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Progressive multiple sclerosis treatment

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https://www.readbyqxmd.com/read/28338498/challenge-of-progressive-multiple-sclerosis-therapy
#1
Alan J Thompson
PURPOSE OF REVIEW: Understanding the mechanisms underlying progression in multiple sclerosis (MS) and identifying appropriate therapeutic targets is a key challenge facing the MS community. This challenge has been championed internationally by organizations such as the Progressive MS Alliance, which has raised the profile of progressive MS and identified the key obstacles to treatment. This review will outline the considerable progress against these challenges. RECENT FINDINGS: New insights into mechanisms underlying progression have opened up potential therapeutic opportunities...
March 23, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28323224/progressive-multifocal-leukoencephalopathy-and-rheumatoid-arthritis-treatments
#2
Gaëlle Clavel, Antoine Moulignier, Luca Semerano
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system due to reactivation of the JC virus (JCV). PML is extremely uncommon despite the high prevalence of the virus in the general population. No specific treatment is available, and the prognosis is bleak. The diagnosis is based on brain imaging findings, detection of the JCV genome in cerebrospinal fluid samples and, in some cases, histological studies of the brain lesions. The pathophysiological mechanisms that drive the development of PML are incompletely understood...
March 16, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28321351/bilateral-birdshot-retinochoroiditis-and-retinal-astrocytoma
#3
Sunil Mamtora, Yun Wong, Dugald Bell, Teresa Sandinha
Background. This case highlights the importance of recognising multiple pathologies within the eye which may not necessarily be linked. Both birdshot retinochoroiditis and astrocytoma are rare conditions. The case underlines the need for early identification and treatment of birdshot retinochoroiditis with steroids and disease modifying drugs. Astrocytoma in the absence of tuberous sclerosis is also uncommon. Case Presentation. A 36-year-old male presented with 3-month history of bilateral progressive flashing lights and floaters...
2017: Case Reports in Ophthalmological Medicine
https://www.readbyqxmd.com/read/28320112/multiple-sclerosis-patients-understanding-and-preferences-for-risks-and-benefits-of-disease-modifying-drugs-a-systematic-review
#4
REVIEW
Gurpreet K Reen, Eli Silber, Dawn W Langdon
BACKGROUND: Multiple sclerosis (MS) patients are faced with complex risk-benefit profiles of disease-modifying drugs (DMDs) when making treatment decisions. For effective shared decision-making, MS patients should understand the risks and benefits of DMDs and make treatment decisions based on personal preferences. METHODS: This is an inclusive systematic review to primarily assess current understanding of MS patients for information about DMDs provided during the standard healthcare system...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319650/-monoclonal-antibodies-in-the-treatment-of-ms-emergence-of-b-cell-targeted-therapies
#5
REVIEW
Ai-Lan Nguyen, Melissa Gresle, Tessa Marshall, Helmut Butzkueven, Judith Field
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS, and one of the most common causes of disability in young adults. Over the last decade, new disease modifying therapies have rapidly emerged, including monoclonal antibodies (mAbs) that have provided highly targeted therapies with superior efficacy compared to platform therapies. In particular, monoclonal antibodies directed against CD20-positive B cells have shown remarkable results in recent clinical trials, and renewed interest in the mechanism of B-cell depleting therapies to ameliorate relapse activity and progression in MS...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28319193/stability-and-predictive-value-of-anti-jcv-antibody-index-in-multiple-sclerosis-a-6-year-longitudinal-study
#6
Harald Hegen, Michael Auer, Gabriel Bsteh, Franziska Di Pauli, Tatiana Plavina, Janette Walde, 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 longitudinal evolution of anti-JCV antibody index and to determine the predictive value of baseline anti-JCV antibody index for long-term stability of anti-JCV antibody status. METHODS: MS patients from the MS centre of Medical University of Innsbruck, who had serum sampling for a time period of 4-6 years at intervals of 6±3 months, were included in this retrospective, longitudinal study...
2017: PloS One
https://www.readbyqxmd.com/read/28303911/comorbidity-in-multiple-sclerosis-implications-for-patient-care
#7
REVIEW
Ruth Ann Marrie
Most efforts aimed at understanding the notable heterogeneity of outcomes in multiple sclerosis (MS) have focused on disease-specific factors, such as symptoms at initial presentation, initial relapse rate, and age at symptom onset. These factors, however, explain relatively little of the heterogeneity of disease outcomes. Owing to the high prevalence of comorbidity in MS and the potential for its prevention or treatment, comorbidity is of rising interest as a factor that could explain the heterogeneity of outcomes...
March 17, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28302760/-11-c-pbr28-or-18-f-pbr111-detect-white-matter-inflammatory-heterogeneity-in-multiple-sclerosis
#8
Gourab Datta, Alessandro Colasanti, Nicola Kalk, David R Owen, Gregory Scott, Eugenii Ilan A Rabiner, Roger Gunn, Anne Lingford-Hughes, Omar Malik, Olga Ciccarelli, Richard Nicholas, Lei Nie, Marco Battaglini, Nicola De Stefano, Paul Matthews
Objective: To assess microglial activation in lesions and in normal appearing white matter of multiple sclerosis (MS) patients using positron emission tomography (PET). Methods: 34 MS patients (7 with secondary progressive MS (SPMS), 27 with relapsing remitting MS (RRMS)) and 30 healthy volunteers, genetically stratified for translocator protein (TSPO), binding status underwent PET scanning with TSPO radioligands ((11)C-PBR28 or (18)F-PBR111). Regional TSPO availability was measured as a distribution volume ratio (DVR) relative to the caudate (a pseudo-reference region)...
March 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#9
Elena K Fetisova, Boris V Chernyak, Galina A Korshunova, Maria S Muntyan, Vladimir P Skulachev
BACKGROUND: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28294696/cerebrospinal-fluid-mtdna-concentration-is-elevated-in-multiple-sclerosis-disease-and-responds-to-treatment
#10
Cyra E Leurs, Petar Podlesniy, Ramon Trullas, Lisanne Balk, Martijn D Steenwijk, Arjan Malekzadeh, Fredrik Piehl, Bernard Mj Uitdehaag, Joep Killestein, Jack van Horssen, C E Teunissen
BACKGROUND: Mitochondrial dysfunction is increasingly recognized as an important feature of multiple sclerosis (MS) pathology and may be relevant for clinical disease progression. However, it is unknown whether mitochondrial DNA (mtDNA) levels in the cerebrospinal fluid (CSF) associate with disease progression and therapeutic response. OBJECTIVES: To evaluate whether CSF concentrations of mtDNA in MS patients can serve as a marker of ongoing neuropathology and may be helpful to differentiate between MS disease subtypes...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28285265/neuropsychiatric-syndromes-of-multiple-sclerosis
#11
REVIEW
Ruth Murphy, Stefani O'Donoghue, Timothy Counihan, Colm McDonald, Peter A Calabresi, Mohammed As Ahmed, Adam Kaplin, Brian Hallahan
Neuropsychiatric signs and symptoms occur frequently in individuals with multiple sclerosis (MS), either as the initial presenting complaint prior to a definitive neurological diagnosis or more commonly with disease progression. However, the pathogenesis of these comorbid conditions remains unclear and it remains difficult to accurately elucidate if neuropsychiatric symptoms or conditions are indicators of MS illness severity. Furthermore, both the disease process and the treatments of MS can adversely impact an individual's mental health...
March 11, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28284338/understanding-the-impact-of-relapses-in-the-overall-course-of-ms-refinement-of-the-2-stage-natural-history-model
#12
REVIEW
Thomas F Scott
Recent studies suggest a need for refinement of the traditional two phase model of relapse onset multiple sclerosis (RMS) to include dynamically changing subgroups within the broad category of secondary progressive MS (SPMS). These studies challenge the traditional notion that relapses play a minor role in comparison to a secondary progressive (perhaps degenerative) process. Patients fulfilling the broad definition for SPMS may take several courses, including variable rates and patterns of overall worsening...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28283486/systematic-literature-review-and-network-meta-analysis-in-highly-active-relapsing-remitting-multiple-sclerosis-and-rapidly-evolving-severe-multiple-sclerosis
#13
Eline Huisman, Katerina Papadimitropoulou, James Jarrett, Matthew Bending, Zoe Firth, Felicity Allen, Nick Adlard
OBJECTIVE: Multiple sclerosis (MS) is a chronic, neurodegenerative autoimmune disorder affecting the central nervous system. Relapsing-remitting MS (RRMS) is the most common clinical form of MS and affects ∼85% of cases at onset. Highly active (HA) and rapidly evolving severe (RES) RRMS are 2 forms of RRMS amenable to disease-modifying therapies (DMT). This study explored the efficacy of fingolimod relative to other DMTs for the treatment of HA and RES RRMS. METHODS: A systematic literature review (SLR) was conducted to identify published randomised controlled trials in HA and RES RRMS...
March 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28282574/long-term-effectiveness-and-safety-of-natalizumab-in-a-portuguese-population
#14
I Correia, S Batista, O Galego, I B Marques, J Jesus-Ribeiro, A I Martins, C Nunes, M C Macário, L Cunha, L Sousa
OBJECTIVES: Natalizumab long-term effectiveness data in real-world relapsing-remitting multiple sclerosis (RRMS) is needed. Our objective is to report the long-term effectiveness and safety of natalizumab in a cohort of RRMS patients. METHODS: This is a retrospective study of natalizumab treatment for two years or longer in RRMS. Annualized relapse rate, Expanded Disability Status Scale (EDSS), brain magnetic resonance imaging T2 lesion volume, JC virus antibody status, previous treatments and adverse events were analysed...
March 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28280497/activation-of-blood-cd3-cd56-cd8-t-cells-during-pregnancy-and-multiple-sclerosis
#15
Clara de Andrés, Lidia Fernández-Paredes, Marta Tejera-Alhambra, Bárbara Alonso, Rocío Ramos-Medina, Silvia Sánchez-Ramón
A striking common feature of most autoimmune diseases is their female predominance, with at least twice as common among women than men in relapsing-remitting multiple sclerosis (MS), the prevailing MS clinical form with onset at childbearing age. This fact, together with the protective effect on disease activity during pregnancy, when there are many biological changes including high levels of estrogens and progesterone, puts sex hormones under the spotlight. The role of natural killer (NK) and NKT cells in MS disease beginning and course is still to be elucidated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28277881/drugs-in-clinical-development-for-the-treatment-of-amyotrophic-lateral-sclerosis
#16
Ana Martinez, Maria Del Valle Palomo Ruiz, Daniel I Perez, Carmen Gil
Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron progressive disorder for which no treatment exists to date. However, there are other investigational drugs and therapies currently under clinical development may offer hope in the near future. Areas covered: We have reviewed all the ALS ongoing clinical trials (until November 2016) and collected in Clinicaltrials.gov or EudraCT. We have described them in a comprehensive way and have grouped them in the following sections: biomarkers, biological therapies, cell therapy, drug repurposing and new drugs...
March 14, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28277827/progress-and-prospects-for-the-use-and-the-understanding-of-the-mode-of-action-of-autologous-hematopoietic-stem-cell-transplantation-in-the-treatment-of-multiple-sclerosis
#17
Fredrika Collins, Majid Kazmi, Paolo A Muraro
A substantial proportion of patients with multiple sclerosis (MS) do not respond to pharmacological treatments and no currently approved therapy has been convincingly demonstrated to prevent or stop disease progression. With MS widely believed to be an auto-immune disease, immunoablative therapy followed by autologous haematopoietic stem cell transplantation (I/AHSCT) is being investigated as an alternative therapeutic option. Areas covered: With the results of phase III comparative trials only a few years away, this article reviews animal and clinical trials of I/AHSCT in the treatment of MS and discusses possible immunological mechanisms behind its action...
March 20, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28276076/managing-the-oral-side-effects-of-medications-used-to-treat-multiple-sclerosis
#18
N Cockburn, K Pateman, M W Taing, A Pradhan, P J Ford
BACKGROUND: Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms. METHODS: The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database...
March 9, 2017: Australian Dental Journal
https://www.readbyqxmd.com/read/28274968/conjoint-analysis-to-understand-preferences-of-patients-with-multiple-sclerosis-for-disease-modifying-therapy-attributes-in-spain-a-cross-sectional-observational-study
#19
Rafael Arroyo, Angel P Sempere, Elena Ruiz-Beato, Daniel Prefasi, Agata Carreño, Montse Roset, Jorge Maurino
OBJECTIVE: To assess patients' preferences for a range of disease-modifying therapy (DMT) attributes in multiple sclerosis (MS). DESIGN: A cross-sectional observational study. SETTING: The data reported were from 17 MS units throughout Spain. PARTICIPANTS: Adult patients with relapsing-remitting MS. MAIN OUTCOME: A conjoint analysis was applied to assess preferences. A total of 221 patients completed a survey with 10 hypothetical DMT profiles developed using an orthogonal design and rating preferences from 1 (most acceptable) to 10 (least acceptable)...
March 8, 2017: BMJ Open
https://www.readbyqxmd.com/read/28273764/extensive-white-matter-lesions-after-2%C3%A2-years-of-fingolimod-progressive-multifocal-leukoencephalopathy-or-ms-relapse
#20
Marine Boudot de la Motte, Céline Louapre, Anne Bertrand, Pauline Reach, Catherine Lubetzki, Caroline Papeix, Elisabeth Maillart
BACKGROUND: Fingolimod is a widely used treatment for highly active relapsing-remitting multiple sclerosis. OBJECTIVES: To describe the case of a 27-year-old patient treated for more than 2 years by Fingolimod, who presented hemiplegia and speech disturbances associated with extensive white matter lesions on brain magnetic resonance imaging (MRI). METHODS: Case study. RESULTS: Although initial presentation questioned the possibility of progressive multifocal leukoencephalopathy, final diagnosis was multiple sclerosis (MS) relapse...
April 2017: Multiple Sclerosis: Clinical and Laboratory Research
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