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Progressive multiple sclerosis

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https://www.readbyqxmd.com/read/29471880/-18-f-fspg-pet-reveals-increased-cystine-glutamate-antiporter-xc-activity-in-a-mouse-model-of-multiple-sclerosis
#1
Aileen Hoehne, Michelle L James, Israt S Alam, John A Ronald, Bernadette Schneider, Aloma D'Souza, Timothy H Witney, Lauren E Andrews, Haley C Cropper, Deepak Behera, Gayatri Gowrishankar, Zhaoqing Ding, Tony Wyss-Coray, Frederick T Chin, Sandip Biswal, Sanjiv S Gambhir
BACKGROUND: The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4S)-4-(3-[18 F]fluoropropyl)-L-glutamate ([18 F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG35-55 ) peptide in complete Freund's adjuvant (CFA) followed by pertussis toxin...
February 22, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29470968/multiple-sclerosis-mechanisms-and-immunotherapy
#2
REVIEW
Clare Baecher-Allan, Belinda J Kaskow, Howard L Weiner
Multiple sclerosis (MS) is an autoimmune disease triggered by environmental factors that act on a genetically susceptible host. It features three clinical stages: a pre-clinical stage detectable only by MRI; a relapsing-remitting (RRMS) stage characterized by episodes of neurologic dysfunction followed by resolution; and a progressive stage, which usually evolves from the relapsing stage. Advances in our understanding of the immune mechanisms that contribute to MS have led to more than ten FDA-approved immunotherapeutic drugs that target effector T cells, regulatory cells, B cells, and cell trafficking into the nervous system...
February 21, 2018: Neuron
https://www.readbyqxmd.com/read/29468178/retrograde-interferon-gamma-signaling-induces-major-histocompatibility-class-i-expression-in-human-induced-pluripotent-stem-cell-derived-neurons
#3
Benjamin D S Clarkson, Misha S Patel, Reghann G LaFrance-Corey, Charles L Howe
Objective: Injury-associated axon-intrinsic signals are thought to underlie pathogenesis and progression in many neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). Retrograde interferon gamma (IFN γ ) signals are known to induce expression of major histocompatibility class I (MHC I) genes in murine axons, thereby increasing the susceptibility of these axons to attack by antigen-specific CD8+ T cells. We sought to determine whether the same is true in human neurons...
February 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29467711/eye-movement-abnormalities-in-multiple-sclerosis-pathogenesis-modeling-and-treatment
#4
REVIEW
Alessandro Serra, Clara G Chisari, Manuela Matta
Multiple sclerosis (MS) commonly causes eye movement abnormalities that may have a significant impact on patients' disability. Inflammatory demyelinating lesions, especially occurring in the posterior fossa, result in a wide range of disorders, spanning from acquired pendular nystagmus (APN) to internuclear ophthalmoplegia (INO), among the most common. As the control of eye movements is well understood in terms of anatomical substrate and underlying physiological network, studying ocular motor abnormalities in MS provides a unique opportunity to gain insights into mechanisms of disease...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29466918/multiple-sclerosis-and-hiv-a-case-of-multiple-sclerosis-immune-reconstitution-inflammatory-syndrome-associated-with-antiretroviral-therapy-initiation
#5
Pria Anand, Deanna Saylor
Studies have suggested that the incidence of multiple sclerosis (MS) in HIV-infected (HIV+) patients is lower than that of the general population. Here, we present a case of MS in an HIV+ patient with a relatively suppressed CD4 cell count who developed clinical and radiographic disease worsening in the setting of antiretroviral therapy (ART) initiation. A 47-year-old HIV+ woman (CD4 cell count 216 cells/µl) presented with decreased vision in her right eye. Magnetic resonance imaging (MRI) revealed optic nerve enhancement and open ring-enhancing lesions in the brain concerning for demyelinating disease...
January 1, 2018: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/29466830/correlating-serum-micrornas-and-clinical-parameters-in-amyotrophic-lateral-sclerosis
#6
Radhika Raheja, Keren Regev, Brian C Healy, Maria Antonietta Mazzola, Vanessa Beynon, Felipe von Glehn, Anu Paul, Camilo Diaz-Cruz, Taha Gholipour, Bonnie I Glanz, Pia Kivisakk, Tanuja Chitnis, Howard L Weiner, James D Berry, Roopali Gandhi
INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a debilitating neurologic disorder with poor survival rates and no clear biomarkers for disease diagnosis and prognosis. METHODS: We compared serum miRNA expression from patients with ALS to healthy controls and patients with multiple sclerosis and Alzheimer's disease. We also correlated miRNA expression in cross-sectional and longitudinal cohorts of ALS patients with clinical parameters. RESULTS: We identified 7 microRNAs (miR-192-5p, miR-192-3p, miR-1, miR-133a-3p, miR-133b, miR-144-5p and miR-19a-3p) that were upregulated and 6 microRNAs (miR-320c, miR-320a, let-7d-3p, miR-425-5p, miR-320b and miR-139-5p) that were downregulated in ALS patients compared to healthy controls, Alzheimer's disease and multiple sclerosis patients...
February 21, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29465579/efficacy-of-alemtuzumab-and-natalizumab-in-the-treatment-of-different-stages-of-multiple-sclerosis-patients
#7
Li Wang, Chun-Hui Qi, Ren Zhong, Chao Yuan, Qiu-Yue Zhong
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease, in which the insulating covers of nerve cells in the brain and spinal cord are demyelinated. This study was conducted to compare the efficacy of alemtuzumab and natalizumab in the treatment of different stages of MS patients. METHODS: A total of 585 patients diagnosed with MS and hospitalized were included and analyzed after which they were divided into the primary progressive MS A and B groups, the relapsing-remitting MS (RRMS) C and D groups, and the secondary progressive MS E and F groups...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29460650/a-comparison-of-human-natural-monoclonal-antibodies-and-aptamer-conjugates-for-promotion-of-cns-remyelination-where-are-we-now-and-what-comes-next
#8
Maria K Perwein, John A Smestad, Arthur E Warrington, Robin M Heider, Mark W Kaczor, Louis J Maher, Bharath Wootla, Ahmad Kunbaz, Moses Rodriguez
Multiple sclerosis (MS) is a chronic and progressive inflammatory demyelinating disease of the human central nervous system (CNS) and is the most common disabling neurological condition in young adults, resulting in severe neurological defects. No curative or long-term progression-inhibiting therapy has yet been developed. However, recent investigation has revealed potential strategies that do not merely modulate potentially pathogenic autoimmune responses, but stimulate remyelination within CNS lesions. Areas Covered: We discuss the history and development of natural human IgM-isotype immunoglobulins (HIgMs) and recently-identified aptamer-conjugates that have been shown to enhance endogenous myelin repair in animal models of demyelination by acting on myelin-producing oligodendrocytes (OLs) or oligodendrocyte progenitor cells (OPCs) within CNS lesions...
February 20, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29460203/time-is-cerebellum
#9
EDITORIAL
Hiroshi Mitoma, Mario Manto, Christiane S Hampe
The cerebellum characteristically has the capacity to compensate for and restore lost functions. These compensatory/restorative properties are explained by an abundant synaptic plasticity and the convergence of multimodal central and peripheral signals. In addition, extra-cerebellar structures contribute also to the recovery after a cerebellar injury. Clinically, some patients show remarkable improvement of severe ataxic symptoms associated with trauma, stroke, metabolism, or immune-mediated cerebellar ataxia (IMCA, e...
February 19, 2018: Cerebellum
https://www.readbyqxmd.com/read/29459346/predictors-of-retinal-atrophy-in-multiple-sclerosis-a-longitudinal-study-using-spectral-domain-optical-coherence-tomography-with-segmentation-analysis
#10
Raed Behbehani, Hussain Adnan, Abdullah Abu Al-Hassan, Ali Al-Salahat, Raed Alroughani
BACKGROUND: Multiple sclerosis is an inflammatory demyelinating disease characterized by progressive axonal loss affecting mainly the inner retinal layers. Optical coherence tomography (OCT) provides in-vivo quantification of the retinal layers and allows measuring progressive retinal changes. Our objective was to assess the longitudinal changes in the retina using spectral domain OCT (SDOCT) and to identify independent predictors affecting retinal thinning in MS patients. METHODS: A prospective study in a tertiary care MS center was conducted to study the longitudinal retinal changes in MS patients...
February 11, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29459257/effect-of-comorbidities-on-the-course-of-multiple-sclerosis
#11
Przemyslaw Puz, Anetta Lasek-Bal, Arkadiusz Steposz, Karina Bartoszek, Patrycja Radecka
OBJECTIVE: The clinical condition of multiple sclerosis (MS) patients depends not only on the course of MS but also on their lifestyle and comorbidities. This study aimed to assess the effect of selected comorbidities, lifestyle-related factors and clinical data available at the time of MS diagnosis, on the disease activity and the disability progression in patients with relapsing-remitting multiple sclerosis (RRMS). PATIENTS AND METHODS: Based on clinical relapses over a period of 12 months of observation and the results of MRI scans, 138 patients with RRMS were qualified into two groups: 'active' or 'stable' course of the disease...
February 11, 2018: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29458916/use-of-complementary-and-alternative-medicine-in-patients-with-multiple-sclerosis-in-germany
#12
Mario Gotta, Christoph A Mayer, Jutta Huebner
BACKGROUND: The use of complementary and alternative medicine (CAM) for chronic diseases such as multiple sclerosis (MS) is becoming an increasingly important issue for those affected. Especially in Germany there are only a few studies dealing with CAM, as yet. The aim of this study was to assess the prevalence, the methods used, the subjective benefits as well as physician/patient communication. METHODS: A structured questionnaire including demographic and disease-specific data, CAM use, perceived benefits as well as physician/patient communication was sent to real and web-based self-help groups for MS in Germany...
February 2018: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/29456537/understanding-progressive-multifocal-leukoencephalopathy-risk-in-multiple-sclerosis-patients-treated-with-immunomodulatory-therapies-a-bird-s-eye-view
#13
REVIEW
Elizabeth A Mills, Yang Mao-Draayer
The increased use of newer potent immunomodulatory therapies for multiple sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has expanded the patient population at risk for developing progressive multifocal leukoencephalopathy (PML). These MS therapies shift the profile of lymphocytes within the central nervous system (CNS) leading to increased anti-inflammatory subsets and decreased immunosurveillance. Similar to MS, PML is a demyelinating disease of the CNS, but it is caused by the JC virus...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29455894/cognitive-behavioural-therapy-for-ms-related-fatigue-explained-a-longitudinal-mediation-analysis
#14
L E van den Akker, H Beckerman, E H Collette, H Knoop, G Bleijenberg, J W Twisk, J Dekker, V de Groot
BACKGROUND: Cognitive behavioural therapy (CBT) effectively reduces fatigue directly following treatment in patients with Multiple Sclerosis (MS), but little is known about the process of change during and after CBT. DESIGN: Additional analysis of a randomized clinical trial. OBJECTIVE: To investigate which psychological factors mediate change in fatigue during and after CBT. METHODS: TREFAMS-CBT studied the effectiveness of a 16-week CBT treatment for MS-related fatigue...
March 2018: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/29455558/investigational-immunosuppressants-in-early-stage-clinical-trials-for-the-treatment-of-multiple-sclerosis
#15
Alberto Gajofatto, Marco Turatti
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with an immune mediated pathogenesis. Several therapies that suppress or modulate diverse immune system functions have been used for decades with the aim of modifying the disease course. However, these treatments have either limited efficacy or potentially serious adverse events that prevent first-line use on large scale. Areas covered. The aim of the present article is to review ongoing or recently completed clinical trials investigating immunosuppressive drugs for MS...
February 19, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29455071/the-use-of-satellite-data-to-measure-ultraviolet-b-penetrance-and-its-potential-association-with-age-of-multiple-sclerosis-onset
#16
Ofer Amram, Nadine Schuurman, Ellen Randall, Feng Zhu, Jameelah Saeedi, Peter Rieckmann, Irene Yee, Helen Tremlett
BACKGROUND: Studies have indicated an association between low Ultraviolet B (UVB) exposure and an increased risk of developing multiple sclerosis (MS). Few studies, however, have explored whether UVB exposure is associated with the age at MS symptom onset. OBJECTIVE: We investigated the potential association between cumulative early life ambient UVB exposure and age at MS onset, using satellite data to measure ambient UVB exposure. METHODS: Adult onset MS patients were selected from the University of British Columbia's MS genetic database (1980-2005)...
February 6, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29453889/mitochondrial-dysfunction-and-axon-degeneration-in-progressive-multiple-sclerosis
#17
REVIEW
Graham Campbell, Don Mahad
The neuron is the target of inflammatory demyelinating processes in multiple sclerosis (MS). In progressive MS, however, there is a gathering body of evidence indicating that molecular changes converge on mitochondria within neuronal cell bodies. The most reproducible change relates to mitochondrial respiratory chain complex deficiency, which compromises the capacity of neurons to generate ATP. The resulting energy failure state is coupled with an increase in demand for energy by the demyelinated axon, being particularly relevant to the long tracts such as corticospinal tracts with long projection axons...
February 17, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29450696/neuroprotective-effects-of-melatonin-on-experimental-allergic-encephalomyelitis-mice-via-anti-oxidative-stress-activity
#18
Ting Long, Yuan Yang, Ling Peng, Zuoxiao Li
Multiple sclerosis (MS) is a chronic auto-inflammatory disease of the central nervous system (CNS) and hard to heal. This study aimed to investigate the effect of melatonin on mice with experimental autoimmune encephalomyelitis (EAE), a widely used MS model, and its potential mechanism underlying the action of MT on anti-oxidative stress. Female C57BL/6 mice were injected with MOG35-55 peptide to set up the EAE model, and for detection of the effect of melatonin (10 mg/kg i.p.) on the development and progression of EAE...
February 15, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29449193/phase-i-trial-of-intrathecal-mesenchymal-stem-cell-derived-neural-progenitors-in-progressive-multiple-sclerosis
#19
Violaine K Harris, James Stark, Tamara Vyshkina, Leslie Blackshear, Gloria Joo, Valentina Stefanova, Gabriel Sara, Saud A Sadiq
BACKGROUND: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system and is one of the leading causes of disability in young adults. Cell therapy is emerging as a therapeutic strategy to promote repair and regeneration in patients with disability associated with progressive MS. METHODS: We conducted a phase I open-label clinical trial investigating the safety and tolerability of autologous bone marrow mesenchymal stem cell-derived neural progenitor (MSC-NP) treatment in 20 patients with progressive MS...
February 3, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29446144/animal-models-of-multiple-sclerosis-focus-on-experimental-autoimmune-encephalomyelitis
#20
REVIEW
Ivana Bjelobaba, Vesna Begovic-Kupresanin, Sanja Pekovic, Irena Lavrnja
Multiple sclerosis (MS) is a chronic, progressive disorder of the central nervous system (CNS) that affects more than two million people worldwide. Several animal models resemble MS pathology; the most employed are experimental autoimmune encephalomyelitis (EAE) and toxin- and/or virus-induced demyelination. In this review we will summarize our knowledge on the utility of different animal models in MS research. Although animal models cannot replicate the complexity and heterogeneity of the MS pathology, they have proved to be useful for the development of several drugs approved for treatment of MS patients...
February 15, 2018: Journal of Neuroscience Research
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