scholarly journals Remyelination Improves Voiding Dysfunction in a Mouse Model of Multiple Sclerosis

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 639-640
Author(s):  
Ramalakshmi Ramasamy ◽  
Cara Hardy ◽  
Stephen Crocker ◽  
Phillip Smith
Keyword(s):  
Multiple Sclerosis ◽  
Bladder Dysfunction ◽  
Demyelinating Disease ◽  
Urinary Symptoms ◽  
Bladder Function ◽  
Cortical Control ◽  
Brainstem Reflex ◽  
The Central Nervous System ◽  
Micturition Frequency ◽  
Cns Myelination

Abstract Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Of note, over 80% of MS patients have urinary symptoms as one of their earliest symptoms. Since MS patients often live into older age, urinary incontinence and retention are significant problems affecting their quality of life. Although several studies show that inflammatory-demyelinating animal models of MS develop bladder dysfunction, the confounding influence of systemic inflammation in these models limits potential interpretation on the contribution of CNS-myelination to bladder dysfunction. We sought to address this knowledge gap using the cuprizone model of demyelination and remyelination. C57Bl/6 mice were treated with dietary cuprizone (0.2%w/w) for four weeks to induce demyelination. One group was allowed four additional weeks for recovery and remyelination. We performed voiding spot assay (VSA), urethane-anesthetized cystometry, and CNS-histology to assess demyelination-induced differences in urinary performance. We observed that cortical demyelination causes significant aberrance in voiding behavior (conscious cortical control) characterized by increased micturition frequency and reduced volume per micturition. Interestingly, remyelination restored healthy bladder function. However, there were no significant changes in the cystometric parameters (brainstem reflex) between the treatment groups. While MS is not classically considered a disease of aging, extending the longevity of these patients has not been reciprocated with improved treatments for their most-bothersome conditions, notably urinary symptoms that persist throughout life. Our data represent a novel compelling connection and strong correlation between CNS-myelination and cortical control of bladder function, which has potential implications in MS, aging, and aging-associated neurological disorders.

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.

Recent advances on immunosuppressive drugs and remyelination enhancers for the treatment of multiple sclerosis

2021 ◽  
Vol 27 ◽  
Author(s):  
Jennifer Cadenas-Fernández ◽  
Pablo Ahumada-Pascual ◽  
Luis Sanz Andreu ◽  
Ana Velasco
Keyword(s):  
Multiple Sclerosis ◽  
Intracellular Signaling ◽  
Demyelinating Disease ◽  
Lipid Synthesis ◽  
Immunosuppressive Drugs ◽  
Nerve Fibers ◽  
Myelin Sheaths ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
Lipid Structures

: Mammalian nervous systems depend crucially on myelin sheaths covering the axons. In the central nervous system, myelin sheaths consist of lipid structures which are generated from the membrane of oligodendrocytes (OL). These sheaths allow fast nerve transmission, protect axons and provide them metabolic support. In response to specific traumas or pathologies, these lipid structures can be destabilized and generate demyelinating lesions. Multiple sclerosis (MS) is an example of a demyelinating disease in which the myelin sheaths surrounding the nerve fibers of the brain and spinal cord are damaged. MS is the leading cause of neurological disability in young adults in many countries, and its incidence has been increasing in recent decades. Related to its etiology, it is known that MS is an autoimmune and inflammatory CNS disease. However, there are no effective treatments for this disease and the immunomodulatory therapies that currently exist have proven limited success since they only delay the progress of the disease. Nowadays, one of the main goals in the MS research is to find treatments which allows the recovery of neurological disabilities due to demyelination. To this end, different approaches, such as modulating intracellular signaling or regulating the lipid metabolism of OLs, are being considered. Here, in addition to immunosuppressive or immunomodulatory drugs that reduce the immune response against myelin sheaths, we review a diverse group of drugs that promotes endogenous remyelination in MS patients and whose use may be interesting as potential therapeutic agents in MS disease. To this end, we compile specific treatments against MS that are currently in the market with remyelination strategies which have entered into human clinical trials for future reparative MS therapies. The method used in this study is a systematic literature review on PubMed, Web of Science and Science Direct databases up to May 31, 2020. To narrow down the search results in databases, more specific keywords, such as, “myelin sheath”, “remyelination”, “demyelination”, “oligodendrocyte” and “lipid synthesis” were used to focus the search. We favoured papers published after January, 2015, but did not exclude earlier seminal papers.

scholarly journals Relapsing Tumefactive Demyelination: A Case Report

2018 ◽  
Vol 47 (2) ◽  
pp. 193
Author(s):  
Ibrahim Omerhodžić ◽  
Almir Džurlić ◽  
Dino Lisica ◽  
Nevena Mahmutbegović ◽  
Maida Nikšić ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Case Report ◽  
Female Patient ◽  
Demyelinating Disease ◽  
Diagnostic Procedures ◽  
Young Female ◽  
Diagnostic Challenge ◽  
Fresh Frozen ◽  
The Central Nervous System ◽  
Tumorlike Lesion

<p><strong>Objective. </strong>We present a case of relapsing tumefactive demyelination in a young female patient, that posed a real diagnostic challenge, with a heterogeneous clinical picture, atypical for multiple sclerosis (MS) presentation, and neuroradiological manifestations with a high suspicion of neoplastic diseases.</p><p><strong>Case Report</strong>. An 18-year old female patient presented to our Neurosurgical Out-patients’ Clinic with symptoms atypical for multiple sclerosis, unremarkable neurological deficit, one tumefactive lesion on MRI, followed by relapse and another two lesions within a period of six months. We decided to perform biopsy of the tumefactive lesion with compressive effect. Serological and clinical data were negative for MS, and the patient did not respond well to corticosteroid therapy. Fresh frozen tumor tissue aroused a strong suspicion of gemistocytic astrocytoma, so total resection was done, but the definitive pathohistological examination confirmed tumefactive demyelination.</p><p><strong>Conclusion</strong>. For clinicians, it is important to consider demyelinating disease in the differential diagnosis of a tumorlike lesion of the central nervous system, in order to avoid invasive and potentially harmful diagnostic procedures, especially in younger patients.</p>

Multiple Sclerosis

2018 ◽  
pp. 209-216
Author(s):  
Samuel W. Samuel ◽  
Jianguo Cheng
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Neuropathic Pain ◽  
Demyelinating Disease ◽  
Spontaneous Pain ◽  
Disease Course ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
Multiple Treatments ◽  
Surgical Treatments

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS). The diagnosis is based on evidence of at lease two different lesions in the CNS, at least two different episodes in the disease course, and chronic inflammation of the CNS as determined by analysis of the cerebrospinal fluid. Central neuropathic pain is the most common form of pain in patients with MS, with an estimated prevalence of about 50%. Along with the classical neuropathic pain features, such as spontaneous pain (dysesthesia and burning) and evoked pain (allodynia and hyperalgesia), patients with MS may also suffer from intermittent neuropathic pain, such as trigeminal neuralgia, Lhermitte sign, and glossopharyngeal neuralgia. In addition to disease-modifying therapies of MS, multiple treatments are available to manage neuropathic pain secondary to MS, including medical, interventional, and surgical treatments with varying levels of evidence.

scholarly journals Exome-Sequence Analyses of Four Multi-Incident Multiple Sclerosis Families

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 988
Author(s):  
Tobias Zrzavy ◽  
Fritz Leutmezer ◽  
Wolfgang Kristoferitsch ◽  
Barbara Kornek ◽  
Christine Schneider ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genome Wide Association Study ◽  
Rare Variants ◽  
Demyelinating Disease ◽  
Phenotypic Variability ◽  
Convincing Evidence ◽  
Risk Variants ◽  
Unbiased Manner ◽  
The Central Nervous System ◽  
Reduced Penetrance

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the Central Nervous System (CNS). Currently, it is estimated that 30–40% of the phenotypic variability of MS can be explained by genetic factors. However, low susceptibility variants identified through Genome Wide Association Study (GWAS) were calculated to explain about 50% of the heritability. Whether familial high-risk variants also contribute to heritability is a subject of controversy. In the last few years, several familial variants have been nominated, but none of them have been unequivocally confirmed. One reason for this may be that genetic heterogeneity and reduced penetrance are hindering detection. Sequencing a large number of MS families is needed to answer this question. In this study, we performed whole exome sequencing in four multi-case families, of which at least three affected individuals per family were analyzed. We identified a total of 138 rare variants segregating with disease in each of the families. Although no single variant showed convincing evidence for disease causation, some genes seemed particularly interesting based on their biological function. The main aim of this study was to provide a complete list of all rare segregating variants to provide the possibility for other researchers to cross-check familial candidate genes in an unbiased manner.

Multiple sclerosis attacks are associated with picornavirus infections

2004 ◽  
Vol 10 (2) ◽  
pp. 145-148 ◽  
Author(s):  
John D Kriesel ◽  
Andrea White ◽  
Frederick G Hayden ◽  
S L Spruance ◽  
Jack Petajan
Keyword(s):  
Multiple Sclerosis ◽  
At Risk ◽  
Demyelinating Disease ◽  
Respiratory Infections ◽  
Risk Period ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Upper Respiratory ◽  
Polymerase Chain

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system, which often follows a relapsing-remitting (RR) course with discrete attacks. MS attacks have been associated with upper respiratory infections (URIs), but the specific viruses responsible have not been identified. We studied a cohort of 16 RRMS patients experiencing URI and followed them for clinically identifiable attacks. The viral causes of 21 separate URIs were investigated using culture and polymerase chain reactio n (PCR) of nasal swab specimens, and by serology. Sibley’s ‘at-risk’ period for MS attacks, beginning two weeks before and continuing for five weeks after a URI, was used for the analysis. Seven of the nine (78%) URIs due to picornaviruses were associated with an MS attack during the at-risk period. By contrast, only two of 12 (17%) picornavirus-negative URIs were associated with an MS attack (P =0.01). The possible role of picornaviruses in the patho genesis of MS deserves further study.

scholarly journals A Pathogenic Role for Myelin-Specific Cd8+ T Cells in a Model for Multiple Sclerosis

2001 ◽  
Vol 194 (5) ◽  
pp. 669-676 ◽  
Author(s):  
Eric S. Huseby ◽  
Denny Liggitt ◽  
Thea Brabb ◽  
Bryan Schnabel ◽  
Claes Öhlén ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Demyelinating Disease ◽  
Clinical Symptoms ◽  
Autoimmune Encephalomyelitis ◽  
Effector Cells ◽  
Cns Autoimmunity ◽  
The Central Nervous System

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) characterized by plaques of infiltrating CD4+ and CD8+ T cells. Studies of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, focus on the contribution of CD4+ myelin-specific T cells. The role of CD8+ myelin-specific T cells in mediating EAE or MS has not been described previously. Here, we demonstrate that myelin-specific CD8+ T cells induce severe CNS autoimmunity in mice. The pathology and clinical symptoms in CD8+ T cell–mediated CNS autoimmunity demonstrate similarities to MS not seen in myelin-specific CD4+ T cell–mediated EAE. These data suggest that myelin-specific CD8+ T cells could function as effector cells in the pathogenesis of MS.

scholarly journals The Role of Fampridine in the Symptomatic Treatment of Gait Impairment in Patients with Multiple Sclerosis

2019 ◽  
Vol 61 (3) ◽  
pp. 199-207
Author(s):  
Michał Piwoński ◽  
Klaudia Żak ◽  
Patrycja Gierszon ◽  
Izabela Morawska ◽  
Dominika Psiuk ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
English Language ◽  
Demyelinating Disease ◽  
Symptomatic Treatment ◽  
Gait Pattern ◽  
Modern Medicine ◽  
Gait Impairment ◽  
Slowing Down ◽  
The Central Nervous System ◽  
Short Time

Introduction: Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system, the treatment of which remains a great challenge for modern medicine. An important part of it, apart from the treatment slowing down the process of demyelination, is the symptomatic treatment of sphincteral disorders, spasticity, muscle weakness, visual disturbances, mood, depression and gait impairment, which have been carried out with the use of fampridine for a short time. Materials and Methods: The study uses the method of literature analysis in the form of full English-language articles available in the PubMed and Google Scholar database describing the assessment of the effectiveness of fampridine in the symptomatic treatment of gait impairment in MS patients. Results: In each of the studies cited, the ability to walk is indicated in patients taking fampridine compared to placebo. An improvement in walking speed, distance and physical activity is observed. The gait pattern changes. In addition, there is a lack of efficacy of 5 mg dalfampridine ER, with a significant effect on the dose rate of 10 mg. After 2 weeks of discontinuation, the improvement is reversed. Conclusion: A significant effect of fampridine in a dose of 10 mg on improvement of walking in patients with MS is observed. However, it seems necessary for the therapy to be carried out without interruption.

scholarly journals Prevalence and burden of multiple sclerosis-related fatigue: a systematic literature review

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Abril Oliva Ramirez ◽  
Alexander Keenan ◽  
Olivia Kalau ◽  
Evelyn Worthington ◽  
Lucas Cohen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
English Language ◽  
Demyelinating Disease ◽  
Direct Costs ◽  
Economic Outcomes ◽  
Continuous Measure ◽  
Eligibility Criteria ◽  
The Central Nervous System

Abstract Background Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that results in progressive and irreversible disability. Fatigue is one of the most common MS-related symptoms and is characterized by a persistent lack of energy that impairs daily functioning. The burden of MS-related fatigue is complex and multidimensional, and to our knowledge, no systematic literature review has been conducted on this subject. The purpose of this study was to conduct a systematic literature review on the epidemiology and burden of fatigue in people with multiple sclerosis (pwMS). Methods Systematic searches were conducted in MEDLINE, Embase, and Evidence-Based Medicine Reviews to identify relevant studies of fatigue in pwMS. English-language records published from 2010 to January 2020 that met predefined eligibility criteria were included. We initially selected studies that reported quality of life (QoL) and economic outcomes according to categories of fatigue (e.g., fatigued vs non-fatigued). Studies assessing associations between economic outcomes and fatigue as a continuous measure were later included to supplement the available data. Results The search identified 8147 unique records, 54 of which met the inclusion criteria. Of these, 39 reported epidemiological outcomes, 11 reported QoL, and 9 reported economic outcomes. The supplementary screen for economic studies with fatigue as a continuous measure included an additional 20 records. Fatigue prevalence in pwMS ranged from 36.5 to 78.0%. MS-related fatigue was consistently associated with significantly lower QoL. Results on the economic impact of fatigue were heterogeneous, but most studies reported a significant association between presence or severity of fatigue and employment status, capacity to work, and sick leave. There was a gap in evidence regarding the direct costs of MS-related fatigue and the burden experienced by caregivers of pwMS. Conclusion Fatigue is a prevalent symptom in pwMS and is associated with considerable QoL and economic burden. There are gaps in the evidence related to the direct costs of MS-related fatigue and the burden of fatigue on caregivers. Addressing fatigue over the clinical course of the disease may improve health and economic outcomes for patients with MS.

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