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Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future

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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 (20 May 2024) | Viewed by 28283

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Prof. Dr. Nikolaos Grigoriadis

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Laboratory of Experimental Neurology and Neuroimmunology, Department of Neurology, AHEPA University Hospital, Stilponos Kiriakides str. 1, 54636 Thessaloniki, Greece.
Interests: neuroscience; multiple sclerosis; demyelinating desease; neurology; neuroimmunology
Special Issues, Collections and Topics in MDPI journals

Dr. Maria Eleptheria Evangelopoulos

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First Department of Neurology, National and Kapodistrian University of Athens, Aeginition Hospital, Athens, Greece
Interests: neurological diseases; multiple sclerosis; demyelinating diseases; neuroinflammation; neurodegenerative diseases
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Dr. Christos Bakirtzis

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Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Interests: neuroimaging; cognition disorders; multiple sclerosis; neuroimmunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advances in diagnostic procedures and therapeutic interventions in Multiple sclerosis have substantially improved disease management and outcome. During the last decade, diagnostic criteria have been refined and allowed an earlier diagnosis, while preclinical conditions such as radiologically isolated syndrome, have been extensively studied. Current research explores the feasibility of the use of advanced neuroimaging techniques and blood biomarkers such as the levels of neurofilament light chains, in clinical practice. Future perspectives include the implementation of digital monitoring tools in everyday clinical practice that may allow early detection and prevention of disease worsening.

This Special Issue of the Journal of Clinical Medicine seeks commentaries, case reports, original research, short reports, and reviews focusing on the advances in research, diagnosis monitoring and treatment of multiple sclerosis and other demyelinating disorders such as neuromyelitis optica and MOG-associated diseases. This Special Issue aims to provide information about advances in phenotyping people with demyelinating disorders, personalization of treatment and long-term monitoring of these disease entities.

Prof. Dr. Nikolaos Grigoriadis
Dr. Maria Eleptheria Evangelopoulos
Dr. Christos Bakirtzis
Guest Editors

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Keywords

multiple sclerosis
demyelination
disease modifying therapies
neurodegeneration
neuromyelitis optica
disease monitoring
diagnostic criteria

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Published Papers (10 papers)

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Editorial

Jump to: Research, Review

3 pages, 166 KiB

Open AccessEditorial

Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future

by Christos Bakirtzis, Maria Elephteria Evangelopoulos and Nikolaos Grigoriadis

J. Clin. Med. 2024, 13(18), 5621; https://doi.org/10.3390/jcm13185621 - 22 Sep 2024

Cited by 1 | Viewed by 1152

Abstract

In the past two decades, there has been a considerable increase of our knowledge with regards to the pathophysiology and management of various demyelinating diseases of the central nervous system [...] Full article

(This article belongs to the Special Issue Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future)

Research

Jump to: Editorial, Review

9 pages, 1161 KiB

Open AccessArticle

Longitudinal Optical Coherence Tomography Imaging Reveals Hyperreflective Foci Characteristics in Relapsing–Remitting Multiple Sclerosis Patients

by Mathias Falck Schmidt, Gorm Pihl-Jensen, Michael Larsen and Jette Lautrup Frederiksen

J. Clin. Med. 2024, 13(17), 5056; https://doi.org/10.3390/jcm13175056 - 26 Aug 2024

Viewed by 1266

Abstract

Background/Objectives: Retinal hyperreflective foci, 25–50 µm in diameter, that can be imaged by noninvasive optical coherence tomography (OCT) may represent microglial activity related to inflammation. This study aimed to detect hyperreflective foci in the OCT-hyporeflective avascular outer nuclear layer of the retina in relapsing–remitting MS (RRMS) patients without ongoing eye or optic nerve disease. Methods: A cohort of 13 RRMS patients (8 eyes with and 18 eyes without prior optic neuritis) underwent retinal OCT at baseline, after 1 month, after 6 months, and then every 6 months for 3 years. The data were compared with single-examination data from 106 eyes in 53 age-matched healthy subjects. Results: The prevalence of hyperreflective foci at baseline was higher in RRMS patients than in healthy subjects (46.2% vs. 1.8%, p < 0.005). Patients with optic neuritis had much more foci than those without (p < 0.001). Hyperreflective foci recurred in 23.1% of RRMS patients, bilaterally in one with prior optic neuritis and unilaterally in two without. Conclusions: Patients with RRMS, notably those with prior optic neuritis, had elevated rates of retinal infiltration in the absence of retinal disease, suggesting that the phenomenon may represent elevated activity of an immune surveillance or housekeeping mechanism rather than retinal disease. Full article

(This article belongs to the Special Issue Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future)

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18 pages, 721 KiB

Open AccessArticle

Influence of STAT4 Genetic Variants and Serum Levels on Multiple Sclerosis Occurrence in the Lithuanian Population

by Akvile Bruzaite, Greta Gedvilaite, Renata Balnyte, Loresa Kriauciuniene and Rasa Liutkeviciene

J. Clin. Med. 2024, 13(8), 2385; https://doi.org/10.3390/jcm13082385 - 19 Apr 2024

Cited by 1 | Viewed by 1371

Abstract

Background: Multiple sclerosis (MS) is an autoimmune disease involving demyelination, inflammation, gliosis, and the loss of neurons. MS is a growing global health problem most likely caused by genetic, immunological, and environmental factors. However, the exact etiology of the disease is still unknown. Since MS is related to a dysregulation of the immune system, it could be linked to signal transducer and activator of transcription 4 (STAT4). To fully comprehend the significance of the STAT4 gene and STAT4 serum levels in MS, further research is required. Methods: A total of 200 MS patients and 200 healthy controls participated in the study. Deoxyribonucleic acid (DNA) was extracted using silica-based membrane technology. Polymerase chain reaction was used in real time for genotyping. Using the ELISA technique, serum levels were measured. Results:STAT4 rs7601754 AA genotype and the A allele were statistically significantly less frequent in MS patients (p = 0.003). Also, rs7601754 was associated with 1.9-fold increased odds of MS occurrence (p = 0.004). The rs7601754 AG genotype was more common in males with MS (p = 0.011) and was associated with 2.5-fold increased odds of MS occurrence in males (p = 0.012). STAT4 serum levels were statistically significantly lower in MS patients compared to the control group (p = 0.007). Conclusions:STAT4 rs7601754 increases the odds of MS occurrence. STAT4 serum levels were statistically significantly lower in MS patients compared to the control group. Full article

(This article belongs to the Special Issue Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future)

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18 pages, 2156 KiB

Open AccessFeature PaperArticle

Long-Term Disability Outcomes in Relapsing–Remitting Multiple Sclerosis Patients: Impact of Clinical and Demographic Factors on Disease Progression

by Laura Barcutean, Smaranda Maier, Zoltan Bajko, Adina Stoian, Oana Mosora, Emanuela Sarmasan, Ion-Bogdan Manescu and Rodica Balasa

J. Clin. Med. 2024, 13(6), 1813; https://doi.org/10.3390/jcm13061813 - 21 Mar 2024

Cited by 1 | Viewed by 2099

Abstract

Background: Multiple sclerosis (MS) is a prevalent chronic inflammatory and neurodegenerative disease of the central nervous system. The main evolving forms, relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS), lack clear delineation. Methods: We conducted an observational study on 523 Caucasian RRMS patients receiving first-line disease-modifying therapies (DMTs), analyzing demographic, clinical, and geographical data. Results: RRMS patients experienced a statistically significant reduction in relapse rates post-DMT initiation. Significant differences in time to reach an Expanded Disability Status Score (EDSS) of 3.0 and 6.0 were observed based on demographics and onset topography. Kaplan–Meier analysis revealed that the onset with optic or supratentorial symptoms is linked to a longer time until EDSS = 3.0 is reached. Urban origin correlated with a prolonged time until EDSS = 3.0. Gender and environment showed no significant associations with the hazard of reaching an EDSS = 6.0. Cox regression analysis revealed no significant impact of relapses on the time to reach EDSS scores of 3.0 and 6.0 in our study cohort. Conclusions: Multivariate analysis identified several predictive factors for disability progression, including environment, age at onset, and disability level at DMT initiation. Full article

(This article belongs to the Special Issue Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future)

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19 pages, 1256 KiB

Open AccessArticle

Visuo-Cognitive Phenotypes in Early Multiple Sclerosis: A Multisystem Model of Visual Processing

by Hariklia Vagias, Michelle L. Byrne, Lyn Millist, Owen White, Meaghan Clough and Joanne Fielding

J. Clin. Med. 2024, 13(3), 649; https://doi.org/10.3390/jcm13030649 - 23 Jan 2024

Cited by 1 | Viewed by 1972

Abstract

Background: Cognitive impairment can emerge in the earliest stages of multiple sclerosis (MS), with heterogeneity in cognitive deficits often hindering symptom identification and management. Sensory–motor dysfunction, such as visual processing impairment, is also common in early disease and can impact neuropsychological task performance in MS. However, cognitive phenotype research in MS does not currently consider the relationship between early cognitive changes and visual processing impairment. Objectives: This study explored the relationship between cognition and visual processing in early MS by adopting a three-system model of afferent sensory, central cognitive and efferent ocular motor visual processing to identify distinct visuo-cognitive phenotypes. Methods: Patients with clinically isolated syndrome and relapsing–remitting MS underwent neuro-ophthalmic, ocular motor and neuropsychological evaluation to assess each visual processing system. The factor structure of ocular motor variables was examined using exploratory factor analysis, and phenotypes were identified using latent profile analysis. Results: Analyses revealed three ocular-motor constructs (cognitive control, cognitive processing speed and basic visual processing) and four visuo-cognitive phenotypes (early visual changes, efferent-cognitive, cognitive control and afferent-processing speed). While the efferent-cognitive phenotype was present in significantly older patients than was the early visual changes phenotype, there were no other demographic differences between phenotypes. The efferent-cognitive and cognitive control phenotypes had poorer performance on the Symbol Digit Modalities Test compared to that of other phenotypes; however, no other differences in performance were detected. Conclusion: Our findings suggest that distinct visual processing deficits in early MS may differentially impact cognition, which is not captured using standard neuropsychological evaluation. Further research may facilitate improved symptom identification and intervention in early disease. Full article

(This article belongs to the Special Issue Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future)

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14 pages, 706 KiB

Open AccessArticle

COVID-19 Vaccination and Disease Course in People with Multiple Sclerosis in Greece

by Christos Bakirtzis, Natalia Konstantinidou, Sotiria Stavropoulou De Lorenzo, Theodoros Moysiadis, Marina-Kleopatra Boziki, Eleni Grigoriadou, Evangelia Kesidou, Paschalis Theotokis, Eleftherios Thireos, Panagiota Mitrou and Nikolaos Grigoriadis

J. Clin. Med. 2023, 12(17), 5460; https://doi.org/10.3390/jcm12175460 - 23 Aug 2023

Viewed by 1550

Abstract

Over the past three years, humanity faced the abrupt spread of COVID-19, responsible for a worldwide health crisis. Initially, it was believed that individuals with chronic disorders, including multiple sclerosis, were more likely to be infected and suffer a worse degree of COVID-19 disease. Therefore, data with regard to COVID-19 disease outcomes in these populations may provide additional insight with regard to the management of chronic diseases during viral pandemics. The objective of this study is to evaluate COVID-19 disease course in people with multiple sclerosis (PwMS) during the COVID-19 pandemic in Greece and explore the impact of vaccination in the outcome of SARS-CoV-2 infection in this population. Anonymized data, extracted from nationwide administrative records between February 2020 and December 2021, were retrospectively analyzed in order to identify PwMS with SARS-CoV-2 infection. Demographic data, as well as data regarding COVID-19 infection and vaccination, were additionally collected. The study sample included 2351 PwMS (65.1% females, 51.2% unvaccinated at the time of infection). A total of 260 PwMS were hospitalized, while 25 PwMS died from COVID-19 disease and its complications. Older age, male sex and the presence of comorbidities were independently associated with a higher probability of hospitalization. The risk of hospitalization was decreased in PwMS receiving some disease-modifying treatments. Anti-CD20s demonstrated high odds ratios without reaching statistical significance. Regarding fatal outcome, only age reached statistical significance. Vaccination provided a significant protective effect against hospitalization but did not exhibit a statistically significant effect on mortality. Full article

(This article belongs to the Special Issue Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future)

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15 pages, 1931 KiB

Open AccessArticle

Frequency and Predictors of Relapses following SARS-CoV-2 Vaccination in Patients with Multiple Sclerosis: Interim Results from a Longitudinal Observational Study

by Niklas Frahm, Firas Fneish, David Ellenberger, Judith Haas, Micha Löbermann, Melanie Peters, Dieter Pöhlau, Anna-Lena Röper, Sarah Schilling, Alexander Stahmann, Herbert Temmes, Friedemann Paul and Uwe Klaus Zettl

J. Clin. Med. 2023, 12(11), 3640; https://doi.org/10.3390/jcm12113640 - 24 May 2023

Cited by 8 | Viewed by 2482

Abstract

Despite protection from severe COVID-19 courses through vaccinations, some people with multiple sclerosis (PwMS) are vaccination-hesitant due to fear of post-vaccination side effects/increased disease activity. The aim was to reveal the frequency and predictors of post-SARS-CoV-2-vaccination relapses in PwMS. This prospective, observational study was conducted as a longitudinal Germany-wide online survey (baseline survey and two follow-ups). Inclusion criteria were age ≥18 years, MS diagnosis, and ≥1 SARS-CoV-2 vaccination. Patient-reported data included socio-demographics, MS-related data, and post-vaccination phenomena. Annualized relapse rates (ARRs) of the study cohort and reference cohorts from the German MS Registry were compared pre- and post-vaccination. Post-vaccination relapses were reported by 9.3% PwMS (247/2661). The study cohort’s post-vaccination ARR was 0.189 (95% CI: 0.167–0.213). The ARR of a matched unvaccinated reference group from 2020 was 0.147 (0.129–0.167). Another reference cohort of vaccinated PwMS showed no indication of increased post-vaccination relapse activity (0.116; 0.088–0.151) compared to pre-vaccination (0.109; 0.084–0.138). Predictors of post-vaccination relapses (study cohort) were missing immunotherapy (OR = 2.09; 1.55–2.79; p < 0.001) and shorter time from the last pre-vaccination relapse to the first vaccination (OR = 0.87; 0.83–0.91; p < 0.001). Data on disease activity of the study cohort in the temporal context are expected for the third follow-up. Full article

(This article belongs to the Special Issue Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future)

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14 pages, 297 KiB

Open AccessArticle

Clinical Characteristics of Headache in Multiple Sclerosis Patients: A Cross-Sectional Study

by Iwona Rościszewska-Żukowska, Sabina Galiniak and Halina Bartosik-Psujek

J. Clin. Med. 2023, 12(10), 3518; https://doi.org/10.3390/jcm12103518 - 17 May 2023

Cited by 11 | Viewed by 2341

Abstract

Primary headaches are known to be associated with multiple sclerosis (MS), but previous studies concerning this relationship are not conclusive. Nowadays, there are no studies assessing the prevalence of headaches in Polish MS patients. The aim of the study was to assess the prevalence and characterise headaches in MS patients treated with disease-modifying therapies (DMTs). In a cross-sectional study of 419 consecutive RRMS patients, primary headaches were diagnosed according to the International Classification of Headache Disorders (ICHD-3) criteria. Primary headaches were observed in 236 (56%) of RRMS patients, with a higher prevalence in women (ratio of 2:1). The most common was migraine 174 (41%) (migraine with aura 80 (45%), migraine without aura 53 (30%), and probable migraine without aura 41 (23%); less frequent was tension-type headache 62 (14%). Female sex was a risk factor for migraines but not for tension-type headaches (p = 0.002). Migraines mostly started before MS onset (p = 0.023). Migraine with aura was associated with older age, longer disease duration (p = 0.028), and lower SDMT (p = 0.002). Longer DMT time was associated with migraine (p = 0.047), particularly migraine with aura (p = 0.035). Typical for migraine with aura were headaches during clinical isolated syndrome (CIS) (p = 0.001) and relapses (p = 0.025). Age and type of CIS, oligoclonal band presence, family MS history, EDSS, 9HTP, T25FW, and type of DMT did not correlate with headache. Headaches are present in more than half of MS patients treated with DMTs; migraines occur almost three times more frequently than tension-type headaches. Migraines with aura headaches during CIS and relapses are typical. Migraine in MS patients had high severity and typical migraine characteristics. DMTs had no correlation with the presence or type of headache. Full article

(This article belongs to the Special Issue Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future)

Review

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37 pages, 2606 KiB

Open AccessReview

Cellular and Molecular Evidence of Multiple Sclerosis Diagnosis and Treatment Challenges

by Zuber Khan, Ghanshyam Das Gupta and Sidharth Mehan

J. Clin. Med. 2023, 12(13), 4274; https://doi.org/10.3390/jcm12134274 - 26 Jun 2023

Cited by 27 | Viewed by 7522

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease that impacts the central nervous system and can result in disability. Although the prevalence of MS has increased in India, diagnosis and treatment continue to be difficult due to several factors. The present study examines the difficulties in detecting and treating multiple sclerosis in India. A lack of MS knowledge among healthcare professionals and the general public, which delays diagnosis and treatment, is one of the significant issues. Inadequate numbers of neurologists and professionals with knowledge of MS management also exacerbate the situation. In addition, MS medications are expensive and not covered by insurance, making them inaccessible to most patients. Due to the absence of established treatment protocols and standards for MS care, India’s treatment techniques vary. In addition, India’s population diversity poses unique challenges regarding genetic variations, cellular and molecular abnormalities, and the potential for differing treatment responses. MS is more difficult to accurately diagnose and monitor due to a lack of specialized medical supplies and diagnostic instruments. Improved awareness and education among healthcare professionals and the general public, as well as the development of standardized treatment regimens and increased investment in MS research and infrastructure, are required to address these issues. By addressing these issues, it is anticipated that MS diagnosis and treatment in India will improve, leading to better outcomes for those affected by this chronic condition. Full article

(This article belongs to the Special Issue Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future)

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16 pages, 835 KiB

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CNS Ageing in Health and Neurodegenerative Disorders

by Evangelia Kesidou, Paschalis Theotokis, Olympia Damianidou, Marina Boziki, Natalia Konstantinidou, Charilaos Taloumtzis, Styliani-Aggeliki Sintila, Panagiotis Grigoriadis, Maria Eleptheria Evangelopoulos, Christos Bakirtzis and Constantina Simeonidou

J. Clin. Med. 2023, 12(6), 2255; https://doi.org/10.3390/jcm12062255 - 14 Mar 2023

Cited by 23 | Viewed by 5253

Abstract

The process of ageing is characteristic of multicellular organisms associated with late stages of the lifecycle and is manifested through a plethora of phenotypes. Its underlying mechanisms are correlated with age-dependent diseases, especially neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and multiple sclerosis (MS) that are accompanied by social and financial difficulties for patients. Over time, people not only become more prone to neurodegeneration but they also lose the ability to trigger pivotal restorative mechanisms. In this review, we attempt to present the already known molecular and cellular hallmarks that characterize ageing in association with their impact on the central nervous system (CNS)’s structure and function intensifying possible preexisting pathogenetic conditions. A thorough and elucidative study of the underlying mechanisms of ageing will be able to contribute further to the development of new therapeutic interventions to effectively treat age-dependent manifestations of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Multiple Sclerosis and Demyelinating Disorders: Past, Present, and Future)

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