Pub Date : 2024-10-16DOI: 10.1016/j.msard.2024.105918
Somayeh Mehrlatifan, Razieh Yousefian Molla
Background
Multiple sclerosis (MS) is an autoimmune disease that can increase the risk of falls in patients due to various factors. Traditional clinical assessments may not effectively identify those at risk of falling.
Objective
This study aimed to use artificial intelligence and machine learning techniques to predict the likelihood of falls in patients with MS based on a review of previous research.
Methods
A systematic review was conducted following PRISMA guidelines, searching electronic databases from 1990 to 2024. Data extraction and quality assessment were carried out.
Results
Seven studies were analyzed, and it was determined that patient-reported outcomes (PROs) such as MSWS-12 and EMIQ performed better than other methods. Sensor-based systems such as GAITRite and Mobility Lab achieved high F1 scores. Random forest classifiers utilizing postural sway measures were effective in discriminating low-risk MS patients from healthy controls. Deep learning models, particularly BiLSTM architectures, outperformed traditional machine learning approaches in identifying recent fallers using wearable accelerometer data.
Conclusion
The findings highlight the potential of PROs, the promise of wearable sensors and deep learning, and the importance of optimizing data collection for effective fall risk assessment in the MS population.
{"title":"AI-assisted assessment of fall risk in multiple sclerosis: A systematic literature review","authors":"Somayeh Mehrlatifan, Razieh Yousefian Molla","doi":"10.1016/j.msard.2024.105918","DOIUrl":"10.1016/j.msard.2024.105918","url":null,"abstract":"<div><h3>Background</h3><div>Multiple sclerosis (MS) is an autoimmune disease that can increase the risk of falls in patients due to various factors. Traditional clinical assessments may not effectively identify those at risk of falling.</div></div><div><h3>Objective</h3><div>This study aimed to use artificial intelligence and machine learning techniques to predict the likelihood of falls in patients with MS based on a review of previous research.</div></div><div><h3>Methods</h3><div>A systematic review was conducted following PRISMA guidelines, searching electronic databases from 1990 to 2024. Data extraction and quality assessment were carried out.</div></div><div><h3>Results</h3><div>Seven studies were analyzed, and it was determined that patient-reported outcomes (PROs) such as MSWS-12 and EMIQ performed better than other methods. Sensor-based systems such as GAITRite and Mobility Lab achieved high F1 scores. Random forest classifiers utilizing postural sway measures were effective in discriminating low-risk MS patients from healthy controls. Deep learning models, particularly BiLSTM architectures, outperformed traditional machine learning approaches in identifying recent fallers using wearable accelerometer data.</div></div><div><h3>Conclusion</h3><div>The findings highlight the potential of PROs, the promise of wearable sensors and deep learning, and the importance of optimizing data collection for effective fall risk assessment in the MS population.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"92 ","pages":"Article 105918"},"PeriodicalIF":2.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Multiple sclerosis (MS) remains a challenging neurological condition for diagnosis and management and is often detected in late stages, delaying treatment. Artificial intelligence (AI) is emerging as a promising approach to extracting MS information when applied to different patient datasets. Given the critical role of metabolites in MS profiling, metabolomics data may be an ideal platform for the application of AI to predict disease. In the present study, a machine-learning (ML) approach was used for a detailed analysis of metabolite profiles and related pathways in patients with MS and healthy controls (HC). This approach identified unique alterations in biochemical metabolites and their correlation with disease severity parameters. To enhance the efficiency of using metabolic profiles to determine disease severity or the presence of MS, we trained an AI model on a large volume of blood-based metabolomics datasets. We constructed this model using an artificial neural network (ANN) architecture with perceptrons. Data were divided into training, validation, and testing sets to determine model accuracy. After training, accuracy reached 87 %, sensitivity was 82.5 %, specificity was 89 %, and precision was 77.3 %. Thus, the developed model seems highly robust, generalizable with a wide scope and can handle large amounts of data, which could potentially assist neurologists. However, a large multicenter cohort study is necessary for further validation of large-scale datasets to allow the integration of AI in clinical settings for accurate diagnosis and improved MS management.
{"title":"Artificial neural network-based prediction of multiple sclerosis using blood-based metabolomics data","authors":"Nasar Ata , Insha Zahoor , Nasrul Hoda , Syed Mohammed Adnan , Senthilkumar Vijayakumar , Filious Louis , Laila Poisson , Ramandeep Rattan , Nitesh Kumar , Mirela Cerghet , Shailendra Giri","doi":"10.1016/j.msard.2024.105942","DOIUrl":"10.1016/j.msard.2024.105942","url":null,"abstract":"<div><div>Multiple sclerosis (MS) remains a challenging neurological condition for diagnosis and management and is often detected in late stages, delaying treatment. Artificial intelligence (AI) is emerging as a promising approach to extracting MS information when applied to different patient datasets. Given the critical role of metabolites in MS profiling, metabolomics data may be an ideal platform for the application of AI to predict disease. In the present study, a machine-learning (ML) approach was used for a detailed analysis of metabolite profiles and related pathways in patients with MS and healthy controls (HC). This approach identified unique alterations in biochemical metabolites and their correlation with disease severity parameters. To enhance the efficiency of using metabolic profiles to determine disease severity or the presence of MS, we trained an AI model on a large volume of blood-based metabolomics datasets. We constructed this model using an artificial neural network (ANN) architecture with perceptrons. Data were divided into training, validation, and testing sets to determine model accuracy. After training, accuracy reached 87 %, sensitivity was 82.5 %, specificity was 89 %, and precision was 77.3 %. Thus, the developed model seems highly robust, generalizable with a wide scope and can handle large amounts of data, which could potentially assist neurologists. However, a large multicenter cohort study is necessary for further validation of large-scale datasets to allow the integration of AI in clinical settings for accurate diagnosis and improved MS management.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"92 ","pages":"Article 105942"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1016/j.msard.2024.105944
Liding Fan , Yunfei Zhang , Shuo Huang , Jie Chen , Junying Wang , Furen Meng , Jiarui Zhang , Qingjie Xue
Objective
This study was to evaluate the effectiveness of stem cell therapies (AHSCT: autologous hematopoietic stem cell transplantation and MSCs: mesenchymal stem cells) compared to non-stem cell therapies in multiple sclerosis (MS) patients.
Design
Clinical trials to investigate the therapeutic effects of stem cells therapy was searched by PubMed, Embase, Web of Science, and the Cochrane Library. The Cochrane Risk of Bias Assessment Tool and data analysis software will be applied.
Results
Data were collected between the earliest available date and August 2023. Ten studies were included, with a sample size of 5288 used in the studies. Results showed that human umbilical cord-derived mesenchymal stem cells reduced the Annualized Relapse Rate (SUCRA: 70.9 %) and Expanded Disability Status Scale (SUCRA: 77.1 %) of MS patients, AHSCT reduced mortality rate (SUCRA: 69.8 %), autologous peripheral blood stem cell transplantation (APBSCT) reduced recurrence rate (SUCRA: 86.7 %) and improved No Evidence of Disease Activity-3 (SUCRA: 92.8 %).
Conclusion
At present, AHSCT and MSCs have been demonstrated to reduce the recurrence rate of multiple sclerosis and improve disability, particularly in the case of hUC-MSCs. However, APBSCT and AHSCT in the context of the NEDA-3 criteria have not yielded the desired outcomes.
{"title":"Effects of multiple treatments with stem cell therapy in patients with multiple sclerosis","authors":"Liding Fan , Yunfei Zhang , Shuo Huang , Jie Chen , Junying Wang , Furen Meng , Jiarui Zhang , Qingjie Xue","doi":"10.1016/j.msard.2024.105944","DOIUrl":"10.1016/j.msard.2024.105944","url":null,"abstract":"<div><h3>Objective</h3><div>This study was to evaluate the effectiveness of stem cell therapies (AHSCT: autologous hematopoietic stem cell transplantation and MSCs: mesenchymal stem cells) compared to non-stem cell therapies in multiple sclerosis (MS) patients.</div></div><div><h3>Design</h3><div>Clinical trials to investigate the therapeutic effects of stem cells therapy was searched by PubMed, Embase, Web of Science, and the Cochrane Library. The Cochrane Risk of Bias Assessment Tool and data analysis software will be applied.</div></div><div><h3>Results</h3><div>Data were collected between the earliest available date and August 2023. Ten studies were included, with a sample size of 5288 used in the studies. Results showed that human umbilical cord-derived mesenchymal stem cells reduced the Annualized Relapse Rate (SUCRA: 70.9 %) and Expanded Disability Status Scale (SUCRA: 77.1 %) of MS patients, AHSCT reduced mortality rate (SUCRA: 69.8 %), autologous peripheral blood stem cell transplantation (APBSCT) reduced recurrence rate (SUCRA: 86.7 %) and improved No Evidence of Disease Activity-3 (SUCRA: 92.8 %).</div></div><div><h3>Conclusion</h3><div>At present, AHSCT and MSCs have been demonstrated to reduce the recurrence rate of multiple sclerosis and improve disability, particularly in the case of hUC-MSCs. However, APBSCT and AHSCT in the context of the NEDA-3 criteria have not yielded the desired outcomes.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"92 ","pages":"Article 105944"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stigma in multiple sclerosis (MS) refers to the negative attitudes, beliefs, and behaviors that patients may encounter as a result of their diagnosis. Patients who hold stigmatizing beliefs are more prone to experiencing anxiety and depression, social isolation, and poor treatment adherence. To mitigate the adverse effects of stigma, it is crucial to assess stigmatizing beliefs; however, there is currently no specific stigma scale available for MS.
Objective
The aim of this study was to develop and validate “Multiple Sclerosis Stigma Scale (MSSS)”.
Methods
This methodological study was conducted in three phases. In the first phase, the concept of stigma in MS was defined. In the second phase, an item pool was generated based on the findings from the first phase. In the third phase, psychometric properties of the scale were evaluated, including face and content validity, construct validity, convergent validity and reliability.
Results
After evaluating the validity (face, content, and construct validity) and reliability, the initial item pool of 276 items was reduced to 12 items. Factor analysis revealed two factors: discrimination and disclosure. The developed questionnaire had excellent reliability, with an internal consistency coefficient of 0.88 and a stability coefficient of 0.87.
Conclusion
The 12-item MSSS is valid and reliable for assessing the level of stigma in Turkish people with MS.
{"title":"Development, validity and reliability of the “Multiple sclerosis stigma scale”","authors":"Hande Sariahmetoglu , Feray Gungor , Zeynep Ezgi Kurtpinar , Devrimsel Harika Ertem , Mesrure Koseoglu , Rabia Gokcen Gozubatik Celik , Burcu Yuksel , Aysun Soysal","doi":"10.1016/j.msard.2024.105945","DOIUrl":"10.1016/j.msard.2024.105945","url":null,"abstract":"<div><h3>Background</h3><div>Stigma in multiple sclerosis (MS) refers to the negative attitudes, beliefs, and behaviors that patients may encounter as a result of their diagnosis. Patients who hold stigmatizing beliefs are more prone to experiencing anxiety and depression, social isolation, and poor treatment adherence. To mitigate the adverse effects of stigma, it is crucial to assess stigmatizing beliefs; however, there is currently no specific stigma scale available for MS.</div></div><div><h3>Objective</h3><div>The aim of this study was to develop and validate “Multiple Sclerosis Stigma Scale (MSSS)”.</div></div><div><h3>Methods</h3><div>This methodological study was conducted in three phases. In the first phase, the concept of stigma in MS was defined. In the second phase, an item pool was generated based on the findings from the first phase. In the third phase, psychometric properties of the scale were evaluated, including face and content validity, construct validity, convergent validity and reliability.</div></div><div><h3>Results</h3><div>After evaluating the validity (face, content, and construct validity) and reliability, the initial item pool of 276 items was reduced to 12 items. Factor analysis revealed two factors: discrimination and disclosure. The developed questionnaire had excellent reliability, with an internal consistency coefficient of 0.88 and a stability coefficient of 0.87.</div></div><div><h3>Conclusion</h3><div>The 12-item MSSS is valid and reliable for assessing the level of stigma in Turkish people with MS.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"92 ","pages":"Article 105945"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1016/j.msard.2024.105941
N Kosior , RL Perrier , C Casserly , SA Morrow , JM Racosta
<div><h3>Background</h3><div>Anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD) and neuromyelitis optica spectrum disease (NMOSD) are antibody mediated diseases characterized by neurological symptoms including recurrent relapses of optic neuritis and/or myelitis, as well as other less frequent syndromes. The current treatment for acute attacks of NMOSD/MOGAD are based on clinical studies for other demyelinating diseases(i.e. Multiple Sclerosis). In NMOSD, high dose corticosteroids (HDS) are considered the standard first line therapy, with emerging evidence supporting the use of plasmapheresis (PLEX) as an acute therapy. In MOGAD, being a relatively new clinical syndrome, the consensus on acute treatments is yet to be reached. The objective of our study was to assess the efficacy of treatment regimens (no treatment vs. HDS vs. HDS and PLEX) on disability outcomes in persons with NMOSD and MOGAD-optic neuritis and myelitis.</div></div><div><h3>Methods</h3><div>We retrospectively extracted data from the MuSicaL-NeMo database using a mixed Natural Language Processing followed by investigators verification. We assessed the change in Expanded Disability Status Scale (EDSS) and Visual Acuity (VA) following HDS and PLEX, in persons with MOGAD and NMOSD following myelitis and optic neuritis. We used the novel statistical measure Wilcoxon-Mann-Whitney Odd (WMW-Odd) to calculate the change through all the spectrum of each ordinal scale (VA and EDSS).</div></div><div><h3>Results</h3><div>Eleven myelitis and 12 optic neuritis in 22 persons with MOGAD and 30 myelitis and 12 optic neuritis in 20 persons with NMOSD were included(15 Aquaporin-4 seropositive). In persons with MOGAD-optic neuritis the group receiving HDS had a WMW-Odd of 15.33(<em>p</em> ≤ 0.001), however those not receiving treatment also tended to improve (WMW-Odd=3.17, <em>p</em> = 0.06). NMOSD-optic neuritis treated with HDS only improve 33.3 % of the times (<em>p</em>=NS). Persons with MOGAD-myelitis receiving HDS significantly improved (WMW-Odd=7.33, <em>p</em> = 0.002). Persons with NMOSD-myelitis treated with HDS had an WMW-Odd of 2.56 (<em>p</em> = 0.002) and those treated with PLEX plus HDS (PLEX+), had similar WMW-Odd of 2.51 (<em>p</em> = 0.03). When correcting for disease severity by restricting inclusion to persons with NMOSD with EDSS≥4, both treatments showed a higher WMW-Odd, however the group receiving HDS continued to show higher WMW-Odd than the PLEX+ group(WMW-Odd= 3.75, <em>p</em> = 0.002 vs. WMW-Odd =3.05, <em>p</em> = 0.02, respectvely)</div></div><div><h3>Conclusion</h3><div>Our study suggests that persons with MOGAD-optic neuritis improve without acute treatments, however they have very marked improvement when using HDS, as previously suggested. Patient with MOGAD-myelitis are also very responsive to HDS, however, as compared to MOGAD-optic neuritis, they displayed less improvement, if not treated. In the NMOSD group the use of PLEX in addition to HDS did
{"title":"New insights into the use of high dose corticosteroids and plasmapheresis in persons with MOGAD and NMOSD","authors":"N Kosior , RL Perrier , C Casserly , SA Morrow , JM Racosta","doi":"10.1016/j.msard.2024.105941","DOIUrl":"10.1016/j.msard.2024.105941","url":null,"abstract":"<div><h3>Background</h3><div>Anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD) and neuromyelitis optica spectrum disease (NMOSD) are antibody mediated diseases characterized by neurological symptoms including recurrent relapses of optic neuritis and/or myelitis, as well as other less frequent syndromes. The current treatment for acute attacks of NMOSD/MOGAD are based on clinical studies for other demyelinating diseases(i.e. Multiple Sclerosis). In NMOSD, high dose corticosteroids (HDS) are considered the standard first line therapy, with emerging evidence supporting the use of plasmapheresis (PLEX) as an acute therapy. In MOGAD, being a relatively new clinical syndrome, the consensus on acute treatments is yet to be reached. The objective of our study was to assess the efficacy of treatment regimens (no treatment vs. HDS vs. HDS and PLEX) on disability outcomes in persons with NMOSD and MOGAD-optic neuritis and myelitis.</div></div><div><h3>Methods</h3><div>We retrospectively extracted data from the MuSicaL-NeMo database using a mixed Natural Language Processing followed by investigators verification. We assessed the change in Expanded Disability Status Scale (EDSS) and Visual Acuity (VA) following HDS and PLEX, in persons with MOGAD and NMOSD following myelitis and optic neuritis. We used the novel statistical measure Wilcoxon-Mann-Whitney Odd (WMW-Odd) to calculate the change through all the spectrum of each ordinal scale (VA and EDSS).</div></div><div><h3>Results</h3><div>Eleven myelitis and 12 optic neuritis in 22 persons with MOGAD and 30 myelitis and 12 optic neuritis in 20 persons with NMOSD were included(15 Aquaporin-4 seropositive). In persons with MOGAD-optic neuritis the group receiving HDS had a WMW-Odd of 15.33(<em>p</em> ≤ 0.001), however those not receiving treatment also tended to improve (WMW-Odd=3.17, <em>p</em> = 0.06). NMOSD-optic neuritis treated with HDS only improve 33.3 % of the times (<em>p</em>=NS). Persons with MOGAD-myelitis receiving HDS significantly improved (WMW-Odd=7.33, <em>p</em> = 0.002). Persons with NMOSD-myelitis treated with HDS had an WMW-Odd of 2.56 (<em>p</em> = 0.002) and those treated with PLEX plus HDS (PLEX+), had similar WMW-Odd of 2.51 (<em>p</em> = 0.03). When correcting for disease severity by restricting inclusion to persons with NMOSD with EDSS≥4, both treatments showed a higher WMW-Odd, however the group receiving HDS continued to show higher WMW-Odd than the PLEX+ group(WMW-Odd= 3.75, <em>p</em> = 0.002 vs. WMW-Odd =3.05, <em>p</em> = 0.02, respectvely)</div></div><div><h3>Conclusion</h3><div>Our study suggests that persons with MOGAD-optic neuritis improve without acute treatments, however they have very marked improvement when using HDS, as previously suggested. Patient with MOGAD-myelitis are also very responsive to HDS, however, as compared to MOGAD-optic neuritis, they displayed less improvement, if not treated. In the NMOSD group the use of PLEX in addition to HDS did ","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"92 ","pages":"Article 105941"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1016/j.msard.2024.105939
Meral Seferoğlu , Abdulkadir Tunç , Ali Özhan Sıvacı , Gülnur Tekgöl Uzuner , Semra Mungan , Yılmaz İnanç , M. Fatih Yetkin , Bilgin Öztürk , Emine Rabia Koç , Şule Aydın Türkoğlu , Selma Aksoy , Şükran Yurtoğulları , Ömer Elçi
Background
Ocrelizumab (OCR) effectively modifies the disease course in multiple sclerosis (MS) patients but may cause a preinfusion "wearing-off phenomenon" (WoP). This study explored the prevalence, timing, and severity of this phenomenon in MS patients using the OCR, as well as the associated symptoms and treatment satisfaction.
Methods
We conducted a prospective multicenter study across 11 MS centers involving MS patients aged 18-70 years who had received at least two OCR doses. The study employed a questionnaire addressing demographic, clinical, and radiological data; symptom progression; and treatment satisfaction.
Results
Of the 409 patients included in the study, 406 participated. A significant portion experienced varying degrees of WoP: 39.2% sometimes, 25.9% usually, and 14.3% always, with 55.9% noting symptom onset over four weeks prior to their next dose. Common symptoms included fatigue, walking difficulties, and pain. Subgroup analysis of 334 patients revealed that 78.1% of patients experienced these effects, which correlated with shorter disease durations, a longer delay between the two doses before the last dose, and a greater rate of relapse (P>0.05).
Conclusion
The WoP of the OCR is prevalent and significant among MS patients and is influenced by the dosing interval, disease duration, and relapse rate. These insights underscore the need for personalized treatment schedules and more research into factors affecting MS management.
{"title":"Exploring the impact of wearing-off phenomenon in ocrelizumab-treated multiple sclerosis patients: Insights from a comprehensive study","authors":"Meral Seferoğlu , Abdulkadir Tunç , Ali Özhan Sıvacı , Gülnur Tekgöl Uzuner , Semra Mungan , Yılmaz İnanç , M. Fatih Yetkin , Bilgin Öztürk , Emine Rabia Koç , Şule Aydın Türkoğlu , Selma Aksoy , Şükran Yurtoğulları , Ömer Elçi","doi":"10.1016/j.msard.2024.105939","DOIUrl":"10.1016/j.msard.2024.105939","url":null,"abstract":"<div><h3>Background</h3><div>Ocrelizumab (OCR) effectively modifies the disease course in multiple sclerosis (MS) patients but may cause a preinfusion \"wearing-off phenomenon\" (WoP). This study explored the prevalence, timing, and severity of this phenomenon in MS patients using the OCR, as well as the associated symptoms and treatment satisfaction.</div></div><div><h3>Methods</h3><div>We conducted a prospective multicenter study across 11 MS centers involving MS patients aged 18-70 years who had received at least two OCR doses. The study employed a questionnaire addressing demographic, clinical, and radiological data; symptom progression; and treatment satisfaction.</div></div><div><h3>Results</h3><div>Of the 409 patients included in the study, 406 participated. A significant portion experienced varying degrees of WoP: 39.2% sometimes, 25.9% usually, and 14.3% always, with 55.9% noting symptom onset over four weeks prior to their next dose. Common symptoms included fatigue, walking difficulties, and pain. Subgroup analysis of 334 patients revealed that 78.1% of patients experienced these effects, which correlated with shorter disease durations, a longer delay between the two doses before the last dose, and a greater rate of relapse (P>0.05).</div></div><div><h3>Conclusion</h3><div>The WoP of the OCR is prevalent and significant among MS patients and is influenced by the dosing interval, disease duration, and relapse rate. These insights underscore the need for personalized treatment schedules and more research into factors affecting MS management.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"92 ","pages":"Article 105939"},"PeriodicalIF":2.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1016/j.msard.2024.105926
Ines El Naggar , Robert Cleaveland , Andreas Panzer , Sandy Molenaar , Laetitia Giorgi , Eva-Maria Wendel , Annikki Bertolini , Michael Karenfort , Charlotte Thiels , Zuzana Libá , Matthias Baumann , Steffen Leiz , Adela Della Marina , Jan G. Hengstler , Kumaran Deiva , Rinze Neuteboom , Markus Reindl , Kevin Rostásy , BIOMARKER study group
Background
We recently described magnetic resonance imaging (MRI) features of children with transverse myelitis (TM) at first event with important and unique differences depending on the underlying disease entity.
Objective
To study the resolution of lesions over time in children with TM due to MOG-antibody associated disorders (MOGAD), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) or double seronegative TM.
Patients and methods
In this prospective study, 78 children from 29 different medical centres with TM as part of MOGAD (n = 34), MS (n = 20), NMOSD (n = 5) and in double seronegative children (n = 19) were included. A grading system consisting of 4 grades (grade 0 = complete resolution; grade 3 = no resolution at all) was used to compare the degree of lesion resolution over time in the different disease entities. Time to lesion resolution was evaluated by Kaplan-Meier statistics and log-rank test.
Results
Significant differences of the interval between first MRI until resolution of lesions were observed between the four disease entities. The most rapid and complete resolution was seen in MOGAD, followed by double seronegative, MS and NMOSD. Median periods until total resolution (grade 0) were 191 days (MOGAD), 750 days (double seronegative), 1117 days (MS), while none of the patients with NMOSD reached a complete resolution during the observation period. The better prognosis of MOGAD compared to MS was independent of sex, age, oligoclonal bands and cell count in the multivariate Cox analysis (P < 0.001).
Conclusion
Children with TM and antibodies to MOG show a faster resolution of radiological lesions compared to children with MS and NMOSD.
{"title":"Long-term follow-up MR imaging in children with transverse myelitis","authors":"Ines El Naggar , Robert Cleaveland , Andreas Panzer , Sandy Molenaar , Laetitia Giorgi , Eva-Maria Wendel , Annikki Bertolini , Michael Karenfort , Charlotte Thiels , Zuzana Libá , Matthias Baumann , Steffen Leiz , Adela Della Marina , Jan G. Hengstler , Kumaran Deiva , Rinze Neuteboom , Markus Reindl , Kevin Rostásy , BIOMARKER study group","doi":"10.1016/j.msard.2024.105926","DOIUrl":"10.1016/j.msard.2024.105926","url":null,"abstract":"<div><h3>Background</h3><div>We recently described magnetic resonance imaging (MRI) features of children with transverse myelitis (TM) at first event with important and unique differences depending on the underlying disease entity.</div></div><div><h3>Objective</h3><div>To study the resolution of lesions over time in children with TM due to MOG-antibody associated disorders (MOGAD), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) or double seronegative TM.</div></div><div><h3>Patients and methods</h3><div>In this prospective study, 78 children from 29 different medical centres with TM as part of MOGAD (<em>n</em> = 34), MS (<em>n</em> = 20), NMOSD (<em>n</em> = 5) and in double seronegative children (<em>n</em> = 19) were included. A grading system consisting of 4 grades (grade 0 = complete resolution; grade 3 = no resolution at all) was used to compare the degree of lesion resolution over time in the different disease entities. Time to lesion resolution was evaluated by Kaplan-Meier statistics and log-rank test.</div></div><div><h3>Results</h3><div>Significant differences of the interval between first MRI until resolution of lesions were observed between the four disease entities. The most rapid and complete resolution was seen in MOGAD, followed by double seronegative, MS and NMOSD. Median periods until total resolution (grade 0) were 191 days (MOGAD), 750 days (double seronegative), 1117 days (MS), while none of the patients with NMOSD reached a complete resolution during the observation period. The better prognosis of MOGAD compared to MS was independent of sex, age, oligoclonal bands and cell count in the multivariate Cox analysis (<em>P</em> < 0.001).</div></div><div><h3>Conclusion</h3><div>Children with TM and antibodies to MOG show a faster resolution of radiological lesions compared to children with MS and NMOSD.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"92 ","pages":"Article 105926"},"PeriodicalIF":2.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
COVID-19 was a viral infection that led to a global pandemic in March 2020. At the beginning of the pandemic, clinicians encountered the challenge of how immunosuppressive treatments would affect the course of COVID-19 infection in people with autoimmune diseases. Neuromyelitis optica spectrum disorder is an autoimmune astrocytopathy that is caused by an inflammation in the CNS. Major treatments to prevent acute relapses include immunosuppressive drugs. Rituximab is a well-established immunosuppressive agent in NMOSD maintenance therapy. Some reports suggested that treatment with Rituximab might increase the risk of COVID-19 infection and its mortality in NMOSD. On the other hand, dose reduction or extended interval treatment might lead to acute relapses of NMOSD and permanent disability.
Methods
In this study, we evaluated the correlation between the dose of rituximab and the relapse rate of NMOSD during an epidemic. This was an observational study on 171 patients among whom 55 cases were seropositive. Some patients received full dose rituximab routinely (1000 mg/dose, every 6 months), but others were treated with half dose (500 mg/dose) during the epidemic. Also, some doses were prescribed with a delay, based on the level of CD19 and CD20.
Results
The Pearson correlation coefficient (r) showed a negative and significant relation (r: - 0.19, p: 0.022) between the amount of drug and the number of relapses in the seropositive group, so low dosage of the drug was related to more acute relapses. In seronegative cases, there was not any valuable relationship. (p: 0.367).
Conclusion
Lower dose of rituximab, especially in seropositive NMOSD patients, can potentially lead to acute relapses. So, the more frequent evaluation of the CD19, CD20, and, CD27 levels, and the general clinical condition of the patients should be considered.
{"title":"The correlation between rituximab dose reduction and acute relapses of neuromyelitis optica spectrum disorder, lessons from COVID-19 epidemic","authors":"Fereshteh Ashtari , Roshanak Mehdipour , Mina Asgari , Arshia Ghalamkari","doi":"10.1016/j.msard.2024.105940","DOIUrl":"10.1016/j.msard.2024.105940","url":null,"abstract":"<div><h3>Background</h3><div>COVID-19 was a viral infection that led to a global pandemic in March 2020. At the beginning of the pandemic, clinicians encountered the challenge of how immunosuppressive treatments would affect the course of COVID-19 infection in people with autoimmune diseases. Neuromyelitis optica spectrum disorder is an autoimmune astrocytopathy that is caused by an inflammation in the CNS. Major treatments to prevent acute relapses include immunosuppressive drugs. Rituximab is a well-established immunosuppressive agent in NMOSD maintenance therapy. Some reports suggested that treatment with Rituximab might increase the risk of COVID-19 infection and its mortality in NMOSD. On the other hand, dose reduction or extended interval treatment might lead to acute relapses of NMOSD and permanent disability.</div></div><div><h3>Methods</h3><div>In this study, we evaluated the correlation between the dose of rituximab and the relapse rate of NMOSD during an epidemic. This was an observational study on 171 patients among whom 55 cases were seropositive. Some patients received full dose rituximab routinely (1000 mg/dose, every 6 months), but others were treated with half dose (500 mg/dose) during the epidemic. Also, some doses were prescribed with a delay, based on the level of CD19 and CD20.</div></div><div><h3>Results</h3><div>The Pearson correlation coefficient (r) showed a negative and significant relation (r: - 0.19, p: 0.022) between the amount of drug and the number of relapses in the seropositive group, so low dosage of the drug was related to more acute relapses. In seronegative cases, there was not any valuable relationship. (p: 0.367).</div></div><div><h3>Conclusion</h3><div>Lower dose of rituximab, especially in seropositive NMOSD patients, can potentially lead to acute relapses. So, the more frequent evaluation of the CD19, CD20, and, CD27 levels, and the general clinical condition of the patients should be considered.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"92 ","pages":"Article 105940"},"PeriodicalIF":2.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.msard.2024.105935
Ana Lídia Neves , Andrea Cabral , Catarina Serrão , Daniela Santos Oliveira , Janice Alves , José Miguel Alves , Mafalda Soares , Ernestina Santos , Mafalda Seabra , Helena Felgueiras , João Ferreira , Eva Brandão , Rui Guerreiro , Carla Cecília Nunes , Filipa Ladeira , José Vale , Maria José Sá , André Jorge
Background
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a heterogeneous entity with either a monophasic or relapsing course. Well-established predictors of relapsing disease are lacking.
Objective
Identifying predictors of relapsing MOGAD, particularly at disease onset.
Methods
A multicentre observational retrospective study was conducted to characterise a cohort of Portuguese adult MOGAD patients. Patients were identified from participating centre databases. Clinical and demographic data were collected from medical records. Bivariate analysis was conducted to compare patients with relapsing and monophasic MOGAD. Significant variables were included in a stepwise multiple regression analysis to identify independent predictors of relapse.
Results
Eighty-seven MOGAD patients from 8 public hospitals were included. Relapsing MOGAD was found in 35.6% (n = 31). Mean diagnostic delay was 3.2 (±6.2) years and time to relapse was 4.4 (±6.4) years. Multiple logistic regression showed that higher neutrophil count (p < 0.01), presence of oligoclonal bands (p = 0.025) and no bridging corticosteroids (p = 0.038) at first attack were predictive of relapsing MOGAD.
Conclusion
Neutrophil count and oligoclonal bands at first attack may facilitate early decision-making regarding maintenance immunotherapy. Bridging corticosteroids may also influence the course of MOGAD. Further studies with prospective design are warranted.
{"title":"Blood neutrophils, oligoclonal bands and bridging corticosteroids as predictive factors for MOGAD course: Insights from a multicentric Portuguese cohort","authors":"Ana Lídia Neves , Andrea Cabral , Catarina Serrão , Daniela Santos Oliveira , Janice Alves , José Miguel Alves , Mafalda Soares , Ernestina Santos , Mafalda Seabra , Helena Felgueiras , João Ferreira , Eva Brandão , Rui Guerreiro , Carla Cecília Nunes , Filipa Ladeira , José Vale , Maria José Sá , André Jorge","doi":"10.1016/j.msard.2024.105935","DOIUrl":"10.1016/j.msard.2024.105935","url":null,"abstract":"<div><h3>Background</h3><div>Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a heterogeneous entity with either a monophasic or relapsing course. Well-established predictors of relapsing disease are lacking.</div></div><div><h3>Objective</h3><div>Identifying predictors of relapsing MOGAD, particularly at disease onset.</div></div><div><h3>Methods</h3><div>A multicentre observational retrospective study was conducted to characterise a cohort of Portuguese adult MOGAD patients. Patients were identified from participating centre databases. Clinical and demographic data were collected from medical records. Bivariate analysis was conducted to compare patients with relapsing and monophasic MOGAD. Significant variables were included in a stepwise multiple regression analysis to identify independent predictors of relapse.</div></div><div><h3>Results</h3><div>Eighty-seven MOGAD patients from 8 public hospitals were included. Relapsing MOGAD was found in 35.6% (<em>n</em> = 31). Mean diagnostic delay was 3.2 (±6.2) years and time to relapse was 4.4 (±6.4) years. Multiple logistic regression showed that higher neutrophil count (<em>p</em> < 0.01), presence of oligoclonal bands (<em>p</em> = 0.025) and no bridging corticosteroids (<em>p</em> = 0.038) at first attack were predictive of relapsing MOGAD.</div></div><div><h3>Conclusion</h3><div>Neutrophil count and oligoclonal bands at first attack may facilitate early decision-making regarding maintenance immunotherapy. Bridging corticosteroids may also influence the course of MOGAD. Further studies with prospective design are warranted.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"92 ","pages":"Article 105935"},"PeriodicalIF":2.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.msard.2024.105936
QinFang Xie , Jing Sun , MengJiao Sun, Qi Wang, ManXia Wang
<div><h3>Background</h3><div>Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating immune-mediated ailment, which is influenced by genetic, epigenetic, and environmental elements. The escalating incidence of NMOSD in recent years implies alterations in environmental risk factors. Recent research has established a correlation between gut microbiomes and the development of NMOSD.</div></div><div><h3>Methods</h3><div>Metagenomic shotgun sequencing and gas chromatography-mass spectrometry (GC–MS) were employed to assess alterations of the structure and function in the fecal microbiome, as well as levels of short-chain fatty acids (SCFAs) in fecal and blood samples, among individuals with neuromyelitis optica spectrum disorder (NMOSD) during the acute phase (<em>n</em> = 25), the remission phase (<em>n</em> = 11), and a group of healthy controls (HCs) (<em>n</em> = 24). We further explored the correlation between gut microbiota and the pathogenesis of NMOSD through fecal microbiota transplantation (FMT). The gut microbiome from human donors diagnosed with NMOSD or HCs was transplanted into germ-free mice, followed by an analysis of the alterations in the structure and functionality of the transplanted mice's gut microbiome. Additionally, the impact of microbiome transfer on the immunity and spinal cord of germ-free mice was assessed through various techniques, including ELISA, flow cytometry, western blot, histopathology, and transcriptome sequencing.</div></div><div><h3>Results</h3><div>(1) At the taxonomic levels of genus and species, there were significant differences in the α-diversity of the microbiome between HCs and NMOSD patients in the acute phase, with NMOSD patients having higher species diversity. (2) In the acute phase, the gut microbiota of NMOSD patients was characterized by <em>Ruminococcaceae_unclassified, Campylobacter, Parabacteroides, Lactobacillus, Akkermansia, Streptococcus oralis, Clostridium leptum, Clostridium asparagiforme, Firmicutes bacterium</em> CAG 238, and <em>Lactobacillus fermentum.</em> (3) The relative abundances of <em>Coprobacter, Turicimonas, Gemmiger, Enterobacter, Roseburia</em> sp.CAG 471, <em>Veillonella tobetsuensis, Proteobacteria bacterium</em> CAG 139, <em>Ruminococcus bicirculans, Lactococcus lactis, Flavonifractor plautii,</em> and <em>Streptococcus cristatus</em> were notably lower in patients experiencing remission compared to NMOSD patients in the acute phase, On the other hand, the relative abundances of <em>Flavonifractor</em> (<em>P</em> = 0.049) and <em>Clostridium aldenense</em> (<em>P</em> = 0.049) were significantly higher. Following medication, the gut microbiome distribution in NMOSD patients during remission closely resembled that of healthy controls (HCs). (4) Compared with HCs, acetate levels in the feces of patients with NMOSD in the acute phase were significantly lower. (5) In addition, we transplanted feces from NMOSD patients into germ-f
{"title":"Perturbed microbial ecology in neuromyelitis optica spectrum disorder: Evidence from the gut microbiome and fecal metabolome","authors":"QinFang Xie , Jing Sun , MengJiao Sun, Qi Wang, ManXia Wang","doi":"10.1016/j.msard.2024.105936","DOIUrl":"10.1016/j.msard.2024.105936","url":null,"abstract":"<div><h3>Background</h3><div>Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating immune-mediated ailment, which is influenced by genetic, epigenetic, and environmental elements. The escalating incidence of NMOSD in recent years implies alterations in environmental risk factors. Recent research has established a correlation between gut microbiomes and the development of NMOSD.</div></div><div><h3>Methods</h3><div>Metagenomic shotgun sequencing and gas chromatography-mass spectrometry (GC–MS) were employed to assess alterations of the structure and function in the fecal microbiome, as well as levels of short-chain fatty acids (SCFAs) in fecal and blood samples, among individuals with neuromyelitis optica spectrum disorder (NMOSD) during the acute phase (<em>n</em> = 25), the remission phase (<em>n</em> = 11), and a group of healthy controls (HCs) (<em>n</em> = 24). We further explored the correlation between gut microbiota and the pathogenesis of NMOSD through fecal microbiota transplantation (FMT). The gut microbiome from human donors diagnosed with NMOSD or HCs was transplanted into germ-free mice, followed by an analysis of the alterations in the structure and functionality of the transplanted mice's gut microbiome. Additionally, the impact of microbiome transfer on the immunity and spinal cord of germ-free mice was assessed through various techniques, including ELISA, flow cytometry, western blot, histopathology, and transcriptome sequencing.</div></div><div><h3>Results</h3><div>(1) At the taxonomic levels of genus and species, there were significant differences in the α-diversity of the microbiome between HCs and NMOSD patients in the acute phase, with NMOSD patients having higher species diversity. (2) In the acute phase, the gut microbiota of NMOSD patients was characterized by <em>Ruminococcaceae_unclassified, Campylobacter, Parabacteroides, Lactobacillus, Akkermansia, Streptococcus oralis, Clostridium leptum, Clostridium asparagiforme, Firmicutes bacterium</em> CAG 238, and <em>Lactobacillus fermentum.</em> (3) The relative abundances of <em>Coprobacter, Turicimonas, Gemmiger, Enterobacter, Roseburia</em> sp.CAG 471, <em>Veillonella tobetsuensis, Proteobacteria bacterium</em> CAG 139, <em>Ruminococcus bicirculans, Lactococcus lactis, Flavonifractor plautii,</em> and <em>Streptococcus cristatus</em> were notably lower in patients experiencing remission compared to NMOSD patients in the acute phase, On the other hand, the relative abundances of <em>Flavonifractor</em> (<em>P</em> = 0.049) and <em>Clostridium aldenense</em> (<em>P</em> = 0.049) were significantly higher. Following medication, the gut microbiome distribution in NMOSD patients during remission closely resembled that of healthy controls (HCs). (4) Compared with HCs, acetate levels in the feces of patients with NMOSD in the acute phase were significantly lower. (5) In addition, we transplanted feces from NMOSD patients into germ-f","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"92 ","pages":"Article 105936"},"PeriodicalIF":2.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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