ePOSTER WALL
Real-world experience on the use of COVID-19 vaccination in patients with multiple sclerosis treated with Cladribine tablets in the Gulf region
1Jihad Inshasi,2Amir Boshra,2Joseph Youssef
1MS Department, Rashid Hospital and Dubai Medical College, Dubai health Authority, Dubai, UAE; 2Merck Serono Middle East FZ Ltd, an affiliate of Merck KgaA, Darmstadt, Germany.
Background:
The Gulf nations were among the first in the world to implement the COVID-19 vaccination. Regional guidelines like MENACTRIMS endorse that MS patients should be vaccinated against COVID-19. The vaccines being offered in the region include Sinopharm, Pfizer-BioNTech, Sputnik V, and Oxford-AstraZeneca. “Adveva™ Gulf is a Merck-sponsored health care provider (HCP) driven patient support program (PSP) for patients treated with cladribine tablets”
Objectives:
To describe the real-world experience on the use of COVID-19 vaccination in multiple sclerosis (MS) patients treated with cladribine tablets participating in the PSP.
Material(s) and Method(s):
MS patients treated with cladribine tablets and participating in the PSP in the Gulf region were asked to participate in a questionnaire-based survey about their COVID-19 vaccination status. The interview was initiated by health educators over the phone, and they submitted the answers on the patient’s behalf. Patient’s verbal consent was required to start the questionnaire. Information collected included: Demographic, Treatment dates, Vaccination, and COVID-19 information.
Result(s):
Of the 106 MS patients, 92 (86%) patients provided consent to participate and completed the questionnaire. 77.5% of patients were females. All patients had been on cladribine tablets since 2018-till Sept 2021 (66% in Year 1, 15% in Year 2, and 19% in year 3 and 4). From the time of initiation of cladribine tablets, no switch to another disease modifying drugs (DMD) were observed. Overall, 74 (80.4%) of the cladribine tablets patients had received the COVID-19 vaccine. 51.4% and 41.9% of patients were vaccinated by the Pfizer and Sinopharm vaccines, respectively. Among those vaccinated in Year 1 and 2 (n=59), the mean time between the last dose of cladribine tablets and the first dose of the vaccine was 129 days. Of the patients who had not received the vaccine (n=18), 72.2% were planning to receive the vaccine. Only 2 patients were not willing to receive the vaccine for fear of complications. After completion of the COVID-19 vaccine regimen, 6 (8%) patients were infected with SARS-CoV-2, 5 of them confirmed by the RT-PCR test. All the cases were mild, and none of the patient’s required hospitalization. No safety concerns were reported after the administration of the COVID-19 vaccine. The mean time from the completion of the vaccine series till the development of the SARS-CoV-2 infection was 79 days.
Conclusion(s):
The outcomes of this survey suggest that the use cladribine tablets didn’t hinder the patients from receiving COVID-19 vaccinations. Few patients developed SARS-CoV-2 infection despite being vaccinated, but all had mild disease and did not require hospitalization. No safety concerns were observed. Continuous monitoring will be required to assess the safety and efficacy of the COVID-19 vaccine in this specific population. Meanwhile, MS patients should be encouraged to receive COVID-19 Vaccination.
Real-world experience on the use of COVID-19 vaccination in patients with multiple sclerosis treated with Cladribine tablets in the Gulf region
1Jihad Inshasi, 2Amir Boshra, 2Joseph Youssef
1MS Department, Rashid Hospital and Dubai Medical College, Dubai health Authority, Dubai, UAE; 2Merck Serono Middle East FZ Ltd, an affiliate of Merck KgaA, Darmstadt, Germany.
Background:
The Gulf nations were among the first in the world to implement the COVID-19 vaccination. Regional guidelines like MENACTRIMS endorse that MS patients should be vaccinated against COVID-19. The vaccines being offered in the region include Sinopharm, Pfizer-BioNTech, Sputnik V, and Oxford-AstraZeneca. “Adveva™ Gulf is a Merck-sponsored health care provider (HCP) driven patient support program (PSP) for patients treated with cladribine tablets”
Objectives:
To describe the real-world experience on the use of COVID-19 vaccination in multiple sclerosis (MS) patients treated with cladribine tablets participating in the PSP.
Material(s) and Method(s):
MS patients treated with cladribine tablets and participating in the PSP in the Gulf region were asked to participate in a questionnaire-based survey about their COVID-19 vaccination status. The interview was initiated by health educators over the phone, and they submitted the answers on the patient’s behalf. Patient’s verbal consent was required to start the questionnaire. Information collected included: Demographic, Treatment dates, Vaccination, and COVID-19 information.
Result(s):
Of the 106 MS patients, 92 (86%) patients provided consent to participate and completed the questionnaire. 77.5% of patients were females. All patients had been on cladribine tablets since 2018-till Sept 2021 (66% in Year 1, 15% in Year 2, and 19% in year 3 and 4). From the time of initiation of cladribine tablets, no switch to another disease modifying drugs (DMD) were observed. Overall, 74 (80.4%) of the cladribine tablets patients had received the COVID-19 vaccine. 51.4% and 41.9% of patients were vaccinated by the Pfizer and Sinopharm vaccines, respectively. Among those vaccinated in Year 1 and 2 (n=59), the mean time between the last dose of cladribine tablets and the first dose of the vaccine was 129 days. Of the patients who had not received the vaccine (n=18), 72.2% were planning to receive the vaccine. Only 2 patients were not willing to receive the vaccine for fear of complications. After completion of the COVID-19 vaccine regimen, 6 (8%) patients were infected with SARS-CoV-2, 5 of them confirmed by the RT-PCR test. All the cases were mild, and none of the patient’s required hospitalization. No safety concerns were reported after the administration of the COVID-19 vaccine. The mean time from the completion of the vaccine series till the development of the SARS-CoV-2 infection was 79 days.
Conclusion(s):
The outcomes of this survey suggest that the use cladribine tablets didn’t hinder the patients from receiving COVID-19 vaccinations. Few patients developed SARS-CoV-2 infection despite being vaccinated, but all had mild disease and did not require hospitalization. No safety concerns were observed. Continuous monitoring will be required to assess the safety and efficacy of the COVID-19 vaccine in this specific population. Meanwhile, MS patients should be encouraged to receive COVID-19 Vaccination.
Patient Reported Outcomes of New Brand-Generic Product of Teriflunomide in Patients with Relapsing-Remitting Multiple Sclerosis: Preliminary Analysis
1Roya Abolfazli, 2Seyed Massood Nabavi, 3Amirereza Azimi, 4Mohammadali Nahayati, 5Koroush Gharegozli, 6Monireh Ghazaeian, 7Hamid Reza Torabi, 8Shahrzad Shahrokhi, 1Sara Samadzadeh
1Tehran University of Medical Sciences – Amiralam Hospital, Department of Neurology, Tehran, Iran; 2Shahed University of Medical Sciences, Department of Neurology, Tehran, Iran; 3Tehran University of Medical Sciences, Sina Hospital, Multiple Sclerosis Research Center, Tehran, Iran; 4Mashhad University of Medical Sciences, Department of Neurology, Mashhad, Iran; 5Shahid Beheshti University of Medical Sciences, Department of Neurology, Tehran, Iran; 6Mazandaran University of Medical Sciences – Faculty of Pharmacy, Department of Clinical Pharmacy, Sari, Iran; 7Jam Hospital, Tehran, Iran; 8Zistdaru Danesh Pharmaceutical Company, Medical Department, Tehran, Iran
Background:
Patient-reported outcomes (PROs) is a useful way to determine the various effects of disease modifying therapy (DMT) on patients daily lives and their disease course. This study aimed to evaluate the patients’ treatment satisfaction after switching to a brand-generic Teriflunomide product (Tebazio®, 14 mg tablet) produced by Zistdaru Danesh biopharmaceutical company and report the tolerability and safety concerns during the period of the treatment.
Material(s) and Method(s):
The study was conducted on patients with confirmed diagnosis of multiple sclerosis (MS) as defined by the Revised McDonald Criteria (2015) from Nov 2019 to Nov 2020. They were ambulatory with a EDSS of 0 to 5.5, and their treatment by Teriflunomide 14 mg was just started. Study outcomes included patients’ satisfaction was measured by Treatment Satisfaction Questionnaire for Medication [Version 1.4] (TSQM) at baseline and week 24, disability status measured by Expanded Disability Status Scale [EDSS] score at baseline and week 24, safety and tolerability evaluated over 6 months.
Result(s):
Of 200 patients enrolled, 100 patients completed the study protocol and evaluated. Patients reported significant improvements in treatment satisfaction scores of convenience and side effects domains of TSQM scores at week 24 following the switch to teriflunomide (Effectiveness: baseline, 66.53, Week 24, 68.97; Convenience: baseline, 66.31, Week 24, 78.97; Side effect: baseline, 67.13, Week 24, 75.60; Overall Satisfaction: baseline, 63 Week 24, 65.42; P < 0.001 in all comparisons). The most common adverse drug reactions were hair thinning (36%), dermatologic (17%), gastrointestinal (23%), liver function test (LFT) dysfunction (11%), and neurologic side effects (9%) which rarely caused treatment discontinuation.
Conclusion(s):
Patients reported significant satisfaction regarding TSQM scores after switching to Tebazio at week 24 which can be impressive to increase patient compliance. The 14 mg brand-generic Teriflunomide product was well tolerated in Iranian RRMS patients and no new alarming signal was detected during the study period.
Long-Term Efficacy for Patients Receiving Cladribine Tablets in CLARITY/CLARITY Extension: Primary Results from 9–15 Years of Follow-Up in the CLASSIC-MS Study
1Gavin Giovannoni, 2Thomas Leist, 3Aida Aydemir, 3Elisabetta Verdun Di Cantogno
1Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; 2Division of Clinical Neuroimmunology, Jefferson University, Philadelphia, United States; 3EMD Serono Research & Development Institute, Inc. (an affiliate of Merck KGaA), Billerica, United States
Background:
CLASSIC-MS (NCT03961204) was an exploratory, ambispective Phase IV study designed to evaluate the long-term efficacy of cladribine tablets (CladT) in the real-world setting, for patients with relapsing multiple sclerosis (MS) who were previously enrolled to Phase III (parent) trials. The objective of this investigation was to report primary results for CLASSIC-MS in terms of long-term mobility and disability beyond the treatment courses that patients received in the parent trials, with the aim of informing future treatment approaches.
Material(s) and Method(s):
This analysis represents patients in CLASSIC-MS who participated in the Phase III CLARITY trial whether or not they participated in CLARITY Extension, and who had received ≥1 course of CladT or placebo. The primary objective of CLASSIC-MS was the evaluation of long-term mobility (no wheelchair use/bedridden; i.e. EDSS <7 in the 3 months prior to first visit in CLASSIC-MS). The main secondary objective was long-term disability status (no requirement for an ambulatory device; i.e. EDSS <6 any time since last parent study dose [LPSD]). Analyses are descriptive and shown in relation to exposed/never exposed to CladT in CLARITY.
Result(s):
The CLASSIC-MS population who previously participated in CLARITY/CLARITY Extension comprised 435 patients with relapsing MS (67.8% female; mean±SD EDSS score, 3.87±2.07 at CLASSIC-MS baseline), with a median time since LPSD of 10.9 (range 9.3–14.9) years and a median disease duration of 20.7 (range 13.9–46.5) years at CLASSIC-MS baseline. A total of 90.6% (n=394) were exposed to CladT during CLARITY/CLARITY Extension, including 160 patients who received the approved cumulative dose of 3.5 mg/kg over 2 years; the remaining 9.4% (n=41) were never exposed. The proportion of patients not using a wheelchair/bedridden in the 3 months prior to CLASSIC-MS (i.e. EDSS <7) was 90.0% of the CladT exposed cohort and 77.8% of the never exposed cohort. Regarding long-term disability status, the proportion of patients with no requirement for an ambulatory device (i.e. EDSS <6) was 81.2% of the CladT exposed and 75.6% of the never exposed cohorts, respectively.
Conclusion(s):
Baseline patient characteristics suggest that patients enrolled in CLASSIC-MS were a representative sample of all patients included in the original parent studies. Reported findings for CLASSIC-MS, with a median of 10.9 years’ follow-up after CLARITY/CLARITY Extension, suggests sustained efficacy of CladT in terms of long-term mobility and disability status.
Pregnancy Outcomes in Patients with Multiple Sclerosis Following Exposure to Ofatumumab
1Bassem Yamout, 2Kerstin Hellwig, 3Riley Bove, 4Pranava Katkuri, 5Ulf Schulze Topphoff, 6Dee Stoneman, 7Ronald Zielman, 8Ratnakar Pingili, 9Maria K. Houtchens
1Neurology Institute and Multiple Sclerosis Center, Harley Street Medical Centre, Abu Dhabi, UAE; 2Department of Neurology, St Josef Hospital, Ruhr University, Bochum, Germany; 3University of California San Francisco, San Francisco, CA, USA; 4Novartis Pharmaceuticals Pvt. Ltd., Hyderabad, India; 5Novartis Pharma GmbH, Nuremberg, Germany; 6Novartis Pharma AG, Basel, Switzerland; 7Novartis Pharma B.V., Amsterdam, Netherlands; 8Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 9Brigham Multiple Sclerosis Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Background:
Ofatumumab, a fully human anti-CD20 monoclonal antibody, is approved for the treatment of relapsing multiple sclerosis (RMS) in adults. As per the ofatumumab label, females of childbearing potential should use effective contraception during and for at least 6 months after discontinuation of treatment. Data on the effect of ofatumumab on pregnancy outcomes are limited in humans. Based on the current knowledge, the maternal-fetal transfer of IgG during the first trimester is minimal and fetal IgG concentration starts to rise from the second trimester. Furthermore, in cynomolgus monkeys, exposure to ofatumumab during gestation did not cause maternal toxicity and there were no adverse effects on the pre- or postnatal development.
Objective(s):
To report pregnancy outcomes from the Novartis Safety Database in women with RMS inadvertently exposed to ofatumumab during pregnancy.
Material(s) and Method(s):
Pregnancy outcomes data from women with RMS exposed to ofatumumab during pregnancy or 6 months prior to last menstrual period were analyzed from clinical trials, and real-world setting in the Novartis Safety Database (cutoff: August 31, 2021). Maternal and infant outcomes including birth defects, congenital anomalies, infections, vaccination, and developmental delays were collected from the reporting of pregnancy up to 1 year of infant age.
Result(s):
As of cutoff date, 32 pregnancies with ofatumumab (ASCLEPIOS I/II, n=4; ALITHIOS, n=14; MIRROR, n=7; post-marketing, n=7) were reported in women with MS; of which 5 were ongoing and in 4 pregnancies, information on the outcomes was not reported. The remaining 23 pregnancies had the following outcomes: therapeutic/induced abortions (n=6), spontaneous abortion (n=5), early intrauterine fetal demise at ~8.5 weeks gestation and patient underwent therapeutic abortion (n=1; not suspected to be related to ofatumumab by the treating physician), and 11 live births of normal babies. Based on followed-up data (up to 1 year of infant age), no B-cell depletion, immunoglobulin/hematological/fetal abnormalities, and serious infections were reported.
Conclusion(s):
In this analysis, no birth defects or congenital anomalies were reported in 23 pregnant women exposed to ofatumumab with known outcomes. There were no reports of B-cell depletion, immunoglobulin/hematological abnormalities, or serious infections in live births to date. Sharing the up-to-date data on pregnancy and infant outcomes with ofatumumab is helpful in counseling women with MS of childbearing potential. A prospective observational registry on maternal and infant outcomes in women exposed to ofatumumab is currently being planned.
Epidemiology of COVID-19 in Patients with MS: A Hospital-Based Registry
1Sharareh Eskandarieh, 1Mohammad Ali Sahraian, 1Vahid Shaygannejad, 1Abdorreza Naser Moghadasi, 1Fereshteh Ashtari, 1Hamidreza Ghalyanchi, 1Seyed Mohammad Baghbanian, 1Hossein Mozhdehipanah, 1Nastaran Majdinasab, 1Samaneh Houseini, 1Maryam Poursadeghfard, 1Nahid Beladimoghadam, 1Nazanin Razazian , 1Zhila Maghbooli
1Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
Background:
Recent Covid-19 outbreak around the world turned into an international public health concern. Generally, people who receives immunosuppressive treatments or have an underlying disease are more likely to be infected. Multiple sclerosis (MS) patients also may have higher risk of infection due to the taking immunosuppressive or immunomodulatory drugs (1).
Objective(s):
To identify the epidemiological characteristics of Covid-19 in patients with MS for improve quality of care and achievement to better diagnosis and treatment in MS patients in Iran.
Material(s) and Method(s):
The present data were obtained from a hospital-based registry in Imam Khomeini hospital, Tehran, Iran. Totally, 88 MS patients who was infected by Covid-19 were registered from May, 2020 to March 2021. Demographic and clinical data was collected (2).
Result(s):
55 (65.5%) of participants were female by the mean age (SD) of 37.48 ± 10.05 years. Covid-19 diagnosis of 4 (4.5%) of patients was based on positive PCR test. The most MS treatment was receiving by patients was Rituximab (20 (22.7%)) following by Dimethyl Fumarate (14 (15.9%)), Fingolimod (10 (11.4%)), Glatiramer acetate (8 (9.1%)), Interferon β-1a (IM) (5 (5.7%)), Interferon β-1a (SQ) (5 (5.7%)), Interferon β-1b (3 (3.4%)), Triflunomide (2 (2.3%)) and Natalizumab (1 (1.1%)). The mean (SD) interval from the last Rituximab injection to Covid-19 infection was 3.80 ± 3.40 months. 37 (42.0%) MS patients continued to take their drugs after Covid-19 infection, while 10 (11.4%) of them stopped taking MS medicine and 7 (8.0%) of them was taking no treatment for controlling MS. 2 (2.3%) of participants was diagnosed by MS after Covid-19 infection. 9 (9.7%) subjects hospitalized due to Covid-19 infection. The mean (SD) duration of hospitalization was 5 ± 7.81 days. One (1.1%) death cases was reported.
Conclusion(s):
Our findings revealed valuable data of Covid-19 characteristics in patients with MS which could be useful for improving health services for MS patients during the Covid-19 pandemic (3-4).
Variables Affecting Disease Modifying Therapy Adherence and Impact of Adherence on Multiple Sclerosis Patients (Egyptian Experience)
1Amr Abdelsalam, 2Rasha Elkabany, 2Ibrahim Alahmar, 2Mona Sabry
1Nasser institute for research and treatment, Cairo, Egypt; 2Menoufia University, Menoufia, Egypt
Objective(s):
To realize the degree of DMT adherence among MS patients in Egypt. To find the barriers contributing to medication adherence. To evaluate the clinical impact of non-adherence on MS patients.
Material(s) and Method(s):
This cross-sectional study was carried out on 150 MS patients from MS unit at Menoufia university hospitals and Nasser institute for research and treatment hospital. The degree of adherence was measured using the Arabic version of eight-item Morisky Medication Adherence Scale (MMAS-8). Other related variables were measured by a questionnaire including socio-demographic data, disease characteristics and previous treatment data.
Result(s):
A total of 150 MS patients were included with mean age ± standard deviation of 32.5±8 years and 78% females. The degree of adherence was (59%). The adherence to DMT was significantly affected by the DMT type and route of administration, MS phenotypes, line of treatment and patient satisfaction (P<0.05). However, the adherence was not affected by degree of disability measured by patients’ current EDSS, median (3.415) in adherent patients and (3.395) in non-adherent patients. The most common causes of non-adherence were forgetfulness (40.3%) and injection site reaction/flu like symptoms (38.7 %). Non-adherent patients had higher number of recurrent hospitalization and relapses (median, 1 vs. 0 times, P<0.05) and shorter time from the last hospitalization compared to adherent patient (mean, 10.5 vs. 14 months, P<0.05).
Conclusion(s):
Many factors affect Adherence to DMT and Non-adherent patients experienced significantly more relapse rate and recurrent hospitalization.
The Effect of Rituximab on Mood Disorders in Multiple Sclerosis
1Maryam Poursadeghfard, 1Mozhgan Sattar, 1Mahnaz Bayat
1Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Background:
Mood disorders are the most concurrent problems in multiple sclerosis (MS) that have a great influence on the quality of life of these patients.
Objective(s):
Disease-modifying drugs (DMDs) could have some positive or negative psychological effects. Rituximab is a drug commonly used as DMD in MS and its effects on mood have not been fully elucidated.
Aim:
In this study, we evaluated the effect of rituximab on mood in MS patients.
Material(s) and Method(s):
In this prospective study, all patients who were going to receives the first dose of rituximab from January 2019 to April 2020 in Fars province, south of Iran were enrolled. HADS questionnaires were filled out before treatment, 3 months after the first course, and 1 month after the second course (7 months later). Data entry and analysis were done using SPSS version 22.
Result(s):
From 108 patients who filled out the questionnaire, 70 patients had inclusion criteria. Mean differences of the HADS scale for depression were 0.54 (CI: -0.24- 1.33; p=0.17) after the first and 0.73 (CI; -0.49-1.55; p=0.30) after the second course of rituximab regarding the base scale which were not significant. For the anxiety, the mean scale at baseline was 6.6 which significantly decreased to 5.6 (p-value= 0.039) after the first and 5.3 (p-value=0.005) after the second course.
Conclusion(s):
According to this study, rituximab could have positive effects on both anxiety (statistically and clinically) and depression (clinically) in M.S patients. As a result of our data, only one dose of rituximab could improve significantly the anxiety of these patients.
Claims-Based Relapse and Hospitalization Rates in Patients with Multiple Sclerosis Treated with Natalizumab or Ocrelizumab
1Jacqueline Nicholas, 2Nick Belviso, 2Geentanjoli Banerjee, 2Caroline Geremakis, 2Robin Avila, 2Karthik Bodhinathan
1OhioHealth MS Center, Riverside Methodist Hospital, Columbus, United States; 2Biogen, Cambridge, United States
Background:
Natalizumab (NTZ) and ocrelizumab (OCR) are high-efficacy disease-modifying therapies (DMTs) approved to treat relapsing forms of multiple sclerosis (MS). Real-world head-to-head data comparing relapses and related hospitalization rates for high-efficacy DMTs, including NTZ vs OCR, are limited. To compare claims-based relapses and relapse-related hospitalization rates for MS patients treated with NTZ or OCR using data from a large insurance claims database.
Material(s) and Method(s):
This retrospective analysis of the Optum claims database included patients with a diagnosis of MS (≥1 inpatient or ≥2 outpatient claims of International Classification of Diseases [ICD]-9 340 or ICD-10 G35 between 1 April 2017 and 30 September 2020), were naive to study DMTs in the year prior to the initial prescription (index date), and were treated with NTZ or OCR during the study period. Relapses included outpatient events with an MS diagnosis code followed by steroid use within 7 days and hospitalization events with MS as the primary diagnosis code. Inverse probability weighting (IPW) was used to adjust for differences between groups in 17 baseline covariates, including age, number of MS symptoms, prior DMT use, comorbidities, and baseline (index) costs.
Result(s):
The analysis included 835 NTZ and 3497 OCR patients. After IPW, NTZ (n=4342) and OCR (n=4333) patients were well balanced with all standardized differences ≤0.1. Mean follow-up time was approximately 0.9 and 1.0 years for NTZ and OCR patients, respectively. NTZ patients had longer time to first relapse vs OCR with hazard ratio (HR) significantly favoring NTZ (0.70 [95% confidence interval (CI): 0.55–0.88]; P<0.01). The HR for time to first MS-related emergency room (ER) visit did not differ significantly between groups. Mean annualized rates were significantly lower with NTZ than with OCR for any relapse (0.30 vs 0.43; mean difference: –0.13 [95% CI: –0.25, –0.02]; P=0.02) and outpatient relapse (0.22 vs 0.36; mean difference: –0.14 [95% CI: –0.24, –0.04]; P=0.01); but did not differ for MS-related ER visits (0.09 vs 0.08; P=0.82) and relapse-related hospitalizations (0.07 vs 0.07; P=0.83).
Conclusion(s):
Rates of relapses overall were significantly lower with NTZ than with OCR. Though relapses were insurance claims-based and not physician reported, these results provide a direct comparison of relapse-related outcomes and healthcare utilization in MS patients treated with NTZ or OCR in real-world settings.
Treatment of Progressive Multifocal Leukoencephalopathy with Pembrolizumab
1Yousef Saleh Aldughaythir, 1Mazen Sulaiman Alamr
1King Fahad Medical City, Riyadh, Saudi Arabia
Background:
Progressive multifocal leukoencephalopathy (PML) is a fatal, rare viral infection of the brain that leads to demyelination and neuronal loss. It develops almost exclusively in patients with a compromised cell-mediated immunity with conditions like acquired immunodeficiency syndrome, hematologic malignancies and treatment with immunosuppression. No treatment is available to reveres or halt the progression of the disease. Pembrolizumab is a monoclonal antibody to programmed cell death-1 (PD-1) protein, inhibiting PD-1 activity allows proliferation of T-cells and enhancing the immune function. Few studies reported the use of pembrolizumab in patients with PML which showed variable response in restoring immune function and halting disease progression.
Material(s) and Method(s):
A single dose of pembrolizumab 2 mg/kg was administered to a patient with PML secondary to treatment of diffuse large B-cell lymphoma. She completed 6 cycles of R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and presented 6 months later with progressive neurologic symptoms of behavioral changes, dysarthria, gait difficulty and left sided weakness. MRI brain reveled asymmetric, confluent, non-enhancing bifrontal white matter T2/FLAIR lesions with no mass effect, edema and no diffusion restriction. PCR of cerebrospinal fluid confirmed the presence of JC virus DNA.
Result(s):
Five weeks following administration of pembrolizumab, her neurologic status deteriorated, she was not producing words, not following commands, developed dysphagia, spastic quadriplegia and generalized seizures. Eventually she was pronouncing dead due to asystole.
Conclusion(s):
The unfortunate rapid progression of the disease in this patient prevented the planned treatment regimen of 3 doses separated by 6 weeks. We are hoping that this case will encourage further investigation into this untreatable fatal disease.
Economic Analysis for Introduction of Cladribine Tablets as a Treatment for Relapsing Multiple Sclerosis Patients with High Disease Activity in Kuwait
1Raed Alroughani, 2Samar Farouk Ahmed, 3Amr Abokoura, 4Essam Alsultan, 5Amir Boshra, 5Rawan Alcharif, 6Rita Ojeil, 7Sujata Basu
1Department of Medicine, Amiri Hospital, Sharq, Kuwait, Neurology Department, 2Neurology Department, Ibn Sina Hospital, Kuwait, Neuropsychiatry Department, Faculty of Medicine, Minia University, Egypt, 3Neurology Division, Mubarak Alkabeer hospital, Kuwait, 4Head of Pharmacy Department, Ibn Sina hospital, Kuwait 5Merck Serono Middle East FZ LTD, an affiliate of Merck KgaA, Darmstadt, Germany, 6HEOR, IQVIA, Middle East, 7HEOR, IQVIA, India.
Introduction/Objective(s):
Multiple sclerosis (MS) is a chronic demyelinating neurological disorder characterized by the loss of sensory and motor functions. In 2019, the estimated prevalence and incidence of MS in Kuwait per 100,000 people was 104.9 and 5.39, respectively. Cladribine tablets are the first oral short-course treatment approved for highly active relapsing multiple sclerosis across various geographies. The objective of the study was to estimate the budget impact (BI) of introducing Cladribine tablets compared to other disease-modifying drugs for the treatment of high-disease activity (HDA) relapsing MS patients from the payer’s perspective in Kuwait.
Material(s) and Method(s):
BI analysis was conducted using an excel-based BI model in the adult population with HDA relapsing MS in Kuwait. Three scenarios, ‘MS Treatments without Cladribine’ and ‘MS Treatments including Cladribine’ and ‘MS Treatments with 100% Cladribine’ were assessed over a five-year time horizon. Model inputs included the total number of RRMS and HDA patients, market shares for the three scenarios, and costs associated with drug acquisition, administration, monitoring, adverse events management, and relapse therapy. All costs were presented in 2021 Kuwaiti Dinars (KWD). Inputs were retrieved from literature and/or obtained from interviews with key experts in Kuwait. All the inputs used in the model were further validated by key experts.
Result(s):
Introducing Cladribine tablets for the treatment of HDA relapsing MS in Kuwait resulted in an estimated decrease in the overall net budget from 4.8% (KWD 984,282) in scenario 2 and up to 28.5% ([RB1] KWD 5,861,086) in scenario 3. The major contributors for cost savings included the drug acquisition costs, expenditure associated with adverse events and rescue treatment.
Conclusion(s):
Introduction of cladribine tablets in Kuwait as a treatment option in HDA relapsing MS patients shows cost-saving from the payer’s perspective. The savings in budget improved with an increase in the cladribine tablets market share.
Primary Results of NOVA: A Randomized Controlled Study of the Efficacy of 6 Week Dosing of Natalizumab Versus Continued 4-Week Treatment for Multiple Sclerosis
1John Foley, 2Gilles Defer, 3Lana Zhovtis Ryerson, 4Jeffrey A. Cohen, 5Douglas L. Arnold, 6Helmut Butzkueven, 7Gary Cutter, 8Gavin Giovannoni, 9Joep Killestein, 10Heinz Wiendl, 11Karen Smirnakis,11Shan Xiao,11George Kong,12Robert Kuhelj,11Nolan Campbell
1Rocky Mountain MS Clinic, Salt Lake City, United States; 2Department of Neurology, Centre Hospitalier Universitaire de Caen, Caen, France; 3Department of Neurology, NYU Langone Health, New York University, New York, United States; 4Cleveland Clinic, Cleveland, United States; 5Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; 6Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Canada; 7University of Alabama School of Public Health, Birmingham, United States; 8Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; 9Department of Neurology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; 10Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany; 11Biogen, Cambridge, MA, USA; 12Biogen, Baar, Switzerland
Background:
Natalizumab 4-week dosing (Q4W) with 300 mg is approved for treatment of relapsing-remitting multiple sclerosis. Dosing frequency of approximately 6 weeks (Q6W) is associated with lower progressive multifocal leukoencephalopathy (PML) risk in retrospective analyses. Real-world data suggest similar effectiveness, but NOVA is the first randomized trial to assess Q6W efficacy. The objective of NOVA was to evaluate the efficacy of natalizumab Q6W in patients previously treated with natalizumab Q4W for ≥12 months compared with continuation of Q4W over 72 weeks.
Material(s) and Method(s):
NOVA is a randomized, controlled, open-label, rater-blinded phase 3b trial. Included patients were treated with natalizumab Q4W without relapse for ≥12 months and had no enhancing lesions at screening. Patients were randomized 1:1 to Q6W or Q4W arms. The primary endpoint was number of new/newly enlarging T2 (N/NET2) hyperintense lesions analyzed by negative binomial regression with baseline (BL) weight, prior natalizumab exposure, and region as covariates. Secondary endpoints included relapses and 24-week confirmed disability worsening (CDW). Primary estimand used all observed data; secondary estimand treated post-intercurrent event data as missing. Missing data were imputed by worst value on treatment or multiple imputation depending on discontinuation reason.
Result(s):
195/248 (79%) Q4W patients and 207/251 (82%) Q6W patients completed NOVA. BL characteristics were well balanced. Proportions of patients with N/NET2 lesions among observed data were low in both arms (Q4W:4.1%; Q6W:4.3%). Mean N/NET2 lesions in the Q4W and Q6W arms with the primary estimand were 0.05 and 0.20 (P=0.0755) and 0.06 and 0.31 (P=0.0437) with the secondary estimand. The difference was mainly due to 2 Q6W patients with high values: (1) 30 lesions that occurred 3 months after natalizumab discontinuation and (2) 25 lesions that occurred with asymptomatic PML observed at week 72. The sum of all other N/NET2 lesions in NOVA was 18 with no other patient having >2. Relapse occurred in 2.1% and 2.8% (P=0.64) and CDW occurred in 8% and 10% (P=0.40) of patients in the Q4W and Q6W arms, respectively. Safety data were consistent with the known drug profile and similar between groups.
Conclusion(s):
Despite a small difference in efficacy between arms, NOVA data suggest the vast majority of patients stable on Q4W dosing can switch to Q6W dosing with no clinically meaningful loss of efficacy. No conclusions on PML risk can be drawn from NOVA.
*Additional authors: Karen Smirnakis (Biogen, Cambridge, USA); Shan Xiao (Biogen, Cambridge, USA); George Kong (Biogen, Cambridge, USA); Robert Kuhelj (Biogen, Baar, Switzerland); Nolan Campbell Biogen, Cambridge, USA).
Comparison of Time to Clinically Meaningful Improvement in Neuro-QOL in Patients Treated with Natalizumab Versus Ocrelizumab
1Carrie M. Hersh, 2Carl De Moor, 3Deborah M. Miller, 2Robin Avila, 2James R. Williams, 4Kathryn C. Fitzgerald, 2Menglan Pang, 3Marisa P. Mcginley, 5Megan Hyland, 6Tjalf Ziemssen, 7Irene Koulinska
1Mellen Program for MS, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, United States; 2Biogen, Cambridge, United States; 3Mellen Center, Cleveland Clinic, Cleveland, United States; 4Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States; 5Department of Neurology, University of Rochester Medical Center, Rochester, United States; 6University Clinic Carl-Gustav Carus, Dresden, Dresden, Germany; 7Biogen, at the time of this study, Cambridge, United States
Background:
Understanding patient-reported changes in physical, mental, and social health after initiation of multiple sclerosis (MS) disease-modifying therapy (DMT) is important to optimize treatment.
Objective(s):
To compare time to improvement in each Quality of Life in Neurological Disorders (Neuro-QoL [NQ]) domain in patients treated with natalizumab (NAT) vs ocrelizumab (OCR).
Material(s) and Method(s):
T-scores of 12 NQ domains were obtained at routine visits in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network. Baseline (BL) was defined as the last NQ measurement ≤1 year prior to initiating NAT or OCR, and eligible patients had >1 follow-up NQ assessment after initiation of NAT or OCR. Patients with primary progressive MS, prior NAT or OCR therapy, and/or a BL NQ score <5 points below the maximum (for positively worded domains) or <5 points above the minimum (for negatively worded domains) were excluded. T-score improvements of ≥5 points from BL were considered clinically meaningful. Time to first ≥5-point NQ improvement in propensity score (PS)–matched NAT and OCR patients was compared using a semiparametric accelerated failure time model for interval-censored data. BL variables for PS matching included age, sex, race, years of education, MS duration, prior DMT, self-reported disability and relapses in prior year, processing speed and manual dexterity test scores, co-medications, and corresponding NQ domain scores.
Result(s):
There were 146 NAT and 632 OCR patients eligible for this analysis. Mean (standard deviation) follow-up times were 1.1 (0.7) and 1.2 (0.7) years for NAT- and OCR-treated patients, respectively. After exclusion based on BL NQ scores, 88–139 NAT and OCR patients were PS matched, depending on NQ domain. For matched patients, time to improvement was significantly shorter with NAT than with OCR for cognitive function (event time ratio: 0.45; P=0.002) and satisfaction with social roles and activities (event time ratio: 0.47; P=0.04). There were no significant differences between groups in the remaining 10 NQ domains.
Conclusion(s):
NAT treatment can shorten the time to clinically meaningful improvement in the NQ domains of cognition and satisfaction with social roles and activities compared with OCR. These results complement previous findings from MS PATHS indicating that NAT treatment can produce meaningful improvements in mental and social health, with overall annualized improvement rates higher than those observed with OCR.
*Additional authors: Irene Koulinska (Biogen, Cambridge, MA, USA, at the time of this study)
Vitamin D3 Improves Behavioral Dysfunction and Promotes Remyelination in Multiple Sclerosis Model Induced by Cuprizone
1,2Kholoud M. Al-Otaibi, 3,4Badrah S Alghamdi, 1Maryam A. Al-Ghamdi, 1Ulfat Omar
1Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Chemistry, Faculty of Science, Al-Baha University, Al-Baha, Saudi Arabia; 3Department of Physiology, Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
Introduction:
Multiple sclerosis (MS) is a chronic demyelination disease of the central nervous system (CNS) that attacks the myelin sheath around the axon and damages it. Therefore, promoting remyelination is a critical strategy for treating MS to resolve and alleviate symptoms and protect myelin sheath from further damage. Vitamin D3 (Vit D3) supplementation is increasingly advised to patients with MS. Thus, this study aimed to investigate the effects of Vit D3 supplementation to improve remyelination in a cuprizone (CPZ) mouse model of MS.
Material(s) and Method(s):
The study was designed as two stages (de and re-myelination) for nine weeks; a total of 45 male SWR/J mice were divided into two groups, Control (n=15) and CPZ (n=30) groups for the first five weeks (demyelination stage). Mice in the control group were received a normal diet with ad libitum access through all experiment stages (de and re-myelination), whereas mice in the CPZ group were fed a diet mixed with 0.3% CPZ for 5 weeks to induce demyelination. After week 5 CPZ diet was discontinued and followed by a normal diet for the last 4 weeks (remyelination stages), and mice in the CPZ group were re-divided into two groups: untreated and treated with Vit D3 orally once daily at 800 IU/kg. The effect of Vit D3 on behavioral changes was determined using grip strength meter and rotarod test. The degree of de and re-myelination in the corpus callosum (CC) of brains were assessed by Luxol Fast Blue (LFB) stain at weeks 5, 7, and 9.
Result(s):
The results showed that CPZ significantly reduced behavior performance in mice and myelin content in CC during the demyelination stage. In contrast, mice’s grip strength and motor coordination performance revealed significantly improved behavior after treatment with Vit D3 at early and last remyelination stages (7 and 9 weeks, respectively). Furthermore, LFB staining showed that Vit D3 significantly promoted remyelination in the CC of the brain compared to the untreated group at the remyelination stages.
Conclusion(s):
In conclusion, these results demonstrated that Vit D3 could improve remyelination in a CPZ-demyelinating mouse model of MS.
Improvements in Quality of Life at 1 Year in Patients Treated with Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: An Interim Analysis of Clarify-MS
1Alessandra Solari, 2Xavier Montalban, 3,4Jeannette Lechner-Scott, 5Fredrik Piehl, 6Bruno Brochet, 7Dawn Langdon, 8Raymond Hupperts, 9Krzysztof Selmaj, 10Eva K. Havrdova, 11Francesco Patti, 12Luis Brieva, 13Eva Maria Maida, 14Nektaria Alexandri, 14Paul Kamudoni, 14Axel Nolting, 14Birgit Keller
1Unit of Neuroepidemiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; 2Department of Neurology-Neuroimmunology Centre of Multiple Sclerosis of Catalonia (Cemcat), University Hospital Vall d’Hebron, Barcelona, Spain; 3University of Newcastle, Newcastle, NSW, Australia; 4Division of Neurology, John Hunter Hospital, Newcastle, NSW, Australia; 5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 6INSERM U 1215, University of Bordeaux, Bordeaux, France; 7Department of Psychology, Royal Holloway, University of London, Egham, UK; 8Zuyderland Medisch Centrum Sittard, Maastricht University Medical Center, Maastricht, The Netherlands; 9Center for Neurology, Lodz, Poland; 10Charles University, First Medical Faculty, Prague, Czech Republic; 11Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, University of Catania, and Azienda Ospedaliero Universitaria Policlinico “G Rodolico”- San Marco, University of Catania, Italy; 12IRBLLEIDA, Hospital Arnau de Vilanova, Lérida, Spain; 13Multiple Sclerosis Center, Vienna, Austria; 14Merck Healthcare KGaA, Darmstadt, Germany
Background/Objective(s):
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system affecting young adults. It is considered one of the major causes of disability in adults. The prevalence of MS is increasing globally. In Saudi Arabia (KSA) it is reported that the projected overall prevalence of MS is 40/100,000 for the total population and higher for Saudi nationals at 61.95/100,000 putting Saudi Arabia above the low-risk zone as per Kurtzke classification (1). With this rising prevalence, and the established significance of multidisciplinary team management, there is a growing need for specialist MS nurses. A group of specialized MS nurses formed an advisory group to support the role of the MS nurse in the management of patients with MS in KSA. This is the first advisory board meeting aiming to optimize nursing care for MS patients in KSA.
Design and Method(s):
In CLARIFY-MS (NCT03369665), patients with highly active relapsing MS were assigned to receive CladT 3.5 mg/kg cumulative dose over 2 years. Patients were recruited as per the EU label. Results in this interim analysis, conducted prior to the second year of treatment, were assessed using a mixed-effects linear model. Analyses were also conducted for cohorts separated by treatment naïve/prior disease-modifying therapy (DMT), and MSQoL reporting performed before/after the start of the COVID-19 pandemic, as defined as the first reported fatality within each country.
Result(s):
Of the 482 patients treated with CladT, 70.1% were female and the mean age was 37.4 years. Of the 426 patients who provided MSQoL-54 data, statistically significant (p<0.0001) improvements from Baseline to Month 12 were observed for physical and mental health composite scores with estimated changes of 4.51 (95% confidence interval [CI] 3.24–5.77) and 4.53 (95% CI 3.00–6.05), respectively. Similar trends were apparent for treatment naïve (n=121) and prior DMT (n=305) cohorts. There was no indication that the start of the COVID-19 pandemic had an impact on MSQoL-54 reporting. Regarding safety, 322 patients (66.8%) experienced at least one treatment-emergent adverse event, most commonly headache (16%), nasopharyngitis (9%), and lymphopenia (9%). The majority of observed post-baseline lymphopenia events were grade 1–2; fewer patients reported grade 3 lymphopenia, no grade 4 lymphopenia was observed.
Conclusion(s):
With only half a therapeutic dose of CladT, this interim analysis demonstrates a statistically significant improvement in the physical and mental health composite scores of MSQoL-54 at 1 year. No new safety concerns were found in this 1-year interim analysis, with no new severe or opportunistic infections that could have an impact on the established benefit:risk profile of CladT in MS.
Multiple Sclerosis Specialized Nurses in Saudi Arabia: Challenge, and Opportunities
1Rola Alarieh, 2Aida Balegh, 3Arij Khan, 4Asmaa Mejally, 5Fatima Almaghrabi, 6Joelle Massouh, 7Omar Saleh, 8Ouhoud Nazmi, 9Qamar Bukhari, 10Richel Sulague, 11Sawsan Almaymani, 12Waad Alsaggaf, 13Ahmed El Boghdady
1King Fahad Medical City, Riyadh, Saudi Arabia; 2King Abdulaziz Hospital (KAH), Al Mahiar, Jeddah, Saudi Arabia; 3King Fahad General Hospital (KFGH), Jeddah, Saudi Arabia; 4King Fahad National Guard Hospital (KFNGH), Riyadh, Saudi Arabia; 5Heraa Hospital, Makkah, Saudi Arabia; 6Nehme and Therese Tohme Multiple Sclerosis Center, Beirut, Lebanon; 7King Fahad Specialist Hospital (KFSH), Dammam, Saudi Arabia; 8King Faisal Specialist Hospital and Research Center (KFSH&RC), Jeddah, Saudi Arabia; 9KFGH, Madinah, Saudi Arabia; 10KFSH, Riyadh, Saudi Arabia; 11King Abdulaziz Medical City (KAMC), Makkah, Saudi Arabia; 12KAMC, Jeddah, Saudi Arabia; 13 Merck Serono Saudi Arabia, an affiliate of Merck KGaA Merck Group, Darmstadt, Germany.
Background/Objective(s):
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system affecting young adults. It is considered one of the major causes of disability in adults. The prevalence of MS is increasing globally. In Saudi Arabia (KSA) it is reported that the projected overall prevalence of MS is 40/100,000 for the total population and higher for Saudi nationals at 61.95/100,000 putting Saudi Arabia above the low-risk zone as per Kurtzke classification (1). With this rising prevalence, and the established significance of multidisciplinary team management, there is a growing need for specialist MS nurses. A group of specialized MS nurses formed an advisory group to support the role of the MS nurse in the management of patients with MS in KSA. This is the first advisory board meeting aiming to optimize nursing care for MS patients in KSA.
Design and Method(s):
A panel of 12 registered MS nurses representing several medical institutions across the KSA were invited to participate. The advisory board was held online on 1st of May, 2021 and was comprised of three main topics to be discussed: “Overview of the Roles of MS Nurse”, “MS specialized nurses (MSSN) Interventions, Challenge, and Opportunities”, and: A Patient-Centric Perspective” in MS care . Each session lasted for approximately two hours and a half hour. Following each section, a nominal group discussion was conducted to come up with a list of challenges and opportunities that are needed to improve the role of MS nurse in KSA.
Result(s):
Panel members reached a consensus on the valuable role of the MS nurse in empowering patients with information regarding the course of the disease, raising awareness on adverse events of disease-modifying drugs, and providing psychological support. It was agreed that a higher level of patient education correlates with a greater need to discuss diagnostic results, relapses, disability, and disease prognosis. They commented on shortages in the required number of trained and certified nurses. They also highlighted the need to empower the role of MS nurses within the MS multidisciplinary team by increasing the number of specialized MS nurses and empowering them with the needed education and knowledge. The advisory group voted on and ranked the possible topics of interest for nurse MS education.
Conclusion(s):
MS Nurses have a vital and important role in the management of MS patient. In KSA there is a clear gap in the availability of MS nurses in general with a clear shortage of certified MS nurses. It has become essential to prepare nurses in Saudi Arabia for MS patient management using preparatory courses and seminars to support their important role in MS patient care and prepare them to get certified.
Expert Opinion on COVID-19 Vaccination and the Use of Cladribine Tablets
1,2Bassem I Yamout, 3Peter Rieckmann, 4Diego Centonze, 5Gavin Giovannoni, 6Le H. Hua, 7,8Celia Oreja-Guevara, 9Daniel Selchen, 10Per Soelberg Sørensen, 11Patrick Vermersch, 12Heinz Wiendl, 13Hashem Salloukh
1Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut, Beirut, Lebanon; 2Neurology Institute, Harley Street Medical Center, Abu Dhabi, UAE; 3Center for Clinical Neuroplasticity, Medical Park Loipl, Bischofswiesen, Department of Neurology, University of Erlangen, Germany; 4Unit of Neurology and Neurorehabilitation, IRCCS Neuromed, Pozzilli (IS), Italy; 5Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; 6Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA; 7Neurology, Hospital Clínico San Carlos, Idissc, Madrid, Spain; 8Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid, Spain; 9University of Toronto, Division of Neurology, St. Michael’s Hospital, Toronto, ON, Canada; 10Danish Multiple Sclerosis Center, Department of Neurology, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark; 11Université de Lille, INSERM-U1172, Centre Hospitalier Universitaire de Lille, Fédératif Hospitalo-Universitaire Precise, Lille, France; 12Department of Neurology, Institute of Translational Neurology, University of Münster, Münster, Germany; 13Ares Trading SA, Eysins, Switzerland (an affiliate of Merck KGaA)
Background/Objective(s):
Gaps in current evidence and guidance leave clinicians with unanswered questions on the use of cladribine tablets for the treatment of multiple sclerosis (MS) during the COVID-19 pandemic, particularly relating to COVID-19 vaccination. We describe a consensus-based program led by international MS experts with the aim of supplementing current guidelines and treatment labels by providing timely recommendations relating to COVID-19 vaccination and the use of cladribine tablets in clinical practice.
Design and Method(s):
A steering committee (SC) of 10 international MS experts identified seven clinical questions to answer concerning the use of cladribine tablets and COVID-19 vaccination, which addressed issues relating to patient selection, timing and efficacy, and safety. Clinical recommendations addressing each question were drafted using available evidence combined with expert opinion from the SC. An extended faculty of 28 MS experts, representing 19 countries, in addition to the SC members, voted on the recommendations. Consensus on recommendations was achieved when ≥75% of respondents expressed an agreement score of 7–9, on a 9-point scale.
Result(s):
Consensus was achieved on all 13 recommendations. Clinical recommendations are provided on whether all patients with MS receiving cladribine tablets should be vaccinated against COVID-19, and whether they should be prioritized; the timing of vaccination around dosing of cladribine tablets (i.e., before and after a treatment course); and the safety of COVID-19 vaccination for these patients.
Conclusion(s):
There was overwhelming consensus that the risks of COVID-19 outweigh risks of vaccination in people with MS who are being treated with cladribine tablets, and all people with MS treated with cladribine tablets should be vaccinated against COVID-19 as soon as possible, unless they have a contraindication. The consensus provides timely guidance on patient selection, timing, efficacy, and safety of COVID-19 vaccination in patients receiving cladribine tablets, which is relevant to decision-making in everyday clinical practice.
Clinical Characteristics of Switching Between Disease Modifying Drugs Among a Sample of Egyptian Multiple Sclerosis Patients
1Asmaa Eissa, 2Tarek Menecie, 3Hoda Massoud, 2Mohammad Abboud, 2Mohammad H. Rashad
1Nasser institute hospital for research and treatment, Cairo, Egypt; 2Alazhar University, Cairo branch, Egypt; 3Alazhar university (for girls), Cairo branch, Egypt
Introduction:
Early and appropriate treatment decision for multiple sclerosis (MS) can markedly reduce disease activity and accumulation of disability to avoid many of the long-term economic and personal expenses that result from unnecessary irreversible disability. The aim of this study is to describe switching patterns between disease modifying therapies (DMTs) in our local practice and investigate clinical characteristics that could be related to the switching process.
Material(s) and Method(s):
This is a cross-sectional study based on records of 274 MS patients who had been actively receiving available DMTs at the MS unit of Nasser Institute Hospital for Research and Treatment. The data was reviewed and collected using local database registry of the unit in the duration between the year 2016 and 2020.
The patients were classified into three groups: lateral, escalation, and multiple switch groups. The data were collected in the form of patients’ demographics, disease history, switching process data, Expanded Disability Status Scale (EDSS), and Symbol Digit Modality Test (SDMT) values.
Result(s):
A total of 274 MS patients were included in the study: 24.1% were males (n=66) and 75.9% were females (n=208). 43 patients were allocated in the lateral switch group, 178 in the escalation switch group and 53 in the multiple switch group. All baselines characteristics were balanced between the three groups except for (1) the time to switch from previous drug to the new one which was longer in the escalation and multiple switch groups compared to the lateral switch group (1.6 years versus 1.4 years versus 1.2 years, respectively; p-value=0.001), (2) the SDMT score which was significantly different between the three groups (6.5 in the multiple switch group versus 5.8 in the lateral switch group versus 5.3 in the escalation group, p-value <0.001) and (3) the mean EDSS was higher in the multiple switch group compared to the lateral and escalation switch groups (p-value <0.001). Escalation switching was the most frequent strategy of shifting between DMTs (n=178; 65%) with fingolimod being the most common drug switch to in this category. However, interferon beta 1a was the most common drug switched to in the other two groups. The most common
causes for switching DMTs was inefficacy followed by tolerability. Multiple logistic regression analysis was performed to study the association between different variables and both the escalation and multiple switch groups as compared to the lateral switch group. Education level and SDMTs were significantly associated with the escalation switching (p-value= 0.035 and p-value <0.001, respectively) while EDSS and SDMT score were significantly associated with the multiple switching strategy (p-value=0.007 and p-value=0.004, respectively).
Conclusion(s):
This cross sectional Egyptian study revealed that escalation switch was the most prominent switching pattern.The most common cause of switch was the lack of efficacy. The most common drug to be switched from was INF beta 1A sc. The most common drug to be switched to was Fingolimod and INF beta 1A sc, more in escalation group and lateral switch group respectively.
Clinical variables that were significantly associated with the escalation switching were the patient’s education, and SDMT score. The variables that were significantly associated with multiple switching were the EDSS, and SDMT score.
Real-World Experience with Cladribine in the MSBase Registry
1Helmut Butzkueven, 2Tim Spelman, 3Suzanne Hodgkinson, 4Sara Eichau Madueño, 4Guillermo Izquierdo, 5Katherine Buzzard, 5Olga Skibina, 1Anneke Van Der Walt, 6Tomas Kalincik, 7François Grand-Maison
1Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; 2MSBase Foundation, Alfred Centre, 99 Commercial Road, Melbourne, Australia; 3Liverpool Hospital, Sydney, Australia; 4Universitary Hospital Virgen Macarena, Seville, Spain; 5Box Hill Hospital, Melbourne, Australia, Melbourne, Australia; 6MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia; 7Neuro Rive-Sud, Greenfield Park, Canada
Background:
Cladribine tablets are approved for relapsing multiple sclerosis (RMS) treatment in many jurisdictions. MSBase investigators are committed to characterizing real-world longitudinal treatment outcomes using this registry data. The objective of this study was to describe cladribine treatment outcomes in the MSBase cohort. These include baseline characteristics, treatment pathways, discontinuation rate, and relapse outcomes.
Material(s) and Method(s):
We extracted data from the MSBase registry for all patients with a confirmed diagnosis of MS who were newly treated with cladribine tablets. Descriptive statistics were used to analyse baseline patient characteristics recorded within 3 months prior to cladribine tablets initiation, including demographics, disease course and duration, prior disease-modifying therapies (DMT), and Expanded Disability Status Scale (EDSS). Relapse and discontinuation outcomes were described in patients with a minimum 6-month observation period.
Result(s):
As of 3rd March 2021, a total of 782 patients, predominantly from Australia, Canada and Spain, were included. From those, 696 were relapsing-remitting MS (RRMS) patients. The median age of cladribine tablets start was 43.8 years and median disease duration was 11.8 years. Median EDSS at cladribine initiation was 2 (IQR 1.5,4). Overall, 13.3% of all RRMS patients initiated cladribine tablets as first-line therapy. Of all RRMS patients switching to cladribine tablets with a treatment gap of <6 months, the most common immediate prior DMT was fingolimod (15%), followed by natalizumab (10%) and teriflunomide (9.5%). Total follow-up time was 629 patient-years. Annualized relapse rate (ARR) on cladribine tablets was 0.11 (95% confidence interval [CI]: 0.09-0.14) compared to a 12-month pre-cladribine ARR of 0.41. Treatment persistence was 96% at 12 months (95% CI: 0.94-0.98) and 90% after 24 months (95% CI: 0.85-0.94).
Conclusion(s):
The growing MSBase real-world cladribine tablets cohort shows excellent outcomes to date. The most common switches to cladribine are from other high-efficacy DMTs such as natalizumab or fingolimod. The annualized relapse rate on treatment is 0.11, consistent with clinical trial data. The observed discontinuation rate over 24 months is very low, at 9%.
Anti-Inflammatory Compounds Ameliorate Locomotion and Anxiety Behaviors in Cuprizone Mouse Model of Multiple Sclerosis
1Rasha Mohammed Alderbi, 1Gadah Ali Alshahrany, 1Kholoud Ahmed Alyami, 1Hadeil Muhanna Alsufiani, 1Ulfat Mohammed Omar, 1Maryam A. Al-Ghamdi, 1Mohammad Z. Alam
1Department of biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
Introduction:
Multiple sclerosis (MS) is an inflammatory, autoimmune disease that affects the central nervous system (CNS). One of the commonly used models to study demyelination and remyelination process involved in MS is Cuprizone (CPZ)-intoxicated mouse model. During the demyelination period, CPZ has been shown to cause impaired locomotion activity and increased anxious behavior in mice. Notably, various compounds have been known for their anti-inflammatory effect on different inflammatory and neurodegenerative diseases in-vitro and in-vivo. These include 6-Shogaol (Sh), Vanillic acid (VA) (4-hydroxy-3-methoxybenzoic acid), and Retinoic acid (RA). Since their anti-inflammatory activities could be regarded as potential treatment/co-treatment for MS disease, this study has been aimed to investigate the therapeutic effect of Sh, VA, and RA on locomotion and anxiety behavior of cuprizone-model mice.
Material(s) and Method(s):
Briefly, 6–8-week-old male SWR/J mice (15-22 g) were used (n=30) and assigned randomly into 5 groups (6 mice/group). Control group has received standard rodent chow during the entire study, while CPZ-intoxicated groups have received 0.3% CPZ-mixed chow for the first 5 weeks to induce demyelination, followed by 4 weeks of standard rodent chow for recovery. During the last 4 weeks, Sh, VA, and RA groups have received intraperitoneal injections of 25 mg/kg Sh, 30 mg/kg VA, and 20 mg/kg RA, respectively. In order to evaluate locomotion and anxiety behaviors, Open Field Test was performed using EthoVision®XT software. Total distance moved (TDM) was calculated as an indicator of locomotion, whereas percentage of time spent in the center was an indicator of anxiety. Firstly, tests were performed in 5th week of the study, where maximum demyelination was achieved, and induction of the disease was confirmed accordingly. After that, the treatment regimens have been started, and the tests were done in 7th week (two weeks after starting treatment) as it represents early spontaneous remyelination. Lastly, the tests were repeated in the 9th week by the end of remyelination progress.
Result(s):
In week 5, all CPZ-intoxicated groups showed a significant decrease in TDM and % time spent in center compared to control group, which insured the induction of the MS before starting treatment. Afterward, TDM of Sh, VA, and RA treated groups were significantly improved in week 7 compared to CPZ group. However, further decrease in % spent in the center of CPZ-intoxicated groups was shown in the same week denoting highly anxious behavior. By week 9, all treated groups exhibited a significant increase in TDM and % spent in the center compared to the CPZ group.
Conclusion(s):
In conclusion, 6-Shogaol, Vanillic acid, and Retinoic acid enhance the locomotor activity and improve anxiety behaviors in the cuprizone mouse model of Multiple sclerosis.
Neurofilament Light Chains: A Reliable Biomarker of Disease Activity in MS
1Ayesha Ashfaq
1Sheikh Zayed Medical Complex, Lahore, Pakistan
Background:
With this study we aim to establish the importance of non radiological biomarkers of MS in establishing Prognostic value of disease activity in CIS. Monitoring disease activity in Relapsing remitting Multiple Sclerosis. Establish the value of quantification of neurofilament light chains in progressive multiple sclerosis in relation to active disease and chronic stable disease
Material(s) and Method(s):
Electronic databases search included the Cochrane and Pudmed library. 12 hits were screened from pubmed out of which 3 were selected for this study and 1 hit from Cochrane which was also selected and included in this study.
Result(s):
Prognostication in CIS: The median baseline level of serum nfl was 22.0 pg/ml (interquartile range [IQR] 11.6–40.4).
- CIS patients subsequently developing MS had higher levels (median 30.2, iqr 16.4–48.7 pg/ml) than patients who did not develop MS (median 9.7, iqr 5.5–18.1 pg/ml, p < 0.001).
- Median CSF nfl level in CIS patients was 731.3 (iqr 346.9–1,194.6) pg/ml and they were directly related with serum levels particularly in patients with gd-enhancing lesions .
- Among 222 patients who were enrolled (mean follow-up 100.6 months), 45 patients (20%) developed CDMS and 141 patients (63.5%) developed 2017 MS at 2 years.
Relapsing remitting type:
Neurofilament light chains in CSF were:-
5 x HIGHER IN REMISSION THAN NINDS. (1896.4 ng/L, vs 365.1 ng/L).
9 x higher in relapse v/s control (3272.2 ng/L vs 364.9 ng/L).
Primary & secondary progressive types:-
Neurofilament light chains in CSF were :-
Twice more than controls (1260.4 ng/L vs 469 ng/L).
Significantly lower than in patients with relapsing remitting type. (2124.8 ng/L vs 1121.4 ng/L).
Conclusion(s):
1. Study proved that serum nfl have a prognostic value for CIS patient conversion to MS.
2. Csf neurofilament light chains correlate with disease activity throughout the course of ms, reflecting the axonal damage .
3 .Relapse is more strongly associated with elevated csf nfl than the development of progression.
4.Nfl could be the most useful marker of disease activity rather than as a marker of disability or disease stage.
The Relationship Between Smoking and Multiple Sclerosis Severity in Saudi Arabia
1,2,3Seraj Makkawi, 4Nedaa Alsulaimani, 1Fahad A Alharbi, 4Reem Brashi, 4Renad Melebary, 4Shuaa Aljabri, 4Khalid Altowairqi, 4Albaraa Ashoor, 4Amal Alkhotani
1College of Medicine, King Saud Bin Abdulaziz University for Health Sciences & King Abdullah International Medical Research Center, Jeddah, Saudi Arabia; 2King Abdullah International Medical Research Center, Jeddah, Saudi Arabia; 3Department of Medicine, Ministry of the National Guard-Health Affairs, Jeddah, Saudi Arabia; 4College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
Background:
Multiple Sclerosis (MS) is an autoimmune disease that can be disabling to patients. Smoking has been proposed to be a risk factor for MS and to increase the risk for progression of the disease and its severity. However, it is still not clear how smoking affects MS patients regarding disease phenotype, symptoms, relapses, course, and disability. We aim to investigate the effect of smoking patients with MS patients living in Saudi Arabia.
Material(s) and Method(s):
This is an online questionnaire-based cross-sectional study. MS patients were randomly contacted through different MS societies and associations to participate in the study. The questionnaire inquired about demographics, MS phenotype and severity, and smoking status of participants. Data were collected between 30th of May 2021 and 5th of July 2021.
Result(s):
429 MS patients participated in the study. The mean age was 33.7, with a mean disease duration of 8.1 years. 61.1% of participants were female. 62.2% did not know the specific MS phenotype they have. 35.7% were current or previous smokers, with a mean smoking duration of 13.9 years. Smoking was significantly associated with the presence of multiple MS symptoms (p-value = 0.009) and their number (p-value = 0.050). In addition, there was a significant positive correlation between pack-years smoking and the number of MS symptoms with a Pearson’s r value of 0.209 (p-value < 0.05). No significant associations were found between smoking and recent relapses and disease progression, disability in terms of walking, needing a cane, or needing a wheelchair.
Conclusion(s):
Smoking was shown to have a significant effect on the number of symptoms experienced by MS patients. Higher pack-years of smoking correlate positively and significantly with a higher number of MS symptoms. Further studies to examine these relations are hence warranted.
Phenotyping the Pediatric Demyelinating Events at the Multiple Sclerosis Center at the American University of Beirut
1Georges Saab, 2Nabil El Ayoubi, 2Samia Khoury
1University of Toronto-BARLO Multiple Sclerosis Center, Toronto, Canada; 2Nehme and Therese Tohme Multiple Sclerosis Center at the American University of Beirut, Beirut, Lebanon
Background:
Multiple Sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system of individuals with peak incidence between the ages of 20-40. A distinct form of MS initially presents in the pediatric population (less than 18 years of age) with the same clinical presentation but a different disease course.
Pediatric Onset Multiple Sclerosis (POMS) occurs in 3-10% of MS cases worldwide with most patients (80-85%) occurring at a peripubertal age. Clinically these patients were found to have a more destructive disease with more aggressive and more frequent attacks throughout their disease course. Risk factors in multiple studies found them to be equivalent to the risk factors in their adult counterparts including low vitamin D levels, smoking, and EBV infections.
The clinical presentations or first clinical relapses in POMS are essentially the same as in adults including optic neuritis, sensory, motor, brainstem, and cerebellar manifestations with an emphasis on brainstem attacks being more highly associated with the development of MS in this population. Optic neuritis as a first clinical attack was found to be less prevalent in the POMS patients than as a first clinical attack in adults with MS. The individual attacks in these patients exhibit more extensive demyelination depicted in their more severe clinical presentation, but also have a better recovery with most patients having a complete recovery with treatment.
POMS patients have been classified in other regions with studies on their epidemiology, phenotype, and disease classification. They have yet to be classified in Lebanon where no study exists to date where the POMS patients are classified. Such a study can help clinicians further confirm the diagnosis in their patients, predict the disease course, and benefit from treatment data to better treat their patients.
Material(s) and Method(s):
All patients presenting to the multiple sclerosis center for the first time younger than 18 years of age who have consented to the AMIR study
Cross sectional (at onset) and longitudinal (retrospective/at last follow up)
Sample Size will depend on the number of patients presenting under the age of 18 from the start of the AMIR study till 15 February 2020
Data was collected from the redcap database of the AMIR study
Data was explored cross sectionally for eligible patients and means, standard deviations, and proportions were explored as appropriate. At last follow up, proportions of patients with certain characteristics was explored (stability of disease including imaging and clinical). Correlations between different clinical predictors and physical disabilities were explored.
Result(s):
62 patients identified, 54 with the relapsing remitting phenotype, 4 with a radiologically isolated syndrome, 2 with neuromyelitis optica spectrum disorder, and 2 with MOG antibody associated disease.
- Mean age at symptom onset (SD): 14.37 (2.64) years
- Mean age at diagnosis (SD): 15.4 (1.9) years
- Female sex (Male): 66.1 (33.9) %
- Median number of attacks before first visit (range): 1 (0-4)
- Mean follow up time (SD): 4.08 (2.26) years (Range=0-9)
- Presenting Symptoms:
- 27.8% Sensory
- 22.2% Motor
- 29.5% Optic Neuritis
- 46.3% Brainstem/Cerebellar
- 1.9% Bowel/Bladder
- 22.2% with a positive family history of MS
- Median EDSS at onset (range): 1.5 (0-6)
- Mean 25-Foot Walk Time at onset (SD): 4.3 (1.6) seconds
- Mean Single Digit Memory Test (SD): 52.89 (13.9)
- Imaging Characteristics:
- Brain lesion load:
- Mild in 17.6%
- Moderate in 45.1%
- Severe in 17.6%
- Spinal Cord lesion load:
- Mild in 47.2%
- Moderate in 22.2%
- Severe in 13.9%
Subgroup of patients with a positive family history of MS did not have significant differences in presenting symptoms, number of relapses, lesion load, severity of disease, or age at onset of diesase.
Treatment with Disease Modifying Therapies:
- 35.3% were on Interferons
- 23.7% on Fingolimod
- 13.5% on Natalizumab
- 10.9% on Dimethyl Fumarate
- 9.4% on Rituximab
- 6.8% on Teriflunomide
- 0.4% on Azathioprine
Conclusion(s):
Patients seemed similar to their adult counterparts in most disease characteristics except for presenting symptom
Good response to treatment achieved and improvement of EDSS with a long follow up time
Limited by the small number of patients and MRI parameters
Lennox-Gastaut Syndrome and MS: Is it a Coincidence?
1Lilia Megherbi, 1Hakim Si Ahmed, 1Smail Daoudi
1Tizi Ouzou University Hospital, Tizi Ouzou, Algeria
Introduction:
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Several associations with MS have been described, including epilepsy but not a particular epileptic syndrome, such as Lennox-Gastaut syndrome. We report an exceptional presentation of MS in a 14-year-old girl child with a childhood history of Lennox-Gastaut syndrome.
Material(s) and Method(s):
A 14-year-old female child presented with a rapid onset left hemiparesis. She was born into a second-degree consanguineous marriage and was diagnosed with West syndrome at the age of 8 months which then progressed to Lennox Gastaut encephalopathy. A brain MRI at the age of four was without abnormalities.
Her epilepsy was relatively stable under treatment with motor and cognitive sequelae.
At the age of 14, she presented a left hemiparesis worsening over few days. Her brain MRI showed figure 1. CSF analysis showed neither hyperproteinorachia nor the oligoclonal band. Antibodies to HIV and viral hepatitis, anti AQP4, anti-MOG, anti NMDA, anti-GABA were negative. The biotinidase activity and autoimmunity tests were correct.
The patient received IV methylprednisolone (1g/day) for three days with a remarkable clinical improvement. Five months later, the left hemiparesis reoccurred. A brain and spinal cord MRI showed a significant increase in the number of lesions with the presence of active lesions (figure 2).
The patient had another relapse after six months, made of left arm weakness with an exacerbation of her seizures. Brain MRI showed the presence of multiple active lesions (figure 3).
Our patient’s clinical and radiological presentation fulfilled the Mc Donald 2017 Criteria of RRMS. Therefore, the diagnosis of MS was retained after ruling out other differential diagnoses, mainly MOGopathy.
Result(s):
MS is a CNS demyelinating disease that is both complex and heterogeneous. Although the disease is characterized by inflammatory lesions in the white matter, various neuropathological and radiological studies demonstrated that it also affects grey matter. Several studies showed that seizures are three to six times more common among MS patients than in the general population. Even though MS can start with epilepsy and that seizure may be the only symptom of an MS relapse, it is still unclear whether the two diseases coexist or whether MS predisposes to seizures or vice versa.
Our patient had a history of classic West syndrome with no acquired aetiology, which progressed to a typical Lennox-Gastaut syndrome, with a normal brain MRI and absence of extra neurological abnormalities. The MRI and clinical presentation at the age of 14 were highly indicative of MS. Despite the fact that these two diseases are utterly different in terms of onset age and clinical and para-clinical manifestations, their co-occurrence in one patient is perplexing, as it is unclear whether this is a coincidence or if there are any common predisposing genetic factors, especially considering the parents’ consanguinity.
Conclusion(s):
MS and Lennox-Gastaut syndrome are two fundamentally different neurological diseases with regard to their physiopathological, clinical, and paraclinical features. Yet genetic factors are frequently reported in these two conditions, opening up new prospects for research in this field.
NMOSD: How Long to Treat
1Rajarshi Chakraborty
1King George Medical University, Lucknow, India
Introduction:
Neuromyelitis optica spectrum disorder is a debilitatively relapsing autoimmune neurological disorder affecting young adults. With the advent of steroids, plasma exchange and immunomodulator therapy, the course of the disorder can be controlled upto a comprehensive extent. But the real question is : how long?
Material(s) and Method(s):
In this case report, i present a 27 year old lady suffering from neuromyelitis optica spectrum disorder, relapsing after 8 years of disease onset, just 15 days after stopping azathioprine therapy. This 27 year old vegan, unmarried, non-smoker, non-diabetic lady was diagnosed as neuromyelitis optica spectrum disorder for last 8 years presenting with weakness of both lower limbs along with bladder symptoms and blurring of vision in both eyes for 2 days. She had longitudinally extensive transverse myelitis from thoracic spinal cord d5 to lumbar spinal cord l5 levels and prolonged visual evoked potentials bilaterally. She was found negative for anti-aquaporin antibody and myelin oligodendrocyte glycoprotein antibody. She was treated with pulse dose methyl prednisolone followed by oral steroids with azathioprine initially for 3 months with subsequent monotherapy with azathioprine. She was improving gradually and within 5 years, she attained a modified rankin score score of 0 from an initial score of 4. She took the immunomodulator drug for another 3 years and then stopped from herself after which she developped dense paraplegia with bowel and bladder involvement along with altered mentation.
Result(s):
She was diagnosed with relapse of neuromyelitis optica spectrum disorder with involvement of spinal cord and brain axes. She was treated with standard pulse steroids with plasma exchange therapy followed by immunomodulator therapy but recovery was poor with modified rankin score of 4 remaining unchanged.
Conclusion(s):
Neuromyelitis optica spectrum disorder has an unpredictable time course of relapse. The debilitative nature of the subsequent relapse(s) in this disorder is very grave. The need for standardisation of lifelong therapy with immunomodulatory agents in neuromyelitis optica spectrum disorder can prudentialise prevention of catastrophic neurological outcome.
The Psychological Effect of COVID19 Pandemic on Neuromyelitis Optica Spectrum Disorder Patients and Their Attitude Change After a Year of the Pandemic in Isfahan, Iran.
1Roshanak Mehdipour Dastjerdi, 1Fereshteh Ashtari
1Isfahan University of Medical Sciences, Isfahan, Iran
Background:
Coronavirus 2019 (called COVID19) is a new coronavirus which has created a pandemic since early 2020. NMOSD patients are more affected by psychological effects of COVID19 pandemic such as anxiety and fear because they may be worried about being infected by COVID19 (due to the nature of disease and treatment by immunosuppressant drugs) and also they concern about their treatment protocol and disease relapses during the pandemic.
Material(s) and Method(s):
The aim of study was to evaluate the anxiety due to COVID19 infection, 3 and 12 months after beginning of epidemic in Iran.The study was done in patients of NMOSD Cohort Clinic of Kashani hospital, Isfahan. We first asked individuals if they were anxious or afraid of the pandemic subjectively. To investigate the objective level of anxiety, Hospital Anxiety and Depression Scale (HADS-A) questionnaire was filled. Also we asked them about respecting general cautions and sanitary protocols to prevent COVID19 infection.
Result(s):
Study included 120 patients (96 female) with mean age of 36.37±9.69 and mean duration of disease about 8.49±5.35 years. A total of 96 cases (80%) experienced anxiety during the first 3 months of pandemic. The point is that their level of anxiety decreased significantly with the prolongation of pandemic after 9 months and just 66 patients (55%) showed anxiety subjectively on the second survey. Based on HADS-A score, 92 patients (76.66%) were anxious on the third month while after one year of epidemic 70 cases (58.33%) showed anxiety. Respecting preventive measures increased in the same period .
Conclusion(s):
Along with the COVID19 pandemic prolongation, the level of anxiety had decreased gradually while the level of alertness and attention was almost high. It should be considered that this awareness must be preserved till the end of epidemic.
A Child with Intractable Vomiting: Brainstem Mass or Neuromyelitis Optica Spectrum Disorder
1Roshanak Mehdipour, 2Vahid Shaygannejad
1Isfahan Neuroscience Research Center, Isfahan University Of Medical Sciences, Isfahan, Iran; 2Isfahan Neuroscience Research Center, Alzahra Research Institute, Isfahan, University of Medical Science, Isfahan, Iran
Background:
NMOSD is an immune-mediated disorder which is characterized by relapsing episodes of optic neuritis and myelitis. Brain stem related symptoms such as Intractable vomiting are not usually considered as the initial presentation and misdiagnosis has been frequently observed. Almost 4% of NMOSD cases are pediatric. Early differentiation of NMOSD from other childhood disorders including ADEM, MS, infections and mass lesions is critical.
Material(s) and Method(s):
11 years old girl presented with intractable vomiting and received several types of gastrointestinal treatments during one month.After that diplopia occurred and also she suffered vertigo. In this stage Brain MRI showed isolated edematous intramedullary lesion with heterogeneous enhancement. Patient received corticosteroid therapy with diagnosis of brain stem mass and the symptoms improved. She was candidate for biopsy to decide for radiation or chemotherapy but her parents didn’t accept. After three months she developed central facial nerve palsy.the brain MRI showed the same lesion. Anti AQP4 ab was positive,so the appropriate treatment started with final diagnosis of NMOSD.
Discussion:
Only about 30% of patients presents with brainstem involvement. It is difficult to diagnosis of NMOSD with presentation of acute brainstem or cerebral or diencephalic syndromes for physicians who are not familiar with its clinical features and diagnostic criteria. Involvement of the area postreoma can lead to the initial presentation of sometimes intractable nausea and vomiting with associated intramedullary lesions on MRI in 16% to 43% of patients.
Conclusion(s):
NMOSD should be considered in differential diagnosis of isolated brain stem lesions to avoid from invasive surgical interventions. Early diagnosis is critical for proper treatment.
Clinical, Evolutionary and Etiological Particularities of Inflammatory Optic Neuropathies: An Algerian Population
1Kediha Mohamed Islam, 1Moualek Dalila, 1Bouakaz Imene Fatma, 1Ali Pacha Lamia
1Neurology Department, Mustapha Bacha University Hospital, Algiers, Algeria
Introduction:
Inflammatory optic neuropathies (ION) represent frequent neuro-ophthalmological emergencies, sources of severe functional handicap. They often pose an etiological problem.
Objective(s):
To study the clinical, radiological, etiological and evolutionary particularities of ION in Algerian patients.
Material(s) and Method(s):
This is a retrospective study of 23 patients, hospitalized at the Neurology Department of the CHU Mustapha of Algiers, over a period of 6 years (from January 2015 to june 2021). All these patients benefited from an exhaustive etiological assessment. Any non-inflammatory cause was excluded as well as any patient whose etiology was multiple sclerosis (MS).
Result(s):
A clear female predominance was observed in this series (21F/2H). The etiologies identified were seropositive neuromyelitis optica (NMO) (10 patients), seronegative NMO (06 patients), idiopathic forms (04 patients), Mogopathies (02 patients) and 01 form linked to an optic nerve glioma. Radiologically, optic nerve lesions with contrast were found in 9 patients whose causes varied between NMO, MOG and idiopathic forms. We will specify the location: anterior, posterior or on the whole nerve as well as the correlation with the causal condition.
Discussion:
NMO seems to be the most frequent Non-MS aetiology of ION, which is consistent with the literature. The response to different immunological treatments is variable. It depends on the proposed treatment and the earliness of its initiation. Nevertheless, a few cases of blindness have been reported despite optimal management.
Conclusion(s):
The management of ION and its prognosis depend on the aetiology and the earliness of the treatment. NMO dominates the causes in our series. The lesions observed on MRI centred on the optic nerve and their extents constitute an additional argument, helping the etiological research.
Cognitive Impairment in Neuromyelitis Optica Spectrum Disorder and Brain Parenchyma Volume by Transcranial Sonography
1Rehab Magdy
1Cairo University, Cairo, Egypt
Background:
Cognitive impairment in neuromyelitis optica spectrum disorder (NMOSD) is not uncommon occurring independent from attacks and lesions. It presents in about 30-70% of NMOSD patients. Psychiatric symptoms may be initial manifestation of NMOSD, and depression is not uncommon. NMOSD patients showed global brain atrophy however it is not associated with brain or spinal lesions. Transcranial sonography (TCS) is a reliable method for assessment of third ventricular diameter and its enlargement can be used as a marker of brain atrophy and cognitive impairment. The aim of the study is to assess the cognitive functions in NMOSD and its relation to brain atrophy using transcranial sonography (TCS) for brain parenchyma.
Material(s) and Method(s):
Observational, case-control study, conducted on 42 subjects, 23 patients with NMOSD, and 19 healthy controls with matching age, sex and years of education. Participants were subjected to cognitive assessment using California verbal learning test 2nd edition (CVLT-II), Controlled Oral Ward Association Test (COWAT) and Trail Making Test-B (TMT) (oral version) and neurosonographic assessment using B-mode TCS for brain parenchyma.
Result(s):
Mean age of the patients with NMOSD was 35.1 ± 10.1 years with mean disease duration was 40.1 ± 51.6 months. While mean age of the healthy control was 29.8 ± 6.8 years. Female to male ratio was 21:2 and 15:4 for patients and control respectively. Mean years of education was 8.8 ± 4.5 years and 10.7 ± 0.8 years for the patients and healthy control respectively. Mean of basic EDSS for the patient was 5.22 ± 1.5. Cognitive performance was significantly worse in NMOSD group compared to healthy control. CVLT-II showed that total recall, short-delay free-recall, short-delay cued-recall, long-delay free-recall and long-delay cued-recall were significantly worse in patients with NMOSD, p value <0.0001, <0.0001, <0.0001, <0.0001 and <0.0001. Trail making test showed that patients with NMOSD had worse executive functions and longer processing speed with p value <0.0001. COWAT, either category or letter, showed no statistically significant difference between patients with NMOSD and healthy control. As regard brain atrophy, assessed by TCS, diameter of the 3rd ventricle was significantly wider among patients with NMOSD than in healthy control with p value 0.03. Rt and Lt thalami were significantly smaller in patients with NMOSD than in healthy control with p value 0.0003 and 0.03 respectively. More patients with NMOSD had interrupted median raphe than healthy control with p value 0.03. In NMOSD group, there was a statistically significant negative correlation between EDSS and scores of CVLT-II (total recall, short-delay free-recall, short-delay cued-recall, long-delay free-recall and long-delay cued-recall) as well as COWAT- letters. There was significant positive correlation between EDSS and TMT-B. No significant correlation was found between EDSS and diameter of 3rd ventricle. There was significant positive correlation between diameter of frontal horns and TMT-B. A significant negative correlation was found between diameter of 3rd ventricle scores of COWAT- letter and as well as CVLT-II total recall.
Conclusion(s):
Patients with NMOSD had poorer cognitive functions than healthy control. Also, they had more brain atrophy than healthy control.
Association of Multiple Sclerosis and COVID-19 Infection: A Case Report
1Ismail Ibrahim Ismail, 1,2Jasem Al-Hashel, 3Raed Alroughani, 1,4Samar Farouk Ahmed
1Ibn Sina Hospital, Kuwait city, Kuwait; 2Health Sciences Centre, Kuwait University, Jabriya, Kuwait; 3Amiri Hospital, Sharq, Kuwait; 4Minia University, Minia, Egypt
Introduction:
Since the declaration of COVID-19 pandemic, several cases of demyelination of both peripheral and central nervous systems have been reported. The association of viral infection and the development of CNS demyelination has long been studied, and this link has recently been reported following SARS-CoV-2 infection as well.
Material(s) and Method(s):
We report a case of a 36-year-old male who developed CNS demyelinating disease, that fulfilled the diagnostic criteria of multiple sclerosis (MS), 2 months after laboratory-confirmed infection with SARS-CoV-2.
Result(s):
A 36-year-old male developed CNS demyelination, 2-months following a laboratory-confirmed SARS-CoV-2 infection, that fulfilled the revised 2017 McDonald diagnostic criteria for MS. He presented with ataxia, and MRI showed multiple demyelinating lesions in the brain, and positive oligoclonal bands in CSF.
Conclusion(s):
To our knowledge, this is the second case report of MS in association with COVID-19 infection, and the first case from Middle East and North Africa (MENA) region. This case report adds to the growing body of evidence of a probable causal relationship between SARS‐CoV‐2 infection and the development of MS. SARS-CoV-2 could potentially trigger a demyelinating process, through an acute or delayed immune-mediated CNS inflammatory response.
Does Multiple Sclerosis Change Lower Limbs Inter-Segmental Coordination During Walking?
1Razieh Mofateh, 2Reza Salehi, 3Hossein Negahban, 1Mohammad Mehravar, 4Shirin Tajali, 1Saeideh Monjezi
1Musculoskeletal Rehabilitation Research Center, Department of Physiotherapy, School of Rehabilitation sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Rehabilitation Research Center, and School of Rehabilitation Sciences, Department of Rehabilitation Management, Iran University of Medical Sciences, Tehran, Iran; 3Mashhad University of Medical Sciences, Mashhad, Iran; 4Department of Physical Therapy, University of Toronto, Toronto, Ontario, Canada., Toronto, Canada
Background:
Gait disturbance is one of the most common and disabling signs in patients with multiple sclerosis (MS). Examining the lower extremities intersegmental coordination, as a higher order property of the human movement system, during walking could explore valuable information about changes in neuromuscular control of gait in patients with MS. Therefore, the aim of this study was to investigate the inter-segmental coordination of the lower extremities during walking in patients with MS.
Material(s) and Method(s):
Three-dimensional coordinate data of the lower extremities were collected from 25 patients with MS and 25 healthy controls while treadmill walking at their preferred walking speed. Mean absolute relative phase (MARP) and deviation phase (DP) were used to examine the thigh-shank and shank-foot coordination pattern and variability in stance and swing phases of the gait cycle.
Result(s):
For the thigh-shank coordination pattern, MARP values were significantly higher in patients with MS compared to healthy controls in stance and swing phases of the gait cycle (p< 0.01, p = 0.03, respectively). For the shank-foot, MARP values of patients with MS were significantly lower compared to healthy controls (p< 0.01). For the thigh-shank coordination variability, patients with MS showed significantly higher DP values compared to healthy controls in stance and swing phases of the gait cycle (p< 0.01). Similar results were found for the shank-foot coordination variability (p = 0.02 and p = 0.04, respectively).
Conclusion(s):
Our results suggest that MS disease could affect the pattern and variability of inter-segmental coordination during walking. Therefore, examining and facilitating lower extremities inter-segmental coordination during walking could be an important factor in the development of rehabilitation interventions aimed at improving the gait pattern in patients with MS.
Cognitive Dual Tasking Impacts Lower Limbs Inter-Segmental Coordination During Walking in Patients with Multiple Sclerosis
1Razieh Mofateh, 2Reza Salehi, 3Hossein Negahban, 1Mohammad Mehravar, 4Shirin Tajali, 1Saeideh Monjezi
1Musculoskeletal Rehabilitation Research Center, Department of Physiotherapy, School of Rehabilitation sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Rehabilitation Research Center, and School of Rehabilitation Sciences, Department of Rehabilitation Management, Iran University of Medical Sciences, Tehran, Iran; 3Mashhad University of Medical Sciences, Mashhad, Iran; 4Department of Physical Therapy, University of Toronto, Toronto, Ontario, Canada., Toronto, Canada
Background:
Gait disturbance is one of the most common and disabling signs in patients with multiple sclerosis (MS). Coordinative ability between segments of lower extremities, as a higher order property of the human movement system, is affected by MS disease. Since intersegmental coordination could be affected by cognitive loading, this study was aimed to investigate the interaction between cognition and lower extremities inter-segmental coordination during walking in patients with MS.
Material(s) and Method(s):
The investigation included 25 patients with MS and 25 matched healthy controls. Participants walked at their preferred speed on a motorized treadmill under two walking conditions in a randomized order: walking only, walking while performing a concurrent cognitive task (counting backward aloud by 3s). The mean absolute relative phase (MARP) and deviation phase (DP) were used to calculate the phase dynamic and variability of inter-segmental coordination over the stance and swing phases of gait for each condition.
Result(s):
The statistical analyses showed that the interaction of task and group was only significant for MARP value of the shank-thigh in stance phase (p=0.02). Group had a significant main effect on DP of shank-thigh and foot-shank in stance and swing phases and MARP of shank-thigh in stance phase and foot-shank in stance and swing phases (p<0.01). In addition, the main effect of task was significant on MARP and DP of shank-thigh and foot-shank in stance and swing phases (p<0.01).
Conclusion(s):
Our results suggest that simultaneous performance of cognitive task and walking could lead to higher changes in the inter-segmental coordination compared to single walking. Thus, therapeutic exercise aimed to improve lower extremities inter-segmental coordination should be considered in the rehabilitative interventions of MS patients.
Effects of Cognitive and Motor Secondary Tasks on Gait Performance in Healthy Controls and Multiple Sclerosis Patients with and Without Fall History
1Razieh Mofateh
1Musculoskeletal Rehabilitation Research Center, Department of Physiotherapy, School of Rehabilitation sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Background:
Deficit in dual- task performance have been commonly reported in patients with MS, potentially leading to increase the likelihood of falls occurring in these patients. The purpose of the current study was to compare the effects of cognitive or motor tasks on gait performance between healthy controls and multiple sclerosis (MS) patients with and without fall history.
Material(s) and Method(s):
The current study design was cross-sectional. The investigation included MS patients with fall history (n=25) and without fall history (n=25) and matched healthy controls (n=25). Participants walked at their preferred speed on a motorized treadmill under three walking conditions in a randomized order: walking only, walking while performing a concurrent cognitive task (counting backward aloud by 3s), and walking while performing a concurrent motor task (carrying a tray with glasses). Gait performance was assessed by cadence, stride length, step width, and swing time. In addition, gait variability was calculated for stride length, stride time, and step width parameters using coefficient of variation. We used a two-way repeated measure analysis of variance for statistical analysis.
Result(s):
The findings showed that in patients with MS, regardless of fall history, spatiotemporal gait parameters were different compared to healthy controls. In contrast to average gait parameters, variability in stride length and stride time could discriminate between MS fallers and non-fallers. Simultaneous performance of cognitive task and walking resulted in higher dual-task costs (DTC) in gait performance compared to the motor dual-task. However, the pattern of change was not different among the three groups. All participants responded to the cognitive task challenges by increasing stride length and decreasing cadence and stride length variability while maintaining cognitive task performance.
Conclusion(s):
The findings may reflect successful adaptation of locomotor system to preserve cognitive task performance under cognitive dual-task condition. Future studies should examine more complex concurrent cognitive and motor tasks to better understand the dual-task-related gait changes and their contribution to falls in patients with MS.
Sleep Disorders in Multiple Sclerosis Patients
1Sondes Bader, 1Emna Ellouz
1Neurology Department, Gabes Hospital, Gabes, Tunisia
Background:
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) common in young adults. Patients with MS have a significant variety of problems that alter their quality of life including sleep disorders which are often underdiagnosed and poorly managed.The aim of our study was to assess the prevalence of sleep disorders among multiple sclerosis patients and to explore their associated sociodemographic and clinical factors.
Material(s) and Method(s):
We conducted a cross-sectional study, carried out on patients with multiple sclerosis who consult in the neurology department in Gabeshospital during a period of five months, from the 1st June 2021 to 25th October 2021.We used a pre-established sheet exploring the socio-demographic, clinical and therapeutic data of the patients.Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI).The Expanded Disability Status Scale (EDSS) to quantify disability in MS patients.The Symbol Digit Modalities Test (SDMT) to detect cognitive impairment.Data were analyzed using the software SPSS (20th edition).
Result(s):
Nineteen patients were included. Eleven(57,9%) were females, mean age was 31,5 (SD=8,06) years.Fifty tow percent were married.Only two patients(10,5%)had a family history of MS.Four patients(21,1%) had a family psychiatric history.Five patients (26,3%) had a psychiatric history including depression in 10,5% anxiety disorder in 10,5% and psychotic disorder in 5,2% of cases.All patients had the remitting form of MS.The average age of onset of the disease was 25 years(19-48).Average course of the disease was 6 years (1-13).Median SDMT score was 29 (18-41).Median score of EDSS was 2,9.Sleep disorders werereported by 52,6 of MS patients, 73.6% of cases reported insomnia and 42,1reported parasomniaincluding nightmaresin 21%.The mean total score on the PSQI scale was 6,7 ± 3,8 [2–15].26,3% of patients were objectively poor sleepers. On univariate analysis, sleep disorders were positively correlated with anxiety symptoms (p=0.013). There is a significant association between sleep disorders and subcortical white matter lesion (p= 0,17; 90% VS 33%), age(p=0,37) and the high educational level(p=0,31).No differences were observed regarding sex, marital and occupational status, family history of psychiatric disorders, disease course, disability according to the EDSS and cognitive impairment according to SDMT.
Conclusion(s):
Our results indicate that sleep disorders are common in MS patients.Age, anxiety symptoms and particular brain lesion were associated with the prevalence and severity of sleep disorders in MS patients.Screening and Managing sleep disorders and associated anxiety symptoms in MS patients may lead to improve their quality of life.
Anxiety in Patients with Multiple Sclerosis
1Sondes Bader, 1Imen Ketata, 1Fatma Sghaier, 1Emna Ellouz
1Neurology Department, Gabes Hospital, Gabes, Tunisia
Background:
Mood disorders, are frequent in people with Multiple Sclerosis (MS). Although anxiety has a well-recognized negative influence on family, work and social life, it has received less attention than depression in MS patients.The aim of our study was to assess anxiety in multiple sclerosis patients and to explore its associated factors
Material(s) and Method(s):
We conducted a cross-sectional study, carried out on patients with MS who consult in the neurology department in Gabes’s hospital during a period of five months, from the 1st June 2021 to 25th October 2021.We used a pre-established sheet exploring the socio-demographic, clinical and therapeutic data of the patients.The State-Trait Anxiety Inventory (STAI) to diagnose anxiety.The Expanded Disability Status Scale (EDSS) to quantify disability in MS patients.The Symbol Digit Modalities Test (SDMT) to detect cognitive impairment.Data were analyzed using the software SPSS (20th edition).
Result(s):
Nineteen patients were included. Eleven (57,9%) were females, mean age: 31,5 (SD=8,06) years. Fifty tow percent were married.Only two patients(10,5%)had a family history of MS.Four patients(21,1%) had a family psychiatric history.Five patients (26,3%) had a psychiatric history before MS onset.Two patients(10,5%)had a history of suicidal attempt before MS onset, the prevalence of anxiety was 57,9% according to STAI score. Median STAI-trait score was 43.5 (30, 49) andSTAI-state was 48,7 (32-67). This represents moderate trait and state anxiety.Median SDMT score was 29 (18-41). was a significant association between anxiety and hallucination symptom (p=0,37;Fisher test) and between anxiety andsubcortical white matter lesion (p=0,07:Fisher test;OR=2,7[1,2-6]). No differences were observed regarding sex, marital and occupational status, education, family history of psychiatric disorders, disease course,disability according to the EDSS and cognitive impairement according to SDMT.
Conclusion(s):
The prevalence of anxiety in our MS population was significantly high.Anxiety was associated with psychotic symptoms such hallucination and subcortical white matter lesion.Early identification of anxiety appear to be crucial for mitigating the impact of anxiety in this population.
Depression in Multiple Sclerosis
1Sondes Bader, 1Imen Ketata, 1Fatma Sghaier, 1Emna Ellouz
1Neurology Department, Gabes Hospital, Gabes, Tunisia
Background:
Depression symptoms and major depression disorderare highly prevalent in multiple sclerosis(MS). Depression can worsen symptoms of MS and significantly reduced the patient’s quality of life and increased the suicidal risk.The aim of our study was to assess depression in multiple sclerosis patients and to explore its associated factors
Material(s) and Method(s):
We conducted a cross-sectional study, carried out on MS patients who consult in the neurology department of Gabes’shospital during a period of five months, from the 1st June 2021 to 25th October 2021.We used a pre-established sheet exploring the socio-demographic, clinical and therapeutic data of the patients.The Beck Depression Inventory (BDI) to measure characteristic attitudes and symptoms of depression The Expanded Disability Status Scale (EDSS) to quantify disability in MS patients.The Symbol Digit Modalities Test (SDMT) to detect cognitive impairment.Data were analyzed using the software SPSS (20th edition).
Result(s):
Nineteen patients were included. Eleven(57,9%) were females, mean age: 31,5 (SD=8,06) years. Fifty tow percent were married.Only two patients(10,5%)had a family history of MS.Four patients(21,1%) had a family psychiatric history.Five patients (26,3%) had a psychiatric history including depression in 10,5% anxiety disorder in 10,5% and psychotic disorder in 5,2% of cases.Two patients(10,5%) with moderate depression according to BDI had a history of suicidal attempt before MS onset. All patient had the remitting form of MS.The prevalence of depression was 89,4% according to BDI withmild depression in 26,3%, moderate depression in 26,3% and severe depression in 36,8%..MedianBDI score was 12,4 (3, 29).This represents moderate depression.Median SDMT score was 29 (18-41)..There was a significant association between depressioncerebellar lesion(p=0,038:Fisher test;OR=14[1,1-185]).Severe depression was more frequently observed in patients with higher EDSS(moderate to significant disability)(71,4% VS 41,7%) also in patient with cognitive impairment (100%VS 91,7%).No differences were observed regarding sex, marital and occupational status, education, family history of psychiatric disorders, disease course,disability according to the EDSS and cognitive impairment according to SDMT.
Conclusion(s):
The results of this study suggest that patients with MS are at risk to develop depression symptoms and that MS patients with severe depression may experience cognitive function impairment and present a high score of disability.Therefore depression should be assessed in MS patients to prevent motor and cognitive worsening.
Serum Neurofilament Light Chain as a Biomarker in Multiple Sclerosis
1Professor Hayder K.Hassoun, 2Professor Akram Al-Mahdawi, 1 Huda Khadi
1Faculty of Medicine, Baghdad University, baghdad, Iraq; 2Faculty of Medicine, Kufa University, Annajaf, Iraq
Background:
Currently MS disease activity, neurodegeneration and treatment response are assessed mainly through clinical evaluation and magnetic resonance imaging. These measures lack sensitivity and accuracy, so new biomarkers are necessary.
Several markers have been studied and to date among the most promising is the neurofilament light chain (NfL).Many studies have shown elevated CSF Nf levels in a wide variety of neurological disorders in which axonal degeneration occurs including MS.The release of NfL into the peripheral blood represents a significant opportunity for monitoring disease activity and progression without the need for the more invasive CSF sampling.this study is conducted to assess the relationship between serum neurofilament (NfL & NfH chain) levels and the disease type, duration, disease activity, severity, and other variables among Iraqi multiple sclerosis patients.
Material(s) and Method(s):
Patients and Methods: A case-control study was conducted in the Middle-Euphrates-Neuroscience Centre, Al-Najaf, over a period of 4 months from June to October, 2019. Fifty-six Adult patients who fulfilled the revised McDonalds
criteria (2017) for the diagnosis of MS and forty four healthy controls were enrolled. Serum samples for NfL and NfH were collected and processed using ELISA method, the results were compared for MS patients and controls ; the serum
results of MS patients were also correlated to type of MS,disease duration,,EDSS, MSSS,and disease activity (as detected by MRI Gadolinium enhancement and clinical relapses) .The NFL and NfH levels were also compared between treated and untreated patients and the treatment group was subdivided and compared to each other according to the type of treatment.
Result(s):
Fifty-six cases were enrolled in the study. Mean age (SD) was 34.3 (9.1) years with a median disease duration of 3 (0 – 14) years. Forty-four subjects were included as controls with a mean age of 33.7 (SD = 7.2). The male: female ratio was 1:3 for the cases and 1:2 for controls. Forty-nine patients (83%) had RRMS, six patients (10%) had SPMS and one patient (1.7%) with PPMS. Forty-eight patients (81%) had no gadolinium-enhanced lesions on MRI. Forty-four patients (74.6%) were on remission at the time of data collection, and twelve patients (24.4%) were in clinical relapse. The mean serum NfL level
for cases was 133.3 (SD = 62.6) pg/ml which is significantly higher than that for controls (Mean = 80 pg/ml; SD = 22.5; p value <0.001). The mean serum NfH level was 3654.5 (SD = 567.8) pg/ml for cases which is also significantly higher
than the levels obtained from healthy subjects (408.8 pg/ml; SD = 343.5; p value < 0.001). The mean serum NfL and NfH levels were not significantly different between patients with negative and positive gadolinium-enhancedlesions. There were no significant correlations between serum NfL and NfH levels, and EDSS, MSSS, age, type and duration of the disease, or treatment status. Regression analysis using NfL and NfH as dependent variables, and age, duration, type of MS, EDSS, MSSS, treatment status,and MRI- enhanced gadolinium lesions as the independent variables didn’t demonstrate any significant relationships.
Conclusion(s):
Measuring serum NfL and NfH may represent a potentially significant biomarker for prognostication and making treatment decisions in MS with avoiding the more invasive and inconvenient CSF sampling. In this study Serum NfL and NfH levels are elevated in patients with MS when compared to controls but they don’t correlate with the presence or number of gadolinium enhanced MRI lesions, disability, or disease severity. however, for the future studies in this field using a more sensitive methods for assessment of NFs in serum with longitudinal sampling may yield a more accurate and reproducible results.
Radiologically Isolated Syndrome Conversion to Multiple Sclerosis
1Fatemeh Sabeti, 1Masoud Etemadifar, 1Negar Ostadsharif
1Isfahan University of Medical Sciences, Isfahan, Iran
Introduction:
Radiologically isolated syndrome (RIS) is currently not a subtype of multiple sclerosis (MS) however, in the individuals with normal neurological examination and no clinical MS signs whose magnetic resonance imaging (MRI) data fulfill MS imaging criteria, RIS is concluded. We aimed to investigate and descriptively report the demographic, clinical and laboratory findings in 41 RIS subjects.
Material(s) and Method(s):
We followed a group of individuals diagnosed with RIS and obtained their demographic and clinical data.
Result(s):
Forty-one RIS patients were included in this study with a mean age of 40.6 ± 8.3 years and a female to male ratio of 4.1:1. We had obtained MRI of these patients (which lead to their RIS diagnosis) for various reasons including: 24 cases due to headache (58.5%), 3 due to dizziness (7.3%), 2 due to syncope (4.8%), 1 due to trauma (2.4%), 1 due to unconsciousness (2.4%) and in 10 cases MRI was taken sporadically (24.3%). We followed these patients for a mean of 5.9 ± 3.1 years and during this time, 10 patients (24.3%) developed MS. First MS symptom of these patients was paresthesia of lower limbs in 6 patients and optic neuritis in 4. During their follow-up period, oligoclonal bands (OCB) were also detected in 3 patients (7.3%). Different medications were also prescribed for these 41 patients (regardless of having developed MS) such as teczifuma in 3 cases (7.3%), sodium valproate in 2 cases (4.8%), rituximab in 2 cases (4.8%), actovex in 1 patient(2.4%), pregabalin in 1 patient (2.4%), divalproex in 1 patient(2.4%) and teriflunomide in 1 patient(2.4%). Spinal MRI was also obtained in these patients and cervical cord lesions was present in 5 cases (12.1%) and thoracic cord lesion was present in 1 (2.4%).
Conclusion(s):
Although this was an observational report and we did not do any data analysis of the patients’ data, the authors conclude that it is necessary to follow RIS patients even for long periods of time in order to catch their MS diagnosis early. Further, it is necessary to investigate each RIS patient’s clinical characteristics (including CSF and spinal MRI) in order to decide on whether to start MS medication earlier rather than later.
A Challenging Case of Central Nervous System (CNS) Involvement with Chronic Lymphocytic Leukaemia (CLL): A Case Report
1Sara Ali Alshamali, 1Jihad Said Salim Inshasi
1Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates
Background:
CNS involvement in CLL is rare and it usually occurs in late-stage CLL disease. There is usual delay in the diagnosis due to its variable manifestations, challenging diagnosis process and possible misdiagnosis with a mimicker condition. I am sharing our relative successful experience with this challenging case that had satisfied outcome after going through comprehensive investigations and treatment journey treating his symptoms until arriving the final diagnosis and getting the best treatment option.
Material(s) and Method(s):
A 42 years old male, with recent COVID-19 infection, presented with multiple progressive neurologic symptoms over one month; started as numbness around the mouth, reduced facial sensation and a feeling of band like sensation below the costal margins. On exam, he had left abduction restriction, diplopia on left gaze and upbeat nystagmus, reduced facial sensation and hyperesthesia. The reflexes were 1+ in the upper limbs, 3+ in the lower limbs, up going planters, tingling from the feet up to T6 level and postural tremor bilaterally.
His CSF showed high protein level. MRI brain/ spine revealed left frontal juxtacortical white matter and bilateral middle cerebral peduncles lesions with post-contrast enhancement and long segment spinal cord demyelinating plaques.
He was initially treated as a case of Acute disseminated encephalomyelitis (ADEM) post viral infection in a background of CLL. The delayed diagnosis was due to temporal relation of neurological manifestation to viral infection, similar MRI lesions to ADEM and multiple negative CSF results of cytology and flow cytometry.
He had persistent disabling symptoms and enhancing lesions in MRI despite being treated with IVMP, IVIG and PLEX.
He was managed for ADEM based on responsiveness to the recommended therapy step by step. Firstly, he received a high-dose corticosteroids, secondly IV immunoglobulin but he was still progressing and considered as steroid-unresponsive ADEM. lastly, plasma exchange was done when he exhibited progressive symptoms with fair improvement.
Interestingly, the patient showed significant improvement in the clinical and radiological parameters after starting him with a new anti-leukemia medication (Acalabrutinib) for his concurrent active condition.
He run out of his medication for around 1 week and he experienced recurrent of the neurological manifestation and the previous lesions in the images. A repeated flow cytometry for the third time came positive for CLL cells and the final diagnosis of CNS involvement by CLL was established. The diagnosis was made after the exclusion of other etiologies.
Result(s):
The patient received Ibrutinib at a standard dose and as a monotherapy. It is an efficient chemotherapy that crosses the blood brain barrier and has showed a favorable clinical, biological and radiological outcome. The patient is back to his work and his daily activities have improved.
Conclusion(s):
In case of inconclusive work up, CSF analysis should be repeated testing for cytology and flow cytometry\immunophenotypes as the false negative results are common.
Our patient had an active CLL proved in his investigations, and the fact that the patient responded very well to the new chemotherapy should alert the diagnosis of CNS involvement by CLL and directs towards repeating investigations and introducing aggressive treatment strategy to target both hematological and neurological complications of the condition.
Psychotic Symptoms Revealing Multiple Sclerosis: Case Report
1Sondes Bader, 1Emna Ellouz, 2Wafa Abbes
1Neurology Department, Gabes Hospital, gabes, Tunisia; 2Psychiatry Department, Gabes Hospital, Gabes, Tunisia
Background:
Multiple sclerosis (MS) is a demyelinating disease that shows variable clinical presentation.The presence of psychotic disorders in MS patients is rare and occurs in 2-3% of cases. Some studies reported that 95% of adult patients with MS experience psychiatric symptoms and up to 1% of MS has psychiatric onset. Little data has been reported on psychotic symptoms occurring during the MS course or preceding the onset of MS population.
Material(s) and Method(s):
We report a case of a male adult patient with psychotic trouble as first recognized manifestation of MS.
Result(s):
A 19- year-old patient who does not have a clinical history was followed in the psychiatry department for psychotic disorder for 2 years. Clinical manifestation include intrapsychic hallucination, imposed ideas, ideas of influence and reference, ideic and affective ambivalence.Hewas treated by several neuroleptic, anxiolytic drugs without improvement. The brain scan did not show any abnormalities.Due to treatment resistance the patient was referred to the neurology department. Neurological examination revealed only lower limbs brisk reflexes. The brain MRI revealed multifocal demyelinating lesions separated in space and analysis of Cerebral spinal fluid (CSF) showed oligoclonal bands and high IgG index. Immunological assessment for systemic diseases was negative.Patient was treated with corticosteroids, Interferon beta on which he showed a significant improvement of psychiatric symptoms.
Conclusion(s):
The diagnosis of MS should be considered in patients with psychotic troubles especially if there is a lack of response to standard treatments
Analysis of Visual Acuity, Contrast Sensitivity and Color Perception in Multiple Sclerosis Patients
1Celia Oreja-Guevara, 1Johnny Quezada-Sánchez, 1Martínez-Pérez E, 1Judit Díaz-Díaz, 1Irene Gómez-Estévez, 1Elda Alba Suárez
1Hospital Clínico San Carlos, Madrid, Spain
Background:
Optic neuritis is a very frequent manifestation in the course of the disease and can lead to changes in visual function. The main objective of this study was to analyze low contrast visual acuity (VA), contrast sensitivity (CS) and color perception in multiple sclerosis patients with and without optic neuritis.
Material(s) and Method(s):
MS patients with more than six months of follow-up and clinically stable in the last six months were analyzed. We performed a complete ophtalmologic study. Low contrast VA was assessed with the ETDRS Bailey-Lovie test at 2.50% and 1.25%, SC with the Pelli-Robson test and chromatic perception with the Ishihara test and the Farnsworth-Munsell D28 test. We compared patients with optic neuritis and those without optic neuritis.
Result(s):
Of the 50 eyes that were evaluated, 16 had some past optic neuritis and 34 had no previous optic neuritis. There were 18 females with a mean age of 42.65 and 7 males with a mean age of 44.69. Patients who had past optic neuritis showed a slight decrease in low contrast VA (greater reduction in the 1.25% test than in the 2.50% test) both monocularly and binocularly, with respect to those who have never had an optic neuritis. In the contrast sensitivity test, reduced values were also observed in those who had previous optic neuritis. In the chromatic preception tests it was observed that the results obtained in the Ishihara test were normal with a reading of 17 lamellae or more, while in the Farnsworth Munsell D28 test only 12 patients were normal trichromats in both eyes, 2 patients clearly showed color defects in the blue-yellow axis (tritan) in both eyes, 2 patients showed an undefined pattern in both eyes and the rest of the patients presented different patterns in each eye.
Conclusion(s):
To discriminate chromatic alterations in patients with MS, it seems that the Farnsworth Munsell D28 test is more sensitive than the Ishihara test in all patients who were evaluated. This leads us to believe that MS may affect color perception more slowly resulting in clearly defined patterns, such as blue-yellow axis defects, in the long term. Patients with optic neuritis have worse low-contrast VA and worse contrast sensitivity.
Depression, Anxiety and Alexithymia in Tunisian Patients with Multiple Sclerosis
1Saloua Mrabet, 1Sirine Boudriga, 1Amira Souissi, 1Alya Gharbi, 1Amina Nasri, 1Mouna Ben Djebara, 1Amina Gargouri, 1Imen Kacem, 1Riadh Gouider
1Department of Neurology, Clinical Investigation Centre Neurosciences and Mental Health, University Hospital Razi, Manouba, Tunisia; 2Faculty of medicine, University Tunis El Manar, Tunis, Tunisia
Background:
Multiple sclerosis (MS) is a disabling chronic inflammatory disease of the central nervous system. Psychiatric disorders in MS are highly prevalent and are often underdiagnosed and poorly treated. The main psychiatric disturbances in MS are depressive, bipolar, anxiety, schizophrenic, and obsessive-compulsive syndromes. The aim of our study was to evaluate the type of psychiatric disorders in a cohort of patients with MS and to correlate the results with sociodemographic, clinical and radiological data.
Material(s) and Method(s):
We conducted a cross-sectional study, including patients who were followed in our MS Unit in the neurology department of Razi University Hospital between June and September 2021.
We used the structured interview of DSM-IV (MINI). We evaluated the severity of symptoms of depression and anxiety using the HAD (Hospital Anxiety and Depression scale) and MADRS (Montgomery–Åsberg Depression Rating Scale), and we measured the difficulty in identifying and describing emotions with the Toronto alexithymia scale (TAS). We reviewed their medical records and collected their demographic, clinical, and radiological characteristics as well as their outcome profile.
Result(s):
The mean age of our 55 patients was 33 years old with a sex ratio (F/M) of 3.2. MS was Relapsing remitting (RR MS) in 49 of our patients and secondary progressive MS in six of them.
Depression was diagnosed in 62.5 % of our population with 5.7% of the patients suffering from severe depression. Attempted drug-induced suicide was found in the medical history of 3 patients. Depression was correlated to a younger age of MS onset (p=0.003) and to MRI lesions load (p = 0.025). Among our patients, general anxiety disorder was diagnosed in 57.1%, while obsessive-compulsive disorder and panic disorder were identified in respectively 12.2% and 24.5%. Annual relapses rate was correlated with the occurrence of a social anxiety disorder (p= 0.003). As for anxiety, female gender (p= 0.69) and young age at disease onset (p=0.548) were not found to be risk factors. Furthermore, our patients presented a high prevalence of Alexithymia (62.5%). It was found to be inversely correlated to disease duration.
Conclusion(s):
Our study showed that psychiatric comorbidity, particularly depression, alexithymia, and anxiety, was common in MS playing an important role in patients with MS life. The occurrence depressive and anxious symptoms in our cohort were higher than what was reported in MS patients in several studies (respectively 25–50% for depression and 13-31.7% for anxiety). It was correlated to an early age of the disease onset, which is in contrast with the 2014’s Tunisian study conducted in another University Hospital. Disease activity, but not its duration, was associated with Anxiety in our patients which is consistent with previous studies. White matter lesion load on MRI was associated to depression in MS patients as reported in several studies.
Adrenoleukodystrophy in Adults: About a Case
1Si Ahmed Hakim, 1Ouardia Belarbi, 1Smail Daoudi, 1Ferroudja Miloudi, 1Massinissa Lounis
1Department of Neurology, Nedir Mohamed Teaching Hospital, Tizi Ouzou, Algeria
Background:
The goal is to think about leukodystrophy which can mimic a progressive picture of multiple sclerosis
Material(s) and Method(s):
We report the observation of a man with adreno-leukodystrophy whose neurological manifestations were late.
Result(s):
The diagnosis of adrenoleukodystrophy is made on a bundle of clinical and radiological arguments (male, presence of adrenal damage, appearance of radiological lesions, encephalic and medullary damage), the diagnosis is confirmed by the determination of very long chain fatty acids.
Conclusion(s):
Adrenoleukodytrophy can mimic certain pathologies, in particular multiple sclerosis in its progressive form, hence the interest of certain paraclinical examinations and a good analysis of the imagery.
Lorenzo’s oil normalizes C26 levels within 4 weeks but has no effect on neurological progression patients already affected. However, this therapeutic management seems to be interesting in patients asymptomatic and not having cerebral involvement.
MRI Findings in Late-Onset Multiple Sclerosis; a Systematic Review and Meta-Analysis
1Amirreza Naseri, 1Ehsan Nasiri, 2Mohammad Ali Sahraian, 3Sara Daneshvar, 3Mahnaz Talebi
1Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 2Sina MS Research Center, Sina hospital, and department of neurology, Tehran University of Medical Sciences,, Tehran, Iran; 3Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran
Background:
Multiple sclerosis (MS) commonly affects young adults at the ages 20 to 40 years old, but it can onset at each age. Late-onset multiple sclerosis (LOMS) is defined as symptoms initiating after the age of 50. Because of similar manifestations between LOMS and other diseases of the elderly, misdiagnosis and a remarkable gap in diagnosis of LOMS is a challenge of the elderly population (1, 2). Since its technical development in the early 1980s, magnetic resonance imaging (MRI) has quickly been adopted as an essential tool in supporting the diagnosis, longitudinal monitoring, evaluation of therapeutic response, and scientific investigations in MS (3). In this systematic review, we elevate the MRI profiles of LOMS cases, based on published studies. As spinal cord involvement is an important cause of disability in patients with MS (4), we also investigated the proportion of spinal cord involvement in LOMS cases.
Material(s) and Method(s):
MEDLINE via PubMed, EMBASE, and Scopus databases were searched with the “multiple sclerosis, MS, late onset and LOMS” keywords, on November, 2020, with no restrictions and updated via hand searching in October 2021. Two independent researchers screened the records in title/abstract and full-text stages and extracted the data using a data extraction table. The meta-analysis was conducted using the Comprehensive Meta-Analysis (CMA) with 95% confidence intervals and 0.05 level of significance for p-value.
Result(s):
733 records were screened in the title/abstract and 70 studies in full-text stages and finally 16 studies were included in this systematic review (figure1). In one of the included studies in a Canadian setting, spinal cord involvement was seen in 100% of patients, but this study was limited by size (n= 12) and the age of patients was above 60 in time of diagnosis of MS. On the other hand, the lowest spinal cord involvement (29.1%) belonged to a study in an Iranian setting with 48 patients. The details of included studies are reported in table 1. Based on the meta-analysis in random effect model 65.4% (95% CI: 49.7% to 78.3%) of LOMS casas had spinal cord involvements with 89.79% I2 heterogeneity (p-value <0.01) (figure2).
Conclusion(s):
There is a significant rate of spinal cord involvement in LOMS cases, which can cause a significant disability in MS patients and affect the patients’ quality of life. Improvement in MRI techniques has allowed a better assessment of correlation between the clinical and radiological parameters. Not only does MRI identify MS-like lesions, but it also excludes other potentially mimicking pathologies, so increasing the knowledge regarding the MRI finding of LOMS cases, can help clinician in timely diagnosis of the disease.
Chitinase-3 Like-Protein-1 in CSF: A Novel Biomarker for Progression in Multiple Sclerosis Patients
1Ahmed Dahshan, 1Christine Ragaie, 1Foraysa El-Sayed Mohammed Talaat
1Cairo University, Cairo, Egypt
Background:
Chitinase -3-Like protein-1 (CHI3L1) is a glycoside secreted by monocytes, microglia, and activated astrocytes. Its distribution in inflammatory lesions suggests that it might be an important component of the astrocytic response to modulate CNS inflammation. CHI3L1 levels in CSF have been found to influence prognosis, disease severity and progression in multiple sclerosis (MS) patients.
Material(s) and Method(s):
52 patients with MS (30 RRMS and 22 Progressive MS) and 35 age, sex matched healthy controls were recruited. They all underwent full clinical assessment and CSF level of CHI3L1. Comparisons were made between patients and controls concerning CSF level of CHI3L1 and correlations between CSF level of CHI3L1 and disability and progression parameters in MS patients.
Result(s):
Patients with MS had higher CSF level of CHI3L1 (p=<0.001) than controls. Patients with progressive MS had higher levels than RRMS (p=<0.001). There were positive correlations between age of disease onset, disease duration, number of attacks and CSF levels of CHI3L1. Also, CSF levels of CHI3L1 correlated significantly with EDSS, performance in MMSE and BICAMS and lesion load in MRI brain and spine. A cut off value of 154 ng / ml have been proposed as a cut off point between RRMS and progressive MS patients.
Conclusion(s):
CHI3L1 can be considered as a biomarker of disease progression. its higher levels were associated with more severe and disabling disease. this could help as an objective parameter in DMD choice decision.
The Role of Gut Microbiata in Multiple Sclerosis
1Caesar Zahka
1American Hospital, Dubai, United Arab Emirates
Background:
- Evaluating the role of the gastrointestinal tract, as a key system in the immune homeostasis.
- Emphasizing the importance of the normal Flora and Microbiata in the human health.
- Studying the effects of the changes in GI Microbiata on the pathogenesis of Multiple sclerosis.
- Evaluating the possible role of Fecal Microbiata Transplanation in the management of the disease.
Review Article:
The gastrointestinal tract has one of the biggest immune and nerve cells’ reservoirs in the body. The gut microbiota is considered a microbial “organ,” and its alteration could lead to the inflammatory activation of the immune system. Studies show that MS gut microbiome, as having general alterations in specific species, some associated with the promotion of inflammatory cytokines and overall inflammation. In addition to these findings, experimental models of the disease have reported that T regulatory cells have deficits in their function as a result of the aberrant gut microbiota composition. Evidence indicates that changes in microbiota composition may result in imbalances that could result in disease, with the gut as a potential novel therapeutic avenue. By understanding the biological effects of aberrant gut microbiome composition, it is possible to postulate current therapeutic options and their efficacy. Definitely, we need more research in this field, but targeting the gut microbiota may lead to the development of some new therapeutic strategies.
COVID-19 in Multiple Sclerosis Patients in Dubai: Observational Study
1Mona Thakre, 2Jihad Inshasi
1Al Zahra Hospital Dubai, Dubai, United Arab Emirates; 2Rashid Dubai, Dubai, United Arab Emirates
Background:
Covid 19 pandemic came with its own challenges of novelty, lack of information uncertainty of treatment and its effect on chronic autoimmune diseases like Multiple sclerosis. The outcome of covid 19 with immunosuppressive and immunomodulatory treatment in multiple sclerosis was not known till this year. We share our observation of multiple sclerosis patients including neuromyelitis optics who contracted Covid 19 in Dubai UAE, during April 2020 to Sep 2021 in 2 major hospitals treating multiple sclerosis.
Material(s) and Method(s):
All Multiple sclerosis Patients following in Rashid hospital and Alzahra Hospital Neurology apartment who had Covid 19 were included in this observational study.
Result(s):
55 MS patient with Covid 19 ( including 2 NMO) were studied .Age of the patients ranged from 19 to 58years. There were 39 females and 16 males. 43 were RRMS, 6 -SPMS,4- CIS,1- PPMS and 2 NMOSD. 6 were on interferons, 2 on teriflunamide, 8 on dimethylfumarate, 12 on fingolimod, 3 on natalizumab, 1 on alemtuzumab, 1 on rituximab, 9 on cladribine, 12 on ocrelizumab and 1 on azathioprine. 47 had fever, 30 anosmia, 28 had fatigue and 42 had sorethroat and cough, 5/ 55 had pneumonia.39/55 had mild covid, 13/55 had moderate and 3 had severe covid 19. 3 /55 needed ICU. There were 2 deaths, first with MS,EDSS 6.5 on ocrelizumab and second with NMO (EDSS 7.0)on rituximab
Conclusion(s):
The disease course and outcomes were mostly favorable with most patients not requiring hospitalization. A higher EDSS score, progressive disease, use of rituximab, and ocrelizumab(antiCD20 therapy) were associated with the mortality encountered. Age, sex, smoking history, and duration of MS were not independent risk factors for increased severity or adverse COVID-19 disease outcomes
Humoral Immune Response to SARS-CoV-2 Vaccination in MS Patients
1Celia Oreja-Guevara, 1Judit Díaz-Díaz, 1Elda Alba Suárez, 1Irene Gómez-Estévez, 1Johnny Quezada Sánchez, 1Cristina Bullón-Sánchez, 1Matilde Castro-Hernández, 1Eduardo Martinez-Pérez, 1Silvia O´Connor Pérez, 1Elvira Baos Muñoz
1Hospital Clínico San Carlos, Madrid, Spain
Objective(s):
The aim of this study was to study the humoral immune response to SARS-CoV-2 following vaccination in MS patients.
Material(s) and Method(s):
We performed a prospective study including all MS patients receiving one of the approved COVID-19 vaccines since January to September 2021. Demographic characteristics, MS treatments and adverse events reports after COVID-19 vaccination of vaccinated MS patients were collected.
We analyzed the antibody response to SARS-CoV-2 vaccines with a chemiluminescent microparticle immunoassay (CMIA) from Abbot in MS patients with different DMTs at week 3, week 6 and month 3 after the first dose. The positivity cutoff is ≥50 AU/ml (manufacturer defined).
200 Healthy healthcare professionals were the control group.
Result(s):
We analyzed 165 vaccinated MS patients: 106 with Pfizer, 14 with Moderna, 42 with both doses of Astra zeneca and 3 with Jannsen.
The mean age of patients was 45 (range: 21-71) and 46 for the controls.
The most frequent adverse events were pain at injection site, headache and fatigue for 24-48 hours. No differences between MS patients and controls. No increased risk of relapse was noted in the first six months.
120 patients have received both doses of mRNA vaccine.
Overall, mean antibody titers response to SARS-CoV-2 SARS-CoV-2 at three weeks was 7910,3 AU/mL (range 0-74947), at 6 weeks 16347,9 UA/mL (range:0-52380,5) and at 3 months 8182,10 UA/ml (range:0-33752,4) in mRNA vaccinated patients.
By the mRNA vaccinated control group mean antibody titers response to SARS-CoV-2 SARS-CoV-2 at three weeks was 9397 AU/mL and at 6 weeks 18120 UA/mL
Performing a subanalysis of the different DMTs: Only 3 out of 20 patients treated with ocrelizumab developed antibodies. Six vaccinated patients treated with rituximab had no antibody response. Four from 16 patients treated with fingolimod failed to develop a post-vaccination humoral response (< 50 AU/ml). 4 of 5 patients treated with ofatumumab developed have an adequate humoral response.
Patients treated with interferon Beta, glatiramer acetate, teriflunomide, dimethyl fumarate, vaccinated with mRNA vaccines developed a similar post vaccination humoral response than healthy controls.
Conclusion(s):
Most of MS treated patients developed enough antibodies to SARS-CoV-2.
The adverse events on MS patients were similar to the general population. No increase of relapse activity was observed.
Some patients treated with ocrelizumab, rituximab and fingolimod have no developed a humoral response to SARS-CoV-2 vaccination.
Hence we conclude that all approved COVID-19 vaccines are safe in MS patients and effective in most patients. However vaccine strategy in patients treated with anti-CD20 and fingolimod need further studies.
Association of COVID-19 with Disability Progression and Disease Exacerbation in People with Relapsing-Remitting Multiple Sclerosis: Evidence from a Year-Long Observational Study
1Nahad Sedaghat, 1Masoud Etemadifar, 1Hosein Nouri, 1Amir Parsa Abhari, 1Shiva Maleki, 1Alireza Amin, 2Mehri Salari
1Isfahan University of Medical Sciences, Isfahan, Iran; 2Shahid Beheshti University of Medical Sciences, Tehran, Iran
Objective(s):
Neurological complications of COVID-19 have raised serious concerns among the experts, and hence, many mechanisms have been proposed to explain it. We sought to collect evidence by investigating the possible effect of the virus on multiple sclerosis (MS) disease course, in COVID-19-contracted people with relapsing-remitting multiple sclerosis (RRMS).
Material(s) and Method(s):
This prospective-retrospective hybrid cohort study conducted from July 2020 until July 2021, compares the rates of probable disease progressions (PDP) and relapses between the pre- and post-COVID-19 periods of RRMS patients, using non-parametric tests, a matched binary logistic model offset by follow-up, Kaplan-Meier plots, and a cox regression model.
Result(s):
The PDP rate (0.06 vs 0.19, P = 0.04) and relapse rate (0.21 vs 0.30, P = 0.30) were both lower in the post-COVID-19 period compared to the pre-COVID-19 period. However, matched binary logistic model offset by follow-up failed to display a significant difference in odds of PDP (OR [95% confidence interval]: 0.41 [0.13, 1.34], P = 0.14) and relapse (OR [95% confidence interval]: 0.99 [0.45, 2.17], P = 0.99), at the endpoints of pre- and post-COVID-19 periods. Kaplan-Meier plots and cox regression model did not show significant difference between the pre- and post-COVID-19 periods, regarding both the PDP rates (HR [95% CI]: 0.46 [0.12, 1.73], P = 0.25) and relapse rates (HR [95% CI]: 0.69 [0.31, 1.53], P = 0.36).
Conclusion(s):
Our results suggest that COVID-19 contraction is unlikely to increase the risk of MS progression and relapse in the following months after infection.
MicroRNA-484 and Apoptotic Protease Activating Factor-1 Gene in Relapsing Remitting Multiple Sclerosis: the Possible Interplay
1,2Alaa Elmazny, 3Dalia Abdel Wahab Mohamed, 2Heba Selim, 2Ali Genena, 3Mai Mohamed Nabil, 2Nevin Mohieldin, 2Hatem Shehata
1Arabian Gulf University, Manama, Bahrain; 2Cairo University, Cairo, Egypt; 3Ain Shams University, Cairo, Egypt
Background:
Emerging evidence suggests that dysregulated apoptosis might be implicated in the pathogenesis of multiple sclerosis (MS). In this study we evaluated the expression of miR-484 and its potential target gene Apoptotic protease activating factor-1 (APAF-1) in relapsing remitting MS patients (RRMS), correlated their expression levels to patients’ clinical characteristics and investigated their role as potential disease biomarkers.
Material(s) and Method(s):
After Bioinformatic analysis was conducted and revealed that APAF-1 is a potential target gene for miR-484. Reverse Transcription-quantitative Real-Time PCR (RT-qPCR) was performed to detect the expression levels of miR-484 and APAF-1 in the peripheral blood mononuclear cells (PBMCs) of 34 RRMS patients and 34 healthy controls.
Result(s):
miR-484 expression was significantly upregulated in patients whereas APAF-1 mRNA was downregulated compared to controls (p < 0.01). APAF-1 mRNA expression was found to be significantly higher in treated patients (median RQ 1.2) compared to those who were not on treatment (median RQ 0.9) (P=0.02). Sensitivity and specificity of miR-484 and APAF-1 to diagnose MS were (88.2%, 86.7%) and (83.3% and 82.4%) respectively.
Conclusion(s):
APAF-1 and miR-484 could play a role as promising therapeutic targets and potential diagnostic biomarkers.
The Effect of Disease Modifying Drugs of Multiple Sclerosis on the Effectiveness of BBIBP-CorV COVID-19 Vaccine
1Mehran Ghaffari, 1Nahid Beladimoghadam, 1Seyed Hossein Aghamiri, 1Mehrdad Haghighi, 1Abdolreza Javadi, 2Mohammadali Nahayati
1Imam Hossein Medical and Educational Center, Tehran, Iran; 2Ghaem Medical and Educational Center, Mashhad, Iran
Background:
Vaccines to prevent SARS-CoV-2 infection are considered the most promising approach for curbing the pandemic. There are many concerns about the effectiveness of vaccination in patients with multiple sclerosis (MS). Few studies have examined the effectiveness of mRNA COVID vaccine in MS patients treated with high potency disease modifying therapies (DMTs). The aim of this study was to evaluate the efficacy of BBIBP-CorV )Sinopharm( vaccine in patients treated with 7 different DMTs.
Material(s) and Method(s):
This quasi-experimental study was conducted on the patients of MS clinics of Imam Hossein hospital in Tehran (capital of Iran) and Ghaem hospital in Mashhad (northeast of Iran). MS patients with:1- no history of COVID infection in the past 6 month, 2- no history of relapse or steroid use in the past 4 weeks, 3- regular use of a DMT for at least 6 months (9 month for glatiramer acetate) and 4- at least 2 months interval between the previous rituximab infusion and vaccination, were enrolled and vaccinated with Sinopharm vaccine (2 doses, 4 weeks apart). In the case of relapse, COVID infection, or If any of the antibodies (anti neucleocapsid IgM and IgG and anti RBD IgG) were positive at the first injection of the vaccine, the patient was excluded from the study. The amount of IgG class antibodies against virus RBD were measured using ELISA SARS-CoV-2 IgG DIAZIST after 28 days of the first vaccination and on the day 56 (28 days after the second vaccination). An index value higher than 1.1 was considered reactive for anti RBD antibodies.
Result(s):
Out of the 208 patients included in the study, 91 patients were excluded and 117 patients were finally analyzed. Humoral response to vaccination based on the DMT used by the patient was as follows: beta interferons: 89.47% (17 out of 19 patients), dimethyl fumarate: 85.71% (12 out of 14 patients), patients without DMT treatment:83.33% (5 out of 6 patients), Natalizumab 83.33% (5 out of 6 patients), glatiramer acetate:71.42% (5 out of 7 patients), teriflunomide: 50% (4 out of 8 patients), rituximab: 38.46% (15 out of 39 patients), and fingolimod: 21.05% (4 out of 19 patients).
Conclusion(s):
According to our findings, the response to vaccination is maintained in patients treated with beta interferons, dimethyl fumarate and natalizumab, but is less than acceptable in patients treated with rituximab and fingolimod.
First Study in Iraq About (HLA)-Drb1 * 15:01 as a Genetic Risk Factor for MS Initiation
1Alaa Hassan Khaliel, 2Ahmed Abdul- Hassan Abbas, 3Anmar Oday Hatem
1Ministry of Health, Baghdad, Iraq; 2College of Medicine, Al-Nahrain University, Baghdad, Iraq; 3Baghdad Teaching Hospital, Baghdad, Iraq
Background:
To assess the genotypes of (HLA)-DRB1 * 15:01 as genetic risk factor for MS development in samples of Iraqi MS patients.
Material(s) and Method(s):
This Case control study involved; fifty MS patients for HLA-DRB1 15:01 investigation; their age were ranged from 14 to 69 years. They attended to seek treatment in the MS out patient’s clinic at Medical City- Baghdad Teaching Hospital in the period, which extended from December 2018 to March 2020. The diagnosis of each case was established according to MC Donald criteria done by a neurologist and confirmed by MRI and certain cases by oligoclonalband test of the CSF. Patients were subjected to a questionnaire about name, age, sex, smoking, family history, the control group involved 50 apparently healthy person. Patients were. The institutional review board (IRB) in the College of Medicine/Al-Nahrain University approved this study, and all samples were obtained with informed consent in accordance with the Ministry of Health declaration. HLA-DRB1 15:01 genotype also was conducted by Sanger sequencing technique.
Result(s):
The Polymerase chain reaction (PCR) products HLA-DRB1 Genes were subjected for Sanger sequencing technique. In addition, the resultant sequences were compared with reference sequences in national center for biotechnology information NCBI. All the genotypes of HLA-DRB1 were analyzed for linkage disequilibrium. There was a very high linkage disequilibrium in rs2213585, rs2213586 and rs3135388 in both patients and control. In concern to the rs3135388, which tags for HLA-DRB1*15:01 the heterozygous genotype (GA) was more frequent in MS patients (28%) than controls (10%) (OR= 3.52, 95%CI=1.16-10.72, p=0.027). Regarding the rs2213585, rs2213586 there were no significance associations between control group and patients.
Conclusion(s):
This is the first study that revealed that HLA-DRB1 15.01genotyp may be considered as genetic risk factor for MS susceptibility in Iraqi MS patients until 2020
Evaluation of Anti-JVC Antibody Index Evolution in Patients with Multiple Sclerosis
1Amal Atrous, 1Saloua Mrabet, 1Amira Souissi, 1Lilia Hmissi, 1Firas Larnoaout, 1Mouna Ben Djebara, 1Amina Gargouri, 1Imen Kacem, 1Riadh Gouider
1Department of Neurology, Clinical Investigation Centre Neurosciences and Mental Health, University Hospital Razi, Manouba, Tunisia; 2Faculty of medicine, University Tunis El Manar, Tunis, Tunisia
Background:
Anti- John Cunningham virus (JCV) antibody index has been reported to correlate with progressive multifocal leukoencephalopathy (PML) risk in seropositive Multiple Sclerosis (MS) patients. Although it is reported that seroconversion occurs in approximately 2–15% of patients per year, there is insufficient evidence on long-term dynamics of anti-JCV antibody index. Our objective was to investigate the longitudinal evolution of anti-JCV antibody index in a cohort of Tunisian MS patients and to evaluate the impact of age, sex and disease modifying therapies (DMT) use in Anti-JCV antibody status.
Material(s) and Method(s):
We studied records of the patients diagnosed with MS according to 2017 Mc Donald criteria and followed at the MS Unit of the department of Neurology of Razi University Hospital in Tunis-Tunisia between 2018 and 2020, with or without DMT. We included patients for whom Anti-JCV antibody serological status and repetitive assessment of JCV antibody index were available.
Result(s):
One hundred patients were included in this study. Seventy-one of them were female. Median follow-up time was 36,19 months, with a median of 3 samples available per patient. At baseline, 49 % of patients were anti-JCV antibody positive with a median anti-JCV antibody index of 1.16. Twelve patients (12%) changed initial serostatus at least once during follow-up: 4% from negative to positive anti-JCV antibody status and 8% from positive to negative anti-JCV antibody status. Baseline anti-JCV antibody index was higher in patients remaining seropositive at follow-up compared to those reverting to seronegativity (1.94 vs. 0.89, p = 0.02). Only 6.1% of our patients did not receive DMT at time of JCV assessment. The 94% of patients were under Rebif (39%), under Avonex (37,4%) and under Natalizumab (46,5%). Natalizumab was stopped in 10 patients because of seroconversion in 4 of them and other side effects in 6 others. The type of DMT did not affect the anti-JCV antibody status. Moreover, no correlation was found between Baseline anti-JCV antibody index and sex or age. 60% of our patients had a second JCV blood sample with a median number of months between the first and second sample of 10,95 months with 91% of stability between the two assessments. 41% of our patients had a third JCV blood sample with 68,3 % of patients remaining negative.
Conclusion(s):
Anti-JCV antibody index remained relatively stable over 3-year follow-up in our Tunisian cohort. Baseline anti-JCV antibody index was higher in positive seroconverters and was not affected by MS patients’ age or gender and the type of DMT use.
Prevalence of MS in Tehran, Iran in 2020 and Its Forecast for the Next 10 Years
1Sharareh Eskandarieh, 1Mohammad Ali Sahraian, 1Saeideh Ayoubi
1Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
Background:
The Middle-east and North Africa (MENA) region had a high prevalence of MS between 1970 and 2015 (1-2). Iran had the highest prevalence of MS among the countries of the Eastern Mediterranean region (72.11/100000) (3).
The prevalence of MS in Tehran was 79.3 cases per 100000 people in 2006 which increased to 162.38 (95% CI:160.27-164.52) cases per 100000 people in 2019 (4).
Objective(s):
To evaluate the development of MS in Tehran in 2020 and forecast the future condition of the disease for the next ten years.
Material(s) and Method(s):
A cross sectional study was designed to compare the latest prevalence of MS in Tehran. This study was based on data obtained from Iranian MS society (IMSS) registry system between 1999 and 2020.
Based on the results of population census that was performed in Iran in 2020 the population of Tehran was 13973000 of which 7016000 were male and 6957000 were female.
IMSS provided patients with a wide range of facilities and neurologists encouraged patients to enroll in IMSS to receive care and treatment services. Data about MS patients is carefully collected based on opinion of experts and the MS registration system (5). Before accepting the registry procedures by patients, the aims of IMSS registry were well explained to them by the interviewers.
The basic characteristics of patients, including the age of onset, age and sex of the subjects and history of familial MS were collected (4).
Patients were asked if they had people affected by MS among their relatives and asked about the degree of their relationship (first, second and third) to the person affected with MS.
For estimating the odds ratio for variables to assess factors associated with pediatric and familial MS recurrence rates, chi-square and logistic regression tests were used.
Result(s):
Results: A total of 23411 cases were registered at this study, including17577 (75.1%) females and 5834 (24.9%) males (female/male ratio = 3.016). The prevalence of MS in 2020 in Tehran was 167.54 cases per 100000 people including 252.65 per 100000 among females and 83.15 per 100000 among males.
Prevalence rate for MS in the total, familial and sporadic in 2029 and ends with 220.84(171.48-266.92), 30.79(24.16–37.15), and 189.33(146.97-230.19) in 2029.
Conclusion(s):
Tehran is one of the cities with the highest MS prevalence rate in Asia (1, 2).
MS prevalence in Tehran has increased compared to previous studies and will increase in early future.
MS is more common in women and young people (1). Having a family member with MS can increase the risk of pediatric MS. Risk of positive familial history was substantially higher among males (4).
Water-Pipe and Cigarette Smoking, Drug Abuse and Alcohol Consumption and the Risk of Primary Progressive Multiple Sclerosis: A Population Based Case-Control Study
1Sharareh Eskandarieh, 1Seyyed Hosein Mortazavi, 2Amir Almasi-Hashiani, 1Abdorreza Naser Moghadasi, 1Mohammad Ali Sahraian
1Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; 2Department of Epidemiology, School of Health, Arak University of Medical Sciences, Arak, Iran
Background:
Multiple sclerosis is a chronic central nervous system disease and primary progressive multiple sclerosis (PPMS) is one the main type of MS which like any other autoimmune disease has undetermined environmental risk factors and can be triggered by smoking, drug substance and alcohol consumption (1).
The aim of the study was to identify possible association of smoking, drug substance and alcohol drinking with PPMS development.
Material(s) and Method(s):
The population-based case–control study was conducted Tehran, Iran from 2019-2020 in. PPMS cases was diagnosed based on the 2017 McDonald criteria by a neurologist in Sina hospital (tertiary care referral center).
The telephone interviews were carried for data collection out by 4 well-trained interviewers, using environmental risk factors in MS questionnaire. The validity and reliability of the Persian version of the questionnaire were approved (2).
The same questionnaire was used for case and control groups.
The standard random digit dialing was used to select control participants from the same source population (3-4). The sex and residency were matched in both groups. Logistic regression analysis was used to estimate adjusted and unadjusted ORs (odds ratio) at 95% confidence intervals (CI) by using SPSS software.
Result(s):
Completely 146 PPMS cases and 294 healthy controls were registered in the study.
The mean age (SD) for cases and controls were 47.0 (9.4) and 37.7 (6.1) years, respectively (P =0.001).
Being passive smoker (OR=2.20 (CI=1.34-3.62)) and having ever smoked cigarette (OR=2.48 (CI=1.44-4.27)) were considered risk factors associated with PPMS development, while having ever smoked water-pipe was not significantly relevant to PPMS risk (OR=1.19 (CI=0.62-2.26)). Those who had all three types of smoking including passive smoking, water-pipe and cigarette smoking (OR=10.45) had 10 times higher risk of PPMS, comparing to those without any type of smoking. There is no significant association between different types of substances abuse and alcohol consumption and PPMS risk, such as Cannabis: OR=1.58 (CI=0.47-5.24), Opioid: OR= 0.90 (CI=0.35-2.29), Stimulants: OR=0.85 (CI=0.14-4.87), Beer: OR=0.61 (CI=0.29-1.26), Wine: OR= 0.73 (CI=0.35-1.53) and Whisky/vodka: OR= 0.71 (CI=0.34-1.49).
Conclusion(s):
The passive smoking and cigarette smoking and are important risk factors for developing PPMS. Using three types of smoking including water-pipe, cigarette and passive smoking may increase risk of PPMS occurrence comparing to subjects without history of smoking (3,4 (. According to regional increase in smoking water-pipe and cigarette in MENA region, this finding indicate the need for necessary health interventions to prevention PPMS risk.
Epidemiology of Multiple Sclerosis in Iraq: Retrospective Review of 4355 Cases and Literature Review
5Hayder K Hassoun, 1Akram Al Mahdawi, 2Nawfal Shaheed, 3Amanj Jamal, 4Sara Sami
1Faculty of Medicine, Baghdad University, Baghdad, Iraq; 2Baghdad Teaching Hospital, Baghdad, Iraq; 3Hawler Teaching Hospital, Erbil, Iraq; 4Marjan teaching hospital, bayblon, Iraq; 5Faculty of Medicine, Kufa University, Annajaf Al ashraf, Iraq
Background:
Multiple sclerosis (MS) is a progressive demyelinating and degenerative disease of the CNS which is highly variable geographically. The objectives are to establish a comprehensive nationwide MS epidemiological data and compare it with similar studies conducted in the regional and international countries. To the best of our knowledge, this is the first nationwide comprehensive epidemiological study conducted in Iraq.
Material(s) and Method(s):
Officially authorized MS clinics and centers in Iraq during the year ranged from January 2000 to December 2018. All cases were diagnosed based on Revised 2018 and 2010 McDonald’s criteria and all patient records were reviewed.
Result(s):
Our study found that 68.51% of MS were females with female to male ratio 2.18:1 and 4.07% of patients were diagnosed before they reached 18-year-old. The mean age was 32.3±9.8. The prevalence was found to be 11.73/100,000, it was 16.2/100,000 among females and 7.3 per 100,000 among males. The Incidence was 0.05 in the year 2000 and 1.5 in the year 2017. Initial symptoms were visual 32.06%, motor 28.11%, and 25.58% were sensory symptoms, and 89.97% of the clinical form was relapsing/remitting MS (RRMS) and 81.65% of patients were on first-line treatment. Meanwhile, 66.97% of cases were diagnosed within weeks or months from symptom onset. Summer and especially July had the most frequencies regarding birth season and month.
Conclusion(s):
MS has a significantly increased incidence in Iraq while prevalence is low compared to the neighboring countries. RRMS was the most common clinical form and visual symptoms showed the highest frequency of the first presenting symptoms.
Multiple Sclerosis During Pregnancy: Data from the MS Clinic in Benghazi Medical Center
1Anwaar Mukhtar Bennour, 1Majda Elshukri, 1Naziha Amer, 1Heba Elzawawi, 1Rabha Elsahli, 1Abdelhamid Elzawawi
1Benghazi Medical Center, Benghazi, Libya
Background:
There are many misconceptions about multiple sclerosis (MS) and pregnancy with issues surrounding disease modifying therapies (DMTs) remains a regular subject of discussion.
Objective(s):
To explore a local practice experience regarding management of women with MS during their family planning and pregnancy.
Material(s) and Method(s):
We reviewed the medical records of the patients registered in the MS clinic from the period 2016 till December 2019. Injectable interferonβ was the DMTs available to the patients. From the medical records we calculated the proportions of cases with planned and unplanned pregnancies and reviewed the disease course during pregnancy and after delivery. We also focus on the action plan taken regarding DMTs during or before pregnancy occur. This includes discontinuing vs maintaining DMTs, delivery methods, time of resumption of DMTs and breast feeding and getting magnetic resonance image (MRI) of the brain available before conception. Also we reviewed patients who refuses to conceive during their illness.
Result(s):
The total number of MS patients registered in the clinic is 360 patients, 169 (72%) were females, 40 (24%) were married. Twenty eight pregnancies were reported in 23 women. Their mean age is 37.9±2.7 (range 24-56) years. The duration of MS diagnosis is 10.2±5.5 (range 1-21) years with a median Expanded Disability Status Scale score (EDSS) of 1.6 ±2.0 (range 0.0-6.0). Thirteen (46.4%) pregnancies were unplanned whereas 15 (53.6%) were planned. All women (100%) with unplanned pregnancy stopped their DMTs when pregnancy was confirmed. All women (100%) with planned pregnancy stopped their DMTs 2-3 months prior to conception. Two (13.3%) patients conceived in the first quarter of 2019, advised and willing to continue their DMTs. Four women delivered by Caesarean section. The mean duration to resume DMTs is 11 (0-60) months after delivery. The median duration for breast feeding is 4 months. No patient has performed MRI of the brain prior to conception. Two patients prefer to avoid pregnancy because they are concerning about the care of the incoming child
Conclusion(s):
This study reflects local practice protocol of women with MS during their pregnancy, addressing issues that are specific for women with MS. In order to make a good progress and to do better with women with MS, it is important to have guidance concerning prescribing decisions of DMTs in MS during all stages of family planning.
COVID-19 Vaccination in People with Multiple Sclerosis. the Kuwait Experience
1,2Raed Alroughani, 3,4Jasem Al-Hashel, 3Fathi Abokalawa, 4Malak Almojel, 3,5Samar Farouk Ahmed
1Amiri Hospital, Kuwait City, Kuwait; 2MS clinic, Ibn Sina Hospital, Kuwait City, Kuwait; 3Neurology Department, Ibn Sina hospital, Kuwait City, Kuwait; 4Kuwait University, Kuwait City, Kuwait; 5Minia University, Minia, Egypt
Background:
Two vaccine (BNT162b2 and ChAdOx1 nCoV-19) have been approved to be used in Kuwait since December 2021
Objective(s):
To assess the safety of the vaccination in MS patients and to determine the occurrence of relapses following COVID-19 vaccination in MS patients.
Material(s) and Method(s):
MS patients were contacted by phone, WhatsApp, or through face-to-face interview and were invited to complete a web-based questionnaire. Demographic, clinical, medications, administration of first and second vaccine doses, symptoms following vaccine, worsening of preexisting MS symptoms and occurrence of relapse were recorded.
Result(s):
482 MS patients answered the web-based questionnaire. Between January 2021 and 20 May 2021, 240 (49.8%) MS patients received at least one dose of the approved vaccination. Their mean age was 37.27 +8.95 and most of them 146 (60.8%) were females. 159 received first dose and 81 received the second dose. 126 revived BNT162b2 vaccine and 114 received ChAdOx1 nCoV-19 . There was one case of COVID-19 infection encountered after the first dose of BNT162b2 vaccine. Nine cases reported worsening of preexisting MS symptoms after vaccine. One patient reported relapse after first BNT162b2 vaccine dose. The most common adverse events of COVID-19 vaccine were pain at the injection site, fatigue, low grade fever and body ache. 28 Patients on anti CD20 needed to postpone vaccine or reschedule their medications.
Conclusion(s):
Both BNT162b2 and ChAdOx1 nCoV-19 are safe for MS patients. There is nNo increased risk of relapse activity or worsening of preexisting MS symptoms were recorded.
Incidence, Severity, Outcomes, and Risk Factors of COVID-19 in Multiple Sclerosis: An Observational Study in the Middle East
1Raed Alroughani, 2Jihad Said Inshasi, 3Jasem Al-Hashel, 4Jaber Alkhaboury, 4Abdullah Alsalti, 2Reem Al Suwaidi, 5Loqman H. Hassino, 6,7Samar Farouk Ahmed
1Division of Neurology, Department of Medicine, Amiri Hospital, Kuwait City, Kuwait; 2Neurology Department, Rashid Hospital and Dubai Medical College, Dubai, United Arab Emirates; 3Faculty of Medicine, Kuwait University, Kuwait City, Kuwait; 4Neurology Unit, College of Medicine and Health Sciences, Sultan Qaboos University and Sultan Qaboos University Hospital, Muscat, Oman; 5Neurology Unit, Department of Medicine Jahra Hospital, Jahra, Kuwait; 6Ibn Sina Hospital, Kuwait City, Kuwait; 7Faculty of Medicine, Minia university, Minia, Egypt
Objective(s):
To evaluate the incidence, severity, and outcomes of coronavirus disease (COVID-19) and to identify demographic and clinical risk factors in patients with multiple sclerosis (MS).
Material(s) and Method(s):
A cross-sectional hospital records-based study was conducted on MS patients from clinics in Oman, Kuwait, and the United Arab Emirates (UAE) between March 2020 and February 2021. Patients diagnosed with MS using the 2010 McDonald criteria or previously accepted diagnostic criteria and with a positive diagnosis of COVID-19 were included in the study. Association between patient demographics, disease characteristics, use of disease-modifying therapies, and outcome of COVID-19 illness was evaluated statistically using an odds ratio estimation.
Result(s):
A total of 134 MS patients with COVID-19 (overall incidence rate of 3.7%) were analyzed in the study (116 with relapsing-remitting MS [RRMS], 11 with progressive MS; and 7 with clinically isolated MS). The median age of patients was 35.5 years. Of the total cohort, 127 (94.8%) patients were on disease-modifying therapy (DMT). A majority of the patients (126 [94.0%]) had mild COVID 19 illness and 122 (91.0%) made a full recovery while 1 (0.7%) patient died. A total of 8 patients (6.0%) were hospitalized; 3 (2.2%) required intensive care, while 2 (1.5%) reported ventilator requirement. The mean EDSS scores reported in the study were low (1.74) with 127 (94.8%) reporting a score between 0 – 4.5. Univariate logistic regression analysis identified a high EDSS score and progressive MS disease as a risk factor for moderate to severe COVID-19 requiring hospitalization. Rituximab use and anti CD20 therapy were also associated with a statistically significant higher risk of developing moderate/severe COVID-19. The presence of comorbidities was associated with a higher risk of non-recovery from the viral infection in both univariate and multivariate analyses.
Conclusion(s):
COVID-19 showed an incidence rate of 3.7% in the studied cohort of MS patients. The disease course and outcomes were mostly favorable with most patients not requiring hospitalization. A higher EDSS score, progressive disease, use of rituximab, and use of antiCD20 therapy were associated with statistically significant increased risk of developing moderate/severe COVID-19, while the presence of comorbidities was associated with a higher risk of non-recovery from COVID-19. Age, sex, smoking history, and duration of MS were not independent risk factors for increased severity or adverse COVID-19 disease outcomes.
Challenges of MS Patients for Receiving Health Care Services
1Sharareh Eskandarieh, 1Niloofar Jahromi, 1Narges Systena, 1Mohhamed Ali Sahraian
1Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
Background:
Multiple sclerosis (MS) is a debilitating non-traumatic neurological disorder in young adults and can reduce quality of life (QoL) by interfering with work ability, leisure activities, and routine living tasks (1). Various studies have shown the dissatisfaction of people with MS in different areas of care services (1-2). Regarding the patient’s dissatisfaction with care services, in this study, we sought to identify the care challenges of MS patients in Iran.
Material(s) and Method(s):
The cross-sectional study was conducted in 2016-2019 through a researcher-made questionnaire (designed by MS Specialists in MS research center).
The questionnaire examined the care challenges in four areas:
- Costs of medication, hospitalization, and rehabilitation services
- Family support, insurance system and job protection
- Access to transportation system and treatment team
- Quality of care and provided services (2-3). The participants answered the challenges based on a five-point Likert scale.
Result(s):
Completed questionnaires were received for 945 respondents. Prioritizing care services challenges are as follows: The cost of pharmaceutical services (49.1%), lack of telephone counseling (47.4%), uninsured home rehabilitation (44.7%), lack of qualified care centers (41.2%), rehabilitation costs (40.2%). There is a significant correlation between the level of education and challenge of medication’s cost (p-value≤0.01), transportation systems (p-value≤0.01), and lack of familial support (p-value≤0.01).
Conclusion(s):
We found that patients who can’t walk at least 20 meters and Unemployed people had more problems and lower QoL. The patients who had non-academic education had more challenges with the cost of medication, transportation and lack of familial support.
This study shows Challenges of MS patients in receiving health care in Iran that vary in age, education, employment and ability to walk. As challenges mentioned above are of great importance in determining quality of life of people with MS, an appropriate solution is recommended by this study to overcome these challenges.
Familial MS in the South Caspian Sea
1Seyedmohammad Baghbanian, 1Hadis Alinejad, 2Sharareh Eskandarieh, 2Mohammadali Sahraian
1Mazandaran University Of Medical Sciences, Sari, Iran; 2Tehran University Of Medical Sciences, Tehran, Iran
Background/Objective(s):
Mazandaran is a Caspian province in the north of Iran and with a population of more than three million people. The Mazanderani people’s ancestors came from the Caucasus region, perhaps displacing an earlier group in the South Caspian1. Multiple sclerosis prevalence and incidence rates have increased in Mazandaran province in the past ten years2. There is limited data on familial M.S and the relationship between factors related to it.
Design and Method(s):
In this population-based cross-sectional study, MS patients (according to McDonald criteria) from Mazandaran province who have been registered in the Iranian national registry program3 from 20 March 2018 to 21 September 2020 were included. The aim of this study was to investigate the prevalence of the familial form of MS and to compare the level of disability of familial form with sporadic form.
Result(s):
Of 1750 patients included in this study, 261 (14.9%) cases had a family history of M.S. Age was significantly higher in the familial group (P-value = 0.02). Sibling relationship was the most common (46%). The patient’s sister was most likely to be involved in 46 (18.9%). In the familial group, 209(83.9%) cases had one affected family member, 33(13.3%) cases had two affected family members, and 7 (2.8%) cases had three or more affected family members. Of note, after first-degree relatives, 97(40%), maternal relatives 62(25%), and paternal relatives 47(19%) involvement were observed in the order of frequency. In our assessments, the risk of having a child with MS increases when three or more of the family members have MS. Our observations showed that the average disability rate of patients with a family history is higher than patients without a family history. (P-value<0.001).
Conclusion(s):
The prevalence of familial M.S in Mazandaran province can be considered as one of the highest reports of familial MS in Iran. It was more than that of the global familial M.S. rate (12.9%). One of the reasons for the higher prevalence of familial MS in this region may be the high probability of consanguineous marriage between these people4. However, differences in environmental factors cannot be ignored. Higher mean disability in familial MS compare to nonfamilial in this study may suggest that a potent drug is better to start at the beginning of treatment in patients with a positive family history.
Gender Based Epidemiologic Survey of Multiple Sclerosis Patients, a Report from Isfahan Province, Iran.
1Roshanak Mehdipour Dastjerdi, 1Fereshteh Ashtari
1Isfahan University of Medical Sciences, Isfahan, Iran; 2Isfahan Neurosciences Research Center, Isfahan, Iran
Background:
The knowledge about gender based different characteristics of multiple sclerosis (MS) is important to find new strategies for further managing and treatment. On the other hand patientˈs sex can be an important risk factor for incidence and also prognosis of multiple sclerosis.
Objective(s)
The aim of this epidemiologic study is to evaluate the gender based clinical and imaging differences among multiple sclerosis patients in Iran.
Material(s) and Method(s):
This is an epidemiological study done in Isfahan Kashani MS clinic as a referral MS center. Overall 1781 patients enrolled the survey with informed consent. The epidemiological questionnaire including 6 question areas (including patients demographics, Family history, MS diagnosis, course of disease, disability and complications, treatment) filled by neurologist for all patients. Pathological findings of the first brain MRI reported by a neuroradiologist in 500 cases (120 men vs 380 women).
Result(s):
75.9% were female with mean age of 36.66±9.94 years and the others (24.1%) were male patients with mean age of 36.60±10.40 years. The mean of disease duration and EDSS didn’t differ between genders. The age at disease onset was higher in men with 32.95 ±12.31 years (p: 0.009). Also smoking(cigarette and hookah) was more popular in male patients (p ˂0.001). The history of head trauma, type 2 diabetes, pulmonary disease, hypothyroidism and autoimmune disorders were more prevalent in female cases. Among signs of MS, both optic neuritis and motor disturbance were higher in female group. There was not any statistical differences between type of drugs. In the first brain MRI,infratentorial and thalamic lesions were more prevalent in men but early cortical atrophy and tumefactive lesions were reported more in women.
Conclusion(s):
The role of sex and genetic, beside to the environmental and acquired factors, is important in both incidence and prognosis of MS. Since there is not any specific diagnostic test for MS, considering gender based characteristics can be helpful in its diagnosis and management.
A Nationwide Pharmaco Epidemiological Study of Multiple Sclerosis in Greece
1Christos Bakirtzis, 1Marina – Kleopatra Boziki, 1Eleni Grigoriadou, 1Evangelia Kesidou, 1Ioannis Nikolaidis, 1Styliani-Aggeliki Sintila, 2Theodoros Moysiadis, 2Dimitra Tsakona, 3Georgios Papazisis, 1Nikolaos Grigoriadis
1Multiple Sclerosis Center, B’ Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece; 3Department of Clinical Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Greece
Background/Objective(s):
Besides Disease Modifying Therapies (DMTs), various pharmacologic agents (PAs) are frequently prescribed to people with multiple sclerosis (PwMS) for the treatment of MS related symptoms and other comorbid conditions. Pharmacoepidemiological data regarding the prescribed PAs in PwMS are scarce. With this study we aim to investigate the types and frequencies of the prescribed PAs to PwMS in Greece, using records of the nationwide digital prescription database.
Design and Method(s):
We have previously analyzed data from the nationwide digital prescription database, dating from June 1, 2017, to May 31, 2019, and identified 21,218 (13,994 or 65.8% females) MS cases, using the ICD-10 code for MS (G35). In this study, we further explored all prescribed PAs to the identified population during this 2-year period. Criterion for the PA identification was at least 3 months of continuous prescription of the agent. Since comorbid disease coding misclassifications may lead to inaccurate results, this analysis was performed on the basis of the active substances. The identified PAs were then classified into various categories according to the WHO Anatomical Therapeutic Chemical (ATC) classification system. Identified cases were further divided into 4 age groups (under 18, 18-39, 40-60, over 60) and we calculated the number and percentage of PwMS under treatment with each PA category.
Result(s):
Overall, 15,520 (73.1 %) PwMS were treated at least once with a DMT during this study period. The most frequently prescribed drugs for symptomatic treatment were anti-spasticity agents (n:3721, 17.5%), followed by fampridine (n:3092, 14.5%). Regarding treatment of comorbid conditions, antihypertensives (n:4483, 21.1%) and drugs for affective disorders such as antidepressants (n:7660, 36.1%) and anxiolytics (n:3444, 16.2%) were the most commonly prescribed PAs. Antiepileptics (n: 2936, 13.8%), anti-ulcers (n: 2919, 13.7%) and urinary antispasmodics (n: 2308, 10.8%) were also frequently prescribed as symptomatic treatment or for comorbid conditions. (table). As expected, with the exception of DMTs, the prescriptions of PAs in the <18 age group were uncommon, while the percentage of PwMS under treatment with all other PA categories, was increasing with age. Regarding prescriptions for comorbid conditions, 10,481 (49.4%) PwMS were not prescribed any PA, 4,455 (21%) were prescribed PAs of one category, 2,949 (13.9%) were prescribed PAs of two categories and 3,314 (15,6%) were prescribed PAs of 3 or more categories (figure).
Conclusion(s):
The present national level study highlights the frequent concomitant use of various PAs in PwMS. Comorbid conditions are commonly observed, especially in advancing age. Although PAs prescribed for the treatment of other medical conditions and for MS related symptoms, are expected to positively affect the quality of life of PwMS, future studies should further investigate their potential drug interactions with DMTs. In addition, the impact of polypharmacy to the disease course should also be further studied.
Prevalence of Urinary Tract Symptoms in Patients with Multiple Sclerosis and Health Care Seeking Behavior: A Cross Sectional Study in Riyadh, Saudi Arabia.
1A. Al Harbi, 1S.Al Mohaisen, 1A.Alotaibi, 1A.Alrumaih, 1I. Ali Alghamdi, 1G.Alghamdi, 1M. Almuhanna
1King Abdullah Bin Abdul-Aziz University Hospital, Riyadh, Saudi Arabia
Background:
Exploring the prevalence of lower urinary tract symptoms (LUTS) in multiple sclerosis (MS) patients may lead to optimizing therapeutic interventions that could improve their quality of life (QoL). The main objective of this study was to assess the prevalence of LUTS in patients with MS in Riyadh, Saudi Arabia.
Material(s) and Method(s):
This cross-sectional study targeted Saudi nationals aged 18-50 who were previously diagnosed with MS and presented with urinary tract dysfunction symptoms. It was conducted from November 2020 to January 2021 through the distribution of a self-administered electronic questionnaire.
Result(s):
Data were collected from 158 patients with MS. Most participants (44.3%) were between 30 and 39 years old, and 64.6% were female. The severity of LUTS is significantly associated with the QoL of patients, where an increase in severity of LUTS would worsen their QoL (p < 0.001). More than half of the sample (52.5%) indicated that they had taken treatment for these symptoms, 40.7% of whom reported using medicinal treatment. The duration of illness, age, or gender was found to have no significant effect on LUTS severity.
Conclusion(s):
We found that there is relatively high prevalence of lower urinary tract symptoms among patients with multiple sclerosis which seem to have a significant negative impact of quality of life of those patients. There is still need to have more patients reporting those symptoms to their health care provider as well as to be started on effective treatment strategies when appropriate.
Medication Adherence Among Patients with Multiple Sclerosis During the COVID-19 Pandemic: Perspective from the Near East Region
1Murad Al-Naqshbandi, 1Hoda Joudi, 1Abed Raki
1Merck Serono Middle East FZ-Ltd (an affiliate of Merck KGaA), Dubai, United Arab Emirates
Background/Objective(s):
Several factors rendered patients with multiple sclerosis (pwMS) likely to be affected by the rapidly evolving events of the COVID-19 pandemic. Globally, pwMS were confronted with limited access to their healthcare team, potential treatment interruption, and concerns about the risk of infection while treated with immunomodulatory disease-modifying therapies (DMTs), particularly high-efficacy DMTs [1,2]. The current study explored treatment-related concerns and their impact on medication adherence during the COVID-19 pandemic in pwMS treated with subcutaneous interferon beta-1a (sc IFN β-1a) in the Near East region.
Material(s) and Method(s):
A total of 3,348 pwMS treated with sc IFN β-1a across five countries of the Near East region (Iran, Iraq, Jordan, Lebanon, and Palestine) participated in a telephone survey. The survey was conducted by nurses, on behalf of the Merck Patient Support Program in the Near East region, from May 1–30, 2021. A standardized questionnaire allowed participants to report their concerns related to COVID-19 and their MS treatment, along with medication adherence over the previous 3 months. Concern with current MS treatment was rated on a scale of 1–10, with levels 1–3 reflecting a low level of concern, levels 4–7 reflecting a moderate level of concern, and levels 8–10 reflecting a high level of concern. Adherence to sc IFN β-1a was defined as administration of the prescribed three weekly injections.
Result(s):
Amongst the countries surveyed, a total of 3,074 participants (92%) reported being concerned about sc IFN β-1a increasing their risk of COVID-19 infection. However, a majority of participants from Iraq (94%), Palestine (88%), Jordan (84%), and Iran (84%) reported a low level of concern (Figure 1). More participants from Lebanon reported high (51%) and moderate (38%) levels of concern about their MS treatment and the risk of COVID-19 infection. Full adherence to sc IFN β-1a over the previous 3 months was reported by 3,293 (98%) participants (Figure 2). Key factors influencing medication adherence included the lack of access to sc IFN β-1a, physician supervision, and adverse events.
Conclusion(s):
This study explored the impact of treatment-related concerns on medication adherence in pwMS treated with sc IFN β-1a during the COVID-19 pandemic in the Near East. Despite a large proportion of study participants being concerned about a potential increase in the risk of COVID-19 infection while on their current treatment, participants were only mildly concerned and the majority remained adherent to the prescribed medication. Furthermore, the fear of COVID-19 infection by participants was not a key factor associated with non-adherence. Instead, limited access to medication and decisions of supervising physicians negatively impacted medication adherence. More than a year after the World Health Organization declared the COVID-19 outbreak a pandemic, safety concerns related to DMTs still exist. Interferons can be prescribed as usual in COVID-19 times [3], and this should be communicated effectively to clinicians and patients.
Inform Interferon Beta Exposure in the 2nd and 3rd Trimester of Pregnancy: A Register-Based Drug Utilisation Study in Finland and Sweden
1Meritxell Sabidó Espin, 2Kiliana Suzart-Woischnik, 3Nydjie Grimes, 4Lisa M Prach, 5Liwei Zhao, 5Katja M Hakkarainen
1Merck Healthcare KGaA, Darmstadt, Germany; 2Bayer AG, Berlin, Germany; 3Biogen Netherlands B.V., Badhoevedorp, Netherlands; 4Novartis Pharma AG, Basel, Switzerland; 5Global Database Studies (GloDaSt), Gothenburg, Sweden
Background/Objective(s):
Previous studies showed no increased risk of interferon beta use before or early in pregnancy among women with multiple sclerosis (MS). However, knowledge about the utilisation and safety of interferon beta in later-stage pregnancy remains limited. This study aims to determine (1) the number of pregnancies in women with MS exposed to interferon beta in later-stage pregnancy (i.e. the second and third trimesters) in Finland and Sweden; (2) whether the number of pregnancies available in Finland and Sweden is adequate for a cohort study to assess the outcomes of interferon beta exposure in later-stage pregnancy.
Material(s) and Method(s):
This observational drug utilisation study, using national register data in Finland (1996–2022) and Sweden (2005–2022), will report the number of pregnancies in women with MS (1) exposed to interferon beta only in later-stage pregnancy and (2) unexposed to any MS disease-modifying drugs. The 95% confidence intervals (Cls) of detectable relative risks (RR) for pre-defined adverse pregnancy outcomes are calculated for study size simulation. Based on the available background prevalence among the unexposed (Pbackground) and assuming 4% of all pregnancies are exposed, 100 exposed pregnancies are expected to be sufficient to detect all anomalies, spontaneous abortions, elective terminations (RR=2.00 [95%CI 1.40–2.89]; Pbackground 12.0%); preterm birth (RR=2.00 [95%CI 1.28–3.18]; Pbackground 8.3%); low birth weight (RR=2.00, [95%CI 1.03–4.05]; Pbackground 4.0%); major congenital anomalies (RR=2.50, [95%CI 1.32–4.92]; Pbackground 3.5%); and small for gestational age (RR=2.50 [95%CI 1.08-6.29]; Pbackground 2.0%).
Result(s):
One hundred exposed later-stage pregnancies are considered the minimum number for a cohort study on the adverse pregnancy outcomes. First results of this drug utilisation study will be reported in 2024. In case of inadequate number of pregnancies, the drug utilisation study will be extended for 2 years.
Conclusion(s):
This drug utilisation study (EUPAS38736) will evaluate whether the accrued number of exposed pregnancies is adequate for a cohort study to evaluate the safety of interferon beta exposure in later-stage pregnancy among women with MS.
Sociodemographic Characteristics of Patients with Multiple Sclerosis Disease in Morocco.
1Rachid Lotfi, 1Fatiha Chigr, 1Mohamed Najimi
1Faculty of Sciences and Techniques, Beni Mellal, Morocco
Objective(s):
To analyze the socio-demographic characteristics of patients with multiple sclerosis disease in Morocco.
Material(s) and Method(s):
This study concerned a sample made up of 420 patients or 6% of the total population estimated by “Atlas of MS”, representing 7 regions of Morocco. In this descriptive study, we used the following methods: a survey through an anonymous questionnaire intended and distributed individually to patients, the collection of data through the admission registers at the level of public hospitals and the study of the files of patients who had a consultation with neurologists or had been hospitalized.
Result(s):
The obtained results, show that, patients with multiple sclerosis are characterized by female dominance (69.8%). In addition, this study showed that patients with this disease are generally young: their average age is 36.33 years. In addition, almost all of the patients (over 92%) are made up of age groups between 18 and 53 years old. Furthemore the results show that nearly 68.2% of the patients surveyed have a university level and more than half (55%) are single.
Finally, the results of this survey also show that nearly 80% of patients are unemployed, more than 77% have no medical coverage and 69% of the patients surveyed live without treatment. Regarding the date of diagnosis of the disease in these patients, it was between 1991 and 2021. However, almost of them (85%) were diagnosed between 2016 and 2021.
Conclusion(s):
To conclude, we point out that we are in the process of completing this research by studying the other characteristics of this disease in Morocco, namely: the clinical and therapeutic characteristics, the risk factors linked to this disease, the quality of life of patients with this disease and the knowledge of health personnel in Morocco on this patholology.
Telemedicine and Multiple Sclerosis Management in the Era of COVID-19, Al-Azhar Experience
1Ahmed Essmat
1Al Azhar University, Cairo, Egypt
Background:
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a challenge for all participants in the healthcare system. At the beginning of the pandemic, many doctors asked themselves how to manage patients with multiple sclerosis(MS).we had followed 87 patient with MS(Al- azhar university MS clinic, cairo,Egypt). With regard to the different disease types and different disease modifying therapies (DMTs),many patients were fear from coming to hospitals and clinics to avoid catching infection. We did follow up through mobile calls, including video calls,to help our patient and encourage telemedicine phenomenon. When looking at the severe and fatal cases, we managed them by cell phones calls and described treatment, it is reasonable to assume that this maneuver could be protective and helpful to MS patients.
Material(s) and Method(s):
At the beginning of the pandemic, many doctors asked themselves how to manage patients with multiple sclerosis(MS).we had followed 87 patient with MS(Al- azhar university MS clinic, cairo,Egypt). With regard to the different disease types and different disease modifying therapies (DMTs),many patients were fear from coming to hospitals and clinics to avoid catching infection
Result(s):
We managed MS patients by cell phones calls and described treatment, it is reasonable to assume that this maneuver could be protective and helpful to MS patients.
Conclusion(s):
MS patients could be easily managed during the era of COVID-19
Initial Clinical and Neuroradiological Features at Presentation of Patients with Multiple Sclerosis: A Hospital-Based Experience from Oman
2Abdullah Al-Asmi, 1Salma Al-Abri, 2Arunodaya R. Gujjar, 2Ahmed Al-Qassabi, 2Haifa Al-Abri
1Internal Medicine Residency Program, Oman Medical Specialty Board (OMSB), Muscat, Oman; 2Neurology Division, Medicine Department, College of Medicine and Health Sciences and Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman
Background/Objective(s):
Multiple sclerosis (MS) is an immune mediated central nervous system demyelinating disorder with a varying disease course, resulting in different degrees of physical disability for affected patients. The current study aimed to present the initial clinical and radiological features of Omani MS patients presenting to a tertiary care center in Oman.
Material(s) and Method(s):
This is a retrospective study where MS patients diagnosed according to McDonald’s diagnostic criteria who attended neurology clinic of Sultan Qaboos University Hospital, Muscat, Oman between 2006 and 2020 were included in the study. Data were collected from the patients’ electronic medical records, including sociodemographic, clinical, neuroimaging, and initial treatment given. The initial disability status of the patients was assessed using the Expanded Disability Status Scale (EDSS).
Result(s):
A total of 155 patients were included with a 2:1 female to male ratio. The mean age at diagnosis was 28.57 ± 7.94 years. The mean duration of symptoms to diagnosis was 1.86 years. MS patients experience a median of 2 relapses (1-7) prior to their first visit to our hospital. Most patients (97.4%) were diagnosed with relapsing-remitting MS (RMS). 84.5% of patients presented with unifocal symptoms. The most common initial symptoms were referred to supratentorial region (34.2%) followed by the optic pathway (33.5%). 94.8% of the patients had EDSS of less than 3.5 by the time they presented to our hospital. Initial brain magnetic resonance (MRI) and cervical MRI were available for analysis in 72 (46.5%) and 47 (30.3%) patients, respectively. For the available MRI brain, 40% had ≥ 20 T2 lesions, while 36.1% had infratentorial lesions. For the available cervical spinal cord MRI, 23.9% had lesions at presentation. The most frequent initial disease-modifying therapy (DMT) used were the injectables (n = 104; 67%), followed by fingolimod (n = 16; 10.3%), Natalizumab (n = 16; 9%) and dimethyl fumarate (n = 4; 2.6%).
Conclusion(s):
The most common initial clinical presentation of Omani MS patients in our center was unifocal symptoms related to the supratentorial lesions. Further studies are needed to include all Oman MS patients from other centers to confirm our findings further.
Demographic and Clinical Characteristics of Patients with Benign MS in Compare with Non-Benign MS
1Nahid Beladi Moghadam, 1Mahran Ghaffari, 2Saba Sadeghi Rashed, 1Tannaz Fazli, 1Omid Hesami
1Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Islamic Azad University Central Tehran Branch, Tehran, Iran
Introduction:
Patients with benign multiple sclerosis (BMS) represent 10–20% of patients with MS, and are characterized by accumulation of modest or no disability over a long period of time. There is currently no generally accepted definition of BMS but most definitions are based on EDSS in connection with disease duration, i.e. EDSS ≤3.0 after 15 years’ disease duration. The aim of this study was to determine the demographic and clinical characteristics of patients with benign MS (BMS) and compare them with non-benign MS (non-BMS) patients over the same period.
Material(s) and Method(s):
Among the 160 patients admitted to the study, 50 were BMS patients and 110 were non-BMS patients. All patients underwent clinical examination and data was gathered on age, sex, marital, educational, and job status as demographic features and clinical features as well as MRI findings and disease-modifying therapies (DMTs).
Result(s):
The majority of patients in both groups were female (P=0.794) in the age range of 20-40 years (P=0.206) with no significant difference. No significant difference was observed in demographic features between the two groups but in educational and job status. In the BMS group, the frequency of people with undergraduate and postgraduate was significantly higher (P <0.001) than non-BMS, as well as half of BMS, were employed while more than 80% of patients in the non-BMS group were either unemployed or housewives (P <0.001). On the other hand, there were no significant differences in clinical features. Optic neuritis had no significant difference (P = 0.056) in BMS group (38.8%) compared to the non-BMS group (23.8%). Also, there was no significant difference regarding the brainstem symptom at the beginning of the disease and the mean frequency of relapses in both groups was similar at different intervals and no significant difference was observed. About the extent of lesions in the first year in patients; callosal lesions were reported in 40% of BMS patients and 52.8% of non-BMS patients with no significant difference. About the onset time of DMT, there was a significant difference (P value <0.020) which in the BMS group was the first year (48% of patients) and in the non-benign group was four years and more.
Conclusion(s):
In our study, no significant difference was observed between the demographic except for educational and job status. No association was found between the presence of cervical lesions between BMS and non-BMS patients.
Impact of Gender on Multiple Sclerosis Natural History: Findings from a Tunisian Cohort
1,2Imen Kacem, 1,2Saloua Mrabet, 1,2Amira Souissi, 1,2Alya Gharbi, 1,2Lilia Hmissi, 1,2Firas Larnaout, 1,2Amina Gargouri, 1,2Riadh Gouider
1Razi University Hospital, Manouba, Tunisia; 2Faculty of medicine, University Tunis El Manar, Tunis, Tunisia
Background:
Multiple sclerosis (MS) is universally reported to be more prevalent in women than men. In Tunisia, gender ratio (women/men) has markedly increased in Tunisian patients with MS since the first reports of Ben Hmida in 1977. The effect of gender on MS prognosis, clinical profile and disability accrual have been reported to be critical. The aim of our study was to investigate the impact of gender on MS characteristics and disease progression in a Tunisian cohort.
Material(s) and Method(s):
A retrospective study was conducted in the department of Neurology of Razi hospital-Tunisia including patients diagnosed with MS according to 2017 McDonald criteria. Patients were compared according to gender on various aspects: MS phenotype (relapsing (RRMS), secondary progressive (SPMS) and primary progressive (PPMS)), first attack characteristics, presence of oligoclonal bands (OCBs), brain and spine MRI features and disability accrual evaluated by the MS severity score (MSSS) and the Progression index (PI).
Result(s):
A total of 504 patients were included: 359 females and 145 males (F/M=2.47). Female predominance was more pronounced during RRMS (n= 389; F/M=2.56) than during SPMS (n=70; F/M=2.88) and PPMS (n=45; F/M=1.5), but was not statistically significant (p=0.2). Gender did not influence first clinical attack symptoms regardless from MS phenotype (table1). However, in the RRMS group, gender was linked with the degree of recovery from the first relapse: partial recovery in 29.4% of males versus 15% of females (p=0.002). OCBs positivity and baseline MRI characteristics were also independent from gender. Males exhibited a higher disability accrual according to MSSS in the RRMS group (3.51 versus 2.79 for females; p=0.011), but not in the SPMS (7.64 versus 7.68; p=0.9) and PPMS groups (8.1 versus 7.42 for females; p=0.2). Females and males’ PI were comparable among the different groups: 0.32 versus 0.34 for RRMS (p=0.6), 0.5 versus 0.57 (p=0.4) for SPMS and 0.8 versus 0.5 (p=0.1).
Conclusion(s):
Our results highlighted an increased MS susceptibility among females and an increased rate of disability progression among males, in particular during RRMS. The phenotype of the first attack, OCBs positivity rates and MRI features were independent from gender. These findings were consistent with previously published data and supported that sex hormones might contribute to or modulate brain damage in MS.
The Effect of Seasonal Variation on Relapse Rate in Patients with Relapsing-Remitting Multiple Sclerosis in Saudi Arabia
1,2,3Seraj Makkawi, 1,2Razaz Felemban, 1Ammar Mohammed Aljabri, 1Ghassan Saeed Bin Lajdam, 1Ammar Abdulwadood Albakistani, 1Abdulrahman Ismail Aljohani, 1Suhail Ali Labban
1College of Medicine, King Saud Bin Abdulaziz University for Health Sciences; 2King Abdullah International Medical Research Center, Jeddah, Saudi Arabia; 3Department of Medicine, Ministry of the National Guard-Health Affairs, Jeddah, Saudi Arabia
Introduction:
Multiple sclerosis (MS) is becoming a global subject of study in which some demographic variations are thought to be correlated to its activity. Relapsing remitting multiple sclerosis (RRMS) is the most common demyelinating disorder characterized by periods of exacerbating attacks followed by partial or complete remission. Several factors might play a role in disease progression and relapse frequency such as vitamin D, ultraviolet B radiation, estrogen levels, smoking, obesity and unhealthy lifestyle. In this study, we identified the relationship between seasonal variation and the relapse rate as well as correlated the latter with gender, age, and vitamin D levels in patients with RRMS in Jeddah, Saudi Arabia.
Material(s) and Method(s):
This retrospective study was carried out in the neurological department at King Abdulaziz Medical City (KAMC), Jeddah. The data was collected from 182 patients with RRMS in the period between 2016 to 2021.
Result(s):
219 relapses in 106 (58.2%) patients were documented. The relapse per patient ratio showed a sinusoidal pattern which peaked in February with a rate of 0.76 and troughed in July with a rate of 0.2. There was no evidence of different relapse rates for males compared to females, X2 (1, N = 182) = 1.166a, p = .280. There was a significant negative correlation between vitamin D levels and relapse rate (r= -.312, p =.024).
Conclusion(s):
The relapse rate was higher during the winter months and correlated with low vitamin D levels. Large population-based studies are needed to understand the role of environmental variables in MS exacerbations in Saudi Arabia.
Demographic and Clinical Characteristics of Progressive Multiple Sclerosis: Findings from a Tunisian Cohort Study
1,2Saloua Mrabet, 1,2Imen Kacem, 1,2Amira Souissi, 1,2Alya Gharbi, 1,2Mohamed Ahmed Nour, 1,2Mouna Ben Djebara, 1,2Amina Gargouri, 1,2Riadh Gouider
1Department of Neurology, Clinical Investigation Centre Neurosciences and Mental Health, University Hospital Razi, Manouba, Tunisia; 2Faculty of medicine, University Tunis El Manar, Tunis, Tunisia
Background:
Multiple Sclerosis (MS) prevalence has increased substantially in Tunisia since the first reports of Ben Hmida in 1977. However, to date, data regarding progressive MS remains limited. Our objective is to describe the demographic and clinical characteristics of progressive MS in a Tunisian cohort.
Material(s) and Method(s):
A retrospective study was conducted in the department of Neurology of Razi hospital-Tunisia including patients diagnosed with primary progressive MS (PPMS) according to 2017 McDonald criteria and secondary progressive MS (SPMS) according to the definition of Lorscheider et al. Data regarding sex-ratio, age of disease onset, first clinical attack characteristics were described and compared between the two groups. Pediatric MS (PoMS) was considered if age of disease onset was below 18 years. Late onset MS (LoMS) was considered for patients whose age of disease onset was above 50 years. Disability progression was evaluated via the median time to reach Expanded disability status scale (EDSS) 4 and 6 and MS severity score (MSSS). A statistically significant difference was validated if p<0.05.
Result(s):
Of the consecutive records of 504 patients diagnosed with MS, 115 (22.8%) were found to be progressive: SPMS (n=70; 13.9%) and PPMS (n=45; 8.9%). Female predominance was more pronounced during SPMS (F/M=2.88) compared with PPMS (F/M=1.5) (p=0.1). MS age of onset was higher in the PPMS group (41 years ±10.7) compared to the SPMS group (28 years±8.4) (p=0.000), and was comparable between individuals from SPMS (40.4 years ±9.7) and PPMS (41 years ±10.7) groups, once the progressive phase was initiated (p=0.5). For SPMS, only one case with PoMS was identified (14 years) followed with a transition to the progressive phase after 22 years. Similarly, in PPMS, only one case with PoMS was noted (16 years). LoMS was described in one patient diagnosed with SPMS versus 11 patients classified as PPMS (p=0.000). During the first clinical attack, motor symptoms were more prevalent in the PPMS group (91.1% versus 58.5%; p=0.000), meanwhile visual symptoms were more frequently reported in the SPMS group (25.7% versus 6.6%; p=0.012). Median time to reach EDSS4 (SPMS=6 years; PPMS=7 years (p=0.7)) and EDSS 6 (SPMS=8.5 years; PPMS=7.5 years (p=0.7)) were comparable between the two groups. MSSS were also comparable between SPMS patients (7.67±1.7) and PPMS (7.87±1.87) (p=0.3).
Conclusion(s):
In our cohort, progressive MS prevalence, sex ratio and age at disease onset were consistent with previous studies. PoMS was not common during these two conditions, meanwhile, late onset MS was more frequent during PPMS. PPMS patients tend to be older with a mean age at onset of first symptoms after forties. Motor symptoms were more frequent during PPMS, which could be related to the higher prevalence of spinal cord lesions during this condition. SPMS was associated with a higher prevalence of visual symptoms, as onset optic neuritis is more common during the relapsing onset MS. SPMS and PPMS, regarding disability accumulation, are comparable. In fact, it was suggested that progressive MS do progress at the same rate, regardless of the events that led up to the onset of progression.