's Ministry of Health and Medical Education, 331,189 persons have been infected with COVID-19 in Iran until August 12, 2020.

Objectives

Multiple sclerosis (MS) is a chronic autoimmune disease that requires long-term treatment with disease-modifying therapies (DMTs) that needs special attention during this pandemic. According to the annual report of the Iranian MS Society, the number of people with MS (pwMS), is approximately 72,000. Immunosuppressive therapy is a primary pharmaceutical intervention that may provide some protection, or may worsen the severity of COVID-19 in pwMS. We believe that by evaluating the relevance between the routinely used MS DMTs associated with the risk of serious infections, an appropriate strategy can be adopted to protect them.

Methods

In the current study, information about 371 pwMS (63.3% female, mean age=39.4, mean follow-up=5.1 years) with a COVID-19 positive test (confirmed by RT-PCR on nasal and pharyngeal swabs) was conducted from two different hospitals that care for Coronavirus infected peoples in Tehran. The patients were taking these drugs: Synovex (195, 52.5%), Rebif (56, 15.2%), Fingolimod (41, 11%), Avonex (24, 6.4%), ReciGen (27, 7.5%), IFN-β (18, 4.9%), Ocrelizumab (3, 0.8%), and unexposed patients (7, 2%).

Results

When diagnosing associations with individual infections, exposure to any of DMTs was associated with a lower risk of pneumonia compared with no DMT exposure. Besides, exposure to fingolimod and Ocrelizumab were associated with an increased risk of an upper respiratory infection when compared to no exposure or other drug exposure.

Conclusions

By analyzing MS DMTs, we thought that IFN-β is associated with a lower risk of pneumonia due to its antiviral effect. Thus, Interferon Beta Drugs can provide a less experienced risk in confronting with COVID-19.

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Biomarkers and Bioinformatics Late Breaking Abstracts

LB1250 - Neuronal integrity is associated to peripheral leukocyte dysfunction in asymptomatic Multiple Sclerosis (MS) first-degree relatives (ID 2136)

Speakers
Presentation Number
LB1250
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Genetic studies suggest that peripheral immune dysfunctions occurs first in the causal chain of events leading to MS. However, these changes are typically not appreciated when patients present with their first symptom or with an asymptomatic inflammatory lesion; we have only sparsely characterized individuals before they develop disease. Thus, the earliest molecular events leading to damage of the CNS parenchyma remain unknown.

Objectives

To investigate the correlation between a marker of neuronal integrity (Neurofilament light chain, NfL) and the transcriptional profile of peripheral immune cells during the pre-symptomatic phase in a cohort of first-degree family members of MS patients.

Methods

Blood samples were collected from 124 asymptomatic first-degree relatives of MS patients part of the Genes & Environment in MS (GEMS) study, 7 MS patients, and 11 patients with other neuroimmune diseases (ONID), age (20-54). Serum samples were used to assess NfL levels using the SIMOA platform. Cryopreserved peripheral blood mononuclear cells (PBMC) were used to generate RNA-sequencing data. ‘CIBERSORT’ was used to estimate the proportions of major PBMC cell types (CD4 and CD8 T, monocyte, B, and NK) from the gene expression data. ‘WGCNA’ was used to to identify PBMC co-expressed gene modules. Available genotyping data were used to calculate a polygenic MS risk score for each individual.

Results

Serum NfL levels from GEMS individuals increased with age (p=2E-14), and were significantly lower than MS and ONID patients, adjusting for the effects of age and sex. NfL was not elevated in high-risk (high polygenic score) vs. low-risk family member subgroups.

After batch variation and technical variable correction 114 GEMS subjects qualified for PBMC bulk RNA-sequencing analysis. ‘WGCNA’ identified 37 co-expressed gene modules, 4 of which were associated with NfL levels (FDR-adjusted p<0.05), adjusting for effects of age, sex and estimated cell type proportions. One particular module is enriched in myeloid cells, and myeloid-mediated immunity and myeloid activation pathways; an association that persisted after accounting for the proportion of different cell types. The other 3 modules were all enriched for genes upregulated in chronic myelogenous leukemia and downregulated gene targets of KLF1 transcription factor.

Conclusions

The transcriptional programs of some peripheral immune cells strongly correlate with NfL levels; ongoing data replication. These results implicate a cross-talk between the peripheral immune system and the CNS that could provide additional insights into MS pathophysiology; the direction of the association is being explored.

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COVID-19 Late Breaking Abstracts

LB1251 - National Multiple Sclerosis Society Healthcare Provider Councils COVID-19 Survey (ID 2138)

Speakers
Presentation Number
LB1251
Presentation Topic
COVID-19

Abstract

Background

The COVID-19 crisis has created unanticipated changes in health care delivery for people living with multiple sclerosis (MS). The pandemic’s rapid evolution has resulted in a knowledge gap about how COVID-19 has affected practice patterns of MS clinicians.

Objectives

To understand how the COVID-19 pandemic has affected clinical practice patterns of a nationwide cohort of MS clinicians across the United States.

Methods

In collaboration with the National Multiple Sclerosis Society (NMSS), we used SurveyMonkeyTM to develop a 28-item electronic questionnaire exploring MS specialists’ perceptions of how COVID-19 has altered how they prescribe MS disease-modifying therapies (DMTs) and provide telehealth and other services, and issues affecting their own well-being including re-deployment to the front lines of COVID-19 care and availability of personal protective equipment. NMSS staff sent a recruitment email containing the electronic survey link to 188 clinicians who serve on regional NMSS Healthcare Provider Councils across the United States, 86 of whom were MS specialist physicians.

Results

Eighty-six respondents (46% of 188 clinicians) from 32 U.S. states completed the survey including 45 physicians, 18 rehabilitation therapists, 7 psychologists, 6 advanced practice clinicians, 4 social workers, 2 nurses, a pharmacist and a researcher. More than 72% of all respondents believed they have adequate personal protective equipment at work, while only 37.2% indicated they could safely distance themselves from others at work. Nearly 6% of respondents reported they had been re-deployed to the front lines of COVID-19 patient care, and an additional 15% anticipated being re-deployed. The physician subgroup had a 54% response rate and included 41 neurologists, 3 physiatrists and 1 family physician. More than one-third of physicians indicated that since the pandemic began, they use telemedicine to provide more than 75% of their clinical care. Nearly 80% believed COVID-19 may have changed how they prescribe DMTs. DMTs prescribed more often during the pandemic included β-interferons (28.6% of 42 prescribers), natalizumab (25%) and glatiramer acetate (21.4%), while DMTs prescribed less often included alemtuzumab (64.2%), cladribine (52.4%), and B cell-depleting agents including ocrelizumab and rituximab (50%). Some MS specialists reported suspending certain DMTs during the pandemic (21.4% each for alemtuzumab and B cell-depleting agents) and/or extending the dosing intervals (38.1% for natalizumab and 11.9% for fingolimod and siponimod).

Conclusions

In this nationwide survey, MS specialist physicians and other clinicians serving on regional NMSS Healthcare Provider Councils across the U.S. reported major changes in their delivery of MS care during the COVID-19 pandemic. Further research is warranted to explore these trends and to develop consensus guidelines on best treatment practices for patients living with MS.

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Disease Modifying Therapies – Risk Management Late Breaking Abstracts

LB1252 - COVID-19 and multiple sclerosis – prevalence and the impact of disease modifying therapies (ID 2142)

Speakers
Presentation Number
LB1252
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

There has been growing concern that disease modifying therapies (DMTs), as used in multiple sclerosis (MS), might increase the risk for an infection with SARS-CoV-2 and alter the clinical course of this infection.

Objectives

To assess the prevalence of COVID-19 in patients with MS (pwMS) and the potential impact of DMTs on its clinical course.

Methods

We used IBM Explorys, a data set covering electronic medical records of more than 72 million unique patients from hospitals in the United States, out of which we identified pwMS with and without PCR-confirmed COVID-19; we assessed baseline characteristics as well as DMTs for risk factors on the prevalence as well as a worse clinical outcome. Comparisons of cumulative prevalence of COVID-19, risk of hospitalization and death were made using logistic regression adjusted for patient age, sex, body mass index (BMI), comorbidities and race.

Results

We identified 30,116 pwMS with an open prescription for a DMT; 170 were COVID-19 positive. The risk of developing COVID-19 in pwMS did not appear to be higher when compared to patients with systemic lupus erythematosus (SLE), another chronic autoimmune disease (infection rate: 0.56% in MS vs. 0.58% in SLE; hospitalization: 30% vs. 36%; deaths: 3% vs 4%). PwMS with older age, male sex, high BMI, and cardiovascular disease were at higher risk to die in the context of this infection. PwMS on interferons appeared less likely to develop COVID-19 (0.35% of the overall group of pwMS) compared with high efficacy DMTs (p < .05), whereas anti-CD20 and anti-CD52 therapies were found to be associated with a higher risk of developing COVID-19 (1.67% and 1.15%) (p < .05).

Conclusions

Our findings demonstrate that MS is not prone to a higher or different risk of infection with SARS-CoV-2. Risk factors are similar to those reported for the general population. Some DMTs, however, appear to be associated with some level of protection, whereas others are associated with an increased risk for COVID-19. Such findings, once confirmed, might be taken into account when treating pwMS.

Supported by: Biogen

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COVID-19 Late Breaking Abstracts

LB1253 - The Impact Of COVID19 Pandemic On NeuromyelitisOptica Spectrum Disorder Patients In Isfahan , Iran. (ID 2146)

Speakers
Presentation Number
LB1253
Presentation Topic
COVID-19

Abstract

Background

Background:

Coronavirus 2019 (COVID-19) is a new coronavirus SARS-CoV-2 that has created a global pandemic with high mortality. People with underlying medical conditions and immune system suppression are more prone to severe infection. Neuromyelitis optica spectrum disorder (NMOSD) is a potentially disabling disease that is treated by immunosuppressive drugs. The nature of disease as well as its treatment potentially predisposes patients to various infections, including Covid-19 infection.

Objectives

Objectives:

The aim of this study was to evaluate the effect of COVID-19 pandemic on the clinical course of NMOSD patients and to assess the level of anxiety and fear in them as well as to evaluate the characteristics of Covid-19 infection in patients with NMOSD. We report some cases of COVID19 infection among our patients.

Methods

Methods and Materials:

A descriptive study was done in 140 patients (116 female and 24 male) in NMOSD Cohort clinic of Kashani hospital, Isfahan, Iran. All patients were contacted by telephone and were asked about their

infection with the Coronavirus and their treatment during its outbreak. Hospital Anxiety and Depression Scale (HADS) questionnaire were filled out via phone calls to assess patients' anxiety in pandemic.

Results

Results:

The study included 140 patients (43 seropositive). Their mean age was 36.83±9.82 and mean duration of disease was 8.06±5.09 years. They experienced overall 43 relapses within the last year (ARR:0.3) and 9 relapses during COVID19 epidemic (ARR:0.19). A total of 112 patients (80%) experienced anxiety or fear during the pandemic period.

Six patients infected by COVID-19 and one of them experienced ICU admission. There was neither death nor serious complication nor atypical presentation of COVID19. All six patients were treated by rituximab and the prevalence of COVID-19 was 4.8% in patients taking rituximab .

The mean age of these 6 patients was 37.80±17.72 and the disease duration was 7.20±3.27 years. There was not statistical difference between the mean age of infected patients and that of the rest of NMOSD population. Of the 124 patients treated with Rituximab, 32 cases postponed their treatment due to fear of infection and hospitalization. (1.95±1.16 months delay averagely).

Conclusions

Conclusion:

Our results showed that in our NMOSD patients, in spite of suppression of the immune system, neither incidence nor the serious complication of covid-19 infection was high. Therefore, regarding the disabling nature of NMOSD as well as prolonged epidemic period, it may be reasonable to continue the routine treatment of these patients along with more training of patients to stick to health protection instructions. We also found that patients with NMOSD are more prone to anxiety and fear of pandemic.

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COVID-19 Late Breaking Abstracts

LB1254 - A real-world data study of Coronavirus-2019 disease severity in patients with multiple sclerosis treated with ocrelizumab (ID 2150)

Speakers
Presentation Number
LB1254
Presentation Topic
COVID-19

Abstract

Background

Ocrelizumab (OCR) is a B-cell depleting monoclonal antibody approved for the treatment of multiple sclerosis (MS), including relapsing and primary progressive forms of MS. The Coronavirus-2019 disease (COVID-19) pandemic raises concerns about clinical course and outcomes of COVID-19 in MS patients undergoing immunosuppressive treatment.

Objectives

To describe the clinical course and outcomes of COVID-19 in multiple sclerosis (MS) patients treated with ocrelizumab (OCR).

Methods

A retrospective cohort study of OCR treated MS patients with COVID-19 diagnosis who received treatment for COVID-19 in the Optum® de-identified COVID-19 Electronic Health Record (EHR) dataset. Inclusion criteria: confirmed COVID-19 diagnosis (ICD10 diagnosis, or positive diagnostic lab test since Feb 20th 2020), and OCR treatment ≤6 months prior to COVID-19 diagnosis. Patients with less than 28 days of follow-up were excluded. COVID-19 severity was categorized according to a 4 level ordinal scale based on worst status experienced during COVID-19 clinical course: 1) not hospitalized, 2) hospitalized, 3) hospitalized requiring invasive mechanical ventilation, 4) death. Secondary outcomes included the proportion of hospitalized patients diagnosed with respiratory failure, bacterial pneumonia, and sepsis on admission.

Results

As of 13 July 2020, there were EHRs for almost 128,000 patients with laboratory or clinically confirmed diagnosis of COVID-19. Forty-seven OCR treated patients were identified (32% male, median age 47 years, median Charlson comorbidity index 1.0, mean BMI 29.4 kg/m2, mean time since OCR initiation 1.3 years). Per COVID-19 severity scale, 75% (n=35) were not admitted to hospital, 21% (n=10) were hospitalized, 2% (n=1) required invasive ventilation and 2% (n=1) died. Compared to OCR cohort, Hospitalized patients (n=12) were older (median age 57.0 years) and consisted of proportionally more males (50%). On hospital admission, of patients not requiring ventilation, 40% (n=4) had respiratory failure, 10% (n=1) bacterial pneumonia and 0% sepsis, while both patients requiring ventilation, one of whom subsequently died, had respiratory failure and sepsis on admission.

Conclusions

In this large US cohort of confirmed/clinically COVID-19, a few treated with OCR were identified with majority experiencing mild disease not requiring hospitalization, and two patients suffering critical illness. This study provides initial real-world insights on the impact of COVID-19 in MS patients treated with OCR.

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COVID-19 Late Breaking Abstracts

LB1255 - Influence of social isolation measures due to Covid-19 on the quality of life of people with Multiple Sclerosis (ID 2151)

Speakers
Presentation Number
LB1255
Presentation Topic
COVID-19

Abstract

Background

People with Multiple Sclerosis (MS) are often treated with immunosuppressants or immunomodulators and are more susceptible to worsening in the course of COVID-19 if they get infected with the SARS-CoV-2 virus. Social isolation is necessary to minimize the risk of infection.

Objectives

To analyze the influence of social isolation measures on the quality of life of people with MS during the COVID-19 pandemic period.

Methods

41 people with MS participated (22RR, 14PP, 5SP), 25 females and 16 males, aged between 18 and 70 years, EDSS from 0 to 8.5. All of them answered a structured questionnaire containing 15 questions about patients perception in the physical, communicative and psychological domains during social isolation.

Results

According to the domains: In physical: changes in daily life (n = 37/90%), fatigue (n = 22/54%), difficulty in walking (n = 28/68%), pain (n = 23/56%) and decreased muscle strength (n = 24/58%). In communicative it was identified difficulty in verbal communication (n = 13/32%), change in activity and communicative frequency (n = 31/76%), with reduced face-to-face communication and increased use of video calls by cell phone. In psychological terms, perception of vulnerability (n = 20/49%), sadness (n = 27/66%), concern / fear (n = 31/75%) and impact on quality of life (n = 33/80%), with the support of family / friends, online treatments, leisure and religiosity, helping to deal with the social isolation.

Conclusions

During the social isolation in Brazil, due to the COVID-19 pandemic, the majority of respondents in this cross-sectional study revealed a moderate to severe impact on quality of life in all domains. In the face of uncertainties, MS specialists must adapt to monitoring for complications in the spheres of physiotherapy, psychology and speech therapy, as well as adopt rehabilitation options applicable to the moment.

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Epidemiology Late Breaking Abstracts

LB1256 - New findings from the 2020 MS Barometer on MS prevalence, practicing neurologists and use of disease-modifying drugs across Europe (ID 2152)

Speakers
Presentation Number
LB1256
Presentation Topic
Epidemiology

Abstract

Background

The European Multiple Sclerosis Platform (EMSP) has conducted a survey of national MS societies periodically since 2008. The ‘Barometer’ measures the performance of health and social care systems using national data and knowledge. It aims to provide an accurate picture of multiple sclerosis (MS) management across Europe and support international benchmarking. The Barometer is designed to be an advocacy tool supporting decision-makers to make evidence-based policies and improve access to treatment, care and quality of life for people with MS. Preliminary findings for three indicators are presented in this poster; the full 2020 MS Barometer will be launched November 2020.

Objectives

To carry out a sub-analysis of the Barometer findings on the number of people with MS, the number of practicing neurologists and the percentage of people with MS on disease-modifying drugs (DMDs) across Europe.

Methods

The Barometer questionnaire was developed in consultation with an expert group composed of representatives from national MS societies, healthcare professionals, industry and the Copenhagen Institute for Future Studies. A SurveyMonkey questionnaire was sent to all national MS societies who are members of EMSP. For all questions related to DMDs, respondents were asked to consider the following treatments: interferon-beta 1a, peginterferon-beta 1a, interferon-beta 1b, glatiramer acetate, teriflunomide, dimethyl fumerate, fingolimod, cladribine (oral), siponimod, natalizumab, alemtuzumab, and ocrelizumab.

Data collection ran between September 2019 and July 2020 with the support of Quality Health and the Health Policy Partnership. Responses were received from 35 countries. The results of this survey were examined and any clarifications required were followed up by EMSP with the national society.

Results

Based on the results from the survey, there are 1,118,485 people with MS living across 35 European countries. Respondents recorded 61,002 practicing neurologists across these countries, a ratio of 18:1 people with MS per neurologist; however, these ratios had a large variance across the surveyed countries. 30 countries reported the percentage of people on DMDs, resulting in a European average of 55% and a median of 51%.

Conclusions

A survey of national MS societies across 35 countries indicates that the number of people with MS in Europe is now over 1,100,000. Countries reported a median of 51% of people with MS on DMDs. Across Europe the survey found approximately 61,000 practicing neurologists.

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COVID-19 Late Breaking Abstracts

LB1257 - Nowcasting Covid-19 in patients with Multiple Sclerosis via social media (ID 2153)

Speakers
Presentation Number
LB1257
Presentation Topic
COVID-19

Abstract

Background

SARS-Cov2 pandemic, starting in December 2019, demonstrated the need to rapidly gather data. Results of multicenter registries were published online first on 30-Apr-2020, 90 days after the 1st report of Covid-19 in Italy. Nevertheless, social media channels like Twitter® reported more promptly, but unstructured about Covid-19 cases.

Objectives

First, we aim to investigate whether an automated big data Twitter® search for reported MS cases with SARS-Cov2 infection can be used to set up a database and fill the timely gap between start of pandemic and publication of registry results. Second, we aim to compare the anonymized Twitter generated registry with the published information on Covid-19 taken from two reports of MS cohorts.

Methods

Twitter® was searched using over fifty hashtags from February 29th until publication of first registry data (30-Apr-2020). The resulting Twitter® data was compared with the Italian and French registry data published in Lancet Neurology and JAMA Neurology, respectively: for both cohorts: age, and sex, for French cohort only: hospitalization due to Covid-19. Chi2 test and a one-sample t-test (for age comparison) with mean age of Italian and French cohort as control values were used.

Results

Until 30-Apr-2020, 40 MS Covid-19 cases were identified and most cases have been published until 31-Mar-2020 (36/40); one month before first registry data was available. All cases were anonymized. MS patients were treated with anti-CD20 13/40, fingolimod 9/40, alemtuzumab 5/40, dimethyl fumarate 4/40, cladribine 3/40, and natalizumab/glatiramer acetate/interferon each 2/40. Information on severity was present in 38/40 cases and 7/38 (18.4%) were hospitalized compared to 73/347 in the French cohort (21.0%, p-value ≥0.05). Age was reported in 21/40 and sex in 20/40 cases with patients being in mean 41.4 years (SD 12.7) old and in 12/20 female. These rates did not differ from reported rates in the Italian or French cohort (each p-value ≥0.05).

Conclusions

Social media demonstrated to rapidly provide limited data on SARS-Cov2 pandemic in patients with MS faster than classical patient registries. Within the reported data, severity, age and sex appeared to be comparable to previous reports, however, for age and sex limited by the amount of missing values. Further limitations are the single point of observation lacking complete follow-up data, and the unstructured reporting within the given limitations of word counts. However, if in the future structured reporting of anonymized data sets could be established and flagged via common hash tags, quality of a social media reporting might serve as complementary strategy to common registry work. The main positive impact of such an approach is the rapid distribution of crucial information in a given emergency setting like the SARS-Cov2 pandemic and the complete availability to all persons without any access restrictions.

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COVID-19 Late Breaking Abstracts

LB1258 - SARS-CoV-2 pandemic lockdown: perceived consequences on multiple sclerosis patients (ID 2154)

Speakers
Presentation Number
LB1258
Presentation Topic
COVID-19

Abstract

Background

SARS-CoV-2 pandemic implied a prolonged lockdown phase, which may have deep consequences for mental and physical health. The effects may be particularly severe for people with chronic diseases such as multiple sclerosis (MS).

Objectives

The aim of the present study was to evaluate the self-reported possible consequences on MS patients of lockdown phase during SARS-CoV-2 pandemic.

Methods

At the end of lockdown phase we performed a telephonic interview on MS patients of our clinic. All patients underwent neurological tele-consult during lockdown phase. We collected demographic and clinical characteristics of the patient. Symptoms of SARS-CoV-2 infection, worsening of anxiety, depression, fatigue, spasticity, changes in physical activity, weight, and change in eating habits were investigated.

Results

Ninety-five patients were enrolled in the study (F 71,3%), with a mean age of 50,3±10,8 years. Median disease duration was 163 months (0-459) and median EDSS at last in-person visit was 2 (0-8,5). Median PDDS was 2 (2-8). The distribution of patients according to disease form was the following: RR 77,7%, SP 13,8%, PP 8,5%. Twenty-two patients reported symptoms suggestive of possible SARS-CoV-2 infection (11,7% fever, 7% cough, 6,4% sore throat, 11,7% cold, 1,1% dyspnoea, 1,1% hyposmia). An increase in spasticity was reported by 18,1% of patients. Fatigue, anxiety and depression were increased in 27,7%, 37,2% and 35,1% of patients, respectively. Fifty-five patients reported worries for SARS-CoV-2 pandemic, with 43,6% of patients believing that the infection could have a particular impact on them compared to general population. The reported aspects on which pandemic and lockdown had a particular impact were: restrictions of personal freedom (27,7%), social retirement (22,3%), work-relate issues (19,1%), reduction of physical activity (7,4%), worries for relatives’ health (6,4%). Forty-six patients had an increase in weight (median increase 2kg, range 1-8), 63,8% reduced their physical activity and 35,1% of them increased the food intake.

Conclusions

Compared to pre-lockdown phase, a high percentage of MS patients report an increase in anxiety, depression, fatigue and spasticity, reduced exercise and increased weight. These aspects could impact particularly on MS patients with high disability.

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Pediatric MS Late Breaking Abstracts

LB1259 - Recurrent CNS Demyelination in a Pediatric Patient with History of Guillain-Barre Syndrome variant Being Treated with IVIG (ID 2155)

Speakers
Presentation Number
LB1259
Presentation Topic
Pediatric MS

Abstract

Background

Guillain-Barre syndrome and multiple sclerosis are well described conditions involving inflammatory demyelination and axonal injury in the peripheral and central nervous system, respectively. Cases of pediatric patients presenting with both syndromes are exceedingly rare. Optic neuritis has been reported as in association with CIDP. Recently, there have also been reports of MOG antibodies in combined central and peripheral demyelination syndromes.

Objectives

We report a pediatric patient with two episodes of right optic neuritis and demyelinating brain lesions, meeting criteria for relapsing remitting multiple sclerosis. Notably, she presented 3 years prior with acute motor axonal neuropathy and was being maintained on scheduled IVIG at the time of her initial presentation with optic neuritis.

Methods

Case report featuring clinical presentation, laboratory, EMG/NCS and neuroimaging results, with discussion of medical decision making, differential diagnosis, and therapies utilized.

Results

A 16-year-old African-American girl presented at age 13 with right hand and left leg weakness that progressed to inability to walk. CSF studies demonstrated albuminocytologic dissociation and spine MRI showed abnormal enhancement and thickening of ventral roots of the cauda equina. EMG/NCS showed conduction block in median, ulnar, tibial and peroneal nerves. MRI brain was normal. She was ultimately diagnosed with acute motor conduction block neuropathy vs. acute onset chronic inflammatory demyelinating disease with axonal involvement. She was acutely treated with IVIG and plasma exchange, and continued on IVIG, initially at every 3 week intervals, gradually spaced to every 8 weeks.

At age 16, she developed right eye pain and vision loss and was found to have optic neuritis and multiple supratentorial white matter lesions favored to represent demyelination. CSF revealed 7 WBCs/mm3, protein 171 mg/dL, and 2 unmatched oligoclonal bands. She was diagnosed with clinically isolated syndrome and treated with IV steroids with improvement. Anti-MOG titer was weakly positive at 1:20 but repeat testing 1 month later was negative. 3 months later, she developed recurrent right optic neuritis and new brain demyelination, meeting criteria for relapsing remitting multiple sclerosis.

Conclusions

Our case highlights the rare existence of peripheral and central nervous system demyelination in a pediatric patient without a clear unifying cause. Weakly positive anti MOG titer normalized rapidly and oligoclonal bands were borderline. A second attack of optic neuritis and new brain demyelination satisfied multiple sclerosis diagnostic criteria. This case represents an unusual presentation with isolated peripheral nervous system disease 3 years prior to developing central nervous system involvement. It is unclear if these occurrences are coincidental or have shared pathological mechanisms.

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COVID-19 Late Breaking Abstracts

LB1260 - Optic neuritis in long standing clinically stable secondary progressive multiple sclerosis after SARS-CoV-2 infection: a mere coincidence? (ID 2156)

Speakers
Presentation Number
LB1260
Presentation Topic
COVID-19

Abstract

Background

The spread of SARS-CoV-2 raised concern of infection susceptibility in patients with autoimmune diseases, multiple sclerosis (MS) in particular. The effects of SARS-CoV-2 on MS disease activity are still unknown. To our knowledge, no increased risk of relapses during or after the infection has been reported.

Objectives

The aim of the present report is to describe the case of a woman with longstanding secondary progressive MS presenting with optic neuritis 4 weeks after SARS-CoV-2 infection.

Methods

A 60-year-old patient was diagnosed with MS in 1999. Her first symptom (diplopia) dated back to 10 years earlier. In the following 10 years she reported 3 episodes of paraparesis. She was treated with interferon beta from 2000. She had no relapses nor new T2 lesions during treatment, but she developed a disease progression. In 2012 a diagnosis of secondary progressive diseases was made and treatment was stopped.

In the following years the EDSS remained stable at 6.5, without relapses. Her 2016 MRI scan revealed 2 new small brain lesions compared to the previous one (2012).

On 19th March 2020 the patient developed fever and hypogeusia, resolved spontaneously in 3 days. Seven days earlier she had made contact with her mother, who was diagnosed with COVID-19 infection. On 21th her orofaringeal swab resulted positive for SARS-CoV-2.

On 7th May a sudden reduction of visual acuity in the left eye (20/50) was reported. Left eye visual evoked potentials showed increased latency, with preserved amplitude. A diagnosis of optic neuritis was made. Visual acuity improved in less than a week. A brain MRI performed 20 days later and did not unveil any new lesion or contrast enhancement.

Results

Inflammatory response via cytokine storm is a key feature in SARS-CoV-2 infection. Some immunomodulating drugs such as tociliziumab, an IL-6 receptor blocker, seem to be effective in this condition. Cytokine storm could also be a trigger for CNS autoimmunity: the increased frequency of acute disseminated encephalomyelitis and the reports of “probable” or seropositive autoimmune encephalitides in SARS-CoV-2 patients further suggest this hypothesis. As far as we know, this is the first report of a relapse after SARS-CoV-2 infection. Intriguingly, the relapse occurred in stabile non active progressive MS.

Conclusions

In conclusion, we report the case of acute ON in a secondary progressive MS patient 50 days after SARS-CoV-2 confirmed infection. We hypothesize a possible role of the infection in MS immune activity resurgence.

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Neuropsychology and Cognition Late Breaking Abstracts

LB1261 - Resting-state neural activity, cognitive functioning and reserve in relapsing-remitting multiple sclerosis: a microstates EEG study. (ID 2157)

Speakers
Presentation Number
LB1261
Presentation Topic
Neuropsychology and Cognition

Abstract

Background

In multiple sclerosis (MS) the prevalence of cognitive impairment (CI) ranges 40–65%. Besides, high level of cognitive reserve (CR) is strongly associated with better cognitive functioning in patients with MS (PwMS). How the cognitive performance and the CR level in PwMS can be associated to the fluctuations of spontaneous EEG is not completely understood.

Objectives

To compare scalp voltage maps (microstates) during resting between PwMS and healthy controls (HCs) and to investigate how the temporal parameters of microstates and the level of CR can predict the cognitive performance.

Methods

50 relapsing-remitting multiple sclerosis (RRMS) patients and 25 HCs, matched for age and sex, were enrolled. For PwMS, we administrated the Brief International Cognitive Assessment (BICAMS) and the Cognitive Reserve Index questionnaire (CRIq). All participants underwent to 15-min of high-density EEG recording (256ch), closed-eyes. EEG data were filtered 1-40Hz, ICA-corrected for artifacts and downsampled to 256Hz. Microstates analysis identified a set of voltage maps representing the EEG activity for all participants that were fitted on the corrected-EEGs to quantify: global explained variance (GEV), mean duration (MD), time coverage (TC) and occurrence (Frequ). Repeated Two-Way ANOVA (Bonferroni comparisons) was used to compare groups and microstates; stepwise multiple linear regression was performed to study the cognitive performance in correlation to the microstates and level of CR; alpha=0.05.

Results

24% of PwMS had CI and 34% reported a low level of CR. Microstates analysis found 4 maps in both groups and PwMS showed a significant increase in Map-A (GEV/TC/Frequ) and Map-B (GEV), while Map-C (MD) and Map-D (MD/TC) were significantly decreased with respect to HCs. Multiple linear regression analysis showed two strong predicted models (p<0.001), respectively, for Brief Visual-Spatial Memory Test (BVMT) and Symbol Digit Memory Test (SDMT). BVMT was predicted by GEV of Map-C improved by CRI_L, reaching 44% of explained variance. SDMT was predicted by Frequ of Map-A and CRI_Edu.

Conclusions

Microstate analysis reveled altered fluctuations of EEG topographies in RRMS patients with low disability and at the first stage of disease. In particular, Map-C (salience network) and leisure as well as Map-A (auditory processing) and education, respectively, predicted BVMR and SDMT scores.

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COVID-19 Late Breaking Abstracts

LB1262 - Low Prevalence of SARS-CoV-2 Antibodies in People with Multiple Sclerosis Residing in Massachusetts (ID 2159)

Abstract

Background

Seroepidemiology is an important tool to characterize the epidemiology and immunobiology of SARS-CoV-2. Most people with multiple sclerosis (MS) are treated with immunomodulators or immunosuppressants, so it is crucial to understand the immune response to the novel SARS-CoV-2 in people with MS.

Objectives

To investigate the prevalence and persistence of the SARS-CoV-2 antibody response in MS and how this relates to MS phenotype and treatment.

Methods

227 consecutive people with MS residing in MA and receiving care at Massachusetts General Hospital or Brigham and Women’s Hospital and 143 of their cohabitants were enrolled May 29-July 23, 2020. In addition, 8 people with MS receiving care elsewhere who tested positive for SARS-CoV-2 nasal swab PCR and 7 cohabitants of that group were enrolled to enrich the sample for select analyses. Each participant remotely submitted a dried blood card for in-house MGH SARS-CoV-2 IgG ELISA assay testing. The assay displays 99.7% sensitivity and 100% specificity >14 days from symptom onset. Participants completed a REDCap questionnaire covering demographics, MS history and treatments, comorbidities, and COVID-19 symptoms and exposure. Antibody prevalence in MS participants will be compared to that in their cohabitants using Pearson’s Chi-squared tests.

Results

The majority of MS participants were characterized as relapsing/remitting (76.8%) and were taking disease modifying therapies (72.6%) at the time of collection. SARS-CoV-2 antibodies were detected in 3.5% of people with MS residing in MA and 6.3% of their cohabitants (X2=1.54, p=0.22). For comparison, ~1.5% of the MA population had tested positive by PCR in this date range. Exposure and treatment data will be presented in 13 cases of antibody discordance between the person with MS and his/her cohabitant; the person with MS was antibody-negative in 10 cases and antibody-positive in 3 cases with discordance. In total there were 6 MS participants and no cohabitants who previously tested positive by nasal swab PCR but lacked antibodies at follow-up. Of the COVID-positive participants (by PCR or antibody), 54.5% (6 of 11) of MS and 88.9% (8 of 9) of cohabitants were asymptomatic (p=0.16).

Conclusions

Antibody prevalence was low overall in people with MS residing in MA. Discordance between MS participants and their cohabitants and lack of detectable antibodies in some people with MS with prior nasal swab PCR positivity suggest SARS-CoV-2 antibodies may be less persistent in people with MS.

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Biomarkers and Bioinformatics Late Breaking Abstracts

LB1263 - Introduction of CSF immunoglobulin κ light chains testing as a complement to oligoclonal bands evaluation (ID 2160)

Speakers
Presentation Number
LB1263
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Background: Detection of oligoclonal (OB) bands in the cerebrospinal fluid (CSF) is an essential tool in the diagnosis of autoimmune inflammatory conditions of the CNS and particularly multiple sclerosis (MS). This method is known to have significant limitations: it is labour intensive, interpretation and evaluation should be restricted to experienced specialists (subjective), standards for testing are frequently absent creating difficulties with reproducibility across labs, it is qualitative, and potentially can be affected by patient's use of therapeutic monoclonal immunoglobulins. Free κ light chain production is known to increase with immune system activation, including autoimmune diseases and can be used for their detection. κ light chains are known to be present in the CSF of patients with MS.

Objectives

Our study's goal was to perform an analysis of κ light chains in CSF and compare results with findings of OB evaluation in the spectrum of neurological conditions including MS.

Methods

200 CSF samples from the regional laboratory were analyzed for both OB bands and κ light chain concentrations. The sensitivity and specificity of each method were evaluated concerning the clinical diagnosis of MS.

Results

κ light chain concentration can be reliably performed in a hospital laboratory setting. This test has excellent sensitivity and specificity to the clinical diagnosis of MS.

Conclusions

Introducing routine reporting of κ light chains CSF concentration will increase confidence in the reproducibility of results, it will help to firmly establish quantitative normative values, and their relationship to meaningful clinical outcomes. κ light chains test is a useful complement to OB bands testing. It has the capacity to replace it over time and provide a quantitative dimension to the evaluation of CNS inflammation.

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Gender Differences, Hormones and Sex Chromosomes Late Breaking Abstracts

LB1264 - Endocrine disrupting chemicals affect T cell phenotypes and show a role for environmental factors in MS pathophysiology. (ID 2162)

Speakers
Presentation Number
LB1264
Presentation Topic
Gender Differences, Hormones and Sex Chromosomes

Abstract

Background

Autoimmune diseases, including Multiple Sclerosis (MS), are more common in females, suggesting that immune-endocrine mechanisms are central for polarizing the immune response and maintaining tolerance. The accelerated use of chemicals in consumer products has called attention to a subset of additives used during manufacturing of goods and materials, termed endocrine disrupting chemicals (EDCs). These synthetic compounds are structural mimics of endogenous hormones and may therefore drive immune cells to enhanced or different outcomes. In recent decades, the increased application of EDCs across daily-use products has been coincident with an increase in the female to male MS susceptibility ratio. Involvement of T cells in MS is an active area of research, but the potential role of environmental factors in T cell differentiation has not been fully resolved and could inform on the sex-bias of MS disease.

Objectives

Our study thus sought to determine whether EDCs adversely modulate T cell phenotypes and to identify which immune populations are most at-risk for deregulation by environmental factors.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated from female healthy controls (HC) and MS patients and in vitro exposure to EDCs, bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP), was maintained throughout T cell conditioned differentiation. Negative selection was carried out on remaining PBMCs to isolate CD4 T cells for additional regulatory T cell (Treg) differentiation. Exposure to EDCs was similarly maintained throughout Treg differentiation. On a set-endpoint, cells were harvested and analyzed by flow cytometry using a Treg or multi-parameter T cell panel. Dimensionality reduction clustering and high parameter discovery using t-distributed stochastic neighbor embedding were used to identify EDC induced changes in T cell phenotypes. Data was collected across two batches (n=8 per group) and validated across one batch (n=3 per group). Final results (n=16) will include batch effect normalization.

Results

EDCs altered the phenotype and activation state of T cells, particularly BPA and low dose DEHP (10 nM) which led to increased central memory T cells (TCM). The TCM population was also more activated across EDC treatments, relative to untreated controls. These observations held true of both CD4 and CD8 T cells. For Treg differentiation, we identified only modest effects for BPA only, on total Tregs (Foxp3+CD25+); EDC treatments had no effect on Treg expression of latency-associated peptide (LAP).

Conclusions

Phenotyping of EDC-regulated T cells helps to elucidate population subtypes that could pose a risk for MS progression and severity. Results also emphasize the role of environmental factors in MS pathophysiology and offer an explanation for the sex-bias of MS disease.

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Neuroprotection, Regeneration and/or Remyelination Late Breaking Abstracts

LB1265 - "TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of CNS demyelination." (ID 2163)

Speakers
Presentation Number
LB1265
Presentation Topic
Neuroprotection, Regeneration and/or Remyelination

Abstract

Background

Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS). In MS, impaired generation of mature oligodendrocytes (OLs) from oligodendrocyte precursor cells (OPCs) leads to persistent demyelination, myelin debris accumulation and axonal damage. Efficient myelin debris removal and clearance by phagocytic cells, such as microglia in the brain, are critical to eliminating inhibitory signals interfering with OPC activation and recruitment. An important modulator of microglia functions is the triggering receptor expressed on myeloid cells-2 (TREM2), an innate immune receptor that promotes microglial survival, proliferation and phagocytic activity. Homozygous loss-of-function mutations in TREM2 genes cause Nasu–Hakola disease (NHD). In the context of mouse models of MS, it has been previously demonstrated that mice lacking TREM2 have a striking defect in microglia activation and myelin debris clearance in the cuprizone (CPZ) model and that intravenous injection of TREM2-transduced myeloid cells is beneficial in experimental autoimmune encephalomyelitis (EAE).

Objectives

The goal of this project is to explore the effect of antibody-mediated TREM2 activation on microglia in the CPZ model of demyelination of the CNS.

Methods

Studies on human post-mortem CNS tissues (8 subjectes with MS and 4 non-MS) were performed on 20 fresh-frozen brain and spinal cord tissues. Trem2+/− mice were fed a 0.2% Bis-(cyclohexanone) oxaldihydrazone (cuprizone) diet for 4 weeks or for 4 weeks followed by 3 days, 7 days, or 14 days on regular chow. Remyelination and axonal integrity were analyzed by transmission electron microscopy, qPCR for myelin transcripts and neurofilament light detection in serum. We analyzed the gene expression profile (Affymetrix HuGene-1_0-st-v1 Microarrays) of macrophages obtained from the peripheral blood of three patients affected by NHD and healthy controls.

Results

We demonstrated that TREM2 was highly expressed on myelin-laden phagocytes in active demyelinating lesions in the CNS of subjects with MS. In gene expression studies, macrophages from subjects affected by Nasu-Hakola (lacking TREM2) displayed a defect in phagocytic pathways. Treatment of Trem2+/− mice with a new TREM2 agonistic antibody promoted the clearance of myelin debris in the cuprizone model of CNS demyelination. Effects included enhancement of myelin uptake and degradation, resulting in accelerated myelin debris removal by microglia. Most importantly, antibody-dependent TREM2 activation on microglia increased density of oligodendrocyte precursors in areas of demyelination, as well as the formation of mature oligodendrocytes thus enhancing remyelination and axonal integrity.

Conclusions

These results are extremely relevant as they propose TREM2 on microglia as a potential new strategy to promote remyelination.

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COVID-19 Late Breaking Abstracts

LB1266 - Descriptive data analysis of covid-19 among patients with multiple  sclerosis; A cross-sectional study of southern Iran (ID 2164)

Presentation Number
LB1266
Presentation Topic
COVID-19

Abstract

Background

The managing of patients who receive immunosuppressive or immunomodulatory drugs rapidly has to change during the current coronavirus disease 2019 (COVID-19) pandemic. Immunosuppression therapy combined with neurological disability such as multiple sclerosis (MS) increases the risk of severe COVID-19 and associated death. Hence, evaluating the risk of Covid-19 in MS patients is an important issue in global healthcare system and demand for data to describe the frequency and the evolution of COVID-19 infection in MS patients grows rapidly around the world.

Objectives

We report our descriptive-analytic study on MS patients with a confirmed or suspected COVID-19. This study was conducted in south of Iran, an area with a high prevalence and incidence of MS. It is also worth noting that Iran is high in prevalence of COVID- 19 and this study was performed in the first pandemic wave in Iran.

Methods

1361 MS patients from fars province, south of Iran were contacted from April 3 to June 20, 2020. Basic demographic data, information about MS disease and any signs, symptoms or laboratory results relevant to COVID-19 were gathered. SPSS version 22 was used for data analysis. P< 0.05 was considered statistically significant.

Results

The frequency of DMT were as follow: rituximab 27.6%, interferons 27.3%, fingolimod 12.5%, dimethyl fumarate 9.1%, glatiramer acetate 7.3%, teriflunomide 1.9%, natalizumab 1.3%. Out of 1361 patients, 68 (5) % were COVID-19 suspected cases. 12 patients showed serious clinical symptoms and required hospital admission. 8 cases had positive PCR, 6 of confirmed cases did not require ICU care or intubation and were discharged from the hospital. 2 of the COVID-19 confirmed cases died. Both of them were on rituximab. The highest frequency of suspected cases had RRMS 87.7%, followed by PPMS7.7% and the lowest percentage of suspected cases was observed in SPMS patients 1.5%. 50% of confirmed cases and 12.5% of suspected cases were on rituximab. .There was significant difference in frequency rate of patients who used corticosteroid (p <0.005) and cardiovascular drugs (p =0.04). 62.5% of confirmed cases had EDSS 6 or higher while 6.4% of suspected and 10.1% of healthy cases requires assistance to walk. In the multivariable regression model, CVD and hyperthyroidism were independently associated with the risk of the suspect or confirmed COVID-19. Patients with hyperthyroidism and CVD were approximately 21.3 and 3.6 times higher at risk of infection.( OR=21.3 95% CL2.95-55.08 P=0.002) (OR=3.69 95% CL1.47-9.21, P=0.005) respectively.

Conclusions

In general, risk of covid- 19 infection and severity and mortality in pwMS seems not to be more than other population; however, type of disease modifying drug, comorbidities and physical disability are the main factors which may threaten these patients. our study showed PPMS and CIS types as well as cases with hyperthyroid and cardiovascular diseases are in a higher risk than the other MS patients.

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Disease Modifying Therapies – Mechanism of Action Late Breaking Abstracts

LB1267 - Teriflunomide Enhanced Innate and Adaptive Immune Regulatory Function in Treating Multiple Sclerosis (ID 2165)

Speakers
Presentation Number
LB1267
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

The efficacy and safety of Teriflunomide (AubagioTM), a disease-modifying therapy (DMT) for relapsing multiple sclerosis (RMS) have been well established in pivotal trials. However, its mechanism of action on adaptive and innate immune cell compartments is yet to be elucidated.

Objectives

To report detailed immune phenotyping and immune cell function analysis from a prospective phase 4 study of relapsing MS patients receiving teriflunomide (NCT03464448).

Methods

27 subjects (age 18-65) were recruited from the University of Michigan MS Center who had been previously diagnosed with relapsing MS and were undergoing therapy with teriflunomide. Blood samples were collected for immunophenotyping and functional analysis. Peripheral blood mononuclear cells (PBMCs) were separated and stained with antibodies to examine cell subsets and analyzed by multicolor flow cytometry. Both adaptive and innate immune cell lineages at baseline pre-treatment and periodically for up to 2 years post teriflunomide treatment were studied.

Results

Teriflunomide treatment showed minimal effect on the frequencies and absolute counts of CD4+ T cells; it moderately reduced the frequency of CD8+ T cells, NK, and NKT cells. It significantly reduced the frequency NK cells, particularly pathogenic CD56dim NK cells, therefore reduced CD56dim/CD56hi ratio. Functional analysis revealed that NK cells from teriflunomide treated patients had increased trend of degranulation. In addition, teriflunomide also increased the expression CD39 and percentage of CD39+ Tregs, which implies an enhanced Treg suppressive function. Furthermore, teriflunomide decreased CXCR3 expression on T helper (Th) cells, which suggests impediment of pathogenic Th cells. Finally, teriflunomide showed a diminishing trend of the frequency of total B cells (specifically switched memory B cells) while it increased naïve B cells and downregulated the expression of co-stimulatory molecules CD80 and CD86.

Conclusions

In conclusion, teriflunomide promotes a tolerogenic immune response and suppresses the pathogenic immune response in relapsing MS patients.

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COVID-19 Late Breaking Abstracts

LB1268 - No evidence for SARS-CoV-2 transcripts and disease exacerbation in COVID-19 multiple sclerosis brain (ID 2166)

Abstract

Background

Although primarily targeting the respiratory system, coronavirus disease 2019 (COVID-19) also manifests with central nervous system (CNS)-related symptoms. Yet, little is known about the clinical course of CNS autoimmune disease and concurrent SARS-CoV-2-infection. Whether multiple sclerosis (MS) renders patients more susceptible to CNS involvement and / or infection during COVID-19 and the impact of SARS-CoV-2 infection on disease activity remain elusive.

Objectives

Here, we assessed whether an impaired blood-brain barrier in MS facilitates viral CNS entry, and whether COVID-19 infection is associated with MS disease exacerbation.

Methods

To that end, we combined an in-depth histopathological assessment with spatial transcriptomic analysis using multiplex in situ hybridization analysis for immune and SARS-CoV-2 transcripts in autoptic brain tissue of an untreated MS patient, who died from COVID-19-associated respiratory failure, compared to a cohort of non-MS COVID-19, non-MS non-COVID-19, and non-COVID-19 viral encephalitis controls.

Results

Despite a general microglia activation in COVID-19 brain parenchyma, we found neither evidence for active demyelinating activity nor presence of SARS-CoV-2 transcripts in COVID-19 MS lesions.

Conclusions

We conclude that neither clinical and morphological signs of MS disease exacerbation nor presence of viral transcripts in MS brain lesions are observed in COVID-19 patients and that no SARS-CoV-2-specific abnormalities are present in MS COVID-19 and non-MS COVID-19 patients. Future studies will yield further insights into the risk profile of COVID-19 in MS and related CNS autoimmune diseases.

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Biomarkers and Bioinformatics Late Breaking Abstracts

LB1269 - Higher parietal and premotor cortex activation and connectivity during treadmill walking in Persons with Multiple Sclerosis versus healthy controls (ID 2167)

Speakers
Presentation Number
LB1269
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Persons with Multiple Sclerosis (pwMS) experience a decline in cognitive and physical performance, which could affect their walking and their ability to attend to their surrounding environment during walking. Therefore, pwMS may show higher recruitment of brain attention network regions like parietal and premotor areas during walking (WALK), a recruitment that could increase more during obstacle avoidance while walking (OBSAV).

Objectives

This study explored Electroencephalography (EEG) based brain activation and brain connectivity during treadmill walking and during walking while avoiding virtual reality obstacles on the treadmill. The study included a group of pwMS and a health control group (HC) matched by age and gender. We expected higher brain activity and brain connectivity in parietal and premotor cortices in the pwMS group, especially in the OBSAV condition.

Methods

Data of 9 pwMS and 8 healthy controls were collected. Kessler Foundation Institutional Review Board (IRB) approved the protocol. Brain and muscles activations were collected as participants walked on an instrumented treadmill (C-MILL, Motekforce, The Netherlands). The C-MILL CueFor2 software was used to collect loading force of each participant during the walking tasks, and captured the timing of the major events of the gait cycle. EEG data were collected using a 64-channel wireless ActiCap EEG system from Brain Products (Munich, Germany). EEG data collection sampling rate was set to 500Hz and FCz EEG channel was chosen as the reference during data collection. Data were collected for a minimum 100 trials of 30-second walking at self-selected speed. Each WALK trial was followed by a 30-second trial of walking while avoiding randomly projected virtual obstacles (OBSAV). Outcomes measures included EEG signal power within alpha (8-12 Hz) and beta (12-30 Hz) bands in 11 regions of interest that included bilateral parietal, premotor, frontal, and motor cortices and supplementary motor area and coherence between these regions.

Results

In comparison to the HC group, the pwMS group showed higher power of EEG signals within the beta band in the left parietal (F=7.8, p=0.008) and left premotor cortex (F=4.11, p=0.05). They also showed higher coherence between left parietal and left premotor cortices and between left premotor and left motor cortices. There was no difference in these outcomes between WALK and OBS conditions.

Conclusions

Our findings confirm the role of attention network in the control of walking and obstacle avoidance in the MS group. Our group will further investigate this network and connectivity between the brain and muscles to acquire better understanding of the interaction between cognitive and motor performance and cortical control centers and muscles participating in walking in pwMS and how that could affect pwMS daily activity.

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Pathogenesis – the Blood-Brain Barrier Late Breaking Abstracts

LB1270 - DICAM : A new cell adhesion molecule involved in myeloid cells infiltration in Multiple Sclerosis (ID 2168)

Speakers
Presentation Number
LB1270
Presentation Topic
Pathogenesis – the Blood-Brain Barrier

Abstract

Background

Disruption of the blood-brain barrier (BBB) and migration of leukocytes from the periphery to the central nervous system (CNS) are early events in lesion formation during multiple sclerosis (MS). Among CNS-infiltrated leukocytes, macrophages and dendritic cells are important contributors to inflammation and tissue damage. They readily cross the BBB to infiltrate the CNS and express pro-inflammatory cytokines. Using proteomic and RNA sequencing techniques, we have identified Dual Ig domain containing Cell Adhesion Molecule (DICAM) as a new adhesion molecule expressed by human TH17 lymphocytes and BBB endothelial cells (ECs). The expression and function of DICAM in MS pathogenesis remain unexplored.

Objectives

The current study aims to evaluate DICAM’s role in monocytes/macrophages and dendritic cells migration to the central nervous system.

Methods

To explore the DICAM expression profile, we performed flow cytometry and qPCR on human BBB-ECs and immune cells subsets isolated from healthy control peripheral blood. Confocal microscopy, flow cytometry and qPCR have been performed to explore DICAM expression in MS lesions and on peripheral immune cells in situ and ex vivo. To further investigate the expression of DICAM by myeloid cells in patients with MS, we performed flow cytometry analysis of peripheral blood mononuclear cells from males and females patients with relapsing remitting MS (n= 19), secondary progressive MS (n= 19) and primary progressive MS (n= 21) aged and sex-matched with controls individuals (n= 39) samples. The role of DICAM in monocytes adhesion to the BBB-ECs was assessed in vitro by blocking DICAM in a flow adhesion assay on a monolayer of human BBB-ECs. Different animal models of MS (EAE) were also used to explore DICAM function in vivo.

Results

We first demonstrated that DICAM and its ligand αvβ3 are upregulated on the BBB within inflammatory lesions in the brains of MS patients. In peripheral blood preliminary results indicates that DICAM expression by myeloid DCs and classical monocytes is associated with RRMS and SPMS forms of the disease. Moreover, blockade of DICAM restricts the adhesion of monocytes on human BBB-ECs and decreases disease severity in several EAE models.

Conclusions

This study aims to characterize the interaction mediated by DICAM between infiltrating leukocytes and the BBB. This adhesion molecule might be involved in MS pathogenesis and therefore, could become a new therapeutic target for MS treatment.

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Imaging Late Breaking Abstracts

LB1271 - MRI insights into myelin damage in Susac Syndrome (ID 2169)

Abstract

Background

Susac’s Syndrome (SuS) is a rare autoimmune endotheliopathy of the brain, retina and cochlea that mimics multiple sclerosis (MS). Lesions presumed to be microinfarcts classically involve the corpus callosum (CC). While one brain biopsy reported demyelination, and MRI studies have shown reduced fractional anisotropy in the CC, the specific processes underlying SuS pathology are not yet clear. Myelin water imaging (MWI) and diffusion basis spectrum imaging (DBSI) can provide information about microstructural changes occurring in SuS. MWI provides a quantitative measurement of myelin, termed the myelin water fraction (MWF). DBSI yields various physiologically relevant metrics characterized by water diffusion: the apparent diffusion coefficient (ADC) which relates to overall tissue damage; fractional anisotropy (FA), which decreases with white matter (WM) damage; and radial diffusivity (RD) which increases with myelin loss.

Objectives

Determine in vivo WM microstructural changes in Susac Syndrome compared to MS and healthy controls (HC) using MWI and DBSI.

Methods

Participants included 7 SuS patients following the proposed European Susac Consortium diagnostic criteria (mean age 43.3y (30-78y), 6F), 10 MS patients (mean age 43.2y (26-70y), 9F) and 10 HC (MWI: 44y (27-64y), 9F, DBSI: 35.9y (22-47y), 5F). 3T MRI included MWI (48-echo 3D GRASE sequence), DBSI (9 b-values, 0-1500 s/mm2, 99 directions) and a 3DT1 for anatomical reference. The CC and global WM (non-lesional tissue) were segmented and registered using FSL and the JHU atlas. One-way ANOVA with Tukey correction compared CC and global WM between groups.

Results

CC: SuS MWF (0.09±0.01) was lower than MS (0.11±0.02, p=0.03) and trending lower than HC (0.11±0.02, p=0.07). SuS ADC (0.84 ± 0.08 x 10-3μm2/ms) was higher than MS (0.73±0.04 x 10-3μm2/ms, p<0.001) and controls (0.71±0.04 x 10-3μm2/ms, p<0.001). SuS FA (0.82±0.02) was lower than HC (0.86±0.02, p= 0.02). SuS RD was higher (0.27±0.03 x 10-3μm2/ms) than HC (0.21±0.01 x 10-3μm2/ms, p=0.004) and trending higher than MS (0.23±0.05 x 10-3μm2/ms, p=0.05).

Global WM: ADC and RD findings in the Global WM were similar to CC, i.e. ADC and RD were significantly higher in SuS compared to MS and HC (all p<=0.03). However, MWF and FA was insignificantly different between the groups.

Conclusions

We report the first use of MWI in SuS. Both CC and the global WM showed non-lesional myelin damage, which was more severe than MS.

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Imaging Late Breaking Abstracts

LB1272 - Distinct co-varying functional-structural patterns in multiple sclerosis for physical disability and cognitive impairment (ID 2171)

Abstract

Background

There is still a need to bridge the gap in linking structural and functional alterations in order to evaluate their relative contribution and location towards clinical picture of patients with MS.

Objectives

To identify how distinct covarying structural-functional patterns are able to explain clinical measures of physical disability and cognitive impairment in MS.

Methods

We applied linked independent component analysis (ICA), a type of fusion approach, to images of grey matter (GM) density, fractional anisotropy (FA) and resting-state functional MRI in patients with relapsing-remitting MS (age: 39.7±10.5 years, 60 female, disease duration: 9.4±6.9 years; median EDSS=1.5, cognitive impairment [CI]: 30%). Loading coefficients across the three MRI modalities of linked ICA were used in multiple stepwise linear regression models for EDSS, CI and Rao Battery test scores, adjusted for age and sex.

Results

Higher EDSS was explained (R2adj=0.46, p<0.001) by a linked covarying pattern of structural damage (40%), including lower GM density (30%) and WM FA (10%) and of altered network-FC (60%). CI was explained (R2adj=0.56, p<0.001) by a linked covarying pattern of structural damage (26%), including lower GM density (18%) WM FA (8%) and especially of altered network-FC (74%). Among the different cognitive domains, attention and processing speed, as measured by symbol digit modalities test (SDMT), was best explained (R2adj =0.62, p<0.001) by a pattern mostly driven by altered network-FC (70%) and including, to a lesser extent, structural damage (30%), with equal contribution from lower GM density and lower WM FA.

Conclusions

The highest contribution of altered network-FC with respect to structural damage in explaining physical disability and cognitive impairment of our MS group with mild disability points out the relevance at this early disease stage of mechanisms of cortical plasticity, which however may undergo exhaustion and downregulation in the more advanced stages of disease.

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COVID-19 Late Breaking Abstracts

LB1273 - Telehealth Utilization in Four MS Centers During the COVID Pandemic: Real-world evidence from the MS-CQI improvement research collaborative. (ID 2172)

Speakers
Presentation Number
LB1273
Presentation Topic
COVID-19

Abstract

Background

MS-CQI is the first multi-center improvement research collaborative for MS care. MS-CQI is a three-year study (2018-2020) to evaluate system-level performance variation and improve MS population health outcomes. Four MS centers are participating, following approximately 5,000 people with MS. The COVID pandemic onset occurred approximately half-way through the third year of the study. Prior to this time, telehealth was not utilized in participating MS-CQI centers, but after COVID onset, MS-CQI centers began utilizing telehealth in various ways. In response to this development, measures of telehealth utilization were collected in order to study system level variation in telehealth utilization for COVID-era MS care during the last 6 months of the MS-CQI study.

Objectives

To describe system-level variation in MS clinical care utilization by type (in-person visit, telephone visit, or video telehealth visit) for the last six months of the MS-CQI study (January-June 2020) during the COVID pandemic.

Methods

Electronic Health Record (EHR) data from clinical encounters at the four participating MS-CQI centers was abstracted for January-June 2020. Participants were adults ≥18 years with MS. Telehealth utilization was categorized into three types: (1) “in-person” (standard clinical visit); (2) “telephone visit;” and (3) “video telehealth visit.” Chi-square tests were used to assess associations across centers and different types of telehealth utilization.

Results

1,969 unique persons with MS (PwMS) were included in our analysis. 75.4% were female, mean age was 50 years and 79.4% had relapsing MS (RRMS). 1,604 (81.4%) of the 1,969 unique PwMS utilized at least one clinic visit, generating 1,805 total encounters. Of these, 814 (45.1%) utilized in-person, 508 (28.1.%) utilized telephone, and 483 (26.8%) utilized video telehealth visits. Utilization types varied significantly (p<0.01) across MS-CQI centers: (1) in-person (3.8%-52.9%); (2) telephone (0%-31.6%); and (3) video telehealth (9.5-43.4%). Urban MS-CQI centers utilized video telehealth more than rural (39.7% vs. 22.3%), and rural centers utilized telephone visits more often (34.2% vs. 10.8%). Academic MS centers utilized video telehealth visits more than non-academic MS centers (47.0% vs. 18.8%), and non-academic MS centers utilized telephone visits more frequently than academic MS centers (34.7% vs. 11.5%).

Conclusions

Telehealth utilization for MS care has increased dramatically since the onset of the COVID pandemic and is likely to remain a lasting part of MS care in the future. Our findings contribute to initial evidence that system-level (small area geographic) variation in telehealth utilization exists in MS care in the COVID era. This invites further study on how MS care systems can best utilize and standardize telehealth to optimize equity, access, and population health outcomes for PwMS.

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Machine Learning/Network Science Late Breaking Abstracts

LB1274 - Modeling subject-level disease progression for Multiple Sclerosis in clinical trials using machine learning (ID 2173)

Speakers
Authors
Presentation Number
LB1274
Presentation Topic
Machine Learning/Network Science

Abstract

Background

Control arms are a mainstay of clinical trials. Accurately predicting Multiple Sclerosis (MS) disease progression for individual patients in the control arm is valuable for therapeutic development, and can be accomplished with a machine-learning model. The abundance of high-quality subject data, collected repeatedly from control arms in past clinical trials, provides an opportunity to build a model that can predict outcomes for control subjects in future trials.

Objectives

To develop a machine-learning model that can accurately predict Multiple Sclerosis (MS) disease progression for individual subjects enrolled in the placebo arm of MS clinical trials.

Methods

We used a machine-learning model called the Conditional Restricted Boltzmann Machine (CRBM) that is designed to predict how clinical variables related to MS change over time. To develop this model, we extracted a machine-learning dataset from data provided by the Multiple Sclerosis Outcome Assessments Consortium comprising 2465 placebo arm subjects across 8 MS clinical trials. Our dataset contains 21 variables including demographic information, functional assessments, and disability measurements every 3 months for up to 48 months. We then trained the model and assessed its ability to generate statistically accurate predictions, using a set of test subjects not used during training.

Results

Given baseline data for placebo subjects, the CRBM model can generate data for the future clinical state of individual subjects that are statistically indistinguishable from actual subject data along a number of key measures, suggesting the model is capable of generating digital subjects equivalent to actual subjects. Notably, the model accurately captures Expanded Disability Status Scale (EDSS) trajectories and relapse rates across MS subtypes.

Conclusions

We have created a subject-level model of MS disease progression that can predict the future state of placebo subjects in clinical trials. Our model has useful applications in clinical trials, including supplementing control arms with digital subjects generated from the model.

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COVID-19 Late Breaking Abstracts

LB1275 - Enriching neuroimmunology telemedicine encounters with objective measures of vision during the SARS-CoV-2 pandemic (ID 2174)

Speakers
Presentation Number
LB1275
Presentation Topic
COVID-19

Abstract

Background


Patients with multiple sclerosis (MS) and antibody-mediated optic neuritis attend periodic outpatient clinic visits to quantify visual acuity, color vision and visual fields. Many of these tests involve prolonged proximity and contact, which patients who are immunocompromised may wish to avoid during the SARS-CoV-2 pandemic. Telemedicine is increasingly used to lessen the need for clinic visits but lacks objective means for vision monitoring.

Objectives

With the goal of enriching pandemic telemedicine encounters, we conducted a pilot study testing the feasibility of telemedicine-guided computer tests for monitoring vision.

Methods

For this pilot study, 22 patients with optic neuropathies from the Neuro-Ophthalmology outpatient clinic were recruited. Participants were asked to repeat their clinic eye exams with a home-based adaptation of the Freiburg Acuity Test (FRACT ), a robust and validated computer-based method for measuring visual acuity, the EYESAGE visual field test (http://www.eyesage.org/?lang=us), and a computer-based Ishihara color perception application. Blinded reviewers interpreted the results of both home-based and outpatient tests, and the correlation of the results was analyzed alongside patient cooperation and reliability indices.

Results

18/22 patients completed the visual monitoring tests during the telemedicine-guided encounters. Patients’ mean age was 44yrs. (SD 13.42), of whom four were male. Patients with low vision (n=2, one patient with hand motion, second patient 6/30) on clinic visit had a similar low visual acuity with the telemedicine guided FRACT method. No patient with good FRACT vision had low visual acuity documented during their clinic visit. Significant visual field defects (n=6, homonymous hemianopsia and quadrantanopia (n=3), inferior altitudinal (n=1) and central scotomas (n=2)) were all picked up by the EYESAGE home method. Smaller nasal steps and peripheral concentric field scotomas were unreliably detected by the EYESAGE method.

Conclusions

This pilot study of enriching telemedicine visits with a method for monitoring vision reveals that FRACT and EYESAGE potentially identify low visual acuities and severe visual field defects. Further improvement of home vision monitoring methods can enrich telemedicine encounters with objective means of monitoring vision. A large-scale multicenter international study is currently underway to examine the sensitivity of these visual monitoring methods in patients with demyelinating disease.

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Biomarkers and Bioinformatics Late Breaking Abstracts

LB1276 - Contribution of antibodies against coagulation components in the circuit of coagulation-immune system: Potential biomarkers of Multiple Sclerosis? (ID 2175)

Speakers
Presentation Number
LB1276
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Coagulation components have a pivotal role to show not only as members of hemostasis system but either as regulators of innate immune response in neuroinflammatory diseases such as Multiple Sclerosis (MS). In fact, thrombin and fibrin(ogen) deposition in vasculature of the central nervous system (CNS) in MS animal models has been shown to modulate the microglia motility upon pre-demyelinated areas, to trigger and sustain inflammatory responses into perivascular lesions and, inevitably, to contribute in the axonal damage and neurodegenerative phenotype. Intriguingly, our early work has reported the presence of IgG antibodies (Abs) against coagulation components in patients with MS, albeit their role in MS pathogenesis is unknown.

Objectives

To characterize the impact of MS-derived IgG Abs against a panel of seven coagulant antigens (VIIa, thrombin, prothrombin, Xa, XII, protein C, plasmin) upon the activation of human astrocytes.

Methods

Purification of IgG Abs from 15 MS patients, who were positive for the presence of IgG against coagulation components and from 15 age and gender matched healthy donors was carried out. A human cell line of astrocytes was then treated with 100μg/ml of purified IgG for 4h and the extracted cell lysates were first quantified and then analyzed by immunoblot for the expression of the protease activator receptor -1 (PAR-1), a thrombin-activated receptor.

Results

Increased levels of PAR-1 expression were observed in astrocytes treated with IgG from MS patients who were positive for the presence of anti-thrombin and anti-plasmin IgG Abs, while not important effect was observed with IgG against other coagulant antigens of interest or with IgG derived from controls.

Conclusions

As the non-coagulation functions of thrombin are mediated by PAR-1, it is necessary to enlighten on the intracellular mechanisms that trigger the activation of PAR-1. Here, we have revealed that selective IgG Abs from MS patients can elicit the PAR-1 expression and thus may be involved in pro-inflammatory pathways that are mediated by thrombin. These findings point toward the importance of these molecules as potential biomarkers for the prognosis and/or diagnosis of MS and may prove valuable in further studies for the establishment of novel therapeutic strategies in MS.

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Clinical Trials Late Breaking Abstracts

LB1277 - Evaluation of intermittent fasting diet in multiple sclerosis (ID 2176)

Speakers
Presentation Number
LB1277
Presentation Topic
Clinical Trials

Abstract

Background

Intermittent fasting (IF) has been explored in recent years as a potential intervention in multiple sclerosis (MS) due to the growing evidence on the possible links between diet, caloric intake and inflammation. IF is also relatively easy to implement, and can be readily monitored using urine ketones. Current evidence on IF in delaying MS progression is limited due to a lack of high-quality clinical trials, short duration of intervention, and heterogeneity in experimental design and parameters investigated. Imaging evidence from FLAIR MRI, a hallmark in MS diagnosis and the detection of disease progression, is mostly absent from the current literature.

Objectives

The primary objective of the study was to review current evidence on intermittent fasting in the setting of MS. A secondary goal was to identify gaps in knowledge and barriers to the practical implementation of IF.

Methods

PUBMED and EMBASE datasets were queried on the studies of IF in MS. Clinical trials database was queried to identify active ongoing clinical trials.

Results

Eight IF-related studies were identified. The advantages and disadvantages of each project were evaluated and reported.

Conclusions

Considering the current evidence, IF represents a useful dietary intervention. However, more studies are needed to demonstrate its clinical benefits to establish long-term feasibility, particularly in the early stages of MS. A new study of IF that includes patient compliance monitoring, magnetic resonance imaging, and biological markers evaluation in patients with clinically isolated syndrome (CIS) is proposed.

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Disease Modifying Therapies – Mechanism of Action Late Breaking Abstracts

LB1278 - Teriflunomide: An Immune Modulating Drug with Antiviral Properties (ID 2177)

Speakers
Presentation Number
LB1278
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

Background: Previously, we evaluated the effect of teriflunomide (TERI) in the Theiler’s encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a model of CNS viral infection and progressive disability in MS. Perhaps the most interesting result of this study was TERI’s antiviral activity in the central nervous system (CNS), indicating it may have a role as an antiviral prophylactic and therapeutic compound for viral infections.

Objectives

Objective: The current study aimed to extend our previous work by focusing on the antiviral effect of TERI to test the hypothesis that TERI would be beneficial for treating viral infections, especially in MS patients with an elevated risk of a subclinical viral reactivation and/or reinfection events. We also reassessed the impact of TERI on disability progression and intrathecal synthesis of immunoglobulins (Igs) by using a more efficient model system.

Methods

Methods: TMEV-IDD was induced by intracerebral injection of Theiler's virus into SJL mice. Ninety-two mice were included: 28 sham controls, 32 TMEV-IDD mice treated with TERI, and 32 TMEV-IDD mice treated with vehicle only. Mice were monitored for neurological impairment by using the Rotarod test and an automated HomeCage analysis (HCA) system. The measures used were Luminex analysis for CSF and serum anti-TMEV antibody (BAbs) and real-time PCR of both brain and spinal RNA for TMEV RNA and IgG1 mRNA. Mice were necropsied at 120 days post-infection, i.e., at the chronic stage of the disease.

Results

Results: at necropsy, 27% of the infected mice had cleared the virus, as PCR for TMEV RNA in spinal cords and brains was negative. Overall, the rate of viral clearance was higher in the TERI- vs. vehicle-treated group (42% vs. 12%; p=0.04). Viral load was slightly lower in the TERI- vs. vehicle-treated animals, but the difference was not statistically significant (p=0.10). The serum and CSF BAbs levels were lower in TERI- vs. vehicle-treated mice (p≤0.041). Levels of IgG1 mRNA within the CNS parenchyma were increased in infected mice compared to sham controls (all p£0.018). No difference in brain IgG1 mRNA was observed in TERI- vs. vehicle-treated mice (p>0.61), but IgG1 mRNA levels in the spinal cord were lower in the TERI-treated group (p<0.06). There was no difference comparing disability progression as tested by Rotarod in TERI vs. vehicle-treated mice (p>0.51). Similarly, the digital activity data from the HCA showed a reduction in the locomotor activity, i.e., distances traveled by the mice throughout the recording, of TMEV-IDD animals relative to sham control mice, without a significant difference in this measure between TERI- and vehicle-treated animals.

Conclusions

Conclusions: present findings confirm our previously published results: in the TMEV-IDD model, TERI treatment shows both anti-inflammatory and antiviral properties, without any significant impact on disability progression.

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Epidemiology Late Breaking Abstracts

LB1279 - Initial Symptom at Onset in newly diagnosed Hispanic MS patients between 2017-2019: An Update (ID 2179)

Speakers