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Recent Advances in Understanding Multiple Sclerosis

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (25 November 2022) | Viewed by 25715

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Prof. Dr. Simona Bonavita

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Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Interests: digital technology; multiple sclerosis; pilates exercise; hydrobike; mood disturbances
Special Issues, Collections and Topics in MDPI journals

Dr. Elisabetta Signoriello

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Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
Interests: multiple sclerosis; rehabilitation; biomarker; clinical neurology
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

In the last few years, new insights have emerged on the pathogenesis and treatments of multiple sclerosis. A principal novelty has been exploring and evaluating chronic inflammation beyond what is detected with common, conventional techniques such as magnetic resonance imaging; therefore, broadening our knowledge on the pathogenetic mechanisms of chronic progressive multiple sclerosis, the pathological features of the disease (meningeal follicles, inflammation of chronic expanding lesions, cortical lesions), and identifying possible therapeutic targets are an active field of scientific research. Based on the role of B lymphocytes in the pathogenesis of multiple sclerosis, new drugs such as B cell depleting agents have been developed for progressive multiple sclerosis. Nevertheless, a drug for secondary progressive multiple sclerosis will be on the market soon. For these reasons, the future challenges will be to better identify the progression of the disease, to intercept the transitional forms, and to understand the target of treatment response in progressive patients.

We welcome articles providing new insights into

(i) humoral/clinical or digital biomarkers to early detect the onset or sustained disease progression;

(ii) markers of treatment response in relapsing and progressive patients with multiple sclerosis;

(iii) management of therapy switch;

(iv) novel clinical approaches to ameliorate symptoms of disease, especially in the progressive phase.

We welcome both solicited and unsolicited submissions that will contribute to this goal.

Prof. Simona Bonavita
Dr. Elisabetta Signoriello
Guest Editors

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

multiple sclerosis
progression
Blymphocytes
biomarkers
treatment response
symptomatic treatment

Related Special Issue

Exercise and Multiple Sclerosis in Journal of Clinical Medicine (7 articles)

Published Papers (11 papers)

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Research

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13 pages, 1932 KiB

Open AccessArticle

Clinically Manifest Infections Do Not Increase the Relapse Risk in People with Multiple Sclerosis Treated with Disease-Modifying Therapies: A Prospective Study

by Giuseppina Miele, Simone Cepparulo, Gianmarco Abbadessa, Luigi Lavorgna, Maddalena Sparaco, Vittorio Simeon, Lorenzo Guizzaro and Simona Bonavita

J. Clin. Med. 2023, 12(3), 1023; https://doi.org/10.3390/jcm12031023 - 28 Jan 2023

Cited by 2 | Viewed by 1666

Abstract

Background: Many factors are believed to be positively associated with the incidence of relapses in people with multiple sclerosis (MS), including infections. However, their role is still controversial. We aimed to investigate whether symptomatic infections in people with MS increase the risk of relapse in the short, medium, or long term. Materials and Methods: We enrolled consecutive patients with relapsing MS (RMS) from October to December 2018. From enrolment up to September 2020, an online questionnaire investigating the occurrence of infections was sent via WhatsApp^® monthly to the enrolled patients, while in-person visits were performed every six months. When patients complained of symptoms compatible with relapses, they attended an extra in-person visit. Results: We enrolled 155 patients with RMS, and 88.38% of patients were treated with disease-modifying therapies. In the dataset, 126,381 total patient days, 78 relapses, and 1202 infections were recorded over a period of about 2 years. No increased risk of relapse after clinically manifest infections was found in the short-, medium-, or long-term period. No correlation was found between all infections and the number of relapses (p = 0.212). The main analyses were repeated considering only those infections that had at least two of the following characteristics: duration of infection ≥ 4 days, body temperature > 37° Celsius, and the use of drugs (antibiotics and/or antivirals), and no significant associations were observed. Conclusions: No associations between infections and relapses were observed, likely suggesting that disease-modifying therapies may protect against the risk of relapse potentially triggered by infections. Full article

(This article belongs to the Special Issue Recent Advances in Understanding Multiple Sclerosis)

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10 pages, 274 KiB

Open AccessArticle

The Clinical and Epidemiological Profile of Paediatric-Onset Multiple Sclerosis in Poland

by Waldemar Brola, Barbara Steinborn, Marek Żak, Maria Mazurkiewicz-Bełdzińska, Sergiusz Jóźwiak, Piotr Sobolewski, Maciej Wilski, Małgorzata Bilska, Magdalena Siedlarska, Iwona Puzio-Bochen, Agnieszka Wencel-Warot, Małgorzata Lemka, Sławomir Kroczka, Elżbieta Czyżyk, Małgorzata Bocheńska, Ewa Emich-Widera, Jerzy Pietruszewski, Leszek Boćkowski, Katarzyna Kapica-Topczewska, Agata Czarnowska, Alina Kułakowska, Barbara Ujma-Czapska, Agata Gruna-Ożarowska, Łukasz Przysło, Katarzyna Połatyńska, Magdalena Dudzińska, Krystyna Mitosek-Szewczyk, Aleksandra Melnyk, Monika Adamczyk-Sowa and Katarzyna Kotulska Show full author list Hide full author list

J. Clin. Med. 2022, 11(24), 7494; https://doi.org/10.3390/jcm11247494 - 17 Dec 2022

Cited by 2 | Viewed by 1722

Abstract

Background. Paediatric-onset MS (POMS) has a unique clinical profile compared to the more prevalent adult-onset MS. For this study, we aimed to determine the demographic and clinical characteristics of POMS in Poland as well as addressing some of its epidemiological aspects. Methods. A retrospective study was conducted based on the Polish Multiple Sclerosis Registry, considering a population of children and adolescents with MS (age ≤ 18 years). Data were collected by all 13 centres across Poland specializing in diagnosing and treating POMS. The actual course of the disease and its clinical properties were compared between child (≤12 years) and juvenile (>12 years) patients. MS onset and its prevalence were assessed at the end of 2019, stratified by age range. Results. A total of 329 paediatric or juvenile patients (228 girls, 101 boys) with a clinically definite diagnosis of MS, in conformity with the 2017 McDonald Criteria, were enrolled. For 71 children (21.6%), the first symptoms appeared before the age of 12. The female: male ratio increased with age, amounting to 1:1 in the ≤12 years group and to 2.9:1 in the >12 years group. In most cases, the disease had multi-symptomatic onset (31.3%), and its course was mostly of a relapsing–remitting character (95.7%). The initial Expanded Disability Status Score for both groups was 1.63 ± 1.1, whereas the annual relapse rate was 0.84 during the first 2 years. The time between the onset of symptoms and diagnosis was longer in the younger patients (8.2 ± 4.2 vs. 4.6 ± 3.6 months; p < 0.005). On 31 December 2019, the age-adjusted prevalence standardized to the European standard population was 5.19/100,000 (95% CI, 4.64–5.78). Significantly higher prevalence was noted in the 13–18 years group (7.12; 95% CI, 6.64–7.86) than in the 9–12 years group (3.41; 95% CI, 2.98–3.86) and the <9 years group (0.56; 95% CI, 0.46–0.64; p < 0.001). Conclusion. POMS commencing at the age of ≤12 years is rare, differing significantly from the juvenile-onset and adult MS in terms of clinical characteristics, course, and incidence, as stratified by gender. Full article

(This article belongs to the Special Issue Recent Advances in Understanding Multiple Sclerosis)

7 pages, 688 KiB

Open AccessArticle

Understanding the Effect of Multiple Sclerosis on General and Dimensions of Mental Health

by Weixi Kang

J. Clin. Med. 2022, 11(24), 7483; https://doi.org/10.3390/jcm11247483 - 16 Dec 2022

Cited by 1 | Viewed by 1229

Abstract

Objective: The objective of the current study is to investigate how general and dimensions of mental health are affected by multiple sclerosis (MS). Methods: Factor analysis, generalized linear models, and one-sample t-tests were used to analyze data from 78 people with MS with a mean age of 52.19 (S.D. = 12.94) years old and 25.64% males and 38,516 people without MS with a mean age of 49.10 (S.D. = 18.24) years old and 44.27% males from Understanding Society. Results: The current study found that there are three underlying factors of the GHQ-12 labeled as GHQ-12A (social dysfunction and anhedonia; 6 items), GHQ-12B (depression and anxiety; 4 items), and GHQ-12C (loss of confidence; 2 items), and the general mental health, GHQ-12A (social dysfunction and anhedonia), and GHQ-12C (loss of confidence) are associated with MS. Conclusions: Effective mental health management in MS patients is important given mental health in people with MS is linked to the onset of MS and exacerbating disease progression/relapses. Full article

(This article belongs to the Special Issue Recent Advances in Understanding Multiple Sclerosis)

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12 pages, 293 KiB

Open AccessArticle

Mental Health Status of People with Multiple Sclerosis during the COVID-19 Pandemic

by Maciej Wilski, Magdalena Koper, Jarosław Gabryelski, Waldemar Brola and Tomasz Tasiemski

J. Clin. Med. 2022, 11(3), 576; https://doi.org/10.3390/jcm11030576 - 24 Jan 2022

Cited by 2 | Viewed by 2237

Abstract

Objective. This study assesses and compares the mental health status of people with multiple sclerosis (PwMS) in Poland during the second wave of the Coronavirus Disease 2019 (COVID-19) pandemic (November 2020) to a similar group whose mental health status was examined in November 2017. It also analyzed the psychological resources such as self-efficacy and health locus of control (HLC) and their relationship to mental health in both groups. Methods. Cross-sectional study included two groups of PwMS with 113 respondents each. The respondents completed the General Health Questionnaire-12 and questionnaires for assessing self-efficacy and HLC. The clinical and demographic data of participants were also collected. Results. No differences in mental health status were observed between the studied groups. A hierarchical regression model of the group studied in 2020 revealed that general self-efficacy (β = −0.21, p = 0.032), HLC—internal (β = −0.21, p = 0.035), and education (β = −0.18, p = 0.048) explained 18% of the variance in the mental health of PwMS, whereas according to the model of the group assessed in 2017 self-efficacy (β = –0.31, p < 0.001), HLC—chance (β = 0.45, p < 0.001), and HLC—internal (β = −0.37, p < 0.001) explained 48% of the variance. Conclusions. Study results suggest that the pandemic and the related lockdown had no effect on the mental health status of PwMS. At the same time, it was noted that well known determinants of mental health such as self-efficacy and HLC seemed to retain their prominent role for mental functioning in the pandemic. Full article

(This article belongs to the Special Issue Recent Advances in Understanding Multiple Sclerosis)

11 pages, 560 KiB

Open AccessArticle

Brain Volume Loss Can Occur at the Rate of Normal Aging in Patients with Multiple Sclerosis Who Are Free from Disease Activity

by Joke Temmerman, Floris Van Der Veken, Sebastiaan Engelborghs, Kaat Guldolf, Guy Nagels, Dirk Smeets, Gert-Jan Allemeersch, Lars Costers, Marie B. D’hooghe, Anne-Marie Vanbinst, Jeroen Van Schependom, Maria Bjerke and Miguel D’haeseleer

J. Clin. Med. 2022, 11(3), 523; https://doi.org/10.3390/jcm11030523 - 20 Jan 2022

Cited by 5 | Viewed by 2904

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disorder of the central nervous system. Accelerated brain volume loss (BVL) has emerged as a promising magnetic resonance imaging marker (MRI) of neurodegeneration, correlating with present and future clinical disability. We have systematically selected MS patients fulfilling ‘no evidence of disease activity-3′ (NEDA-3) criteria under high-efficacy disease-modifying treatment (DMT) from the database of two Belgian MS centers. BVL between both MRI scans demarcating the NEDA-3 period was assessed and compared with a group of prospectively recruited healthy volunteers who were matched for age and gender. Annualized whole brain volume percentage change was similar between 29 MS patients achieving NEDA-3 and 24 healthy controls (−0.25 ± 0.49 versus −0.24 ± 0.20, p = 0.9992; median follow-up 21 versus 33 months; respectively). In contrast, we found a mean BVL increase of 72%, as compared with the former, in a second control group of MS patients (n = 21) whom had been excluded from the NEDA-3 group due to disease activity (p = 0.1371). Our results suggest that neurodegeneration in MS can slow down to the rate of normal aging once inflammatory disease activity has been extinguished and advocate for an early introduction of high-efficacy DMT to reduce the risk of future clinical disability. Full article

(This article belongs to the Special Issue Recent Advances in Understanding Multiple Sclerosis)

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13 pages, 493 KiB

Open AccessArticle

Coping Strategies and Their Impact on Quality of Life and Physical Disability of People with Multiple Sclerosis

by Silvia Cerea, Marta Ghisi, Marco Pitteri, Maddalena Guandalini, Lauren B. Strober, Simona Scozzari, Francesco Crescenzo and Massimiliano Calabrese

J. Clin. Med. 2021, 10(23), 5607; https://doi.org/10.3390/jcm10235607 - 29 Nov 2021

Cited by 7 | Viewed by 3060

Abstract

The aim of the study is to investigate the impact of coping strategies on Health-Related Quality of Life (HRQoL) and physical disability assessed with the Expanded Disability Status Scale (EDSS) of people with multiple sclerosis (pwMS). PwMS were asked to focus on “MS diagnosis” as the core stressor. One hundred eight pwMS completed the Coping Responses Inventory-Adult form (CRI-Adult), the Multiple Sclerosis Quality of Life-29 (MSQoL-29), and the Depression Anxiety Stress Scale-21 (DASS-21). Multiple regression analyses (first block: EDSS, disease duration, and DASS-21) revealed that physical MSQoL-29 was positively associated with Alternative Rewards and negatively with Resigned Acceptance of the CRI-Adult. The mental MSQoL-29 was positively associated with Problem-Solving and negatively with Emotional Discharge. The Expanded Disability Status Scale (EDSS; first block: disease duration and general distress) was negatively associated with Positive Reappraisal. The Analysis of covariance (ANCOVA) revealed that pwMS with lower physical disability showed higher scores in Positive Reappraisal and lower scores in Emotional Discharge than pwMS with a higher physical disability. Coping strategies can play a role on HRQoL and physical disability in pwMS above and beyond EDSS, disease duration, and general distress. Psychological interventions should be considered in pwMS since the time of diagnosis to promote engagement in adaptive coping strategies and contrast the maladaptive ones. Full article

(This article belongs to the Special Issue Recent Advances in Understanding Multiple Sclerosis)

10 pages, 21236 KiB

Open AccessArticle

IL-15 Is Overexpressed in γδ T Cells and Correlates with Disease Severity in Relapsing-Remitting Multiple Sclerosis

by Michał K. Zarobkiewicz, Wioleta Kowalska, Izabela Morawska, Paweł Halczuk, Konrad Rejdak and Agnieszka Bojarska-Junak

J. Clin. Med. 2021, 10(18), 4174; https://doi.org/10.3390/jcm10184174 - 15 Sep 2021

Cited by 1 | Viewed by 2169

Abstract

Interleukin 15 (IL-15) is known to be involved in the pathogenesis of multiple sclerosis (MS). An animal study revealed a distinct subset of IL-15-producing γδ T cells that correlate with disease severity. The aim of the current study was to test whether such a subset is also present in humans and its importance for the pathogenesis of MS. The peripheral blood from 29 patients with relapsing-remitting MS (including 6 relapses) and 22 controls was stained with monoclonal antibodies and analyzed with flow cytometry. The existence of IL-15+ γδ T cells was confirmed. Moreover, the percentage of IL-15+ γδ T is significantly increased in MS patients and correlates with disease severity. Nevertheless, additional functional studies are needed to fully understand the importance of those cells in multiple sclerosis pathogenesis Full article

(This article belongs to the Special Issue Recent Advances in Understanding Multiple Sclerosis)

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Review

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11 pages, 759 KiB

Open AccessReview

Angiogenesis and Multiple Sclerosis Pathogenesis: A Glance at New Pharmaceutical Approaches

by Maria Teresa Gentile, Gianluca Muto, Giacomo Lus, Karl-Olof Lövblad, Åsa Fex Svenningsen and Luca Colucci-D’Amato

J. Clin. Med. 2022, 11(16), 4643; https://doi.org/10.3390/jcm11164643 - 09 Aug 2022

Cited by 2 | Viewed by 2091

Abstract

Multiple sclerosis is a chronic disease of the central nervous system characterized by demyelination and destruction of axons. The most common form of the disease is the relapsing-remitting multiple sclerosis in which episodic attacks with typical neurological symptoms are followed by episodes of partial or complete recovery. One of the underestimated factors that contribute to the pathogenesis of multiple sclerosis is excessive angiogenesis. Here, we review the role of angiogenesis in the onset and in the development of the disease, the molecular mechanisms underlying angiogenesis, the current therapeutic approaches, and the potential therapeutic strategies with a look at natural compounds as multi-target drugs with both neuroprotective and anti-angiogenic properties. Full article

(This article belongs to the Special Issue Recent Advances in Understanding Multiple Sclerosis)

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17 pages, 1004 KiB

Open AccessReview

Relevance of Pathogenetic Mechanisms to Clinical Effectiveness of B-Cell-Depleting Monoclonal Antibodies in Multiple Sclerosis

by Luca Massacesi, Alice Mariottini and Ferdinando Nicoletti

J. Clin. Med. 2022, 11(15), 4288; https://doi.org/10.3390/jcm11154288 - 23 Jul 2022

Cited by 2 | Viewed by 2527

Abstract

Evidence of the effectiveness of B-cell-depleting monoclonal antibodies (mAbs) in multiple sclerosis (MS) prompted a partial revisitation of the pathogenetic paradigm of the disease, which was, so far, considered a T-cell-mediated autoimmune disorder. Mechanisms underlying the efficacy of B-cell-depleting mAbs in MS are still unknown. However, they likely involve the impairment of pleiotropic B-cell functions different from antibody secretion, such as their role as antigen-presenting cells during both the primary immune response in the periphery and the secondary response within the central nervous system (CNS). A potential impact of B-cell-depleting mAbs on inflammation compartmentalised within the CNS was also suggested, but little is known about the mechanism underlying this latter phenomenon as no definite evidence was provided so far on the ability of mAbs to cross the blood–brain barrier and reliable biomarkers of compartmentalised inflammation are lacking. The present paper briefly summarises the immunopathogenesis of MS with a focus on onset of autoimmunity and compartmentalisation of the immune response; mechanisms mediating B-cell depletion and underlying the effectiveness of B-cell-depleting mAbs are also discussed. Full article

(This article belongs to the Special Issue Recent Advances in Understanding Multiple Sclerosis)

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13 pages, 446 KiB

Open AccessReview

Pelvic Floor Dysfunctions and Their Rehabilitation in Multiple Sclerosis

by Maddalena Sparaco and Simona Bonavita

J. Clin. Med. 2022, 11(7), 1941; https://doi.org/10.3390/jcm11071941 - 31 Mar 2022

Cited by 4 | Viewed by 3166

Abstract

Urinary, bowel, and sexual dysfunctions are the most frequent and disabling pelvic floor (PF) disorders in patients with multiple sclerosis (MS). PF dysfunction negatively impacts the performance of daily living activities, walking, and the physical dimension of quality of life (QoL) in people with MS. Patient-reported outcomes on sphincteric functioning could be useful to detect PF disorders and their impact on patients’ lives. PF rehabilitation proposed by Kegel is based on a series of regularly repeated exercises for “the functional restoration of the perineal muscles”. Over time, various therapeutic modalities have been added to PF muscles exercises, through the application of physical or instrumental techniques, such as intravaginal neuromuscular electrical stimulation, electromyographic biofeedback, transcutaneous tibial nerve stimulation. PF rehabilitation has been applied in MS treatment, with improvements of lower urinary tract symptoms severity, QoL, level of anxiety and depression, and sexual dysfunction. This review aims to examine the different PF disorders in MS to evaluate the application of PF rehabilitation in MS and to highlight its advantages and limits, suggesting a multidisciplinary management of PF disorders, with a well-deserved space reserved for PF rehabilitation. Full article

(This article belongs to the Special Issue Recent Advances in Understanding Multiple Sclerosis)

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Other

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6 pages, 226 KiB

Open AccessBrief Report

Personality Traits Predict 7-Year Risk of Diagnosis of Multiple Sclerosis: A Prospective Study

by Weixi Kang

J. Clin. Med. 2023, 12(2), 682; https://doi.org/10.3390/jcm12020682 - 15 Jan 2023

Cited by 4 | Viewed by 1379

Abstract

Objective: The objective of the current study is to investigate how Big Five personality traits could predict the risk of multiple sclerosis (MS) diagnosis in 7 years. Methods: A binary logistic regression was used to analyze data from 17,791 participants who responded to questions at Wave 3 (collected between 2011 to 2012) and Wave 10 (collected between 2018 to 2019) using a binary logistic regression from UKHLS with a mean age of 47.01 (S.D. = 16.31) years old with 42.62% males. Results: The current study found that Openness (OR = 0.68, p < 0.01, 95% C.I. (0.51, 0.89)) and Conscientiousness (OR = 0.70, p < 0.05, 95% C.I. (0.52, 0.93)) are positively associated with a reduced risk of MS diagnosis in 7 years. Conclusion: Health professionals can use findings from the current study as evidence for developing tools for assessing the risk of MS, and providing interventions for people who may be at high risk of MS based on their personality traits. Full article

(This article belongs to the Special Issue Recent Advances in Understanding Multiple Sclerosis)

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