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Progressive multiple sclerosis treatment

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https://read.qxmd.com/read/30771580/trial-of-intrathecal-rituximab-in-progressive-multiple-sclerosis-patients-with-evidence-of-leptomeningeal-contrast-enhancement
#1
Pavan Bhargava, Cassie Wicken, Matthew D Smith, Roy E Strowd, Irene Cortese, Daniel S Reich, Peter A Calabresi, Ellen M Mowry
BACKGROUND: Leptomeningeal inflammation is associated with increased cortical damage and worse clinical outcomes in MS. It may be detected on contrast-enhanced T2-FLAIR imaging as focal leptomeningeal contrast-enhancement (LME). OBJECTIVE: To assess the safety of intrathecal (IT) rituximab in progressive MS (PMS) and to assess its effects on LME and CSF biomarkers. METHODS: PMS patients had a screening MRI to detect LME. Participants satisfying eligibility criteria underwent two IT administrations of 25 mg rituximab 2 weeks apart...
February 11, 2019: Multiple Sclerosis and related Disorders
https://read.qxmd.com/read/30771578/increased-cerebrospinal-fluid-neurofilament-light-chain-in-central-nervous-system-inflammatory-demyelinating-disease
#2
Lijun Peng, Chongfeng Bi, Deyu Xia, Linling Mao, Hairong Qian
BACKGROUND: Central nervous system (CNS) inflammatory demyelinating disease (IDD) is an immune-mediated disease that is pathologically characterized by demyelination and inflammatory infiltration in the CNS and includes clinically isolated syndrome (CIS), multiple sclerosis (MS), and neuromyelitis optica spectrum disorders (NMOSD). IDD is usually characterized by variable symptoms, multivariate imaging, uncertain reactions to treatment, and a variable prognosis, which makes it difficult to diagnose early...
February 8, 2019: Multiple Sclerosis and related Disorders
https://read.qxmd.com/read/30770703/gut-microbiota-dependent-ccr9-cd4-t-cells-are-altered-in-secondary-progressive-multiple-sclerosis
#3
Atsushi Kadowaki, Ryoko Saga, Youwei Lin, Wakiro Sato, Takashi Yamamura
The mechanism underlying the progression of relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis (SPMS), characterized by accumulating fixed disability, is yet to be fully understood. Although alterations in the gut microbiota have recently been highlighted in multiple sclerosis pathogenesis, the mechanism linking the altered gut environment with the remote CNS pathology remains unclear. Here, we analyse human CD4+ memory T cells expressing the gut-homing chemokine receptor CCR9 and found a reduced frequency of CCR9+ memory T cells in the peripheral blood of patients with SPMS relative to healthy controls...
February 15, 2019: Brain: a Journal of Neurology
https://read.qxmd.com/read/30763907/tolerability-treatment-satisfaction-and-quality-of-life-outcomes-in-stable-multiple-sclerosis-patients-switched-from-injectable-therapies-to-auto-injected-intramuscular-interferon-beta-1a-the-sfera-study
#4
Chiara Zecca, Zbyšek Pavelek, Kateřina Přikrylová, Mascia Ghielmetti, Andreas Beeler, Claudio Gobbi
BACKGROUND: Interferon beta (IFNB) and Glatiramer acetate, long-term first line disease modifying treatments (DMTs) for multiple sclerosis (MS), have different injection frequencies crucial for injection site related side effects. We aimed at investigating whether switching to intramuscular IFNB-1a injected once/week with the Avonex®Pen™ device improves treatment tolerability and quality of life in stable MS patients. METHODS: Clinically stable MS patients, whom their treating neurologist switched from high frequency injectable DMTs to weekly intramuscular IFNB-1a because of bothersome injection site reactions, were included...
February 6, 2019: Multiple Sclerosis and related Disorders
https://read.qxmd.com/read/30756407/dimethyl-fumarate-a-two-edged-drug-current-status-and-future-directions
#5
REVIEW
Nathaniel Edward Bennett Saidu, Niloufar Kavian, Karen Leroy, Claus Jacob, Carole Nicco, Frédéric Batteux, Jérôme Alexandre
Dimethyl fumarate (DMF) is a fumaric acid ester registered for the treatment of relapsing-remitting multiple sclerosis (RRMS). It induces protein succination leading to inactivation of cysteine-rich proteins. It was first shown to possess cytoprotective and antioxidant effects in noncancer models, which appeared related to the induction of the nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) pathway. DMF also displays antitumor activity in several cellular and mice models. Recently, we showed that the anticancer mechanism of DMF is dose-dependent and is paradoxically related to the decrease in the nuclear translocation of NRF2...
February 12, 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30755165/the-neutrophil-to-lymphocyte-and-monocyte-to-lymphocyte-ratios-are-independently-associated-with-neurological-disability-and-brain-atrophy-in-multiple-sclerosis
#6
Christopher C Hemond, Bonnie I Glanz, Rohit Bakshi, Tanuja Chitnis, Brian C Healy
BACKGROUND: Serum hematological indices such as the neutrophil-lymphocyte ratio (NLR) or monocyte-lymphocyte ratio (MLR) have been used as biomarkers of pathogenic inflammation and prognostication in multiple areas of medicine; recent evidence shows correlation with psychological parameters as well. OBJECTIVES/AIMS: To characterize clinical, neuroimaging, and psycho-neuro-immunological associations with NLR and MLR in persons with multiple sclerosis (MS). METHODS: We identified a large cohort of clinically well-defined patients from our longitudinal database that included MS-related outcomes, disease-modifying therapy, patient-reported outcome (PRO) measures, and quantified cerebral MRI at 1...
February 12, 2019: BMC Neurology
https://read.qxmd.com/read/30741103/the-efficacy-of-the-modified-story-memory-technique-in-progressive-ms
#7
Nancy D Chiaravalloti, Nancy B Moore, John DeLuca
BACKGROUND: Impairments in new learning and memory are common in individuals with multiple sclerosis (MS), negatively impacting everyday life, including occupational and social functioning. OBJECTIVE: This study examined the efficacy of the modified Story Memory Technique (mSMT) in a progressive multiple sclerosis (PMS) sample through a double-blind, placebo-controlled, randomized clinical trial (RCT). METHODS: Thirty (30) individuals with PMS, naïve to the mSMT, were randomized to the treatment or placebo control group...
February 11, 2019: Multiple Sclerosis: Clinical and Laboratory Research
https://read.qxmd.com/read/30738877/kappa-free-light-chains-could-predict-early-disease-course-in-multiple-sclerosis
#8
D Vecchio, I Crespi, E Virgilio, P Naldi, M P Campisi, R Serino, U Dianzani, G Bellomo, R Cantello, C Comi
BACKGROUND: Cerebrospinal fluid (CSF) kappa free light chains (KFLC) have been suggested as quantitative alternative to oligoclonal bands (OB) in multiple sclerosis (MS) diagnosis. Despite OB have been associated to poor disease prognosis, little is known on KFLC in predicting MS early progression. Our aim is to evaluate the prognostic value of KFLC in a cohort of Italian MS patients. METHODS: 100 patients (64 females) underwent CSF analysis during their diagnostic MS work-up...
February 5, 2019: Multiple Sclerosis and related Disorders
https://read.qxmd.com/read/30738876/increased-level-of-plasma-salusin-%C3%AE-and-salusin-%C3%AE-in-patients-with-multiple-sclerosis
#9
Murat Çakır, Seda Sabah-Özcan, Hikmet Saçmacı
BACKGROUND: Multiple Sclerosis (MS) is a potentially progressive autoimmune disorder of the central nervous system. The pathology of MS is characterized by inflammation, demyelination, reactive gliosis and neuronal damage. Salusin-α and salusin-β have been shown to be widely expressed in many tissues, including the central nervous system. In our study, we investigated whether salusin-α and salusin-β peptides had a relation with inflammation and whether it is related to Relapsing-Remitting Multiple Sclerosis (RRMS) disease...
February 5, 2019: Multiple Sclerosis and related Disorders
https://read.qxmd.com/read/30738875/disease-modifying-therapies-continue-to-drive-up-health-care-cost-among-individuals-with-multiple-sclerosis
#10
Youngran Kim, Trudy Millard Krause, Philip Blum, Léorah Freeman
BACKGROUND: Multiple sclerosis (MS) is a leading cause of disability in adults and requires lifelong treatment. Specialty drugs referred to as disease-modifying therapies (DMTs) have become the standard for multiple sclerosis treatment since the 1990s as they have been shown to reduce the risk of relapses and to delay disease progression. While more DMTs became available, prices of DMTs including existing drugs continue to rise and remain very expensive. This study is to estimate recent drug costs for DMTs and examine its impact on overall health care costs among individuals with MS enrolled in commercial insurance...
February 5, 2019: Multiple Sclerosis and related Disorders
https://read.qxmd.com/read/30735970/determinants-of-quality-of-life-in-relapsing-remitting-and-progressive-multiple-sclerosis
#11
Yavor Yalachkov, Dilara Soydaş, Johannes Bergmann, Stefan Frisch, Marion Behrens, Christian Foerch, Johannes Gehrig
BACKGROUND: Numerous factors can affect multiple sclerosis (MS) patients' quality of life (QoL). We investigated how physical impairment, upper extremity function, cognitive impairment, cognitive reserve, symptoms of psychological distress, depression, fatigue as well as age and disease duration contribute to patient-reported measures of QoL in relapse-remitting MS (RRMS) and progressive MS (PMS). METHODS: 39 patients with RRMS and 16 patients with PMS were evaluated for physical impairment (EDSS assessed by a neurologist), upper extremity function (9-hole peg test), cognitive deficits (broad neuropsychological test battery), cognitive reserves (highest obtained degree of education and vocabulary), symptoms of psychological distress (Symptom Checklist-90-R), depression (Beck Depression Inventory) and fatigue (Fatigue Scale for Motor and Cognitive Functions)...
January 30, 2019: Multiple Sclerosis and related Disorders
https://read.qxmd.com/read/30735638/bone-marrow-mononuclear-cell-therapy-in-a-mouse-model-of-amyotrophic-lateral-sclerosis-functional-outcomes-from-different-administration-routes
#12
Fernanda Gubert, Igor Bonacossa-Pereira, Ana B Decotelli, Michelle Furtado, Andreia Vasconcelos-Dos-Santos, Rosalia Mendez-Otero, Marcelo F Santiago
Amyotrophic lateral sclerosis (ALS) is a chronic degenerative disease that mainly affects motor neurons, leading to progressive paralysis and death. Recently, cell therapy has emerged as a therapeutic alternative for several neurological diseases, including ALS, and bone-marrow cells are one of the major cell sources. Considering the importance of pre-clinical trials to determine the best therapeutic protocol and the hope of translating this protocol to the clinical setting, we tested bone-marrow mononuclear cell (BMMC) therapy administered by different routes in the SOD1G93A model of ALS...
February 5, 2019: Brain Research
https://read.qxmd.com/read/30723784/alpha-1-antitrypsin-substitution-for-extrapulmonary-conditions-in-alpha-1-antitrypsin-deficient-patients
#13
Boris M Baranovski, Ronen Schuster, Omer Nisim, Ido Brami, Yotam Lior, Eli C Lewis
Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder which most commonly manifests as pulmonary emphysema. Accordingly, alpha-1 antitrypsin (AAT) augmentation therapy aims to reduce the progression of emphysema, as achieved by life-long weekly slow-drip infusions of plasma-derived affinity-purified human AAT. However, not all AATD patients will receive this therapy, due to either lack of medical coverage or low patient compliance. To circumvent these limitations, attempts are being made to develop lung-directed therapies, including inhaled AAT and locally-delivered AAT gene therapy...
September 19, 2018: Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation
https://read.qxmd.com/read/30718443/-sports-and-physical-exercise-in-multiple-sclerosis
#14
Hirofumi Ochi
Multiple sclerosis (MS) is a complex immune-mediated disease of the central nervous system. It is characterized by inflammatory and neurodegenerative processes that result in progressive neurological disability. In the past two decades, there have been major therapeutic advances in the treatment of MS, and a substantial number of disease-modifying drugs (DMDs) have been used in clinical practice. The currently available DMDs are effective in controlling inflammatory activity, but not neurodegenerative processes...
February 2019: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://read.qxmd.com/read/30707107/internet-usage-by-polish-patients-with-multiple-sclerosis-a-multicenter-questionnaire-study
#15
Andrzej Potemkowski, Waldemar Brola, Anna Ratajczak, Marcin Ratajczak, Jacek Zaborski, Elżbieta Jasińska, Anna Pokryszko-Dragan, Ewa Gruszka, Marta Dubik-Jezierzańska, Aleksandra Podlecka-Piętowska, Monika Nojszewska, Krystyna Gospodarczyk-Szot, Adam Stępień, Katarzyna Gocyła-Dudar, Marzena Maciągowska-Terela, Jacek Wencel, Radosław Kaźmierski, Alina Kułakowska, Katarzyna Kapica-Topczewska, Witold Pawełczak, Halina Bartosik-Psujek
BACKGROUND: The internet is a source of knowledge and medium widely used in services that facilitate access to information and networking. Multiple sclerosis (MS) patients find the possibility of acquiring information relating to their condition particularly rewarding. OBJECTIVE: We aimed to identify Polish MS patients' preferences by analyzing a percentage of internet users and determining the most common search subjects and patients' approach to information on the internet...
February 1, 2019: Interactive Journal of Medical Research
https://read.qxmd.com/read/30703524/a-clinical-screening-tool-for-objective-and-subjective-cognitive-disorders-in-multiple-sclerosis
#16
Laurent Guilloton, Jean-Philippe Camdessanche, Dominique Latombe, Philippe Neuschwander, Sylvie Cantalloube, Catherine Thomas-Anterion, Bernadette Mercier, Stéphanie Roggerone, Delphine Maucort-Boulch, Sylvain Roche, Sophie Jacquin-Courtois
BACKGROUND: Cognitive dysfunction is common in multiple sclerosis (MS). Deficits can affect attention, concentration, planning, and memory. They can have severe functional consequences in many domains. Cognitive complaints are frequently associated with other confounding factors (fatigue, anxiety, depression, or treatment side effects). In most cases, cognitive assessment is proposed after a spontaneous complaint, but determining the extent of discomfort perceived by the patient, the influence of co-existing factors, or the optimal timing for a more complete neuropsychological assessment is difficult...
January 28, 2019: Annals of Physical and Rehabilitation Medicine
https://read.qxmd.com/read/30692524/ifn%C3%AE-enhances-mesenchymal-stromal-stem-cells-immunomodulatory-function-through-stat1-3-activation-and-mtor-associated-promotion-of-glucose-metabolism
#17
Tiziana Vigo, Claudia La Rocca, Deriggio Faicchia, Claudio Procaccini, Maddalena Ruggieri, Marco Salvetti, Diego Centonze, Giuseppe Matarese, Antonio Uccelli
Administration of mesenchymal stem cells (MSC) ameliorate experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), at both clinical and neuropathological levels. The therapeutic properties of MSC in EAE are mainly mediated by the modulation of pathogenic immune response, but other neurotropic effects, including decreased demyelination and axonal loss as well as promotion of tissue repair, play also a role. Properly controlled phase II clinical trials to explore the potential of MSC transplantation as a treatment for MS are underway...
January 28, 2019: Cell Death & Disease
https://read.qxmd.com/read/30683115/a-novel-neurotherapeutic-for-multiple-sclerosis-ischemic-injury-methamphetamine-addiction-and-traumatic-brain-injury
#18
REVIEW
Arthur A Vandenbark, Roberto Meza-Romero, Gil Benedek, Halina Offner
Neurovascular, autoimmune, and traumatic injuries of the central nervous system (CNS) all have in common an initial acute inflammatory response mediated by influx across the blood-brain barrier of activated mononuclear cells followed by chronic and often progressive disability. Although some anti-inflammatory therapies can reduce cellular infiltration into the initial lesions, there are essentially no effective treatments for the progressive phase. We here review the successful treatment of animal models for four separate neuroinflammatory and neurodegenerative CNS conditions using a single partial MHC class II construct called DRa1-hMOG-35-55 or its newest iteration, DRa1(L50Q)-hMOG-35-55 (DRhQ) that can be administered without a need for class II tissue type matching due to the conserved DRα1 moiety of the drug...
January 23, 2019: Journal of Neuroinflammation
https://read.qxmd.com/read/30681867/synthesis-and-characterization-of-multivalent-protein-based-soluble-antigen-arrays-for-juvenile-diabetes
#19
Martin A Leon, Scott M Wemlinger, Nicholas R Larson, Justin K Ruffalo, C Russell Middaugh, John C Cambier, Cory Berkland
Autoimmune diseases are believed to be highly dependent on loss of immune tolerance to self-antigens. Currently, no treatments have been successful clinically in inducing autoantigen-specific tolerance, including efforts to utilize antigen-specific immunotherapy (ASIT) to selectively correct the aberrant autoimmunity. Soluble antigen arrays (SAgAs) represent a novel autoantigen delivery system composed of a linear polymer, hyaluronic acid (HA), displaying multiple copies of conjugated autoantigen. We have previously reported that Soluble Antigen Arrays proteolipid protein (SAgAPLP) induced tolerance to a specific multiple sclerosis (MS) autoantigen, proteolipid peptide (PLP)...
January 25, 2019: Molecular Pharmaceutics
https://read.qxmd.com/read/30678613/oxidative-status-in-multiple-sclerosis-and-off-targets-of-antioxidants-the-case-of-edaravone
#20
Cristina Agresti, Rosella Mechelli, Stefania Olla, Caterina Veroni, Cecilia Eleuteri, Giovanni Ristori, Marco Salvetti
BACKGROUND: MS is a chronic inflammatory disease of the CNS leading to demyelination and neurodegeneration, with a complex and still to be clarified aetiology. Several data, coming from patients' samples and from animal models, show that oxidative status (OS) plays an important role in MS pathogenesis. Overproduction of reactive oxidative species by macrophages/microglia can bring about cellular injury and ensuing cell death by oxidizing cardinal cellular components. Oxidized molecules are present in active MS lesions and are associated with neurodegeneration...
January 24, 2019: Current Medicinal Chemistry
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