10th Anniversary of Biomedicines—Advances in Multiple Sclerosis

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 19242

Special Issue Editor


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Guest Editor
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
Interests: demyelinating disorders; multiple sclerosis; epidemiology and genetic aspects; therapeutic trials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The year 2022 marks the 10th anniversary of Biomedicines, a peer-reviewed, open access journal containing research pertaining to biomedicine. So far, Biomedicines has published more than 2,700 papers from more than 17,000 authors. We appreciate each author, reviewer, and academic editor whose support has brought us to where we are today.

To celebrate this significant milestone, we are publishing a Special Issue entitled 10th Anniversary of Biomedicines—Advances in Multiple Sclerosis. Multiple sclerosis (MS), an inflammatory demyelinating disease of the CNS, has attracted worldwide recognition due to its increasing global prevalence, including populations previously considered not to be commonly affected. Genetics and environmental factors play a determining role in its pathogenesis. Notable progress has been accomplished in diagnostic criteria (which evolve continuously) as well as therapeutic advances. In fact, in less than three decades, more therapies with diverse mechanisms of action (MOAs) for relapsing and progressive MS have been developed for MS than for any other neurological disorder. Magnetic resonance imaging (MRI), the golden tool for diagnosis, is essential for monitoring the evolution of the disease and the response to therapy.

The aim of this Special Issue is to highlight studies and opinions on risk factors related to the development of the disease, molecular aspects of its pathogenesis, and the effects of disease-modifying therapies on relapsing and progressive forms of MS.

Prof. Dr. Víctor M. Rivera
Guest Editor

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Keywords

  • multiple sclerosis
  • pathogenesis
  • progressive MS
  • MRI
  • monoclonal antibodies
  • demyelinating disorders
  • cognitive dysfunction
  • intestinal microbiota

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Related Special Issue

Published Papers (9 papers)

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Research

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16 pages, 2667 KiB  
Article
Decreased Expression of the EAAT5 Glutamate Transporter at Photoreceptor Synapses in Early, Pre-Clinical Experimental Autoimmune Encephalomyelitis, a Mouse Model of Multiple Sclerosis
by Ali El Samad, Julia Jaffal, Dalia R. Ibrahim, Karin Schwarz and Frank Schmitz
Biomedicines 2024, 12(11), 2545; https://doi.org/10.3390/biomedicines12112545 - 7 Nov 2024
Viewed by 742
Abstract
Background: Multiple sclerosis is a frequent neuroinflammatory and neurodegenerative disease of the central nervous system that includes alterations in the white and gray matter of the brain. The visual system is frequently affected in multiple sclerosis. Glutamate excitotoxicity might play a role in [...] Read more.
Background: Multiple sclerosis is a frequent neuroinflammatory and neurodegenerative disease of the central nervous system that includes alterations in the white and gray matter of the brain. The visual system is frequently affected in multiple sclerosis. Glutamate excitotoxicity might play a role in disease pathogenesis. Methodology: In the present study, we analyzed with qualitative and quantitative immunofluorescence microscopy and Western blot analyses whether alterations in the EAAT5 (SLC1A7) glutamate transporter could be involved in the previously observed alterations in structure and function of glutamatergic photoreceptor ribbon synapses in the EAE mouse model of MS. EAAT5 is a presynaptic glutamate transporter located near the presynaptic release sites. Results: We found that EAAT5 was strongly reduced at the photoreceptor synapses of EAE retinas in comparison to the photoreceptor synapses of the respective control retinas as early as day 9 post-immunization. The Western blot analyses demonstrated a decreased EAAT5 expression in EAE retinas. Conclusions: Our data illustrate early alterations of the EAAT5 glutamate transporter in the early pre-clinical phase of EAE/MS and suggest an involvement of EAAT5 in the previously observed early synaptic changes at photoreceptor synapses. The precise mechanisms need to be elucidated by future investigations. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Multiple Sclerosis)
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12 pages, 2412 KiB  
Article
Diagnoses and Treatment Recommendations—Interrater Reliability of Uroflowmetry in People with Multiple Sclerosis
by Anke K. Jaekel, Julia Rieger, Anna-Lena Butscher, Sandra Möhr, Oliver Schindler, Fabian Queissert, Aybike Hofmann, Paul Schmidt, Ruth Kirschner-Hermanns and Stephanie C. Knüpfer
Biomedicines 2024, 12(7), 1598; https://doi.org/10.3390/biomedicines12071598 - 18 Jul 2024
Viewed by 821
Abstract
Background: Uroflowmetry (UF) is an established procedure in urology and is recommended before further investigations of neurogenic lower urinary tract dysfunction (NLUTD). Some authors even consider using UF instead of urodynamics (UD). Studies on the interrater reliability of UF regarding treatment recommendations are [...] Read more.
Background: Uroflowmetry (UF) is an established procedure in urology and is recommended before further investigations of neurogenic lower urinary tract dysfunction (NLUTD). Some authors even consider using UF instead of urodynamics (UD). Studies on the interrater reliability of UF regarding treatment recommendations are rare, and there are no relevant data on people with multiple sclerosis (PwMS). The aim of this study was to investigate the interrater reliability (IRR) of UF concerning diagnosis and therapy in PwMS prospectively. Methods: UF of 92 PwMS were assessed by 4 raters. The diagnostic criteria were normal findings (NFs), detrusor overactivity (DO), detrusor underactivity (DU), detrusor–sphincter dyssynergia (DSD) and bladder outlet obstruction (BOO). The possible treatment criteria were as follows: no treatment (NO), catheter placement (CAT), alpha-blockers, detrusor-attenuating medication, botulinum toxin (BTX), neuromodulation (NM), and physiotherapy/biofeedback (P/BF). IRR was assessed by kappa (κ). Results: κ of diagnoses were NFs = 0.22; DO = 0.17; DU = 0.07; DSD = 0.14; and BOO = 0.18. For therapies, the highest κ was BTX = 0.71, NO = 0.38 and CAT = 0.44. Conclusions: There is a high influence of the individual rater. UD should be subject to the same analysis and a comparison should be made between UD and UF. This may have implications for the value of UF in the neuro-urological management of PwMS, although at present UD remains the gold standard for the diagnostics of NLUTD in PwMS. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Multiple Sclerosis)
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10 pages, 1417 KiB  
Article
Multiple Sclerosis and Clostridium perfringens Epsilon Toxin: Is There a Relationship?
by André Huss, Franziska Bachhuber, Cécile Feraudet-Tarisse, Andreas Hiergeist and Hayrettin Tumani
Biomedicines 2024, 12(7), 1392; https://doi.org/10.3390/biomedicines12071392 - 23 Jun 2024
Viewed by 1059
Abstract
Recent research has suggested a link between multiple sclerosis and the gut microbiota. This prospective pilot study aimed to investigate the composition of the gut microbiota in MS patients, the presence of Clostridium perfringens epsilon toxin in the serum of MS patients, and [...] Read more.
Recent research has suggested a link between multiple sclerosis and the gut microbiota. This prospective pilot study aimed to investigate the composition of the gut microbiota in MS patients, the presence of Clostridium perfringens epsilon toxin in the serum of MS patients, and the influence of disease-modifying drugs (DMDs) on epsilon toxin levels and on the microbiota. Epsilon toxin levels in blood were investigated by two methods, a qualitative ELISA and a highly sensitive quantitative ELISA. Neither epsilon toxin nor antibodies against it were detected in the analyzed serum samples. 16S ribosomal RNA sequencing was applied to obtain insights into the composition of the gut microbiota of MS patients. No significant differences in the quantity, diversity, and the relative abundance of fecal microbiota were observed in the gut microbiota of MS patients receiving various DMDs, including teriflunomide, natalizumab, ocrelizumab, and fingolimod, or no therapy. The present study did not provide evidence supporting the hypothesis of a causal relationship between Clostridium perfringens epsilon toxin and multiple sclerosis. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Multiple Sclerosis)
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16 pages, 2072 KiB  
Article
The Association of Age, Sex, and BMI on Lower Limb Neuromuscular and Muscle Mechanical Function in People with Multiple Sclerosis
by Anne Geßner, Maximilian Hartmann, Katrin Trentzsch, Heidi Stölzer-Hutsch, Dirk Schriefer and Tjalf Ziemssen
Biomedicines 2024, 12(5), 971; https://doi.org/10.3390/biomedicines12050971 - 28 Apr 2024
Cited by 1 | Viewed by 1188
Abstract
(1) Background: The countermovement jump (CMJ) on a force plate could be a sensitive assessment for detecting early lower-limb muscle mechanical deficits in the early stages of multiple sclerosis (MS). CMJ performance is known to be influenced by various anthropometric, physiological, and biomechanical [...] Read more.
(1) Background: The countermovement jump (CMJ) on a force plate could be a sensitive assessment for detecting early lower-limb muscle mechanical deficits in the early stages of multiple sclerosis (MS). CMJ performance is known to be influenced by various anthropometric, physiological, and biomechanical factors, mostly investigated in children and adult athletes. Our aim was to investigate the association of age, sex, and BMI with muscle mechanical function using CMJ to provide a comprehensive overview of lower-limb motor function in people with multiple sclerosis (pwMS). (2) Methods: A cross-sectional study was conducted with pwMS (N = 164) and healthy controls (N = 98). All participants performed three maximal CMJs on a force plate. Age, sex, and BMI were collected from all participants. (3) Results: Significant age, sex, and BMI effects were found for all performance parameters, flight time, and negative and positive power for pwMS and HC, but no significant interaction effects with the group (pwMS, HC) were detected. The highest significant effects were found for sex on flight time (η2 = 0.23), jump height (η2 = 0.23), and positive power (η2 = 0.13). PwMS showed significantly lower CMJ performance compared to HC in middle-aged (31–49 years), with normal weight to overweight and in both women and men. (4) Conclusions: This study showed that age, sex, and BMI are associated with muscle mechanical function in pwMS and HC. These results may be useful in developing reference values for CMJ. This is a crucial step in integrating CMJ into the diagnostic assessment of people with early MS and developing individualized and effective neurorehabilitative therapy. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Multiple Sclerosis)
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13 pages, 2603 KiB  
Article
Countermovement Jumps Detect Subtle Motor Deficits in People with Multiple Sclerosis below the Clinical Threshold
by Anne Geßner, Heidi Stölzer-Hutsch, Katrin Trentzsch, Dirk Schriefer and Tjalf Ziemssen
Biomedicines 2023, 11(3), 774; https://doi.org/10.3390/biomedicines11030774 - 3 Mar 2023
Cited by 4 | Viewed by 2275
Abstract
In the early stages of multiple sclerosis (MS), there are currently no sensitive assessments to evaluate complex motor functions. The countermovement jump (CMJ), a high-challenge task in form of a maximal vertical bipedal jump, has already been investigated as a reliable assessment in [...] Read more.
In the early stages of multiple sclerosis (MS), there are currently no sensitive assessments to evaluate complex motor functions. The countermovement jump (CMJ), a high-challenge task in form of a maximal vertical bipedal jump, has already been investigated as a reliable assessment in healthy subjects for lower extremity motor function. The aim was to investigate whether it is possible to use CMJ to identify subthreshold motor deficits in people with multiple sclerosis (pwMS). All participants (99 pwMS and 33 healthy controls) performed three maximal CMJs on a force plate. PwMS with full motor function and healthy controls (HC) did not differ significantly in age, disease duration, Body Mass Index and the Expanded Disability Scale Score. In comparison to HC, pwMS with full motor function demonstrated a significantly decreased CMJ performance in almost all observed kinetic, temporal and performance parameters (p < 0.05). With increasing disability in pwMS, it was also observed that jump performance decreased significantly. This study showed that the CMJ, as a high challenge task, could detect motor deficits in pwMS below the clinical threshold of careful neurological examination. Longitudinal studies are pending to evaluate whether the CMJ can be used as a standardized measure of disease progression. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Multiple Sclerosis)
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16 pages, 323 KiB  
Communication
Genetic Markers for Thrombophilia and Cardiovascular Disease Associated with Multiple Sclerosis
by Maria S. Hadjiagapiou, George Krashias, Elie Deeba, George Kallis, Andri Papaloizou, Paul Costeas, Christina Christodoulou, Marios Pantzaris and Anastasia Lambrianides
Biomedicines 2022, 10(10), 2665; https://doi.org/10.3390/biomedicines10102665 - 21 Oct 2022
Cited by 2 | Viewed by 2885
Abstract
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) with an unknown etiology, although genetic, epigenetic, and environmental factors are thought to play a role. Recently, coagulation components have been shown to provide immunomodulatory and pro-inflammatory effects in [...] Read more.
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) with an unknown etiology, although genetic, epigenetic, and environmental factors are thought to play a role. Recently, coagulation components have been shown to provide immunomodulatory and pro-inflammatory effects in the CNS, leading to neuroinflammation and neurodegeneration. The current study aimed to determine whether patients with MS exhibited an overrepresentation of polymorphisms implicated in the coagulation and whether such polymorphisms are associated with advanced disability and disease progression. The cardiovascular disease (CVD) strip assay was applied to 48 MS patients and 25 controls to analyze 11 genetic polymorphisms associated with thrombosis and CVD. According to our results, FXIIIVal34Leu heterozygosity was less frequent (OR: 0.35 (95% CI: 0.12–0.99); p = 0.04), whereas PAI-1 5G/5G homozygosity was more frequent in MS (OR: 6.33 (95% CI: 1.32–30.24); p = 0.016). In addition, carriers of the HPA-1a/1b were likely to have advanced disability (OR: 1.47 (95% CI: 1.03–2.18); p = 0.03) and disease worsening (OR: 1.42 (95% CI: 1.05–2.01); p = 0.02). The results of a sex-based analysis revealed that male HPA-1a/1b carriers were associated with advanced disability (OR: 3.04 (95% CI: 1.22–19.54); p = 0.01), whereas female carriers had an increased likelihood of disease worsening (OR: 1.56 (95% CI: 1.04–2.61); p = 0.03). Our findings suggest that MS may be linked to thrombophilia-related polymorphisms, which warrants further investigation. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Multiple Sclerosis)
12 pages, 1427 KiB  
Article
T Lymphocyte Serotonin 5-HT7 Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients
by Flora Reverchon, Colleen Guillard, Lucile Mollet, Pascal Auzou, David Gosset, Fahima Madouri, Antoine Valéry, Arnaud Menuet, Canan Ozsancak, Maud Pallix-Guyot and Séverine Morisset-Lopez
Biomedicines 2022, 10(10), 2418; https://doi.org/10.3390/biomedicines10102418 - 27 Sep 2022
Cited by 2 | Viewed by 2319
Abstract
Serotonin (5-HT) is known as a potent immune cell modulator in autoimmune diseases and should be protective in the pathogenesis of multiple sclerosis (MS). Nevertheless, there is limited knowledge about receptors involved in 5-HT effects as well as induced mechanisms. Among 5-HT receptors, [...] Read more.
Serotonin (5-HT) is known as a potent immune cell modulator in autoimmune diseases and should be protective in the pathogenesis of multiple sclerosis (MS). Nevertheless, there is limited knowledge about receptors involved in 5-HT effects as well as induced mechanisms. Among 5-HT receptors, the 5-HT7 receptor is able to activate naïve T cells and influence the inflammatory response; however, its involvement in the disease has never been studied so far. In this study, we collected blood sample from three groups: acute relapsing MS patients (ARMS), natalizumab-treated MS patients (NTZ), and control subjects. We investigated the 5-HT7 expression on circulating lymphocytes and evaluated the effects of its activation on cytokine production with peripheral blood mononuclear cell (PBMC) cultures. We found a significant increase in the 5-HT7 surface expression on T lymphocytes and on the different CD4+ T cell subsets exclusively in NTZ-treated patients. We also showed that the selective agonist 5-carboxamidotryptamine (5-CT)-induced 5-HT7R activation significantly promotes the production of IL-10, a potent immunosuppressive cytokine in PBMCs. This study provides for the first time a dysregulation of 5-HT7 expression in NTZ-MS patients and its ability to promote IL-10 release, suggesting its protective role. These findings strengthen the evidence that 5-HT7 may play a role in the immuno-protective mechanisms of NTZ in MS disease and could be considered as an interesting therapeutic target in MS. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Multiple Sclerosis)
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Review

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10 pages, 625 KiB  
Review
Health Disparities in Multiple Sclerosis among Hispanic and Black Populations in the United States
by Michael Z. Moore, Carlos A. Pérez, George J. Hutton, Hemali Patel and Fernando X. Cuascut
Biomedicines 2023, 11(4), 1227; https://doi.org/10.3390/biomedicines11041227 - 20 Apr 2023
Cited by 4 | Viewed by 2415
Abstract
Multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system (CNS). Historically, research on MS has focused on White persons with MS. This preponderance of representation has important possible implications for minority populations with MS, from developing effective therapeutic agents [...] Read more.
Multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system (CNS). Historically, research on MS has focused on White persons with MS. This preponderance of representation has important possible implications for minority populations with MS, from developing effective therapeutic agents to understanding the role of unique constellations of social determinants of health. A growing body of literature involving persons of historically underrepresented races and ethnicities in the field of multiple sclerosis is assembling. Our purpose in this narrative review is to highlight two populations in the United States: Black and Hispanic persons with multiple sclerosis. We will review the current understanding about the patterns of disease presentation, genetic considerations, response to treatment, roles of social determinants of health, and healthcare utilization. In addition, we explore future directions of inquiry as well as practical methods of meeting these challenges. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Multiple Sclerosis)
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24 pages, 995 KiB  
Review
A Review of Compartmentalised Inflammation and Tertiary Lymphoid Structures in the Pathophysiology of Multiple Sclerosis
by Rachael Kee, Michelle Naughton, Gavin V. McDonnell, Owain W. Howell and Denise C. Fitzgerald
Biomedicines 2022, 10(10), 2604; https://doi.org/10.3390/biomedicines10102604 - 17 Oct 2022
Cited by 10 | Viewed by 3921
Abstract
Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system (CNS). The most common form of MS is a relapsing–remitting disease characterised by acute episodes of demyelination associated with the breakdown of the blood–brain barrier (BBB). In the relapsing–remitting [...] Read more.
Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system (CNS). The most common form of MS is a relapsing–remitting disease characterised by acute episodes of demyelination associated with the breakdown of the blood–brain barrier (BBB). In the relapsing–remitting phase there is often relative recovery (remission) from relapses characterised clinically by complete or partial resolution of neurological symptoms. In the later and progressive stages of the disease process, accrual of neurological disability occurs in a pathological process independent of acute episodes of demyelination and is accompanied by a trapped or compartmentalised inflammatory response, most notable in the connective tissue spaces of the vasculature and leptomeninges occurring behind an intact BBB. This review focuses on compartmentalised inflammation in MS and in particular, what we know about meningeal tertiary lymphoid structures (TLS; also called B cell follicles) which are organised clusters of immune cells, associated with more severe and progressive forms of MS. Meningeal inflammation and TLS could represent an important fluid or imaging marker of disease activity, whose therapeutic abrogation might be necessary to stop the most severe outcomes of disease. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Multiple Sclerosis)
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