Journal of Clinical Medicine

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12 pages, 1719 KiB

Open AccessArticle

Trans-Endothelial Migration of Memory T Cells Is Impaired in Alemtuzumab-Treated Multiple Sclerosis Patients

by Kristy Nguyen, Pierre Juillard, Simon Hawke, Georges E. Grau and Felix Marsh-Wakefield

J. Clin. Med. 2022, 11(21), 6266; https://doi.org/10.3390/jcm11216266 - 24 Oct 2022

Cited by 5 | Viewed by 1503

Abstract

The breakdown of the blood–brain barrier (BBB) and the trans-endothelial migration of lymphocytes are central events in the development of multiple sclerosis (MS). Autoreactive T cells are major players in MS pathogenesis, which are rapidly depleted following alemtuzumab treatment. This modulation, in turn, [...] Read more.

The breakdown of the blood–brain barrier (BBB) and the trans-endothelial migration of lymphocytes are central events in the development of multiple sclerosis (MS). Autoreactive T cells are major players in MS pathogenesis, which are rapidly depleted following alemtuzumab treatment. This modulation, in turn, inhibits CNS inflammation, but alemtuzumab’s effect on T cell migration into the CNS has been less studied. Human brain endothelial cells were stimulated with pro-inflammatory cytokines to mimic an inflamed BBB in vitro. Peripheral blood mononuclear cells from healthy controls, untreated or alemtuzumab-treated patients with relapsing-remitting MS (RRMS) were added to the BBB model to assess their transmigratory capacity. Here, the migration of CD4⁺ effector memory T (T^EM) and CD8⁺ central memory T (T^CM) cells across the BBB was impaired in alemtuzumab-treated patients. Naïve T (T^naïve) cells were unable to migrate across all groups. CD38 was lowly expressed on CD8⁺ T^CM cells, particularly for RRMS patients, compared to CD8⁺ T^naïve cells. CD62L expression was lower on CD4⁺ T^EM cells than CD4⁺ T^naïve cells and decreased further in alemtuzumab-treated patients. These data suggest that repopulated memory T cells are phenotypically different from naïve T cells, which may affect their transmigration across the BBB in vitro. Full article

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

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13 pages, 919 KiB

Open AccessArticle

Cladribine Reduces Trans-Endothelial Migration of Memory T Cells across an In Vitro Blood–Brain Barrier

by Rachel K. Ford, Pierre Juillard, Simon Hawke, Georges E. Grau and Felix Marsh-Wakefield

J. Clin. Med. 2022, 11(20), 6006; https://doi.org/10.3390/jcm11206006 - 12 Oct 2022

Cited by 7 | Viewed by 1550

Abstract

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS) induced by immune dysregulation. Cladribine has been championed for its clinical efficacy with relatively minor side effects in treating MS. Although it is proposed that cladribine exerts an anti-migratory [...] Read more.

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS) induced by immune dysregulation. Cladribine has been championed for its clinical efficacy with relatively minor side effects in treating MS. Although it is proposed that cladribine exerts an anti-migratory effect on lymphocytes at the blood–brain barrier (BBB) in addition to its lymphocyte-depleting and modulating effects, this has not been properly studied. Here, we aimed to determine if cladribine treatment influences trans-endothelial migration of T cell subsets across an inflamed BBB. Human brain endothelial cells stimulated with pro-inflammatory cytokines were used to mimic the BBB. Peripheral blood mononuclear cells were obtained from healthy controls, untreated and cladribine-treated MS patients. The trans-endothelial migration of CD4⁺ effector memory T (T^EM) and CD8⁺ central memory T (T^CM) cells was reduced in cladribine-treated MS patients. CD28 expression was decreased on both CD4⁺ T^EM and CD8⁺ T^CM cells, suggesting lowered peripheral activation of these cells thereby maintaining the integrity of the BBB. In addition, these cells have likely reconstituted following cladribine treatment, revealing a long-term anti-migratory effect. These results highlight new mechanisms by which cladribine acts to control MS pathogenesis. Full article

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

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14 pages, 1744 KiB

Open AccessArticle

The Rate of Hospitalization of Pregnant Women with Multiple Sclerosis in Poland

by Dorota Walkiewicz, Bożena Adamczyk, Michał Maluchnik, Jakub Perwieniec, Krzysztof Podwójcic, Mateusz Szeląg, Michał Zakrzewski, Konrad Rejdak, Agnieszka Słowik, Marcin Wnuk and Monika Adamczyk-Sowa

J. Clin. Med. 2022, 11(19), 5615; https://doi.org/10.3390/jcm11195615 - 23 Sep 2022

Viewed by 1467

Abstract

Multiple sclerosis (MS) is most often diagnosed in women of childbearing age. Therefore, it is important to examine the impact of pregnancy on the course of MS and to enable patients to make decisions about motherhood based on reliable data. The main objective [...] Read more.

Multiple sclerosis (MS) is most often diagnosed in women of childbearing age. Therefore, it is important to examine the impact of pregnancy on the course of MS and to enable patients to make decisions about motherhood based on reliable data. The main objective of this study was to assess the impact of pregnancy on the course of MS by comparing the frequency of MS-related hospitalizations during pregnancy and 40 weeks postpartum versus 40 weeks before pregnancy. We used administrative health claims to identify female patients with MS, their deliveries, and their MS-related hospital admissions and calculated the frequency of MS-related hospital admissions before, during, and after pregnancy. We observed that MS is diagnosed approximately three times less often during pregnancy than before or after pregnancy. The number of MS-related hospital admissions decreased during pregnancy, especially in the third trimester. In contrast with other studies, we did not observe an increased level of MS-related admissions postpartum. The number of hospitalizations reported with steroid injections and emergency department visits also decreased during pregnancy. Our results show that pregnancy has a protective effect on the course of MS. Full article

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

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16 pages, 1266 KiB

Open AccessArticle

Assistive Technology in Multiple Sclerosis Patients—Two Points of View

by Agnieszka Korchut, Veronique Petit, Ewelina Szwedo-Brzozowska and Konrad Rejdak

J. Clin. Med. 2022, 11(14), 4068; https://doi.org/10.3390/jcm11144068 - 14 Jul 2022

Viewed by 1808

Abstract

Objective: The goal of our study was determining the current needs and acceptance of patients with multiple sclerosis (MS) in the field of assistive technologies using materials from the “RAMCIP” project (Robotic Assistant for Mild Cognitive Impairment Patient at Home). Methods: There were [...] Read more.

Objective: The goal of our study was determining the current needs and acceptance of patients with multiple sclerosis (MS) in the field of assistive technologies using materials from the “RAMCIP” project (Robotic Assistant for Mild Cognitive Impairment Patient at Home). Methods: There were two target groups: a population with MS, and medical personnel experienced in treating MS patients. This study was based on a two-step design method (workshops and surveys). Using the Likert scale, we identified the prioritization of users’ needs. Additionally, demographic and disease-specific data and their correlations with each other and with the level of priority of functionality were analyzed. Moreover, the acceptance aspect of the assistant robot and the respondents’ readiness to use it were determined. Results: We gathered 307 completed surveys (176 from MS patients, 131 from medical personnel). Functional capabilities from the safety category were a high priority in most cases. The medium priority functions concerned daily activities that required physical assistance and home management. The differences in prioritization between the two groups were also found. Variables such as age, level of disability, cognitive impairment, depression, and fatigue were associated with the priority level of the functionalities. Conclusion: In summary, our findings might contribute to a better adaptation of robotic assistants to the needs and expectations of the MS population. Full article

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

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9 pages, 610 KiB

Open AccessArticle

by Jakub Perwieniec, Krzysztof Podwójcic, Michał Maluchnik, Mateusz Szeląg, Dorota Walkiewicz, Michał Zakrzewski, Amelia Droździkowska, Bogumił Kamiński, Adriana Zasybska, Marcin Wnuk, Agnieszka Słowik and Konrad Rejdak

J. Clin. Med. 2021, 10(17), 3821; https://doi.org/10.3390/jcm10173821 - 26 Aug 2021

Cited by 5 | Viewed by 2750

Abstract

Increasing evidence supports the observation that multiple sclerosis (MS) has a preclinical period, with various prodromal signs and symptoms more frequently represented in patients with confirmed MS many years later. Considering the apparent gender differences in the incidence and clinical course of MS, [...] Read more.

Increasing evidence supports the observation that multiple sclerosis (MS) has a preclinical period, with various prodromal signs and symptoms more frequently represented in patients with confirmed MS many years later. Considering the apparent gender differences in the incidence and clinical course of MS, it remains unclear whether it could be reflected in prodromal symptom features. This study aimed to compare a broad spectrum of prodromal signs and symptoms between males and females in the 7-year period before the definite diagnosis of MS. Data came from the central register of the national payer of services, financed under the public healthcare system in Poland. They covered a 7-year period of patient health record claims, from 2009 to 2016. The following groups of symptoms were significant with women: musculoskeletal (p < 0.001), ophthalmic (p < 0.001), laryngological (p < 0.001), digestive system (p < 0.001), urinary tract (p < 0.001), mental (p < 0.001), cardiovascular (p < 0.001), complaints and headaches (p < 0.001). There was also a weak correlation with head injuries (p = 0.03) while dermatological and reproductive system complaints did not appear to be significant (p < 0.05). For males, the following groups of symptoms were significant: musculoskeletal (p < 0.001), ophthalmic (p < 0.001), laryngological (p = 0.007), cardiovascular system symptoms (p < 0.001), and headaches (p < 0.001). Interestingly, reproductive system problems were overrepresented in the male population (p = 0.008). There was no significant correlation with MS risk for dermatological, digestive, urinary, and mental complaints. Similarly, head injuries were not significant. Our results shed more light on well-known differences in the epidemiological and clinical characteristics between sexes in multiple sclerosis, and show differences in prodromal complaints before MS onset. Full article

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

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Review

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13 pages, 1663 KiB

Open AccessReview

MSProDiscuss™ Clinical Decision Support Tool for Identifying Multiple Sclerosis Progression

by Tjalf Ziemssen, Jo Vandercappellen, Valeria Jordan Mondragon and Gavin Giovannoni

J. Clin. Med. 2022, 11(15), 4401; https://doi.org/10.3390/jcm11154401 - 28 Jul 2022

Cited by 4 | Viewed by 3051

Abstract

This article describes the rationale for the development of the MSProDiscuss™ clinical decision support (CDS) tool, its development, and insights into how it can help neurologists improve care for patients with multiple sclerosis (MS). MS is a progressive disease characterized by heterogeneous symptoms [...] Read more.

This article describes the rationale for the development of the MSProDiscuss™ clinical decision support (CDS) tool, its development, and insights into how it can help neurologists improve care for patients with multiple sclerosis (MS). MS is a progressive disease characterized by heterogeneous symptoms and variable disease course. There is growing consensus that MS exists on a continuum, with overlap between relapsing–remitting and secondary progressive phenotypes. Evidence demonstrates that neuroaxonal loss occurs from the outset, that progression can occur independent of relapse activity, and that continuous underlying pathological processes may not be reflected by inflammatory activity indicative of the patient’s immune response. Early intervention can benefit patients, and there is a need for a tool that assists physicians in rapidly identifying subtle signs of MS progression. MSProDiscuss, developed with physicians and patients, facilitates a structured approach to patient consultations. It analyzes multidimensional data via an algorithm to estimate the likelihood of progression (the MSProDiscuss score), the contribution of various symptoms, and the impact of symptoms on daily living, enabling a more personalized approach to treatment and disease management. Data from CDS tools such as MSProDiscuss offer new insights into disease course and facilitate informed decision-making and a holistic approach to MS patient care. Full article

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

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10 pages, 269 KiB

Open AccessReview

Novel Drugs in a Pipeline for Progressive Multiple Sclerosis

by Klaudia Sapko, Anna Jamroz-Wiśniewska and Konrad Rejdak

J. Clin. Med. 2022, 11(12), 3342; https://doi.org/10.3390/jcm11123342 - 10 Jun 2022

Cited by 5 | Viewed by 2978

Abstract

Multiple sclerosis (MS) is a widely known inflammatory, demyelinating disease of the central nervous system. The pathogenesis of progressive multiple sclerosis (PMS) is a complex, multi-level process that causes therapeutic difficulties. Along with variables such as age and duration of the disease, pathogenetic [...] Read more.

Multiple sclerosis (MS) is a widely known inflammatory, demyelinating disease of the central nervous system. The pathogenesis of progressive multiple sclerosis (PMS) is a complex, multi-level process that causes therapeutic difficulties. Along with variables such as age and duration of the disease, pathogenetic mechanisms change from inflammatory to neurodegenerative processes. Therefore, the efficacy of available anti-inflammatory drugs approved for the treatment of PMS, such as ocrelizumab or siponimod, is limited in time. In search of innovative solutions, several research studies have been conducted to evaluate the effectiveness of drugs with neuroprotective or remyelinating effects in PMS, including biotin, ibudilast, simvastatin, alpha-lipoic acid, clemastine, amiloride, fluoxetine, riluzole, masitinib, opicinumab, and lamotrigine. The current review includes those compounds, which have entered the clinical phase of assessment, and the authors discuss future prospects for successful PMS treatment. Full article

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

14 pages, 642 KiB

Open AccessReview

Obesity and Multiple Sclerosis—A Multifaceted Association

by Thomas-Gabriel Schreiner and Tudor-Marcel Genes

J. Clin. Med. 2021, 10(12), 2689; https://doi.org/10.3390/jcm10122689 - 18 Jun 2021

Cited by 30 | Viewed by 3466

Abstract

Background: Given the common elements in the pathophysiological theories that try to explain the appearance and evolution of obesity and multiple sclerosis, the association between the two pathologies has become an increasingly researched topic in recent years. On the one hand, there is [...] Read more.

Background: Given the common elements in the pathophysiological theories that try to explain the appearance and evolution of obesity and multiple sclerosis, the association between the two pathologies has become an increasingly researched topic in recent years. On the one hand, there is the chronic demyelinating inflammation caused by the autoimmune cascade of multiple sclerosis, while on the other hand, according to the latest research, it has been shown that obesity shares an inflammatory component with most chronic diseases. Methods: The authors performed independent research of the available literature in the most important electronic databases (PubMed, Google Scholar, Embase, and Science Direct) in February 2021. After applying the exclusion criteria, the reviewers focused on the most relevant articles published during the last 10 years with respect to epidemiology and pathophysiology. Results: The data presented are a step forward in trying to elucidate the intricate relationship between obesity and MS, especially the causal relationship between childhood and adolescent obesity and MS, focusing on the epidemiological associations observed in the most relevant observational studies conducted in recent years. In the second part, the authors comment on the latest findings related to the pathophysiological mechanisms that may explain the correlations between obesity and multiple sclerosis, focusing also on the role of adipokines. Conclusions: Based on available epidemiological data, obesity in early life appears to be strongly associated with a higher risk of MS development, independent of other risk factors. Although much research has been done on the pathophysiology of obesity, MS, their possible common mechanism, and the role of adipokines, further studies are needed in order to explain what remains unknown. No relevant data were found regarding the association between obesity, disability (high EDSS score), and mortality risk in MS patients. Thus, we consider that this topic should be elucidated in future research. Full article

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

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Other

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8 pages, 240 KiB

Open AccessBrief Report

Modified Rio Score with Platform Therapy Predicts Treatment Success with Fingolimod and Natalizumab in Relapsing-Remitting Multiple Sclerosis Patients

by Anna Jamroz-Wiśniewska, Radosław Zajdel, Agnieszka Słowik, Monika Marona, Marcin Wnuk, Monika Adamczyk-Sowa, Bożena Adamczyk, Anetta Lasek-Bal, Przemysław Puz, Arkadiusz Stęposz, Ewa Krzystanek, Maja Patalong-Ogiewa, Anna Pokryszko-Dragan, Sławomir Budrewicz, Dorota Koziarska, Anna Karbicka, Sławomir Wawrzyniak, Waldemar Fryze, Marzena Furtak-Niczyporuk and Konrad Rejdak

J. Clin. Med. 2021, 10(9), 1830; https://doi.org/10.3390/jcm10091830 - 22 Apr 2021

Cited by 6 | Viewed by 3170

Abstract

Background: Reliable markers of disease outcomes in multiple sclerosis (MS) would help to predict the response to treatment in patients treated with high efficacy drugs. No evidence of disease activity (NEDA) has become a treatment goal whereas the modified Rio score (MRS) predicts [...] Read more.

Background: Reliable markers of disease outcomes in multiple sclerosis (MS) would help to predict the response to treatment in patients treated with high efficacy drugs. No evidence of disease activity (NEDA) has become a treatment goal whereas the modified Rio score (MRS) predicts future suboptimal responders to treatment. The aim of our study was to identify factors that would predict poor response to treatment with natalizumab and fingolimod. Methods: In the multicenter prospective trial, 336 subjects were enrolled, initiating therapy with natalizumab (n = 135) or fingolimod (n = 201). Data on relapse rate, the expanded disability status scale, and MRI results were collected, and MRS was estimated. Results: NEDA-3 after the first year of therapy was 73.9% for natalizumab and 54.8% for fingolimod (p < 0.0001). Patients with MRS = 0 in the last year on platform therapy had the best NEDA-3 (71%) and patients with MRS = 3 had the worst NEDA-3 (41%) in the first year of treatment with the second-line therapy. Conclusion: We conclude that switching to the second-line therapy should occur earlier to enable better results for patients treated with natalizumab or fingolimod. The outcome on both drugs is better with better neurological conditions and lower MRS of the patient on the platform therapy. Full article

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

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