scholarly journals Balancing Early Aggression Against Risk of Progression in Multiple Sclerosis

2015 ◽  
Vol 43 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Pierre Duquette ◽  
Paul S. Giacomini ◽  
Virender Bhan ◽  
Marika Hohol ◽  
Robyn Schecter
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Time Window ◽  
Disease Onset ◽  
Response To Treatment ◽  
Close Monitoring ◽  
Brain Volume Loss ◽  
Risk Of Progression ◽  
The Central Nervous System ◽  
Relapsing Remitting Multiple Sclerosis

AbstractMultiple sclerosis is a chronic demyelinating disease characterized by focal and diffuse inflammation of the central nervous system resulting in significant physical and cognitive disabilities. Disease-modifying therapies targeting the dysfunctional immune response are most effective in the first few years after disease onset, indicating that there is a limited time window for therapy to influence the disease course. No evidence of disease activity is emerging as a new standard for treatment response and may be associated with improved long-term disability outcomes. An aggressive management strategy, including earlier use of more potent immunomodulatory agents and close monitoring of the clinical and radiologic response to treatment, is recommended to minimize early brain volume loss and slow the progression of physical and cognitive impairments in patients with relapsing-remitting multiple sclerosis.

scholarly journals Assessment of the influence of various risk factors on the severity of psycho-emotional disorders in patients with multiple sclerosis

2021 ◽  
Vol 17 (5) ◽  
pp. 31-35
Author(s):  
T.A. Odintsova ◽  
O.O. Kopchak
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Emotional Disorders ◽  
Demyelinating Disease ◽  
External Factors ◽  
Depression And Anxiety ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Severity Levels ◽  
Relapsing Remitting Multiple Sclerosis

Multiple sclerosis is an insidious disabling, both physically and mentally, demyelinating disease of the central nervous system. People with multiple sclerosis, apart from the classic manifestations, can also experience depression and anxiety. The study was aimed to assess peculiarities of influence of socio-demographic, external factors, and characteristics of the disease on depression and anxiety among patients with relapsing-remitting multiple sclerosis. The following article highlights the main risk factors and their ways of influence on the aforementioned disorders, distinguished by the multifactorial analysis. Also, it estimates the frequency of different severity levels of either depression or anxiety depending on the pre-sence of each risk factor.

scholarly journals Alterations of Gut Microbiota and the Brain-Immune-Intestine Axis in Patients With Relapsing-Remitting Multiple Sclerosis After Treatment With Oral Cladribine: Protocol for a Prospective Observational Study (Preprint)

2019 ◽  
Author(s):  
Jeske van Pamelen ◽  
Lynn van Olst ◽  
Andries E Budding ◽  
Helga E de Vries ◽  
Leo H Visser ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Disease Onset ◽  
Oral Microbiota ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Moment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Brain

BACKGROUND Immunological factors are the key to the pathogenesis of multiple sclerosis (MS). Conjointly, environmental factors are known to affect MS disease onset and progression. Several studies have found that the intestinal microbiota in MS patients differs from that of control subjects. One study found a trend toward lower species richness in patients with active disease versus in patients in remission. The microbiota plays an important role in shaping the immune system. Recent studies suggest the presence of an association between the gut microbiota and inflammatory pathways in the central nervous system. However, the function of this brain-immune-intestine axis and its possible value for predicting treatment effect in MS patients is currently unknown. OBJECTIVE Our goal is to examine if the changes in gut and oral microbiota and simultaneous changes in the immune response are a predictor for the treatment response in subjects with active relapsing-remitting MS (RRMS) who are being treated with oral cladribine. METHODS This is a prospective, observational, multicenter study. Eligible subjects are patients with RRMS, between the ages of 18 and 55 years, who will start treatment with oral cladribine. Patients who used probiotics 1 month prior to the start of oral cladribine will be excluded. At baseline (ie, before start) and after 3, 12, and 24 months, the Expanded Disability Status Scale (EDSS) score will be assessed and fecal, oral, and blood samples will be collected. Also, subjects will be asked to register their food intake for 7 consecutive days following the visits. After 24 months, a magnetic resonance imaging (MRI) assessment of the brain will be performed. Responders are defined as subjects without relapses, without progression on the EDSS, and without radiological progression on MRI. RESULTS Inclusion started in January 2019. A total of 30 patients are included at the moment. The aim is to include 80 patients from 10 participating centers during a period of approximately 24 months. Final results are expected in 2024. CONCLUSIONS The results of the BIA Study will contribute to precision medicine in patients with RRMS and will contribute to a better understanding of the brain-immune-intestine axis. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/16162

scholarly journals lincR-Ccr2-5′AS and THRIL as potential biomarkers of multiple sclerosis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Olfat Gamil Shaker ◽  
Amr Hassan ◽  
Asmaa Mohammed Mohammed ◽  
Shereen Rashad Mohammed
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Fold Change ◽  
Motor Weakness ◽  
Tnf Α ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
The Central Nervous System ◽  
Nuclear Ribonucleoprotein ◽  
Relapsing Remitting Multiple Sclerosis

Abstract Background Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system (CNS). Long non-coding RNAs (lncRNAs) were believed to play a role in the pathogenesis of neurological disorders including MS. lincR-Ccr2-5′AS is expressed in the T helper2 (Th2) lineage. TNF-α heterogeneous nuclear ribonucleoprotein L (THRIL) causes the induction of TNF-α and regulates innate immune response and inflammation. We investigated the expression of lincR-Ccr2-5′AS and THRIL in MS to clarify their association with MS risk and the clinical features. Results LincR-Ccr2-5′AS was significantly downregulated in MS patients (fold change = 0.43±0.29, p = 0.03). The expression level was significantly low in patients with motor weakness and optic neuritis, patients with Expanded Disability Status Scale (EDSS) ≥5.5, and treatment-naïve patients. THRIL was significantly upregulated in MS patients (fold change = 6.18±2, p = 0.02). Its expression was significantly higher in patients with relapsing-remitting multiple sclerosis (RRMS), patients with motor weakness, patients with EDSS ≤5, and patients who received interferon. Conclusion Our results showed the downregulation of lincR-Ccr2-5′AS and the upregulation of lncRNA THRIL in MS patients. This differential expression of both lncRNAs may have an important role in MS pathogenesis.

scholarly journals Alterations of Gut Microbiota and the Brain-Immune-Intestine Axis in Patients With Relapsing-Remitting Multiple Sclerosis After Treatment With Oral Cladribine: Protocol for a Prospective Observational Study

10.2196/16162 ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. e16162
Author(s):  
Jeske van Pamelen ◽  
Lynn van Olst ◽  
Andries E Budding ◽  
Helga E de Vries ◽  
Leo H Visser ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Disease Onset ◽  
Oral Microbiota ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Moment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Brain

Background Immunological factors are the key to the pathogenesis of multiple sclerosis (MS). Conjointly, environmental factors are known to affect MS disease onset and progression. Several studies have found that the intestinal microbiota in MS patients differs from that of control subjects. One study found a trend toward lower species richness in patients with active disease versus in patients in remission. The microbiota plays an important role in shaping the immune system. Recent studies suggest the presence of an association between the gut microbiota and inflammatory pathways in the central nervous system. However, the function of this brain-immune-intestine axis and its possible value for predicting treatment effect in MS patients is currently unknown. Objective Our goal is to examine if the changes in gut and oral microbiota and simultaneous changes in the immune response are a predictor for the treatment response in subjects with active relapsing-remitting MS (RRMS) who are being treated with oral cladribine. Methods This is a prospective, observational, multicenter study. Eligible subjects are patients with RRMS, between the ages of 18 and 55 years, who will start treatment with oral cladribine. Patients who used probiotics 1 month prior to the start of oral cladribine will be excluded. At baseline (ie, before start) and after 3, 12, and 24 months, the Expanded Disability Status Scale (EDSS) score will be assessed and fecal, oral, and blood samples will be collected. Also, subjects will be asked to register their food intake for 7 consecutive days following the visits. After 24 months, a magnetic resonance imaging (MRI) assessment of the brain will be performed. Responders are defined as subjects without relapses, without progression on the EDSS, and without radiological progression on MRI. Results Inclusion started in January 2019. A total of 30 patients are included at the moment. The aim is to include 80 patients from 10 participating centers during a period of approximately 24 months. Final results are expected in 2024. Conclusions The results of the BIA Study will contribute to precision medicine in patients with RRMS and will contribute to a better understanding of the brain-immune-intestine axis. International Registered Report Identifier (IRRID) DERR1-10.2196/16162

scholarly journals The Emerging Role of Neutrophil Granulocytes in Multiple Sclerosis

2018 ◽  
Vol 7 (12) ◽  
pp. 511 ◽  
Author(s):  
Tonia Woodberry ◽  
Sophie Bouffler ◽  
Alicia Wilson ◽  
Rebecca Buckland ◽  
Anne Brüstle
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Disease Onset ◽  
Common Disease ◽  
Neutrophil Granulocytes ◽  
Current State ◽  
The Central Nervous System ◽  
And Function ◽  
Ms Pathogenesis

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a strong autoimmune, neurodegenerative, and neuroinflammatory component. Most of the common disease modifying treatments (DMTs) for MS modulate the immune response targeting disease associated T and B cells and while none directly target neutrophils, several DMTs do impact their abundance or function. The role of neutrophils in MS remains unknown and research is ongoing to better understand the phenotype, function, and contribution of neutrophils to both disease onset and stage of disease. Here we summarize the current state of knowledge of neutrophils and their function in MS, including in the rodent based MS model, and we discuss the potential effects of current treatments on these functions. We propose that neutrophils are likely to participate in MS pathogenesis and their abundance and function warrant monitoring in MS.

scholarly journals Altered cortical phase- and amplitude-coupling in Multiple Sclerosis

2021 ◽  
Author(s):  
Marcus Siems ◽  
Johannes Tünnerhoff ◽  
Ulf Ziemann ◽  
Markus Siegel
Keyword(s):  
Multiple Sclerosis ◽  
Large Scale ◽  
Demyelinating Disease ◽  
Disease Stage ◽  
Functional Changes ◽  
Non Invasive ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

AbstractMultiple Sclerosis is a demyelinating disease of the central nervous system that can result in cognitive decline and physical disability. However, related functional changes in large-scale brain interactions remain poorly understood and corresponding non-invasive biomarkers are sparse. Here, we measured magnetoencephalography in 17 relapsing-remitting Multiple Sclerosis patients at an early disease stage (median EDSS = 1.5, range 0 to 3.5) and 17 healthy controls to investigate brain-wide phase- and amplitude-coupling of frequency specific neuronal activity. We developed a new analysis approach that combines dimensionality reduction, bootstrap aggregating and multivariate classification to identify changes of brain-wide coupling in Multiple Sclerosis. We identified systematic and non-redundant changes of both phase- and amplitude-coupling. Changes included both, increased and decreased neuronal coupling in wide-spread, bilateral neuronal networks across a broad range of frequencies. These changes allowed to successfully classify patients and controls with an accuracy of 84%. Furthermore, classification confidence predicted behavioral scores of disease severity. Our results unravel systematic changes of large-scale neuronal coupling in Multiple Sclerosis and suggest non-invasive electrophysiological coupling measures as powerful biomarkers of Multiple Sclerosis.

scholarly journals Multiple Sclerosis Biomarker Discoveries by Proteomics and Metabolomics Approaches

2021 ◽  
Vol 16 ◽  
pp. 117727192110133
Author(s):  
Ameneh Jafari ◽  
Amirhesam Babajani ◽  
Mostafa Rezaei-Tavirani
Keyword(s):  
Multiple Sclerosis ◽  
Complex Disease ◽  
Biomarker Discovery ◽  
Response To Treatment ◽  
Inflammatory Disorder ◽  
Protein Marker ◽  
Complex Disorders ◽  
New Information ◽  
The Central Nervous System ◽  
Monitoring Treatment

Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system (CNS) resulting in demyelination and axonal loss in the brain and spinal cord. The precise pathogenesis and etiology of this complex disease are still a mystery. Despite many studies that have been aimed to identify biomarkers, no protein marker has yet been approved for MS. There is urgently needed for biomarkers, which could clarify pathology, monitor disease progression, response to treatment, and prognosis in MS. Proteomics and metabolomics analysis are powerful tools to identify putative and novel candidate biomarkers. Different human compartments analysis using proteomics, metabolomics, and bioinformatics approaches has generated new information for further clarification of MS pathology, elucidating the mechanisms of the disease, finding new targets, and monitoring treatment response. Overall, omics approaches can develop different therapeutic and diagnostic aspects of complex disorders such as multiple sclerosis, from biomarker discovery to personalized medicine.

scholarly journals Regulation of CTLA-4 and PD-L1 Expression in Relapsing-Remitting Multiple Sclerosis Patients after Treatment with Fingolimod, IFNβ-1α, Glatiramer Acetate, and Dimethyl Fumarate Drugs

2021 ◽  
Vol 11 (8) ◽  
pp. 721
Author(s):  
Afshin Derakhshani ◽  
Zahra Asadzadeh ◽  
Hossein Safarpour ◽  
Patrizia Leone ◽  
Mahdi Abdoli Shadbad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Immune Checkpoints ◽  
Peripheral Blood Mononuclear ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that is characterized by inflammation which typically results in significant impairment in most patients. Immune checkpoints act as co-stimulatory and co-inhibitory molecules and play a fundamental role in keeping the equilibrium of the immune system. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and Programmed death-ligand 1 (PD-L1), as inhibitory immune checkpoints, participate in terminating the development of numerous autoimmune diseases, including MS. We assessed the CTLA-4 and PD-L1 gene expression in the different cell types of peripheral blood mononuclear cells of MS patients using single-cell RNA-seq data. Additionally, this study outlines how CTLA-4 and PD-L1 expression was altered in the PBMC samples of relapsing-remitting multiple sclerosis (RRMS) patients compared to the healthy group. Finally, it investigates the impact of various MS-related treatments in the CTLA-4 and PD-L1 expression to restrain autoreactive T cells and stop the development of MS autoimmunity.

scholarly journals Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
S. Viswanathan ◽  
N. Rose ◽  
A. Masita ◽  
J. S. Dhaliwal ◽  
S. D. Puvanarajah ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Demyelinating Disease ◽  
Age At Onset ◽  
Positive Family History ◽  
Disease Onset ◽  
Demyelinating Diseases ◽  
Lesion Length ◽  
Relapsing Remitting ◽  
Spectrum Disorders

Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country.Objectives. To investigate the spectrum of multiple sclerosis in Malaysia.Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia.Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald’s criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders.Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.

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