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Progressive multiple sclerosis treatment

Zhifeng Mao, César Álvarez-González, Kimberley Allen-Philbey, Stefania De Trane, Ozlem Yildiz, Tom Campion, Ashok Adams, Benjamin P Turner, Monica Marta, Sharmilee Gnanapavan, Maria Espasandin, Joela Mathews, Gavin Giovannoni, David Baker, Klaus Schmierer
BACKGROUND: Whilst there is a broad selection of drugs licensed as disease modifying treatments (DMTs) for people with relapsing multiple sclerosis (pwRMS), access to DMTs remains restricted, particularly for people with progressive MS (pwPMS). Cladribine has shown efficacy at all stages of MS. Following withdrawal from the market of oral cladribine in 2011, partly due to issues associated with lymphopenia, and following a thorough risk assessment, we started using subcutaneously injected cladribine (Litak® ) to treat both pwRMS and pwPMS...
November 2, 2018: Multiple Sclerosis and related Disorders
Luigi Lavorgna, Giovanna Borriello, Sabrina Esposito, Gianmarco Abbadessa, Rocco Capuano, Laura De Giglio, Alessandra Logoteta, Carlo Pozzilli, Gioacchino Tedeschi, Simona Bonavita
BACKGROUND: In order to anticipate the diagnosis of Multiple Sclerosis (MS), the diagnostic criteria had been reviewed several times in the last years. OBJECTIVE: We wanted to understand whether earlier diagnoses of MS have impacted on therapeutic management of the disease. METHODS: We designed a 22-item survey posted on SMsocialnetwork, a webplatform with a medical supervision, dedicated to Italian MS patients. We collected socio-demographic data, disease and treatment-related information of 1000 patients...
November 5, 2018: Multiple Sclerosis and related Disorders
Yusei Miyazaki, Masaaki Niino
Since the initial observation of increased immunoglobulin concentrations in the cerebrospinal fluid of patients with multiple sclerosis (MS) in the 1940s, B cells have been considered to participate in the pathology of MS through the production of autoantibodies reactive against central nervous system antigens. However, it is now recognized that B cells contribute to MS relapses by antibody-independent activities, including presenting antigens to T cells and releasing pro-inflammatory cytokines. In addition, the recent identification of B cell-rich follicle-like structures in the meninges of patients with MS suggests that pathogenic roles of B cells also exist at the progressive phase...
November 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
Arthur R Chaves, Elizabeth M Wallack, Liam P Kelly, Ryan W Pretty, Hailey D Wiseman, Alice Chen, Craig S Moore, Mark Stefanelli, Michelle Ploughman
OBJECTIVES: Investigate whether asymmetrical corticospinal excitability exists in Multiple Sclerosis (MS) and its association with MS symptoms. METHODS: Bilateral resting and active motor thresholds (RMT, AMT) were gathered using transcranial magnetic stimulation among 82 MS patients. Corticospinal excitability (CSE) asymmetry was expressed as the ratio between weaker and stronger sides' RMT and AMT. Stronger and weaker side was determined by pinch and grip strength...
November 6, 2018: Behavioural Brain Research
Harald Hegen, Janette Walde, Gabriel Bsteh, Michael Auer, Sebastian Wurth, Anne Zinganell, Franziska Di Pauli, Florian Deisenhammer, Thomas Berger
Background: Risk of natalizumab-related progressive multifocal leukoencephalopathy is associated with the presence of anti-JC-virus (JCV) antibodies. Objective: To investigate the impact of disease-modifying treatments (DMT) on the longitudinal evolution of anti-JCV antibody index. Methods: Patients with multiple sclerosis who had serum sampling at intervals of 6 ± 3 months over up to 6 years and who either started DMT (interferon-β, glatiramer acetate or natalizumab) during the observation period with at least one serum sample available before and after treatment initiation or received no DMT during the observation period were included...
2018: Frontiers in Immunology
Massimo Filippi, Amit Bar-Or, Fredrik Piehl, Paolo Preziosa, Alessandra Solari, Sandra Vukusic, Maria A Rocca
Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. This disorder is a heterogeneous, multifactorial, immune-mediated disease that is influenced by both genetic and environmental factors. In most patients, reversible episodes of neurological dysfunction lasting several days or weeks characterize the initial stages of the disease (that is, clinically isolated syndrome and relapsing-remitting MS). Over time, irreversible clinical and cognitive deficits develop...
November 8, 2018: Nature Reviews. Disease Primers
Ludwig Rasche, Friedemann Paul
Ozanimod is a selective sphingosine 1-phosphate receptor 1 and 5 modulator under development by Celgene, for the treatment of relapsing remitting multiple sclerosis. Extensive clinical experience has become available for the related compound fingolimod, favoring the sphingosine 1-phosphate therapeutic concept. Off-target effects have been attributed to its low receptor specificity and have prompted the development of next generation sphingosine 1-phosphate receptor modulators. Areas covered: The authors evaluate the literature of ozanimod, using the PubMed database as well as repositories of the European Committee for Treatment and Research in Multiple Sclerosis and the American and European Academy of Neurology...
November 8, 2018: Expert Opinion on Pharmacotherapy
Simona Portaro, Elisabetta Morini, Maria Elena Santoro, Maria Accorinti, Pietro Marzullo, Antonino Naro, Rocco Salvatore Calabrò
RATIONALE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative multisystem disorder, presenting with limb or bulbar onset. To date, there is no cure for ALS. At some stage of the disease, patients may complain of breathlessness due to respiratory failure, thus needing a noninvasive mechanical ventilation (NIMV) support. However, breathlessness is a symptom that may be induced by different causes that must be taken into consideration in ALS management. PATIENTS CONCERNS: We report the case of an 81-year-old man, with a spinal onset ALS, who was admitted to our clinic to start NIMV because of respiratory involvement...
November 2018: Medicine (Baltimore)
J I Rojas, F Sanchez, F Caro, J Miguez, L Patrucco, J Funes, E Cristiano
The objective of our study was to evaluate the relationship of percentage of annualized brain volume loss (aBVL) and no evidence of disease activity (NEDA) in multiple sclerosis (MS) patients under interferon beta 1-a subcutaneous treatment (IFN-beta) during 3 years of follow up. Relapsing remitting MS (RRMS) patients, with less than three years from disease onset, expanded disability status scale (EDSS) ≤3 and in which IFN beta 1-a 44 mcg was indicated, were included. Demographic, clinical and structural parameters from the magnetic resonance (MR) during the 3 years of follow up were analyzed and compared between patients with and without NEDA (defined as the absence of: (a) three-month confirmed disability progression defined as an increase in EDSS score of 1...
November 3, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Spyros N Deftereos, Evangelos Koutlas, Efrosini Koutsouraki, Athanassios Kyritsis, Panagiotis Papathanassopoulos, Nikolaos Fakas, Vaia Tsimourtou, Nikolaos Vlaikidis, Antonios Tavernarakis, Konstantinos Voumvourakis, Michalis Arvanitis, Dimitrios Sakellariou, Filippo DeLorenzo
BACKGROUND: Little is known about whether tolerability and adherence to treatment can be influenced by weather and temperature conditions. The objective of this study was to assess monthly and seasonal adherence to and safety of sc IFN-β1a (Rebif®, Merck) in relapsing-remitting multiple sclerosis (RRMS) patients using the RebiSmart® electronic autoinjector. METHODS: A multicentre, prospective observational study in Greece in adult RRMS patients with EDSS < 6, under Rebif®/RebiSmart® treatment for ≤6 weeks before enrollment...
November 6, 2018: BMC Neurology
Yara Dadalti Fragoso, Joseph B Bidin Brooks, Audred C Biondo Eboni, Leticia Fezer, Paulo Diniz da Gama, Sidney Gomes, Marcus Vinicius M Gonçalves, Suzana Nunes Machado, Rogerio Rizo Morales, Maria Lucia Vellutini Pimentel, Heloisa Helena Ruocco, Gutemberg Augusto Santos, Simone Scherpenhuijzen, Nise Alessandra Carvalho Sousa
Previous infection with John Cunningham virus (JCV) increases the risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS) undergoing treatment with natalizumab. Patients who test negative for JCV antibodies must be assessed every six months due to the risk of seroconversion. Data from the United States of America, Portugal, Holland, France, United Kingdom and Sweden have shown a strong correlation between the use of natalizumab and JCV seroconversion. The authors present now data on patients from Brazil, as there are no data from Latin American countries published on this subject yet...
November 2, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Liu Yang, Faping Xing, Xinyan Han, Qi Li, Hui Wu, Hailian Shi, Zhifei Wang, Fei Huang, Xiaojun Wu
CD4+ T cells, especially T-helper (Th) cells (Th1, Th2 and Th17) and regulatory T cells (Treg) play pivotal role in the pathogenesis of multiple sclerosis (MS), a demyelinating autoimmune disease occurring in central nervous system (CNS). Astragaloside IV (ASI, CAS: 84687-43-4) is one of the saponins isolated from Astragalus membranceus, a traditional Chinese medicine with immunomodulatory effect. So far, whether ASI has curative effect on experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and how it affects the subsets of CD4+ T cells, as well as the underlying mechanism have not been clearly elucidated...
October 29, 2018: Toxicology and Applied Pharmacology
Konstantin Huhn, Daniela Senger, Kathrin S Utz, Manuel Schmidt, Kilian Fröhlich, Anne Waschbisch, Frank Seifert, Arnd Dörfler, De-Hyung Lee, Ralf A Linker
BACKGROUND: Over the last decade, therapy of relapsing remitting multiple sclerosis (RRMS) has evolved with the approval of several new treatment concepts. Thus, treatment goals have become more ambitious aiming at "no evidence of disease activity" (NEDA). As NEDA-3, this concept comprises freedom of clinical disease progression and relapses as well as inflammatory MRI activity. So far, data on NEDA status mainly stem from post-hoc analyses of drug approval studies. Yet, less is known about the significance of NEDA in "real-world" clinical settings...
October 23, 2018: Multiple Sclerosis and related Disorders
B Mark Hoffman, Nuhad Abou Zeid, Umar Alam, James B Caress
BACKGROUND: Alemtuzumab administration is known to cause secondary autoimmune disease but has not been associated with the development of neurologic autoimmune conditions. Lambert-Eaton myasthenic syndrome (LEMS) is caused by autoantibodies directed against calcium channels on the neuromuscular junction. CASE REPORT: We report a case of a patient with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab who develop generalized weakness initially attributed to progression of MS but eventually determined to be due to LEMS...
October 22, 2018: Multiple Sclerosis and related Disorders
Liesbet M Peeters, Caspar Ep van Munster, Bart Van Wijmeersch, Robin Bruyndonckx, Ilse Lamers, Niels Hellings, Veronica Popescu, Christoph Thalheim, Peter Feys
Personalized treatment is highly desirable in multiple sclerosis (MS). We believe that multidisciplinary measurements including clinical, functional and patient-reported outcome measures in combination with extensive patient profiling can enhance personalized treatment and rehabilitation strategies. We elaborate on four reasons behind this statement: (1) MS disease activity and progression are complex and multidimensional concepts in nature and thereby defy a one-size-fits-all description, (2) functioning, progression, treatment, and rehabilitation effects are interdependent and should be investigated together, (3) personalized healthcare is based on the dynamics of system biology and on technology that confirms a patient's fundamental biology and (4) inclusion of patient-reported outcome measures can facilitate patient-relevant healthcare...
November 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Su Hyun Kim, Min Su Park, Woojun Kim, So Young Huh, Hyun June Shin, Jae Won Hyun, Ho Jin Kim
BACKGROUND AND PURPOSE: This study assessed the long-term outcomes of disease-modifying therapies (DMTs) in Korean multiple sclerosis (MS) patients treated in real-world clinical settings in Korea. METHODS: We retrospectively evaluated the medical records of 160 patients with an initial diagnosis of clinically isolated syndrome or relapsing-remitting MS who were treated for at least 2 years. A status of 3 for no evidence of disease activity (NEDA3) was defined as no relapse, disability progression, or active lesions in annual magnetic resonance imaging (MRI) evaluations...
October 26, 2018: Journal of Clinical Neurology
Gustavo Saposnik, Muhammad Mamdani, Maria Terzaghi, Maria Laura Saladino, Berenice Silva, Philippe N Tobler, Fernando Caceres
Importance: The prescription of generic (non-proprietary) compared to brand-name drugs is increasing worldwide. In many developing and emerging countries, generics companies market products at similar costs as brand-name competitors benefiting from more flexible compliance rules and regulations for marketing their products in the health system. Together, this phenomenon may influence prescriber's behavior (e.g., maintaining the same treatment despite guideline's recommendations or despite evidence of disease progression)...
2018: Frontiers in Neurology
Marcel Gebhardt, Peter Kropp, Frank Hoffmann, Uwe K Zettl
AIMS: Headaches have not been considered a typical symptom of multiple sclerosis (MS), although since 2000, almost every study showed high prevalence. We screened 50 MS patients at the time of first occurrence of neurological symptoms and found the highest prevalence of headache in MS that was ever recorded (78%). Postmortem histological analyses of MS patients' brains revealed lymphoid follicle-like structures in the cerebral meninges and a pathophysiological link between headache, and high inflammatory activity especially in the initial phase of MS could be suspected...
October 26, 2018: European Neurology
Konrad Rejdak, Zbigniew Stelmasiak, Paweł Grieb
BACKGROUND: There has been long-term interest in cladribine as a drug for the treatment of MS. The current study focused on the effect of cladribine on oligoclonal bands (OCB) expression in the CSF in relapsing-remitting MS (RRMS) patients observed over 10 years. METHODS: 29 treatment-naive subjects with RRMS were prospectively enrolled and received induction therapy with subcutaneous parenteral cladribine (at a cumulative dose of 1.8 mg/kg; divided into 6 courses every 5 weeks given for 4-6 days, depending on patients' body weight)...
October 10, 2018: Multiple Sclerosis and related Disorders
Tara A Nazareth, Andrew R Rava, Jackie L Polyakov, Edward N Banfe, Royce W Waltrip Ii, Kristine B Zerkowski, Leslie B Herbert
BACKGROUND: Underestimation of relapse in multiple sclerosis (MS) is detrimental to the patient as well as to their relationship with their MS healthcare professional (HCP). OBJECTIVE: To obtain direct insight into relapse prevalence, symptoms, and HCP engagement from patients with MS who responded to the Multiple Sclerosis in America (MSIA) 2017 survey. METHODS: Information on patient demographics, health insurance coverage, symptoms, disability, relapses, and related HCP interactions were captured...
September 7, 2018: Multiple Sclerosis and related Disorders
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