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Progressive multiple sclerosis treatment

Chenyi Wang, Mark R Kotter
Multiple sclerosis (MS) is a chronic autoimmune, inflammatory disease in the central nervous system (CNS) characterized by loss of oligodendrocytes, myelin axons, and neurons. Remyelination is an endogenous repair mechanism, which recovers the loss of myelin and is able to preserve functional axons. The hope is that the development of new treatments aiming at promoting remyelination will halt and potentially partially reverse the progressive neurological decline in MS. The development of such drugs requires adequate models...
2018: Methods in Molecular Biology
Richard Hughes, Marinos C Dalakas, Ingemar Merkies, Norman Latov, Jean-Marc Léger, Eduardo Nobile-Orazio, Gen Sobue, Angela Genge, David Cornblath, Martin Merschhemke, Carolyn Marie Ervin, Catherine Agoropoulou, Hans-Peter Hartung
BACKGROUND: Fingolimod is approved for the treatment of relapsing-remitting multiple sclerosis and was effective in experimental autoimmune neuritis in rats, a possible model for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We aimed to evaluate the efficacy of fingolimod in delaying disability progression in patients with CIDP who withdrew from currently effective treatments (intravenous immunoglobulin [IVIg] or corticosteroids). METHODS: This double-blind, multicentre, randomised, placebo-controlled, parallel-group, event-driven study was done at 48 neurology centres in Australia, Canada, Israel, Japan, the USA, and nine countries in Europe...
July 6, 2018: Lancet Neurology
Nimish J Thakore, Brittany R Lapin, Tyler G Kinzy, Erik P Pioro
OBJECTIVES: Propose an empirical amyotrophic lateral sclerosis (ALS) staging approach called Fine'til 9 (FT9) based on how many of the patient's ALS functional rating scale (ALSFRS-R) subscores are 9 or less (of normal 12). Gain insights into progression of ALS by applying Markov models to ALS stages by multiple systems (King's, Milan-Torino system (MITOS) and FT9). METHODS: Patients from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) dataset were staged using ALSFRS-R responses...
July 12, 2018: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Noémie Chartier, Jonathan Epstein, Marc Soudant, Camille Dahan, Maud Michaud, Sophie Pittion-Vouyovitch, Francis Guillemin, Marc Debouverie, Guillaume Mathey
BACKGROUND: Mitoxantrone has been used to treat patients with aggressive multiple sclerosis (MS) for decades. We aimed to describe the effectiveness and adverse events over 10 years post-mitoxantrone in relapsing and progressive MS patients from an exhaustive real-life database. METHODS: Data from patients who received mitoxantrone before January 1, 2006, were collected from the MS Lorraine registry. Expanded disability status scale (EDSS) scores and annual relapse rates (ARR) year by year during follow-up and the year prior to mitoxantrone were compared...
July 11, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Hao Li, Fang-Hong Shi, Shi-Ying Huang, Shun-Guo Zhang, Zhi-Chun Gu, Ji-Fu Wei
BACKGROUND: Natalizumab (NAT), a humanized monoclonal antibody, which binds in both α4β1 integrins and α4β7 integrins, is approved for the treatment of multiple sclerosis (MS) and Crohn's disease (CD). An uncommon but serious adverse event from NAT treatment is known as progressive multifocal leukoencephalopathy (PML). However, clinical comprehensive safety evidence of NAT is limited. METHODS: We will search Medline, Embase, Cochrane library, and ClinicalTrials...
July 2018: Medicine (Baltimore)
Julian Gold, Monica Marta, Ute C Meier, Tove Christensen, David Miller, Daniel Altmann, David Holden, Lucia Bianchi, Rocco Adiutori, David MacManus, Tarek Yousry, Klaus Schmierer, Benjamin Turner, Gavin Giovannoni
BACKGROUND: Although the aetiology of multiple sclerosis (MS) remains elusive, it is clear that Epstein Barr virus (EBV) and possibly other viruses play a role in the pathogenesis of MS. Laboratory evidence suggests that human endogenous retroviruses (HERVs) could also have a role, but no interventional therapy has determined what will happen if HERVs are suppressed. Recent epidemiological evidence indicates patients with HIV infection have a significantly lower risk of developing MS and that HIV antiretroviral therapies may be coincidentally inhibiting HERVs, or other retroelements, that could be implicated in MS...
June 28, 2018: Multiple Sclerosis and related Disorders
Piera Versura, Giuseppe Giannaccare, Marco Pellegrini, Stefano Sebastiani, Emilio C Campos
Neurotrophic keratitis (NK) is a degenerative corneal disease caused by damage of trigeminal corneal innervation, which leads to spontaneous epithelial breakdown and corneal ulceration. The impairment of corneal sensory innervation causes the reduction of both protective reflexes and trophic neuromodulators that are essential for the vitality, metabolism, and wound healing of ocular surface tissues. A wide range of ocular and systemic conditions, including herpetic keratitis, ocular chemical burns, corneal surgery, diabetes, multiple sclerosis, and neurosurgical procedures, can cause NK by damaging trigeminal innervation...
2018: Eye and Brain
Veria Vacchiano, Nicola Frattaruolo, Luca Mancinelli, Matteo Foschi, Antonio Carotenuto, Cinzia Scandellari, Maurizio Piattelli, Vincenzo Brescia Morra, Alessandra Lugaresi
BACKGROUND: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis (RRMS) with a consistent safety profile in clinical trials. We report three cases of multiple teeth loss during teriflunomide treatment. CASE REPORTS: Case 1: a 39 year-old woman started teriflunomide for RRMS, switching from interferon beta. Four months later she complained about mandibular pain followed by the sudden loss of 4 teeth, in the absence of bleeding or trauma...
June 30, 2018: Multiple Sclerosis and related Disorders
Saima Nazish, Rizwana Shahid, Azra Zafar, Foziah Alshamrani, Abdullah Al Sulaiman, Majed Alabdali, Danah Aljaafari, Esraa Al Wabari, Fahd A Alkhamis
BACKGROUND AND PURPOSE: The objective of this study was to determine the frequencies of different clinical presentations and the phenotypic spectrum of multiple sclerosis (MS). METHODS: This cross-sectional study was performed in the Neurology Department of King Fahd Hospital of University Alkhobar in the Kingdom of Saudi Arabia (KSA). Data of 190 MS patients who fulfilled the McDonald criteria were retrieved from medical records and analyzed. RESULTS: The age at disease onset was 26...
July 2018: Journal of Clinical Neurology
Luis Hernandez, Malinda O'Donnell, Maarten Postma
BACKGROUND: Numerous cost-effectiveness analyses (CEAs) of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) have been published in the last three decades. Literature reviews of the modeling methods and results from these CEAs have also been published. The last literature review that focused on modeling methods, without country or time horizon in the inclusion criteria, included studies published up to 2012. Since then, new DMTs have become available, and new models and data sources have been used to assess their cost effectiveness...
July 3, 2018: PharmacoEconomics
Janos Groh, Michaela Hörner, Rudolf Martini
BACKGROUND: Genetically caused neurological disorders of the central nervous system (CNS) are mostly characterized by poor or even fatal clinical outcome and few or no causative treatments are available. Often, these disorders are associated with low-grade, disease-promoting inflammation, another feature shared by progressive forms of multiple sclerosis (PMS). We previously generated two mouse lines carrying distinct mutations in the oligodendrocytic PLP1 gene that have initially been identified in patients diagnosed with MS...
July 3, 2018: Journal of Neuroinflammation
Floriana De Angelis, Domenico Plantone, Jeremy Chataway
Multiple sclerosis is an immune-mediated inflammatory disease of the central nervous system characterised by demyelination, neuroaxonal loss and a heterogeneous clinical course. Multiple sclerosis presents with different phenotypes, most commonly a relapsing-remitting course and, less frequently, a progressive accumulation of disability from disease onset (primary progressive multiple sclerosis). The majority of people with relapsing-remitting multiple sclerosis, after a variable time, switch to a stage characterised by gradual neurological worsening known as secondary progressive multiple sclerosis...
July 3, 2018: CNS Drugs
Yinan Zhang, Crystal Wright, Angela Flores
BACKGROUND: We report the development of asymptomatic progressive multifocal leukoencephalopathy in a patient with multiple sclerosis on natalizumab therapy. Progressive multifocal leukoencephalopathy often presents with debilitating neurologic symptoms. Very few cases have documented a completely asymptomatic course of the disease. CASE PRESENTATION: A 26-year-old white woman with multiple sclerosis was treated with natalizumab. She was diagnosed as having progressive multifocal leukoencephalopathy based on characteristic magnetic resonance imaging lesions after 27 infusions of natalizumab...
July 1, 2018: Journal of Medical Case Reports
Eduardo Duarte-Silva, Shyrlene Meiry da Rocha Araújo, Wilma Helena Oliveira, Deniele Bezerra de Lós, Maria Eduarda Rocha de França, Amanda Pires Bonfanti, Gabriela Peron, Livia de Lima Thomaz, Liana Verinaud, Ana Karolina de Santana Nunes, Christina Alves Peixoto
Apoptosis is one form of cell death that is intimately related to health and pathological conditions. In most neuroinflammatory and/or neurodegenerative diseases, apoptosis is associated with disease development and pathology and inhibition of this process leads to considerable amelioration. It is becoming evident that apoptosis also participates in the pathogenesis of Multiple Sclerosis (MS) and its animal model, Experimental Autoimmune Encephalomyelitis (EAE). Drugs such as Sildenafil, a Phosphodiesterase type 5 Inhibitor (PDE5I), have proven to be neuroprotective in MS models...
August 15, 2018: Journal of Neuroimmunology
Katie Streicher, Sriram Sridhar, Mike Kuziora, Christopher A Morehouse, Brandon W Higgs, Yinong Sebastian, Christopher J Groves, Fernanda Pilataxi, Philip Z Brohawn, Ronald Herbst, Koustubh Ranade
OBJECTIVES: B cells impact systemic sclerosis (SSc) progression through multiple pathogenic mechanisms. CD19 inhibition in mice reduced skin thickness, collagen production, and autoantibody levels, consistent with CD19 expression on plasma cells (PCs), the source of antibody production. Plasma cell depletion could effectively reduce collagen deposition and inflammation in SSc; therefore, we investigated effects on SSc disease activity. METHODS: A PC gene signature was evaluated in SSc skin biopsies in two phase I clinical trials...
June 29, 2018: Arthritis & Rheumatology
Maria Petracca, Monica Margoni, Giulia Bommarito, Matilde Inglese
Imaging markers for monitoring disease progression in progressive multiple sclerosis (PMS) are scarce, thereby limiting the possibility to monitor disease evolution and to test effective treatments in clinical trials. Advanced imaging techniques that have the advantage of metrics with increased sensitivity to short-term tissue changes and increased specificity to the structural abnormalities characteristic of PMS have recently been applied in clinical trials of PMS. In this review, we (1) provide an overview of the pathological features of PMS, (2) summarize the findings of research and clinical trials conducted in PMS which have applied conventional and advanced magnetic resonance imaging techniques and (3) discuss recent advancements and future perspectives in monitoring PMS with imaging techniques...
June 28, 2018: Neurology and Therapy
Massimo Filippi, Paolo Preziosa, Maria A Rocca
PURPOSE OF REVIEW: To summarize recent findings from the application of MRI in the diagnostic work-up of patients with suspected multiple sclerosis (MS), and to review the insights into disease pathophysiology and the utility of MRI for monitoring treatment response. RECENT FINDINGS: New evidence from the application of MRI in patients with clinically isolated syndromes has guided the 2017 revision of the McDonald criteria for MS diagnosis, which has simplified their clinical use while preserving accuracy...
August 2018: Current Opinion in Neurology
Alexandra K Roth, Douglas R Denney, Jeffrey M Burns, Sharon G Lynch
OBJECTIVE: Progress in the treatment of multiple sclerosis (MS) has resulted in larger numbers of patients living to an advanced age, but little is known about the cognitive status of these individuals. The primary purpose of this study was to identify differences in the cognitive performance between elderly individuals with MS and those with amnestic mild cognitive impairment (aMCI). METHOD: Three groups ranging in age from 60 to 80 were compared: patients with MS (n = 64), patients with aMCI (n = 58), and healthy adults (n = 70)...
June 25, 2018: Neuropsychology
Albulena Bajrami, Marco Pitteri, Marco Castellaro, Francesca Pizzini, Chiara Romualdi, Stefania Montemezzi, Salvatore Monaco, Massimiliano Calabrese
INTRODUCTION: The mechanism of action of fingolimod within the central nervous system and its efficacy in reducing/preventing both focal and diffuse grey matter (GM) damage in active multiple sclerosis (MS) are not completely understood. METHODS: In this longitudinal, 2-year prospective, phase IV, single-blind study, 40 MS patients treated with fingolimod and 39 untreated age, gender, and disability-matched MS patients were enrolled. Each patient underwent a neurological examination every 6 months and a 3T MRI at the beginning of the treatment and after 24 months...
June 25, 2018: Journal of Neurology
Nastaran Majdinasab, Foroogh Namjoyan, Mohsen Taghizadeh, Hamid Saki
Background: Multiple sclerosis (MS) is a chronic progressive and inflammatory disease of the central nervous system that is characterized by demyelination in the central nervous system. In regard to the prevalence of diseases and enormous costs imposed on society and the health system, finding a way to stop the progression of the disease using drugs with fewer side effects seems a serious sanitation issue to the health of the international community. This study aimed to evaluate the effect of evening primrose oil (EPO) on fatigue and quality of life in patients with MS...
2018: Neuropsychiatric Disease and Treatment
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