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Progressive multiple sclerosis treatment

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https://www.readbyqxmd.com/read/28228569/no-evidence-of-beneficial-effects-of-plasmapheresis-in-natalizumab-associated-pml
#1
Doriana Landi, Nicola De Rossi, Sara Zagaglia, Cristina Scarpazza, Luca Prosperini, Maria Albanese, Fabio Buttari, Francesco Mori, Girolama Alessandra Marfia, Maria Pia Sormani, Ruggero Capra, Diego Centonze
OBJECTIVE: To examine retrospectively the effects of plasmapheresis (PLEX) on the survival and clinical outcomes of patients with multiple sclerosis (MS) and natalizumab (NTZ)-associated progressive multifocal leukoencephalopathy (PML). METHODS: The medical literature was searched for the terms natalizumab and progressive multifocal leukoencephalopathy. A total of 193 international and 34 Italian NTZ-PML cases were included. Clinical outcome was determined by comparing the patients' clinical status at PML diagnosis with status after PML resolution...
February 22, 2017: Neurology
https://www.readbyqxmd.com/read/28219110/estimating-inverse-probability-weights-using-super-learner-when-weight-model-specification-is-unknown-in-a-marginal-structural-cox-model-context
#2
Mohammad Ehsanul Karim, Robert W Platt
Correct specification of the inverse probability weighting (IPW) model is necessary for consistent inference from a marginal structural Cox model (MSCM). In practical applications, researchers are typically unaware of the true specification of the weight model. Nonetheless, IPWs are commonly estimated using parametric models, such as the main-effects logistic regression model. In practice, assumptions underlying such models may not hold and data-adaptive statistical learning methods may provide an alternative...
February 20, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28215060/efficacy-of-aquatic-therapy-for-multiple-sclerosis-a-systematic-review
#3
Iluminada Corvillo, Enrique Varela, Francisco Armijo, Antonio Alvarez-Badillo, Onica Armijo, Francisco Maraver
BACKGROUND: Multiple sclerosis (MS) is a chronic, inflammatory, progressive, disabling autoimmune disease affecting the central nervous system. Symptoms and signs of MS vary widely and patients may lose their ability to walk. To date the benefits of aquatic therapy often used for rehabilitation in MS patients have not been reviewed. OBJECTIVE: To systematically review the current state of aquatic treatment for persons with MS (hydrotherapy, aquatic therapy, aquatic exercises, spa therapy) and to evaluate the scientific evidence supporting the benefits of this therapeutic option...
February 17, 2017: European Journal of Physical and Rehabilitation Medicine
https://www.readbyqxmd.com/read/28211007/daclizumab-a-review-in-relapsing-multiple-sclerosis
#4
Matt Shirley
Daclizumab (Zinbryta(®); previously known as daclizumab high-yield process) is a therapeutic monoclonal antibody that has recently been approved for the treatment of relapsing forms of multiple sclerosis (MS) in adults. Daclizumab is a humanized IgG1 monoclonal antibody directed against CD25, the alpha subunit of the high-affinity interleukin-2 receptor. As demonstrated in the phase III DECIDE trial, once-monthly subcutaneous daclizumab was superior to once-weekly intramuscular interferon (IFN) β-1a in reducing the clinical relapse rate and radiological measures of disease in patients with relapsing-remitting MS...
February 17, 2017: Drugs
https://www.readbyqxmd.com/read/28209373/cost-utility-of-first-line-disease-modifying-treatments-for-relapsing-remitting-multiple-sclerosis
#5
Erkki Soini, Jaana Joutseno, Marja-Liisa Sumelahti
PURPOSE: This study evaluated the cost-effectiveness of first-line treatments of relapsing-remitting multiple sclerosis (RRMS) (dimethyl fumarate [DMF] 240 mg PO BID, teriflunomide 14 mg once daily, glatiramer acetate 20 mg SC once daily, interferon [IFN]-β1a 44 µg TIW, IFN-β1b 250 µg EOD, and IFN-β1a 30 µg IM QW) and best supportive care (BSC) in the health care payer setting in Finland. METHODS: The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained, 3%/y discounting)...
February 13, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28206827/validity-of-the-symbol-digit-modalities-test-as-a-cognition-performance-outcome-measure-for-multiple-sclerosis
#6
Ralph Hb Benedict, John DeLuca, Glenn Phillips, Nicholas LaRocca, Lynn D Hudson, Richard Rudick
Cognitive and motor performance measures are commonly employed in multiple sclerosis (MS) research, particularly when the purpose is to determine the efficacy of treatment. The increasing focus of new therapies on slowing progression or reversing neurological disability makes the utilization of sensitive, reproducible, and valid measures essential. Processing speed is a basic elemental cognitive function that likely influences downstream processes such as memory. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28203468/nonconvulsive-status-epilepticus-resembling-clinical-absence-with-atypical-eeg-pattern
#7
Channaiah Srikanth Mysore, Najib Murr, Rana Zabad, John Bertoni
Objective. We are reporting two cases: a patient with steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) and another patient with secondary progressive multiple sclerosis (SPMS), both presenting with altered mental status (AMS) and later diagnosed with nonconvulsive atypical absence status epilepticus (AS), with atypical EEG changes. Methods. A report of two cases. Results. A patient with history of SREAT and the other with SPMS had multiple admissions due to AMS. For both, EEG revealed the presence of a high voltage generalized sharply contoured theta activity...
2017: Case Reports in Neurological Medicine
https://www.readbyqxmd.com/read/28203098/health-care-resource-utilization-before-and-after-natalizumab-initiation-among-patients-with-multiple-sclerosis-in-germany
#8
Crystal Watson, Christine Prosser, Sebastian Braun, Pamela B Landsman-Blumberg, Erika Gleissner, Sarah Naoshy
BACKGROUND: Multiple sclerosis (MS), a progressive neurodegenerative disease, greatly impacts the quality of life and economic status of people affected by this disease. In Germany, the total annual cost of MS is estimated at €40,000 per person with MS. Natalizumab has shown to slow MS disease progression, reduce relapses, and improve the quality of life of people with MS. OBJECTIVE: To evaluate MS-related and all-cause health care resource utilization and costs among German MS patients during the 12 months before and after initiation of natalizumab in a real-world setting...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28197174/extremely-low-frequency-electromagnetic-fields-stimulation-modulates-autoimmunity-and-immune-responses-a-possible-immuno-modulatory-therapeutic-effect-in-neurodegenerative-diseases
#9
REVIEW
Fabio Guerriero, Giovanni Ricevuti
Increasing evidence shows that extremely low frequency electromagnetic fields (ELF-EMFs) stimulation is able to exert a certain action on autoimmunity and immune cells. In the past, the efficacy of pulsed ELF-EMFs in alleviating the symptoms and the progression of multiple sclerosis has been supported through their action on neurotransmission and on the autoimmune mechanisms responsible for demyelination. Regarding the immune system, ELF-EMF exposure contributes to a general activation of macrophages, resulting in changes of autoimmunity and several immunological reactions, such as increased reactive oxygen species-formation, enhanced phagocytic activity and increased production of chemokines...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28187977/retinal-and-optic-nerve-degeneration-in-patients-with-multiple-sclerosis-followed-up-for-5-years
#10
Elena Garcia-Martin, Jose R Ara, Jesus Martin, Carmen Almarcegui, Isabel Dolz, Elisa Vilades, Laura Gil-Arribas, Francisco J Fernandez, Vicente Polo, Jose M Larrosa, Luis E Pablo, Maria Satue
PURPOSE: To quantify retinal nerve fiber layer (RNFL) changes in patients with multiple sclerosis (MS) and healthy controls with a 5-year follow-up and to analyze correlations between disability progression and RNFL degeneration. DESIGN: Observational and longitudinal study. PARTICIPANTS: One hundred patients with relapsing-remitting MS and 50 healthy controls. METHODS: All participants underwent a complete ophthalmic and electrophysiologic exploration and were re-evaluated annually for 5 years...
February 7, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28185158/outcome-measures-in-clinical-trials-for-multiple-sclerosis
#11
REVIEW
Caspar E P van Munster, Bernard M J Uitdehaag
Due to the heterogeneous nature of the disease, it is a challenge to capture disease activity of multiple sclerosis (MS) in a reliable and valid way. Therefore, it can be difficult to assess the true efficacy of interventions in clinical trials. In phase III trials in MS, the traditionally used primary clinical outcome measures are the Expanded Disability Status Scale and the relapse rate. Secondary outcome measures in these trials are the number or volume of T2 hyperintense lesions and gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) of the brain...
February 9, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28183276/peginterferon-beta-1a-improves-mri-measures-and-increases-the-proportion-of-patients-with-no-evidence-of-disease-activity-in-relapsing-remitting-multiple-sclerosis-2-year-results-from-the-advance-randomized-controlled-trial
#12
Douglas L Arnold, Peter A Calabresi, Bernd C Kieseier, Shifang Liu, Xiaojun You, Damian Fiore, Serena Hung
BACKGROUND: Subcutaneous peginterferon beta-1a has previously been shown to reduce the number of T2-hyperintense and gadolinium-enhancing (Gd+) lesions over 2 years in patients with relapsing-remitting multiple sclerosis (RRMS), and to reduce T1-hypointense lesion formation and the proportion of patients showing evidence of disease activity, based on both clinical and radiological measures, compared with placebo over 1 year of treatment. The objectives of the current analyses were to evaluate T1 lesions and other magnetic resonance imaging (MRI) measures, including whole brain volume and magnetization transfer ratio (MTR) of normal appearing brain tissue (NABT), and the proportions of patients with no evidence of disease activity (NEDA), over 2 years...
February 10, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28179807/sex-influences-in-neurological-disorders-case-studies-and-perspectives
#13
Janine Austin Clayton
Beginning in the late 1980s and early 1990s, scientists and the public alike recognized that, for too long, women had been underrepresented in clinical trials. While much progress was made in the following decades, preclinical research still often ignores sex as a fundamental biological variable. Many neurological disorders, including multiple sclerosis and migraine, show strong sex differences in incidence and disease manifestation. In this commentary, we highlight case studies of neurological disorders affecting men and women to demonstrate the need for more such studies...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28167648/natalizumab-for-multiple-sclerosis-a-case-in-point-for-the-impact-of-translational-neuroimmunology
#14
Afsaneh Shirani, Olaf Stüve
Advances in translational neuroimmunology over the last two decades have revolutionized the treatment of relapsing forms of multiple sclerosis. A pathological hallmark of multiple sclerosis is the presence of leukocytes in the areas of disease activity in the CNS. Natalizumab inhibits the trafficking of lymphocytes from the blood into the brain and spinal cord by blocking the adhesion molecule α4-integrin. Representing the enormous success of a molecular targeted approach, natalizumab was the first mAb approved for the treatment of relapsing-remitting multiple sclerosis...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28166654/open-label-study-to-assess-the-safety-of-vm202-in-subjects-with-amyotrophic-lateral-sclerosis
#15
Robert L Sufit, Senda Ajroud-Driss, Patricia Casey, John A Kessler
OBJECTIVE: To assess safety and define efficacy measures of hepatocyte growth factor (HGF) DNA plasmid, VM202, administered by intramuscular injections in patients with amyotrophic lateral sclerosis (ALS). METHODS: Eighteen participants were treated with VM202 administered in divided doses by injections alternating between the upper and lower limbs on d 0, 7, 14, and 21. Subjects were followed for nine months to evaluate possible adverse events. Functional outcome was assessed using the ALS Functional Rating Scale-Revised (ALSFRS-R) as well as by serially measuring muscle strength, muscle circumference, and forced vital capacity...
February 6, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28165319/progressive-multifocal-leukoencephalopathy-in-two-natalizumab-treated-stepsisters-an-intriguing-coincidence
#16
Frédéric Bacchetta, Amandine Mathias, Myriam Schluep, Renaud Du Pasquier
BACKGROUND: Natalizumab, a treatment used in multiple sclerosis (MS), is associated with cases of progressive multifocal leukoencephalopathy (PML). OBJECTIVE: We describe two cases of PML in related but not genetically apparented natalizumab-treated MS patients who are stepsisters. Reported cases/outcomes: While Patient 1 developed PML, Patient 2 was on natalizumab and had contacts with Patient 1. Patient 2 was diagnosed with PML 5 months after Patient 1. CONCLUSION: The clinical and temporal data highly suggest that there was JC virus (JCV) transmission from one patient to the other with development of PML as primo-infection in Patient 2...
February 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28157751/inherited-and-uncommon-causes-of-stroke
#17
Jennifer Juhl Majersik
PURPOSE OF REVIEW: This article is a practical guide to identifying uncommon causes of stroke and offers guidance for evaluation and management, even when large controlled trials are lacking in these rarer forms of stroke. RECENT FINDINGS: Fabry disease causes early-onset stroke, particularly of the vertebrobasilar system; enzyme replacement therapy should be considered in affected patients. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), often misdiagnosed as multiple sclerosis, causes migraines, early-onset lacunar strokes, and dementia...
February 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/28153091/effect-of-fingolimod-on-neural-stem-cells-a-novel-mechanism-and-broadened-application-for-neural-repair
#18
Yuan Zhang, Xing Li, Bogoljub Ciric, Cun-Gen Ma, Bruno Gran, Abdolmohamad Rostami, Guang-Xian Zhang
Inflammatory demyelination and axonal damage of the CNS are hallmarks of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Fingolimod (FTY720), the first FDA-approved oral medication for MS, suppresses acute disease but is less effective at the chronic stage, and whether it has a direct effect on neuroregeneration in MS and EAE remains unclear. Here we show that FTY720, at nanomolar concentrations, effectively protected survival of neural stem cells (NSCs) and enhanced their development into mature oligodendrocytes (OLGs) in vitro, primarily through the S1P3 and S1P5 receptors...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28148632/serum-neurofilament-is-associated-with-progression-of-brain-atrophy-and-disability-in-early-ms
#19
Jens Kuhle, Bardia Nourbakhsh, Donna Grant, Steve Morant, Christian Barro, Özgür Yaldizli, Daniel Pelletier, Gavin Giovannoni, Emmanuelle Waubant, Sharmilee Gnanapavan
OBJECTIVE: To investigate a potential effect of riluzole on serum neurofilaments (Nf) compared to placebo and the relationship between longitudinal clinical and MRI outcomes and serum Nf levels. METHODS: Serum samples were obtained from participants enrolled in a randomized double-blind trial of neuroprotection with riluzole vs placebo as an add-on to weekly interferon-β (IFN-β)-1a IM initiated 3 months after randomization. Nf measurements were performed by ELISA and electrochemiluminescence immunoassay...
February 1, 2017: Neurology
https://www.readbyqxmd.com/read/28147220/intersections-of-pathways-involving-biotin-and-iron-relative-to-therapeutic-mechanisms-for-progressive-multiple-sclerosis
#20
Rebecca M Heidker, Mitchell R Emerson, Steven M LeVine
While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression...
December 2016: Discovery Medicine
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