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Progressive multiple sclerosis treatment

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https://www.readbyqxmd.com/read/28445498/metabolic-profiles-by-1h-magnetic-resonance-spectroscopy-in-natalizumab-associated-post-pml-lesions-of-multiple-sclerosis-patients-who-survived-progressive-multifocal-leukoencephalopathy-pml
#1
Ruth Schneider, Barbara Bellenberg, Robert Hoepner, Eva-Maria Kolb, Gisa Ellrichmann, Aiden Haghikia, Ralf Gold, Carsten Lukas
PURPOSE: Early diagnosis and treatment of multiple sclerosis-related progressive multifocal leukoencephalopathy (PML) significantly improve clinical outcomes. However, there is a lack of information regarding the restart of immunomodulatory therapy in the post-PML setting, when multiple sclerosis activity reappears. We aimed at the examination of metabolic differences using 1H-magnetic resonance spectroscopy (1H-MRS) in multiple sclerosis patients at various post-PML stages and at the exploration of differences according to their disease and JC virus (JCV) status...
2017: PloS One
https://www.readbyqxmd.com/read/28444098/the-cerebrospinal-fluid-in-multiple-sclerosis-far-beyond-the-bands
#2
Renan Barros Domingues, Gustavo Bruniera Peres Fernandes, Fernando Brunale Vilela de Moura Leite, Charles Peter Tilbery, Rodrigo Barbosa Thomaz, Gisele Sampaio Silva, Cristóvão Luis Pitangueira Mangueira, Carlos Augusto Senne Soares
The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency...
January 2017: Einstein
https://www.readbyqxmd.com/read/28443372/cord-blood-as-a-potential-therapeutic-for-amyotrophic-lateral-sclerosis
#3
Svitlana Garbuzova-Davis, Jared Ehrhart, Paul R Sanberg
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord. Treatment options are limited due to the complexity of underlying disease factors. Cell therapy, using human umbilical cord blood (hUCB) cells may be a promising new treatment for ALS, mainly by providing a protective microenvironment for motor neuron survival. Areas covered: Composition and in vitro and in vivo differentiation of hUCB cells and the advantages of cord blood as a source of transplant cells are discussed...
April 26, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28442634/pharmacologic-targeting-erk1-2-attenuates-the-development-and-progression-of-hyperuricemic-nephropathy-in-rats
#4
Na Liu, Liuqing Xu, Yingfeng Shi, Lu Fang, Hongwei Gu, Hongrui Wang, Xiaoqiang Ding, Shougang Zhuang
The pathogenesis of hyperuricemia-induced chronic kidney disease is largely unknown. In this study, we investigated whether extracellular signal-regulated kinases1/2 (ERK1/2) would contribute to the development of hyperuricemic nephropathy (HN). In a rat model of HN induced by feeding mixture of adenine and potassium oxonate, increased ERK1/2 phosphorylation and severe glomerular sclerosis and renal interstitial fibrosis were evident, in parallel with diminished levels of renal function and increased urine microalbumin excretion...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28440858/treatment-with-disease-modifying-drugs-for-people-with-a-first-clinical-attack-suggestive-of-multiple-sclerosis
#5
REVIEW
Graziella Filippini, Cinzia Del Giovane, Marinella Clerico, Omid Beiki, Miriam Mattoscio, Federico Piazza, Sten Fredrikson, Irene Tramacere, Antonio Scalfari, Georgia Salanti
BACKGROUND: The treatment of multiple sclerosis has changed over the last 20 years. The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the understanding and management of multiple sclerosis. With the support of magnetic resonance imaging early diagnosis is possible, enabling treatment initiation at the time of the first clinical attack. As most of the disease-modifying drugs are associated with adverse events, patients and clinicians need to weigh the benefit and safety of the various early treatment options before taking informed decisions...
April 25, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28437430/cerebellar-volume-as-imaging-outcome-in-progressive-multiple-sclerosis
#6
Matilde Inglese, Maria Petracca, Enricomaria Mormina, Anat Achiron, Rebecca Straus-Farber, Shmuel Miron, Michelle Fabian, Stephen Krieger, Aaron Miller, Fred Lublin, Maria Pia Sormani
BACKGROUND AND PURPOSE: To assess whether cerebellar volumes changes could represent a sensitive outcome measure in primary-progressive MS. MATERIAL AND METHODS: Changes in cerebellar volumes over one-year follow-up, estimated in 26 primary-progressive MS patients and 20 controls with Freesurfer longitudinal pipeline, were assessed using Wilcoxon test and tested for their correlation with disability worsening by a logistic regression. Clinical worsening was defined as EDSS score increase or change of >20% for 25-foot walk test or 9-hole peg test scores at follow-up...
2017: PloS One
https://www.readbyqxmd.com/read/28431609/benefit-risk-perception-of-natalizumab-therapy-in-neurologists-and-a-large-cohort-of-multiple-sclerosis-patients
#7
Christoph Heesen, Ingo Kleiter, Sven G Meuth, Julia Krämer, Jürgen Kasper, Sascha Köpke, Wolfgang Gaissmaier
BACKGROUND: Natalizumab (NAT) is associated with the risk of progressive multifocal leukoencephalopathy (PML). Risk stratification algorithms have been developed, however, without detectable reduction of PML incidence. OBJECTIVE: To evaluate to which extent patients and physicians understand and accept risks associated with NAT treatment. METHODS: Prospective observational cohort study in German MS centers (n=73) among NAT-treated MS patients (n=801) and their neurologists (n=99)...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28429241/pharmacological-approaches-to-the-management-of-secondary-progressive-multiple-sclerosis
#8
REVIEW
A Nandoskar, J Raffel, A S Scalfari, T Friede, R S Nicholas
It is well recognised that the majority of the impact of multiple sclerosis (MS), both personal and societal, arises in the progressive phase where disability accumulates inexorably. As such, progressive MS (PMS) has been the target of pharmacological therapies for many years. However, there are no current licensed treatments for PMS. This stands in marked contrast to relapsing remitting MS (RRMS) where trials have resulted in numerous licensed therapies. PMS has proven to be a more difficult challenge compared to RRMS and this review focuses on secondary progressive MS (SPMS), where relapses occur before the onset of gradual, irreversible disability, and not primary progressive MS where disability accumulation occurs without prior relapses...
April 20, 2017: Drugs
https://www.readbyqxmd.com/read/28428206/current-and-emerging-therapies-in-multiple-sclerosis-implications-for-the-radiologist-part-2-surveillance-for-treatment-complications-and-disease-progression
#9
REVIEW
C McNamara, G Sugrue, B Murray, P J MacMahon
An understanding of the new generation of MS drugs in conjunction with the key role MR imaging plays in the detection of disease progression, opportunistic infections, and drug-related adverse effects is of vital importance to the neuroradiologist. Part 1 of this review outlined the current treatment options available for MS and examined the mechanisms of action of the various medications. It also covered specific complications associated with each form of therapy. Part 2, in turn deals with the subject of pharmacovigilance and the optimal frequency of MRI monitoring for each individual patient, depending on his or her unique risk profile...
April 20, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28427689/demographic-and-clinical-profile-of-multiple-sclerosis-in-kashmir-a-short-report
#10
Insha Zahoor, Ravouf Asimi, Ehtishamul Haq, Irfan Yousuf Wani
BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease of the central nervous system (CNS). There have been only few population/hospital based studies on MS in India, and at the same time there is no data on its profile in Kashmir. METHODS: A total of 41 MS patients diagnosed on the basis of 2010 Revised Mc Donald criteria were enrolled in this study from Kashmir region of India. Clinical, demographic, radiological and biochemical parameters were analyzed for most of the patients...
April 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28422748/therapeutic-inhibition-of-soluble-brain-tnf-promotes-remyelination-by-increasing-myelin-phagocytosis-by-microglia
#11
Maria Karamita, Christopher Barnum, Wiebke Möbius, Malú G Tansey, David E Szymkowski, Hans Lassmann, Lesley Probert
Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are important for remyelination in experimental MS models, but it is unknown whether soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration processes. Here, we investigated the specific contribution of solTNF to demyelination and remyelination in the cuprizone model. Treatment with XPro1595, a selective inhibitor of solTNF that crosses the intact blood-brain barrier (BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss and demyelination, but it permitted profound early remyelination due to improved phagocytosis of myelin debris by CNS macrophages and prevented disease-associated decline in motor performance...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28414661/delayed-presentation-of-tuberour-sclerosis-complex-in-adult-women
#12
J Manalac, S Sadd, G Akoghlanian, T Benoit-Clark
INTRODUCTION: Tuberous sclerosis complex (TSC); is an autosomal dominant disorder characterized by the formation of hamartomatous lesions in multiple organs, with a birth incidence of around one in 10,000. Although it usually manifests itself in early life, we present a case of an adult woman who we diagnosed with TSC. CASE: A 27 year old woman presented to Emergency Department with worsening right flank pain and progressive dyspnea. Physical examination findings revealed Shagreen patches and multiple angiomyolipomas of the skin...
March 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28413713/catastrophic-outcome-of-patients-with-a-rebound-after-natalizumab-treatment-discontinuation
#13
Inés González-Suarez, Luis Rodríguez de Antonio, Aida Orviz, Sara Moreno-García, María D Valle-Arcos, Jordi A Matias-Guiu, Cristina Valencia, Manuela Jorquera Moya, Celia Oreja-Guevara
INTRODUCTION: Natalizumab (NTZ) is an effective drug for the treatment of relapsing-remitting multiple sclerosis. In some patients discontinuation is mandatory due to the risk of progressive multifocal leukoencephalopathy. However, severe clinical and radiological worsening has been described after drug cessation. Our aim was to describe the clinical and radiological features of the rebound phenomenon. MATERIAL AND METHODS: Patients switched from NTZ to Fingolimod (FTY) who had presented a rebound after discontinuation were selected...
April 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28408630/current-and-emerging-therapies-in-multiple-sclerosis-implications-for-the-radiologist-part-1-mechanisms-efficacy-and-safety
#14
REVIEW
C McNamara, G Sugrue, B Murray, P J MacMahon
Imaging for the diagnosis and follow-up of patients with suspected or confirmed multiple sclerosis is a common scenario for many general radiologists and subspecialty neuroradiologists. The field of MS therapeutics has rapidly evolved with multiple new agents now being used in routine clinical practice. To provide an informed opinion in discussions concerning newer MS agents, radiologists must have a working understanding of the strengths and limitations of the various novel therapies. The role of imaging in MS has advanced beyond monitoring and surveillance of disease activity to include treatment complications...
April 13, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28406921/is-the-risk-of-progressive-multifocal-leukoencephalopathy-the-real-reason-for-natalizumab-discontinuation-in-patients-with-multiple-sclerosis
#15
Julia Krämer, Jan-Gerd Tenberge, Ingo Kleiter, Wolfgang Gaissmaier, Tobias Ruck, Christoph Heesen, Sven G Meuth
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is one of the major risks of natalizumab therapy. Despite introduction of the currently employed PML risk stratification algorithm, the incidence of natalizumab-associated PML cases is not decreasing. OBJECTIVES: We addressed the following questions: How do natalizumab-treated multiple sclerosis patients and their treating physicians assess and deal with PML risk? Is PML risk the real reason for natalizumab discontinuation? METHODS: 699 natalizumab-treated multiple sclerosis patients and 99 physicians were included in this prospective observational study...
2017: PloS One
https://www.readbyqxmd.com/read/28406354/human-endogenous-retroviruses-and-multiple-sclerosis-causation-association-or-after-effect
#16
Elena Morandi, Rachael E Tarlinton, Radu Tanasescu, Bruno Gran
From the early days of MS discovery, infections have been proposed as a possible cause of the disease. In the last three decades, an association between human endogenous retrovirus expression and MS has been further investigated and confirmed. Nevertheless, the role of such retroviruses in the disease needs clarification. In this review, we introduce MSRV/HERV-W and describe its association with MS. We then summarize the evidence for the involvement of MSRV/HERV-W in the aetiology and progression of MS and its possible role as biomarker and drug target...
April 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28402456/smoking-cessation-and-the-reduction-of-disability-progression-in-multiple-sclerosis-a-cohort-study
#17
Radu Tanasescu, Cris S Constantinescu, Christopher R Tench, Ali Manouchehrinia
Background: Smoking is associated with a more severe disease course in people with multiple sclerosis (MS). The magnitude of effect of smoking cessation on MS progression is unknown. The aim of this study was to quantify the impact of smoking cessation on reaching MS disability milestones. Methods: This is a cross-sectional study with retrospective reports. A comprehensive smoking questionnaire was sent to 1270 patients with MS registered between 1994 and 2013 in the Nottingham University Hospital MS Clinics database...
April 10, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/28397126/protein-tyrosine-phosphatases-in-systemic-sclerosis-potential-pathogenic-players-and-therapeutic-targets
#18
REVIEW
Cristiano Sacchetti, Nunzio Bottini
PURPOSE OF REVIEW: The pathogenesis of systemic sclerosis depends on a complex interplay between autoimmunity, vasculopathy, and fibrosis. Reversible phosphorylation on tyrosine residues, in response to growth factors and other stimuli, critically regulates each one of these three key pathogenic processes. Protein tyrosine kinases, the enzymes that catalyze addition of phosphate to tyrosine residues, are known players in systemic sclerosis, and tyrosine kinase inhibitors are undergoing clinical trials for treatment of this disease...
May 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28397112/cell-therapy-for-multiple-sclerosis
#19
REVIEW
Pamela Sarkar, Claire M Rice, Neil J Scolding
Cell therapy is considered a promising potential treatment for multiple sclerosis, perhaps particularly for the progressive form of the disease for which there are currently no useful treatments. Over the past two decades or more, much progress has been made in understanding the biology of MS and in the experimental development of cell therapy for this disease. Three quite distinct forms of cell therapy are currently being pursued. The first seeks to use stem cells to replace damaged myelin-forming oligodendrocytes within the CNS; the second aims, in effect, to replace the individual's misfunctioning immune system, making use of haematopoietic stem cells; and the third seeks to utilise endogenous stem cell populations by mobilisation with or without in vitro expansion, exploiting their various reparative and neuroprotective properties...
April 10, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28396093/what-s-new-about-oral-treatments-in-multiple-sclerosis-immunogenetics-still-under-question
#20
REVIEW
Cristiana Pistono, Cecilia Osera, Chiara Boiocchi, Giulia Mallucci, Mariaclara Cuccia, Roberto Bergamaschi, Alessia Pascale
Multiple Sclerosis (MS) is a chronic pathology affecting the Central Nervous System characterized by inflammatory processes that lead to demyelination and neurodegeneration. In MS treatment, disease modifying therapies (DMTs) are essential to reduce disease progression by suppressing the inflammatory response responsible for promoting lesion formation. Recently, in addition to the classical injectable DMTs like Interferons and Glatiramer acetate, new orally administered drugs have been approved for MS therapy: dimethyl fumarate, teriflunomide and fingolimod...
April 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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