Journal Description
Sclerosis
Sclerosis
is an international, peer-reviewed, open access journal on sclerosis and related diseases, published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- Rapid Publication: first decisions in 16 days; acceptance to publication in 5.8 days (median values for MDPI journals in the first half of 2024).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names are published annually in the journal.
- Sclerosis is a companion journal of JCM.
Latest Articles
The Road Well Traveled: From Inflammasomes to Collagen Export During Fibrosis
Sclerosis 2024, 2(4), 378-393; https://doi.org/10.3390/sclerosis2040025 - 5 Dec 2024
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Collagen export from the endoplasmic reticulum is required for normal tissue homeostasis, and yet, in fibrotic disorders, this process is significantly upregulated. In this review, we will focus on the signaling cascade from the inflammasome and how that promotes collagen via proinflammatory/profibrotic cytokines.
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Collagen export from the endoplasmic reticulum is required for normal tissue homeostasis, and yet, in fibrotic disorders, this process is significantly upregulated. In this review, we will focus on the signaling cascade from the inflammasome and how that promotes collagen via proinflammatory/profibrotic cytokines. Concordantly, these cytokines also induce the expression of TANGO1 to cope with the increased movement of collagen through the endoplasmic reticulum. In normal and fibrotic cells, this pathway is finely tuned to meet the necessary demand in collagen export. Currently, the role of TANGO1 in fibrotic disorders and how the inflammasome induces its expression is not well understood. In this review, we will assimilate the current information concerning inflammasome activation and how it induces TANGO1 expression, leading to fibrosis.
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Open AccessArticle
A 2-Year Longitudinal Neuropsychological Study in Relapsing-Remitting Multiple Sclerosis: A Selective Decline in Social Cognition?
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Nathalie Ehrlé and Margot Papinsac
Sclerosis 2024, 2(4), 365-377; https://doi.org/10.3390/sclerosis2040024 - 30 Nov 2024
Abstract
Background/Objectives. Social cognition (SC), which implies the emotional and intellectual understanding of oneself and others, is an important facet of neuropsychological functioning concurrently to academic cognition (AC), which concerns non-social abilities (memory, language…). In relapsing-remitting multiple sclerosis (RRMS), it is not clear whether
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Background/Objectives. Social cognition (SC), which implies the emotional and intellectual understanding of oneself and others, is an important facet of neuropsychological functioning concurrently to academic cognition (AC), which concerns non-social abilities (memory, language…). In relapsing-remitting multiple sclerosis (RRMS), it is not clear whether a cognitive decline occurs in both SC and AC nor whether a link exists between these two cognitive domains. The objective of the present longitudinal study was to conduct an extensive examination of both AC and SC in RRMS to document a 2-year evolution and to look for potential correlations between AC and SC. Methods. The neuropsychological results (AC and SC) of 48 RRMS patients obtained in clinical practice were retrospectively considered; 38 of the patients (30 females) were assessed again about 2 years later. Non-parametric tests were applied to test the intra-group cognitive evolution (Wilcoxon) and the link between AC and SC evolution (Spearman). Results. Whereas AC showed a stability or an improvement of performances during the retest, SC presented the reverse pattern, with a stability or a significant decline in facial emotion (recognition and discrimination) and humor perception. No significant statistical correlation was found between the significant modification of AC and SC during follow-up. Conclusions. The short-term deleterious evolution observed selectively for SC in the present study suggests that SC should be selected as a cognitive marker for RRMS follow-up, and that extensive examination may be preferred to investigate specific SC changes.
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(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis)
Open AccessOpinion
The Conjecture of Poser on the Origins of Multiple Sclerosis: New Theoretical Considerations and Proposal
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Victor M. Rivera
Sclerosis 2024, 2(4), 355-364; https://doi.org/10.3390/sclerosis2040023 - 14 Nov 2024
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The origins of multiple sclerosis (MS) have been a subject intriguing researchers and scholars for generations. The multifactorial etiological nature of the disease continues to be studied as a complex combination of genetic aspects and environmental or external risk elements contributing to the
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The origins of multiple sclerosis (MS) have been a subject intriguing researchers and scholars for generations. The multifactorial etiological nature of the disease continues to be studied as a complex combination of genetic aspects and environmental or external risk elements contributing to the development of the disease. Descriptions of symptoms or clinical disorders suggestive of MS affecting historical figures or prominent individuals (i.e., Lidwina of Schiedam, Heinrich Heine, Augustus d’Este) did not provide clues on the origin of the disease, except for the observation that all these early possible cases were white European individuals. MS was initially framed as a neurological entity and named in the 19th century by the historical participation of the French masters Cruveilhier, Vulpian, and Charcot, among others, but the question of how the disease originated was not addressed until Charles Poser raised his conjecture on the origins of MS in two historical essays (1994 and 1995), raising the question if the Viking voyages and invasions from the 8th to the 11th century carried the Scandinavian MS genetic risk factor to Europe and the rest of the known world at that time. Poser did not have the benefit of access to ancient molecular DNA data and based his theoretical postulation on interesting historical and archeological observations. A series of studies and opinions published in 2024, utilizing sophisticated genetic analyses and genome identification, archeological DNA analysis, and other advanced techniques and biological computation, distinctly demonstrate the installation of HLA-DRB1*15:01 (class II allele) in Europe (with a higher prevalence in Scandinavia) following the massive Yamnaya pastoralists migration from the Pontic Steppe in Eurasia to western Europe (~5000 to 2500 BCE). The data suggest HLA-DRB1*15:01, the strongest genetic association with MS, underwent an evolutive switch (“thrifty drift”) from immune protector against novel zoonotic diseases appearing among the early pastoralists of the Yamnaya civilization to an autoimmune deleterious reactor to molecular mimicry and self-antigens, enabled by lifestyle changes and reduction of pastoralism once communities settled in Europe after the migration from the Pontic Steppe. This writer offers a new perspective on the origins of MS through a phase 1, the ancient east to west migration in the late Bronze Age, consolidating the HLA-DRB1*15:01 haplotype in Europe, and phase 2, the additional dissemination of the genetic MS risk through the Viking invasions, reinforcing inheritability by enabling a homozygous dominant inheritance.
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Open AccessFeature PaperArticle
Resilience, Mental Health, Sleep, and Smoking Mediate Pathways Between Lifetime Stressors and Multiple Sclerosis Severity
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Carri S. Polick, Hala Darwish, Leonardo Pestillo de Oliveira, Ali Watson, Joao Ricardo Nickenig Vissoci, Patrick S. Calhoun, Robert J. Ploutz-Snyder, Cathleen M. Connell, Tiffany J. Braley and Sarah A. Stoddard
Sclerosis 2024, 2(4), 341-354; https://doi.org/10.3390/sclerosis2040022 - 30 Oct 2024
Abstract
Introduction: Lifetime stressors (e.g., poverty, violence, discrimination) have been linked to features of multiple sclerosis (MS); yet mechanistic pathways and relationships with cumulative disease severity remain nebulous. Further, protective factors like resilience, that may attenuate the effects of stressors on outcomes, are seldom
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Introduction: Lifetime stressors (e.g., poverty, violence, discrimination) have been linked to features of multiple sclerosis (MS); yet mechanistic pathways and relationships with cumulative disease severity remain nebulous. Further, protective factors like resilience, that may attenuate the effects of stressors on outcomes, are seldom evaluated. Aim: To deconstruct pathways between lifetime stressors and cumulative severity on MS outcomes, accounting for resilience. Methods: Adults with MS (N = 924) participated in an online survey through the National MS Society listserv. Structural equation modeling was used to examine the direct and indirect effects of lifetime stressors (count/severity) on MS severity (self-reported disability, relapse burden, fatigue, pain intensity, and interference) via resilience, mental health (anxiety and depression), sleep disturbance, and smoking. Results: The final analytic model had an excellent fit (GFI = 0.998). Lifetime stressors had a direct relationship with MS severity (β = 0.27, p < 0.001). Resilience, mental health, sleep disturbance, and smoking significantly mediated the relationship between lifetime stressors and MS severity. The total effect of the mediation was significant (β = 0.45). Conclusions: This work provides foundational evidence to inform the conceptualization of pathways by which stress could influence MS disease burden. Resilience may attenuate the effects of stressors, while poor mental health, smoking, and sleep disturbances may exacerbate their impact. Parallel with usual care, these mediators could be targets for early multimodal therapies to improve the disease course.
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(This article belongs to the Special Issue Exploring Environmental Risk Factors for Disease Progression in Multiple Sclerosis and Amyotrophic Lateral Sclerosis)
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Open AccessReview
Preclinical and Clinical Data on Current Therapeutic Options for Micro- and Macrovascular Abnormalities in Systemic Sclerosis
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Konstantina Bakopoulou, Issa El Kaouri, Elina Siliogka, Periklis Siliogkas, Russka Shumnalieva and Tsvetelina Velikova
Sclerosis 2024, 2(4), 322-340; https://doi.org/10.3390/sclerosis2040021 - 29 Oct 2024
Abstract
Background: Systemic sclerosis (SSc) represents a multidimensional disease affecting various organs and systems, with the common denominator being the vascular pathology encountered in the micro- and macrocirculation of SSc patients. Recently, much progress has been made toward understanding the molecular basis of endothelial
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Background: Systemic sclerosis (SSc) represents a multidimensional disease affecting various organs and systems, with the common denominator being the vascular pathology encountered in the micro- and macrocirculation of SSc patients. Recently, much progress has been made toward understanding the molecular basis of endothelial injury and subsequent fibroblast activation, thus paving the way for specific therapy that can target and counteract these processes. Aim: In this review, we examined the latest preclinical and clinical data on therapeutic options to address vascular abnormalities in SSc. Results: We discuss the efficacy of current treatments, including pharmacological agents and emerging therapies, in mitigating vascular damage and improving patient outcomes based on preclinical models and clinical trials that offer evidence of their safety and effectiveness. Conclusions: Although promising therapeutic strategies emerge, optimizing the management of vascular abnormalities in SSc requires further research.
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(This article belongs to the Special Issue Recent Advances in Understanding Systemic Sclerosis)
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Open AccessCase Report
Multiple Sclerosis and Subcutaneous Panniculitis-like T Cell Lymphoma with Hemophagocytic Syndrome: The Role of Treatment Sequencing in the Pathogenetic Mechanism
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Assunta Trinchillo, Antonio Carotenuto, Antonio Luca Spiezia, Daniele Caliendo, Alessandro Severino, Cristina Di Monaco, Carmine Iacovazzo, Giuseppe Servillo, Vincenzo Brescia Morra and Roberta Lanzillo
Sclerosis 2024, 2(4), 314-321; https://doi.org/10.3390/sclerosis2040020 - 28 Oct 2024
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Introduction: Although panniculitis-like T cell lymphoma (SPTCL) and hemophagocytic syndrome (HSP) have been described as complications following immunosuppressive treatments, there are no reported cases of concomitant SPTCL/HSP and multiple sclerosis (MS). Materials and Methods: We describe the case of a patient affected by
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Introduction: Although panniculitis-like T cell lymphoma (SPTCL) and hemophagocytic syndrome (HSP) have been described as complications following immunosuppressive treatments, there are no reported cases of concomitant SPTCL/HSP and multiple sclerosis (MS). Materials and Methods: We describe the case of a patient affected by an aggressive phenotype of relapsing remitting MS, characterized by consecutive severe relapses with no complete remission. He developed panniculitis-like T cell lymphoma (SPTCL) and hemophagocytic syndrome (HSP) after receiving multiple immunosuppressive treatments in sequence. Despite the aggressive nature of these complications, the patient responded well to a combination of Gemcitabine and Cisplatin. Discussion and Conclusions: With this case, we suggest that physicians always consider blood diseases as possible MS therapy complications, especially in the sequencing setting, and also consider uncommon treatments in those with autoimmune predispositions.
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Open AccessFeature PaperReview
Insights and Future Perspectives in Calcinosis Cutis Associated with Systemic Sclerosis
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Luna Lazar, Mette Mogensen, Mikael Ploug Boesen and Anne Braae Olesen
Sclerosis 2024, 2(4), 302-313; https://doi.org/10.3390/sclerosis2040019 - 10 Oct 2024
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Introduction: Calcinosis cutis (CC), the pathological deposition of calcium salts in the skin, is a frequent and challenging complication of systemic sclerosis (SSc). Despite its high prevalence, the underlying pathophysiology remains poorly understood, complicating treatment strategies. Material and Methods: This narrative review synthesizes
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Introduction: Calcinosis cutis (CC), the pathological deposition of calcium salts in the skin, is a frequent and challenging complication of systemic sclerosis (SSc). Despite its high prevalence, the underlying pathophysiology remains poorly understood, complicating treatment strategies. Material and Methods: This narrative review synthesizes the literature on CC in the context of SSc. The current understanding and treatment of CC in SSc is reviewed, focusing on the role of hypoxia in its pathogenesis and the therapeutic potential of sodium thiosulfate (STS). Results and Discussion: Research indicates a potential link between hypoxia and the development of CC in SSc, shedding light on novel pathogenic mechanisms. Additionally, promising results from treatments such as STS spurs interest in conducting larger, randomized controlled trials to validate these findings.
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(This article belongs to the Special Issue Recent Advances in Understanding Systemic Sclerosis)
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Open AccessReview
A Narrative Review of Therapeutic Options in Systemic Sclerosis Associated Interstitial Lung Disease
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Robert Harrington, Patricia Harkins and Richard Conway
Sclerosis 2024, 2(4), 288-301; https://doi.org/10.3390/sclerosis2040018 - 30 Sep 2024
Abstract
Background: Interstitial lung disease (ILD) has replaced scleroderma renal crisis as the leading cause of mortality in systemic sclerosis (SSc), with a 10-year mortality of 40%. There have been well-powered randomised control trials (RCTs) demonstrating the effect of cyclophosphamide (CYC), mycophenolic acid (MMF),
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Background: Interstitial lung disease (ILD) has replaced scleroderma renal crisis as the leading cause of mortality in systemic sclerosis (SSc), with a 10-year mortality of 40%. There have been well-powered randomised control trials (RCTs) demonstrating the effect of cyclophosphamide (CYC), mycophenolic acid (MMF), nintedanib and tocilizumab (TCZ) in SSc-ILD but a paucity of sufficiently powered studies investigating other agents in the disease. Methods: This is a narrative review which examines the existing evidence for immunosuppressive treatments, transplant and adjunctive therapies in SSc-ILD by reviewing the key landmark trials in the last two decades. Results: MMF for 2 years is as effective as oral CYC for 1 year. Rituximab (RTX) is non-inferior to CYC. TCZ appears to have a beneficial effective regardless of the extent of lung involvement. Conclusions: There is now a strong evidence base supporting the use of MMF as the first line option in SSc-ILD. RTX, CYC and TCZ are viable therapeutic options if there is ILD progression on MMF. Anti-fibrotic and pulmonary arterial (PAH) treatments likely add long-term synergistic benefits. There remains a role for lung transplantation in select patients.
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(This article belongs to the Special Issue Recent Advances in Understanding Systemic Sclerosis)
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Open AccessCommunication
Burden in Multiple Sclerosis Caregivers: A Single-Center Experience
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Miranda Melgar-de-la-Paz, Moisés Manuel Gallardo-Pérez, Luis Enrique Hamilton-Avilés, Paola Negrete-Rodríguez, Gloria Erendy Cruz-Pérez, Danae García-Vélez, Guillermo Ocaña-Ramm, Olivia Lira-Lara, Juan Carlos Olivares-Gazca, Guillermo J. Ruiz-Delgado and Guillermo J. Ruiz-Argüelles
Sclerosis 2024, 2(3), 280-287; https://doi.org/10.3390/sclerosis2030017 - 22 Sep 2024
Abstract
Objective: To analyze the relation between Zarit and the MSQol-54 scales in caregivers and patients with multiple sclerosis (MS). Methods: Our study included 167 caregivers of 153 patients with MS in a single center, from July 2021 to December 2023. Results: Evaluation of
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Objective: To analyze the relation between Zarit and the MSQol-54 scales in caregivers and patients with multiple sclerosis (MS). Methods: Our study included 167 caregivers of 153 patients with MS in a single center, from July 2021 to December 2023. Results: Evaluation of the Zarit score revealed a median score of 11 (IQR = 4–21.75). Up to 126 caregivers had a low burden level, while 8 had moderate–severe burden, and 1 caregiver showed a severe burden score. Correlation analysis revealed that the Zarit score significantly correlated positively with the following variables: patient age (r = 0.25) and EDSS (r = 0.40); and a significant negative correlation was observed with the following variables: Physical Health Composite Score (r = −0.48) and Mental Health Composite Score (r = −0.34). Conclusions: Most caregivers either carry a low burden or none, as well as an inverse correlation between the Zarit and the Physical and Mental Health composite scores of the MSQol-54 instrument.
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(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis)
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Open AccessArticle
Assessing the Relationship between Personality Traits and Clinical Aspects in Individuals with Multiple Sclerosis
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Cosima Meier, Andreas Edelmann, Marlon Pflüger and Pasquale Calabrese
Sclerosis 2024, 2(3), 266-279; https://doi.org/10.3390/sclerosis2030016 - 15 Sep 2024
Abstract
Personality traits significantly impact chronic diseases, affecting disease management, coping strategies, psychological well-being, and overall quality of life. People with Multiple Sclerosis (MS) often exhibit dysfunctional personality traits associated with negative disease outcomes, including personality changes and disorders. Our study explored personality traits
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Personality traits significantly impact chronic diseases, affecting disease management, coping strategies, psychological well-being, and overall quality of life. People with Multiple Sclerosis (MS) often exhibit dysfunctional personality traits associated with negative disease outcomes, including personality changes and disorders. Our study explored personality traits and their connection to clinical aspects and cognitive functioning in MS patients. We used two assessment tools: the NEO-FFI and the Lüscher Color Test, which is based on color preferences. The aim was to investigate the applicability of the Lüscher Color Test in MS patients. The study included 20 participants from the Swiss Multiple Sclerosis Cohort. The results showed elevated scores in neuroticism, openness, agreeableness, and conscientiousness in MS patients, while there was no effect for extraversion. A significant positive correlation was found between neuroticism and the preference for green-blue color shades, as well as a rejection of orange-reddish color shades in the Lüscher Color Test, indicating avoidance of stimulation and engagement. Another notable positive association was found between openness and the preference for lighter shades in the Lüscher Color Test. Although this relation did not reach the level of statistical significance, it suggests a potential trend. Neuroticism on its own predicted anxiety and fatigue, while the preference for lighter shades in the Lüscher Color Test correlated with EDSS scores. No significant correlations were found between personality traits and cognitive aspects. Despite the limitations of this study, our results highlight the importance of assessing personality traits in MS patients, using either the NEO-FFI or the Lüscher Color Test, to improve treatment strategies and explore emotional conflicts related to the disease.
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(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis)
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Open AccessReview
Anti-Inflammatory Benefits of Vitamin D and Its Analogues against Glomerulosclerosis and Kidney Diseases
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Theodora Adamantidi, George Maris, Petroula Altantsidou and Alexandros Tsoupras
Sclerosis 2024, 2(3), 217-265; https://doi.org/10.3390/sclerosis2030015 - 26 Aug 2024
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Apart from the significant progress the scientific community has made during the last few decades, inflammation-mediated kidney-related diseases like chronic and diabetic kidney diseases (CKD and DKD) and glomerulosclerosis still continue to raise mortality rates. Recently, conventional therapeutic interventions have been put aside,
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Apart from the significant progress the scientific community has made during the last few decades, inflammation-mediated kidney-related diseases like chronic and diabetic kidney diseases (CKD and DKD) and glomerulosclerosis still continue to raise mortality rates. Recently, conventional therapeutic interventions have been put aside, since natural vitamin D-derived treatment has gained attention and offered several promising outcomes. Within this article, the utilization of vitamin D and its analogues as potential treatment toward kidney-related diseases, due to their anti-inflammatory, antioxidant and anti-fibrotic activity, is outlined. Vitamin D analogues including calcitriol, paricalcitol and 22-oxacalcitriol have been previously explored for such applications, but their hidden potential has yet to be further elucidated. Several clinical trials have demonstrated that vitamin D analogues’ supplementation is correlated with inflammatory signaling and oxidative stress regulation, immunity/metabolism augmentation and subsequently, kidney diseases and healthcare-related infections’ prevention, and the results of these trials are thoroughly evaluated. The highlighted research outcomes urge further study on a plethora of vitamin D analogues with a view to fully clarify their potential as substantial anti-inflammatory constituents of renal diseases-related treatment and their health-promoting properties in many kidney-associated healthcare complications and infections.
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Open AccessReview
Lung Involvement in Systemic Sclerosis—From Pathogenesis to Prediction
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Issa El Kaouri, Konstantina Bakopoulou, Ivan Padjen, Velik Lazarov, Paraskevas Panagiotis Sdralis, Tsvetelina Velikova and Russka Shumnalieva
Sclerosis 2024, 2(3), 199-216; https://doi.org/10.3390/sclerosis2030014 - 17 Aug 2024
Abstract
Systemic sclerosis (SSc) is a rare, multifactorial autoimmune disease characterized by widespread vascular damage and fibrosis. Pulmonary involvement is a significant manifestation of SSc, contributing to considerable morbidity and mortality. Therefore, identifying reliable biomarkers is of the utmost importance. This review explores emerging
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Systemic sclerosis (SSc) is a rare, multifactorial autoimmune disease characterized by widespread vascular damage and fibrosis. Pulmonary involvement is a significant manifestation of SSc, contributing to considerable morbidity and mortality. Therefore, identifying reliable biomarkers is of the utmost importance. This review explores emerging biomarkers to enhance diagnostic accuracy, prognostic assessment, and disease monitoring in SSc lung involvement. We discuss recent findings in immunological biomarkers, inflammatory indicators, and other parameters that can function as potential diagnostic and prognostic tools. A comprehensive understanding of these biomarkers could result in earlier and more accurate detection of pulmonary complications in SSc, aiding in timely intervention. Furthermore, we explore the advances in disease monitoring through innovative biomarkers, focusing on their roles in disease activity and treatment response. Integrating these novel biomarkers into current clinical practice and therapeutic protocols through clinical trials can revolutionize the management of SSc-related lung disease, ultimately improving patient outcomes and quality of life.
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(This article belongs to the Special Issue Recent Advances in Understanding Systemic Sclerosis)
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Open AccessSystematic Review
Pseudobulbar Affect in Patients with Multiple Sclerosis: A Systematic Review
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Silvia Chiereghin, Giulia Purpura, Anna Riva, Renata Nacinovich and Andrea Eugenio Cavanna
Sclerosis 2024, 2(3), 186-198; https://doi.org/10.3390/sclerosis2030013 - 6 Aug 2024
Abstract
Multiple sclerosis (MS) is associated with a high prevalence of emotional disorders affecting the health-related quality of life of patients and their families. Pseudobulbar affect (PBA), also referred to as pathological laughing and crying, is an under-recognized and under-treated co-morbidity. We conducted a
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Multiple sclerosis (MS) is associated with a high prevalence of emotional disorders affecting the health-related quality of life of patients and their families. Pseudobulbar affect (PBA), also referred to as pathological laughing and crying, is an under-recognized and under-treated co-morbidity. We conducted a systematic literature review of 16 studies to determine the prevalence and clinical characteristics of PBA in patients with MS of all ages. Based on conservative figures available from 8/16 studies, the prevalence of PBA in the context of MS was found to range between 2% and 10% (median 10%), with higher percentages in the female population. Possible reasons for the observed variability in the prevalence data include heterogeneity of the diagnostic methodologies and common presence of confounding factors, such as co-morbid affective disorders. The clinical presentation was found to be comparable to that of PBA in the context of other neurological disorders, as it reflected the location of underlying lesions (especially in the brainstem) rather than the associated pathology. Clinicians should be prompted to consider PBA in the differential diagnosis of emotional disorders in the context of MS by using both clinical criteria and psychometric instruments. Further studies should be conducted to develop standardized diagnostic protocols and to optimize therapeutic approaches for the clinical management of this patient population.
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(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis)
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Open AccessSystematic Review
Biomarkers Differentiating RRMS and SPMS in Multiple Sclerosis—A Systematic Review
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Camilla Toftegaard, Charlotte Marie Severinsen and Henrik Boye Jensen
Sclerosis 2024, 2(3), 166-185; https://doi.org/10.3390/sclerosis2030012 - 31 Jul 2024
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Background: This systematic review searched to identify a potential biomarker in serum/plasma or cerebrospinal fluid (CSF) to differentiate between relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). There is currently no definitive method for determining whether a patient is in the
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Background: This systematic review searched to identify a potential biomarker in serum/plasma or cerebrospinal fluid (CSF) to differentiate between relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). There is currently no definitive method for determining whether a patient is in the RRMS course or has converted to the SPMS course. A biomarker could therefore aid the clinician to make this diagnosis. The aim of this study is to assess if there are biomarkers or combinations of biomarkers in serum/plasma or CSF that can detect secondary progression in multiple sclerosis at an early stage. Methods: The PubMed and EMBASE databases were searched to identify relevant studies. Both MeSH terms and text words in the title/abstract were used in both search strategies. The method included forward and backward citation searches. A risk of bias tool was used to assess all the studies that were included. Results: A total of 7581 articles were identified from the initial search. Additionally, 3386 articles were added after the citation search. Of these, 39 articles fulfilled the inclusion criteria and none of the exclusion criteria. The review investigated 28 different biomarkers in CSF and serum/plasma. Discussion: Of the 28 different biomarkers, six biomarkers appeared to be the most promising: neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), Galectin-9, YKL-40/CHI3L1, osteopontin, and MCP-1. This review provides new insights into potential directions for future studies to investigate biomarkers as a diagnostic tool for SPMS.
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Open AccessArticle
Diet-Induced Changes in Functional Disability among People with Multiple Sclerosis: A Secondary Pooled Analysis of Two Randomized Controlled Pilot Trials
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Allison R. Groux, Elizabeth S. Walker, Farnoosh Shemirani, Jennifer E. Lee, Amanda K. Irish, Linda M. Rubenstein, Linda G. Snetselaar, Warren G. Darling, Terry L. Wahls and Tyler J. Titcomb
Sclerosis 2024, 2(3), 156-165; https://doi.org/10.3390/sclerosis2030011 - 4 Jul 2024
Abstract
Emerging evidence links dietary interventions to favorable multiple sclerosis (MS) outcomes; however, evidence for the efficacy of dietary interventions on functional disability remains sparse. Data from two 12-week, randomized, controlled pilot trials were pooled to investigate the efficacy of a modified Paleolithic diet
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Emerging evidence links dietary interventions to favorable multiple sclerosis (MS) outcomes; however, evidence for the efficacy of dietary interventions on functional disability remains sparse. Data from two 12-week, randomized, controlled pilot trials were pooled to investigate the efficacy of a modified Paleolithic diet (Paleo) on functional disability, as assessed by the MS Functional Composite (MSFC), among people diagnosed with MS. Pooled baseline-referenced MSFC scores were calculated from the nine-hole peg test (NHPT), timed 25-foot walk (T25FW), and Paced Auditory Serial Addition Test (PASAT) Z-scores. There was no significant difference in the mean change in MSFC scores between groups (p = 0.07). In the Paleo group, a significant increase was observed in the MSFC scores (p = 0.03), NHPT (p < 0.001), and PASAT (p = 0.04) Z-scores at 12 weeks, indicating reduced functional disability compared to baseline values. No significant changes were observed within the Control group. Study-specific differences in the MSFC changes between groups were observed. Functional disability was reduced compared to the baseline in the Paleo group, possibly depending on MS type. These results provide preliminary observations on the efficacy of a modified Paleolithic diet for reducing or maintaining functional disability in MS.
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(This article belongs to the Special Issue Exploring Environmental Risk Factors for Disease Progression in Multiple Sclerosis and Amyotrophic Lateral Sclerosis)
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Open AccessArticle
Elucidating the Epigenetic and Protein Interaction Landscapes in Amyotrophic Lateral Sclerosis: An Integrated Bioinformatics Analysis
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Katerina Kadena and Panagiotis Vlamos
Sclerosis 2024, 2(3), 140-155; https://doi.org/10.3390/sclerosis2030010 - 30 Jun 2024
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Background: Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative disorder characterized by the progressive degeneration of motor neurons, leading to muscle weakness and paralysis. Understanding the molecular basis of ALS is crucial for the development of effective therapies. Objective: This study aims to
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Background: Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative disorder characterized by the progressive degeneration of motor neurons, leading to muscle weakness and paralysis. Understanding the molecular basis of ALS is crucial for the development of effective therapies. Objective: This study aims to explore the genetic and epigenetic underpinnings of ALS, focusing on the interplay between gene mutations, protein interactions, and epigenetic factors. Methods: We conducted an extensive analysis of key ALS-associated genes including TARDBP, SOD1, ANG, VAPB, and CHMP2B. We used computational tools to assess the functional consequences of identified mutations on neuronal health and explored DNA methylation patterns in gene promoters to investigate epigenetic regulation. Results: Our findings reveal that mutations in ALS-associated genes disrupt critical processes such as amyloid fibril formation and autophagy. We also identified altered DNA methylation patterns, suggesting a mechanism for changes in gene expression linked to ALS. Molecular docking studies highlighted Humulene and Buddledin C as compounds with high binding affinities to the SOD1 enzyme, suggesting their potential to mitigate hallmark features of ALS pathology such as SOD1 aggregation and oxidative stress. Conclusions: Our comprehensive analysis underscores the complexity of ALS pathogenesis, combining genetic, epigenetic, and proteomic approaches. The insights gained not only enhance our understanding of ALS but also pave the way for novel therapeutic strategies, highlighting the importance of integrated approaches in tackling this challenging neurodegenerative disease.
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Open AccessFeature PaperReview
Multiple Sclerosis: Immune Cells, Histopathology, and Therapeutics
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Manisha S. Patil, Linda Y. Lin, Felix Marsh-Wakefield, Elizaveta J. James, Mainthan Palendira, Simon Hawke and Georges E. Grau
Sclerosis 2024, 2(3), 117-139; https://doi.org/10.3390/sclerosis2030009 - 27 Jun 2024
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Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system (CNS). In MS, oligodendrocytes and myelin that surround axons to facilitate transmission of neuronal signals are destroyed by adaptive and innate immune cells, resulting in the formation of demyelinating plaques.
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Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system (CNS). In MS, oligodendrocytes and myelin that surround axons to facilitate transmission of neuronal signals are destroyed by adaptive and innate immune cells, resulting in the formation of demyelinating plaques. For many years, research into MS pathophysiology has identified immune cell populations in lesions such as T cells, B cells, and myeloid and innate lymphoid cells. In this review, we discuss the involvement of these immune cells in MS pathophysiology and demonstrate how findings from histopathology studies and single-cell analyses in animal and human models have identified which immune cell subsets contribute to disease. This knowledge has facilitated the introduction of numerous immune-targeted therapeutics towards CD20, CD52, interferon-beta, sphingosine-1-phosphate receptor, Bruton’s tyrosine kinase, and many more. These treatments have shown effective reduction in new lesion formation and management of symptoms in MS patients. Furthermore, as MS is a chronic disease, these therapeutics slow disease progression, reduce cognitive disabilities, and prevent relapses. Further research is required to develop a cure for MS with limited side effects. The ongoing research that utilises innovative methods to identify and assess MS pathophysiology could transform the treatment landscape for patients in the future.
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Open AccessArticle
The Cognitive Reserve May Influence Fatigue after Rehabilitation in Progressive Multiple Sclerosis: A Secondary Analysis of the RAGTIME Trial
by
Ambra Balzeri, Nicola Lamberti, Andrea Baroni, Nino Basaglia, Antonella Bergonzoni, Franca Stablum, Fabio Manfredini and Sofia Straudi
Sclerosis 2024, 2(2), 108-116; https://doi.org/10.3390/sclerosis2020008 - 29 May 2024
Abstract
Cognitive reserve (CR) seems to be an ability to adapt cognitive processes in response to brain disease and may influence rehabilitation outcomes. This is a secondary analysis of the “Robot-Assisted Gait Training versus conventional therapy on mobility in severely disabled progressive MultiplE sclerosis
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Cognitive reserve (CR) seems to be an ability to adapt cognitive processes in response to brain disease and may influence rehabilitation outcomes. This is a secondary analysis of the “Robot-Assisted Gait Training versus conventional therapy on mobility in severely disabled progressive MultiplE sclerosis patients” (RAGTIME) trial to investigate the influence of CR on the outcomes after gait rehabilitation in people with multiple sclerosis (PwMS). We included 53 PwMS and severe gait disability (EDSS 6–7). The participants were randomized into two groups to receive either robot-assisted gait training or overground walking (three times/week over four weeks). CR was evaluated by the Cognitive Reserve Index questionnaire (CRIq), which encompasses three sections (CRI Education, CRI Working Activity, and CRI Leisure Time). We stratified the patients using the 115 cut-off CRIq total score of at least a medium-high CR. The outcome measures were Timed 25-Foot Walk, 6 min walking test, Berg Balance Scale, Multiple Sclerosis Impact Scale—29, Multiple Sclerosis Walking Scale—12, Patient Health Questionnaire—9, and Fatigue Severity Scale (FSS). After gait rehabilitation, the FSS was significantly improved in those patients with higher CR compared with the others (F = 4.757, p = 0.015). In our study, CR did not affect the gait, balance, disability perception, and depression. Conversely, it positively influenced the fatigue after gait rehabilitation.
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(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis)
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Open AccessReview
Current and Emerging Treatment Options in Pediatric Onset Multiple Sclerosis
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Artemis Mavridi, Maria Eleni Bompou, Aine Redmond, Paraschos Archontakis-Barakakis, George D. Vavougios, Dimos D. Mitsikostas and Theodoros Mavridis
Sclerosis 2024, 2(2), 88-107; https://doi.org/10.3390/sclerosis2020007 - 1 Apr 2024
Abstract
Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of
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Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, this review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.
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Open AccessReview
Risk Factors for Cognitive Impairment in Multiple Sclerosis Patients
by
Thomas Gabriel Schreiner, Iustina Mihoc, Ecaterina Grigore and Oliver Daniel Schreiner
Sclerosis 2024, 2(2), 77-87; https://doi.org/10.3390/sclerosis2020006 - 22 Mar 2024
Cited by 1
Abstract
Cognitive impairment is one of the most significant burdens among the many neurological complaints in multiple sclerosis patients. Cognitive deficits negatively impact these patients’ quality of life, leading to partial or total loss of several mental functions, such as learning, memory, perception, or
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Cognitive impairment is one of the most significant burdens among the many neurological complaints in multiple sclerosis patients. Cognitive deficits negatively impact these patients’ quality of life, leading to partial or total loss of several mental functions, such as learning, memory, perception, or problem-solving. While the precise mechanisms involved in the onset and evolution of cognitive decline remain unknown, several risk factors have been associated with intellectual disability. With increasing data on this topic in recent years, the main aim of this review is to summarize the most relevant risk factors correlated with cognitive impairment in multiple sclerosis patients. Firstly, the authors demonstrate the importance of mental disability based on epidemiological data from multiple sclerosis patient cohorts. Subsequently, the intensely debated major risk factors for cognitive decline are discussed, with brief insights into the pathophysiology and possible underlying mechanisms. Finally, the authors describe the impact of medication on cognitive impairment in multiple sclerosis patients, highlighting the main research directions for future studies.
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(This article belongs to the Special Issue Neuropsychiatric and Quality of Life (QoL) Aspects of Multiple Sclerosis)
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