scholarly journals Potential Pathological Biomarkers in Multiple Sclerosis

2020 ◽  
Author(s):  
Deepali Mathur ◽  
Soumyashree Rout ◽  
Bikash Kumar Mishra ◽  
Gerardo Lopez Rodas ◽  
Jayalakshmi Vallamkondu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Outcome ◽  
Disease Activity ◽  
Complex Disease ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Imaging Biomarkers ◽  
Disability Progression ◽  
Cerebrospinal Fluid Biomarkers ◽  
The Central Nervous System ◽  
Monitoring Treatment

Multiple Sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves the intricate interplay of different immune cells going awry leading to inflammation, demyelination, and neurodegeneration. Its diagnosis is quite arduous because of the baffling number of symptoms it elicits and the varied clinical manifestation it presents. The simplified criteria (in form of Macdonald’s Criteria) which have got modified several times is now the single most important criteria accepted by neurology bodies for diagnosing MS. Biomarkers from time to time have been explored to simplify the diagnosis and prognosticate MS along with anecessity to monitor treatment outcome. In recent years, research on biomarkers has advanced rapidly due to their ability to be easily and rapidly measured, their specificity, safety, and their ability to yield precise results. Biomarkers are classified into various categories including predictive, diagnostic, prognostic, related to disease activity, and monitoring treatment outcome. Each representative of the disease activity category reflects a variety of pathological processes of MS such as neuroaxonal loss, gliosis, demyelination, disability progression, remyelination, etc. This review discusses several promising serum and cerebrospinal fluid biomarkers and imaging biomarkers used in clinical practice. Myelin oligodendrocyte glycoprotein antibody disease which is recently recognized as a definite disease will also be discussed. Furthermore, it sheds light on the criteria and the challenges a biomarker faces to be considered as a standard one.

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.

Multiple Sclerosis: Monitoring Disease Activity and Progression

2017 ◽  
Author(s):  
Pavan Bhargava ◽  
Shiv Saidha
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Disease Activity ◽  
Cerebrospinal Fluid Biomarkers ◽  
The Central Nervous System ◽  
Degenerative Disorder ◽  
Clinical Measures ◽  
Assessment Strategies

Multiple sclerosis is a chronic inflammatory and degenerative disorder of the central nervous system. Measuring disease activity and progression are an integral part of the management of the disorder. A number of different approaches, including clinical measures, imaging metrics, and blood/cerebrospinal fluid biomarkers have been investigated for their utility in monitoring disease activity and progression. Each of these different approaches has certain advantages, as well as limitations, and this chapter provides an overview of these different assessment strategies.

scholarly journals Potential Biomarkers Associated with Multiple Sclerosis Pathology

2021 ◽  
Vol 22 (19) ◽  
pp. 10323
Author(s):  
Deepali Mathur ◽  
Bikash Kumar Mishra ◽  
Soumyashree Rout ◽  
Francisco Jose Lopez-Iranzo ◽  
Gerardo Lopez-Rodas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Immune Cells ◽  
Complex Disease ◽  
Response To Treatment ◽  
Imaging Biomarkers ◽  
Diagnosis And Prognosis ◽  
The Central Nervous System ◽  
Shed Light ◽  
Potential Biomarkers

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves an intricate and aberrant interaction of immune cells leading to inflammation, demyelination, and neurodegeneration. Due to the heterogeneity of clinical subtypes, their diagnosis becomes challenging and the best treatment cannot be easily provided to patients. Biomarkers have been used to simplify the diagnosis and prognosis of MS, as well as to evaluate the results of clinical treatments. In recent years, research on biomarkers has advanced rapidly due to their ability to be easily and promptly measured, their specificity, and their reproducibility. Biomarkers are classified into several categories depending on whether they address personal or predictive susceptibility, diagnosis, prognosis, disease activity, or response to treatment in different clinical courses of MS. The identified members indicate a variety of pathological processes of MS, such as neuroaxonal damage, gliosis, demyelination, progression of disability, and remyelination, among others. The present review analyzes biomarkers in cerebrospinal fluid (CSF) and blood serum, the most promising imaging biomarkers used in clinical practice. Furthermore, it aims to shed light on the criteria and challenges that a biomarker must face to be considered as a standard in daily clinical practice.

scholarly journals HIV infection and multiple sclerosis: a case with unexpected “no evidence of disease activity” status

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199957
Author(s):  
Fernando Labella ◽  
Fernando Acebrón ◽  
María del Carmen Blanco-Valero ◽  
Alba Rodrígez-Martín ◽  
Ángela Monterde Ortega ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Hiv Infection ◽  
Disease Activity ◽  
Demyelinating Disease ◽  
Clinical Course ◽  
Disease Modifying Drugs ◽  
Immunodeficiency Virus ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system whose etiology remains unclear. It has been suggested that MS can be triggered by certain viruses; however, human immunodeficiency virus (HIV) infection is associated with reduced incidence of MS. We present the case of a young patient diagnosed with active relapsing-remitting MS whose clinical course substantially improved following HIV infection and treatment. The patient achieved no evidence of disease activity status without any disease-modifying drugs. Both HIV-induced immunosuppression and antiretroviral therapy may have attenuated the clinical course in this patient.

scholarly journals CSF levels of glutamine synthetase and GFAP to explore astrocytic damage in seronegative NMOSD

2020 ◽  
Vol 91 (6) ◽  
pp. 605-611
Author(s):  
Iris Kleerekooper ◽  
Megan K Herbert ◽  
H Bea Kuiperij ◽  
Douglas Kazutoshi Sato ◽  
Kazuo Fujihara ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Glutamine Synthetase ◽  
Glial Fibrillary Acidic Protein ◽  
Optic Neuritis ◽  
Disease Activity ◽  
Similar Pattern ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Csf Levels

ObjectiveTo explore levels of astrocytopathy in neuromyelitis optica spectrum disorder (NMOSD) by measuring levels of the astrocytic enzyme glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), an established astrocytic biomarker known to be associated with disease activity in multiple sclerosis.MethodsCerebrospinal fluid concentrations of GS and GFAP were measured by ELISA in patients with NMOSD (n=39, 28 aquaporin-4 (AQP4)-Ab-seropositive, 3 double-Ab-seronegative, 4 myelin oligodendrocyte glycoprotein (MOG)-Ab-seropositive and 4 AQP4-Ab-seronegative with unknown MOG-Ab-serostatus), multiple sclerosis (MS) (n=69), optic neuritis (n=5) and non-neurological controls (n=37).ResultsGFAP and GS concentrations differed significantly across groups (both p<0.001), showing a similar pattern of elevation in patients with AQP4-Ab-seropositive NMOSD. GS and GFAP were significantly correlated, particularly in patients with AQP4-Ab-seropositive NMOSD (rs=0.70, p<0.001). Interestingly, GFAP levels in some patients with double-Ab-seronegative NMOSD were markedly increased.ConclusionsOur data indicate astrocytic injury occurs in some patients with double-Ab-seronegative NMOSD, which hints at the possible existence of yet undiscovered astrocytic autoimmune targets. We hypothesise that elevated GS and GFAP levels could identify those double-Ab-seronegative patients suitable to undergo in-depth autoimmune screening for astrocytic antibodies.

scholarly journals Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS

2019 ◽  
pp. jnnp-2019-321124 ◽  
Author(s):  
Kumaran Deiva ◽  
Peter Huppke ◽  
Brenda Banwell ◽  
Tanuja Chitnis ◽  
Jutta Gärtner ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Phase Iii ◽  
Disability Progression ◽  
Double Blind ◽  
Younger Patients ◽  
Treatment Groups ◽  
Registration Number ◽  
Treatment Naïve ◽  
Post Hoc

BackgroundIn PARADIGMS, a double-blind phase III trial in 215 paediatric patients with multiple sclerosis (MS) (10 to <18 years), fingolimod administered for up to 2 years significantly reduced the annualised relapse rate (ARR) and rate of new/newly enlarged T2 (n/neT2) lesions compared with interferon (IFN) β-1a.ObjectivesTo investigate (1) differences between treatment groups across subpopulations (treatment-naïve, younger/prepubertal patients); (2) disability progression.MethodsARRs at 10, 11 and 12 years were estimated based on predefined modelling extrapolations. Changes in Expanded Disability Status Scale (EDSS), and in 3 month (3M) and 6 month (6M) confirmed disability progression (CDP) were evaluated post hoc.ResultsIn the treatment-naïve subpopulation, fingolimod reduced ARR and n/neT2 lesions by 85.8% and 53.4%, respectively versus INF β-1a (both p<0.001), compared with 81.9% and 52.6% in the overall population. Model-based ARR reductions in younger patients (≤12 years) were 91.9%–94.6%. Twice as many IFN β-1a-treated than fingolimod-treated patients had worse EDSS scores at study end (20.6% vs 10.5%, p=0.043). Risk reductions in 3M-CDP and 6M-CDP were 77.2% (p=0.007) and 80.2% (p=0.040), respectively.ConclusionsFingolimod in paediatric MS was associated with consistent control of disease activity versus IFN β-1a (including treatment-naïve and younger patients) and resulted in less disability progression for up to 2 years.Trial registration numberNCT01892722.

scholarly journals A Review of Various Antioxidant Compounds and their Potential Utility as Complementary Therapy in Multiple Sclerosis

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1528 ◽  
Author(s):  
Elzbieta Dorota Miller ◽  
Angela Dziedzic ◽  
Joanna Saluk-Bijak ◽  
Michal Bijak
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Complex Disease ◽  
Early Stage ◽  
Symptomatic Treatment ◽  
Complementary Therapy ◽  
Antioxidant Compounds ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Stress Mediators

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS). The etiology of this multifactorial disease has not been clearly defined. Conventional medical treatment of MS has progressed, but is still based on symptomatic treatment. One of the key factors in the pathogenesis of MS is oxidative stress, enhancing inflammation and neurodegeneration. In MS, both reactive oxygen and nitrogen species are formed in the CNS mainly by activated macrophages and microglia structures, which can lead to demyelination and axon disruption. The course of MS is associated with the secretion of many inflammatory and oxidative stress mediators, including cytokines (IL-1b, IL-6, IL-17, TNF-α, INF-γ) and chemokines (MIP-1a, MCP-1, IP10). The early stage of MS (RRMS) lasts about 10 years, and is dominated by inflammatory processes, whereas the chronic stage is associated with neurodegenerative axon and neuron loss. Since oxidative damage has been known to be involved in inflammatory and autoimmune-mediated processes, antioxidant therapy could contribute to the reduction or even prevention of the progression of MS. Further research is needed in order to establish new aims for novel treatment and provide possible benefits to MS patients. The present review examines the roles of oxidative stress and non-pharmacological anti-oxidative therapies in MS.

Biological markers in body fluids for activity and progression in multiple sclerosis

1999 ◽  
Vol 5 (4) ◽  
pp. 287-290
Author(s):  
Per Soelberg Sùrensen
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Biological Markers ◽  
Body Fluids ◽  
Therapeutic Effects ◽  
Therapeutic Decisions ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
The Individual ◽  
Relapsing Remitting Multiple Sclerosis

Reliable biological markers in body fluids for disease activity and progression are important for our understanding of the pathophysiology and therapeutic decisions in various subtypes of multiple sclerosis. Sampling from body fluids such as cerebrospinal fluid, blood, and urine constitutes the problem that the local immuno-inflammatory process takes place in the central nervous system whereas the disease activity is only to some extent reflected in the systemic immune compartment. Promising results have been obtained in studies of adhesion molecules, pro-inflammatory cytokines, co-stimulatory molecules and neopterin as markers of disease activity in relapsing-remitting multiple sclerosis. However, these results apply to groups of patients but not necessarily to individual patients. Currently no single body fluid marker is sufficiently correlated to disease activity to be used in the individual patient in monitoring disease activity, progression, or therapeutic effects.

scholarly journals MRI Prognostic Factors in Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, and Myelin Oligodendrocyte Antibody Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Rosa Cortese ◽  
Antonio Giorgio ◽  
Gianmarco Severa ◽  
Nicola De Stefano
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Neuromyelitis Optica ◽  
Structural Changes ◽  
Spectrum Disorder ◽  
Demyelinating Diseases ◽  
Imaging Biomarkers ◽  
Specific Information ◽  
Clinical Effects ◽  
Neuromyelitis Optica Spectrum Disorder

Several MRI measures have been developed in the last couple of decades, providing a number of imaging biomarkers that can capture the complexity of the pathological processes occurring in multiple sclerosis (MS) brains. Such measures have provided more specific information on the heterogeneous pathologic substrate of MS-related tissue damage, being able to detect, and quantify the evolution of structural changes both within and outside focal lesions. In clinical practise, MRI is increasingly used in the MS field to help to assess patients during follow-up, guide treatment decisions and, importantly, predict the disease course. Moreover, the process of identifying new effective therapies for MS patients has been supported by the use of serial MRI examinations in order to sensitively detect the sub-clinical effects of disease-modifying treatments at an earlier stage than is possible using measures based on clinical disease activity. However, despite this has been largely demonstrated in the relapsing forms of MS, a poor understanding of the underlying pathologic mechanisms leading to either progression or tissue repair in MS as well as the lack of sensitive outcome measures for the progressive phases of the disease and repair therapies makes the development of effective treatments a big challenge. Finally, the role of MRI biomarkers in the monitoring of disease activity and the assessment of treatment response in other inflammatory demyelinating diseases of the central nervous system, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte antibody disease (MOGAD) is still marginal, and advanced MRI studies have shown conflicting results. Against this background, this review focused on recently developed MRI measures, which were sensitive to pathological changes, and that could best contribute in the future to provide prognostic information and monitor patients with MS and other inflammatory demyelinating diseases, in particular, NMOSD and MOGAD.

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