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https://www.readbyqxmd.com/read/28211007/daclizumab-a-review-in-relapsing-multiple-sclerosis
#1
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
#2
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/28208701/excitotoxins-mitochondrial-and-redox-disturbances-in-multiple-sclerosis
#3
REVIEW
Cecilia Rajda, Dániel Pukoli, Zsuzsanna Bende, Zsófia Majláth, László Vécsei
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions, but also by neurodegenerative processes. There is cumulating evidence that neurodegenerative processes, for example mitochondrial dysfunction, oxidative stress, and glutamate (Glu) excitotoxicity, seem to play an important role in the pathogenesis of MS. The alteration of mitochondrial homeostasis leads to the formation of excitotoxins and redox disturbances...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28206827/validity-of-the-symbol-digit-modalities-test-as-a-cognition-performance-outcome-measure-for-multiple-sclerosis
#4
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/28205364/altered-neural-mechanisms-of-cognitive-control-in-patients-with-primary-progressive-multiple-sclerosis-an-effective-connectivity-study
#5
Ekaterina Dobryakova, Maria Assunta Rocca, Paola Valsasina, John DeLuca, Massimo Filippi
Primary progressive multiple sclerosis (PPMS) leads to physical and cognitive disability. Specifically, cognitive deficits in PPMS have been explained by both grey matter atrophy and white matter lesions. However, existing research still lacks in the understanding of how the brain of a patient with PPMS functions under cognitive control demands. Thus, the aim of the current study was to examine information integration in patients with PPMS using a search-based effective connectivity method. Fourteen patients with PPMS and 22 age- and gender-matched healthy controls (HC) performed the Stroop task, a cognitively demanding interference task that taxes neural resources required for cognitive control and response inhibition...
February 16, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28203530/longitudinal-evaluation-of-cerebral-and-spinal-cord-damage-in-amyotrophic-lateral-sclerosis
#6
Milena de Albuquerque, Lucas Melo T Branco, Thiago Junqueira R Rezende, Helen Maia Tavares de Andrade, Anamarli Nucci, Marcondes Cavalcante França
OBJECTIVE: To evaluate MRI-based parameters as biomarkers of Amyotrophic Lateral Sclerosis (ALS) progression. METHODS: Twenty-seven patients and 27 controls performed two clinical and MRI acquisitions 8 months apart. ALSFRS-R scale was used to quantify disease severity at both time points. Multimodal analyses of MRI included cortical thickness measurements (FreeSurfer software), analysis of white matter integrity using diffusion-tensor imaging (tract-based spatial statistics-TBSS) and measurement of cervical spinal cord cross-sectional area (SpineSeg software)...
2017: NeuroImage: Clinical
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/28197337/defective-t-cell-control-of-epstein-barr-virus-infection-in-multiple-sclerosis
#9
Michael P Pender, Peter A Csurhes, Jacqueline M Burrows, Scott R Burrows
Mounting evidence indicates that infection with Epstein-Barr virus (EBV) has a major role in the pathogenesis of multiple sclerosis (MS). Defective elimination of EBV-infected B cells by CD8(+) T cells might cause MS by allowing EBV-infected autoreactive B cells to accumulate in the brain. Here we undertake a comprehensive analysis of the T-cell response to EBV in MS, using flow cytometry and intracellular IFN-γ staining to measure T-cell responses to EBV-infected autologous lymphoblastoid cell lines and pools of human leukocyte antigen (HLA)-class-I-restricted peptides from EBV lytic or latent proteins and cytomegalovirus (CMV), in 95 patients and 56 EBV-seropositive healthy subjects...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28197176/multiple-sclerosis-integration-of-modeling-with-biology-clinical-and-imaging-measures-to-provide-better-monitoring-of-disease-progression-and-prediction-of-outcome
#10
REVIEW
Shikha Jain Goodwin
Multiple Sclerosis (MS) is a major cause of neurological disability in adults and has an annual cost of approximately $28 billion in the United States. MS is a very complex disorder as demyelination can happen in a variety of locations throughout the brain; therefore, this disease is never the same in two patients making it very hard to predict disease progression. A modeling approach which combines clinical, biological and imaging measures to help treat and fight this disorder is needed. In this paper, I will outline MS as a very heterogeneous disorder, review some potential solutions from the literature, demonstrate the need for a biomarker and will discuss how computational modeling combined with biological, clinical and imaging data can help link disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism...
December 2016: Neural Regeneration Research
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
#11
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/28192539/optical-coherence-tomography-segmentation-analysis-in-relapsing-remitting-versus-progressive-multiple-sclerosis
#12
Raed Behbehani, Abdullah Abu Al-Hassan, Ali Al-Salahat, Devarajan Sriraman, J D Oakley, Raed Alroughani
INTRODUCTION: Optical coherence tomography (OCT) with retinal segmentation analysis is a valuable tool in assessing axonal loss and neuro-degeneration in multiple sclerosis (MS) by in-vivo imaging, delineation and quantification of retinal layers. There is evidence of deep retinal involvement in MS beyond the inner retinal layers. The ultra-structural retinal changes in MS in different MS phenotypes can reflect differences in the pathophysiologic mechanisms. There is limited data on the pattern of deeper retinal layer involvement in progressive MS (PMS) versus relapsing remitting MS (RRMS)...
2017: PloS One
https://www.readbyqxmd.com/read/28191860/hypothalamic-damage-in-multiple-sclerosis-correlates-with-disease-activity-disability-depression-and-fatigue
#13
E Kantorová, H Poláček, M Bittšanský, E Baranovičová, P Hnilicová, D Čierny, Š Sivák, V Nosáľ, K Zeleňák, E Kurča
OBJECTIVES: Disturbances in the hypothalamo-pituitary axis are supposed to modulate activity of multiple sclerosis (MS). We hypothesised that the extent of HYP damage may determine severity of MS and may be associated with the disease evolution. We suggested fatigue and depression may depend on the degree of damage of the area. METHOD: 33 MS patients with relapsing-remitting and secondary progressive disease, and 24 age and sex-related healthy individuals (CON) underwent 1H-MR spectroscopy (1H-MRS) of the hypothalamus...
February 13, 2017: Neurological Research
https://www.readbyqxmd.com/read/28187977/retinal-and-optic-nerve-degeneration-in-patients-with-multiple-sclerosis-followed-up-for-5-years
#14
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
#15
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
#16
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
#17
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/28178867/the-relationship-between-white-matter-fiber-damage-and-gray-matter-perfusion-in-large-scale-functionally-defined-networks-in-multiple-sclerosis
#18
Ashley Y Ma, Rita C Vitorino, Seyed-Parsa Hojjat, Alannah D Mulholland, Liying Zhang, Liesly Lee, Timothy J Carroll, Charles G Cantrell, Chase R Figley, Richard I Aviv
BACKGROUND: Recent studies utilizing perfusion as a surrogate of cortical integrity show promise for overall cognition, but the association between white matter (WM) damage and gray matter (GM) integrity in specific functional networks is not previously studied. OBJECTIVE: To investigate the relationship between WM fiber integrity and GM node perfusion within six functional networks of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients...
January 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28168214/cerebrospinal-fluid-protein-carbonylation-identifies-oxidative-damage-in-autoimmune-demyelination
#19
David N Irani
Oxidative damage occurs in multiple sclerosis, but is difficult to identify antemortem and remains an unknown contributor to disease progression. Carbonylation is a quantitative measure of protein oxidation. Cerebrospinal fluid samples from multiple sclerosis patients showed elevated carbonylated protein levels compared to controls. In experimental autoimmune encephalomyelitis, carbonylated protein levels in cerebrospinal fluid correlated tightly with those found in inflamed spinal cord tissues. Furthermore, concentrations in cerebrospinal fluid and spinal cord responded in parallel to an antioxidant intervention that also attenuated disease symptoms...
February 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28168207/additive-amelioration-of-als-by-co-targeting-independent-pathogenic-mechanisms
#20
Ashley E Frakes, Lyndsey Braun, Laura Ferraiuolo, Denis C Guttridge, Brian K Kaspar
OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which glia are central mediators of motor neuron (MN) death. Since multiple cell types are involved in disease pathogenesis, the objective of this study was to determine the benefit of co-targeting independent pathogenic mechanisms in a familial ALS mouse model. METHODS: Recently, our laboratory identified that ALS microglia induce MN death in an NF-κB-dependent mechanism. We also demonstrated that a single, post-natal, intravenous injection of adeno-associated viral vector serotype 9 encoding a shRNA against mutant SOD1 is able to traverse the blood-brain barrier of ALS mice and reduce SOD1-expression in astrocytes and MNs...
February 2017: Annals of Clinical and Translational Neurology
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