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Progressive multiple sclerosis

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https://www.readbyqxmd.com/read/28822986/insights-in-pathogenesis-of-multiple-sclerosis-nitric-oxide-may-induce-mitochondrial-dysfunction-of-oligodendrocytes
#1
Minghong Lan, Xiaoyi Tang, Jie Zhang, Zhongxiang Yao
Demyelinating diseases, such as multiple sclerosis (MS), are kinds of common diseases in the central nervous system (CNS), and originated from myelin loss and axonal damage. Oligodendrocyte dysfunction is the direct reason of demyelinating lesions in the CNS. Nitric oxide (NO) plays an important role in the pathological process of demyelinating diseases. Although the neurotoxicity of NO is more likely mediated by peroxynitrite rather than NO itself, NO can impair oligodendrocyte energy metabolism through mediating the damaging of mitochondrial DNA, mitochondrial membrane and mitochondrial respiratory chain complexes...
August 21, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28822119/five-questions-answered-a-review-of-autologous-hematopoietic-stem-cell-transplantation-for-the-treatment-of-multiple-sclerosis
#2
REVIEW
Harold L Atkins, Mark S Freedman
Multiple sclerosis (MS) is thought to be an autoimmune disease targeting the central nervous system leading to demyelination, and axonal and neuronal damage, resulting in progressive disability. More intensive therapies such as immunodepletion with hematopoietic stem-cell rescue are being used at a time prior to patients becoming irreversibly disabled. Over the last 15 years, there has been a shift away from using autologous hematopoietic stem-cell transplants (aHSCT) to treat patients with progressive MS, towards treating those with active inflammation and relapses...
August 18, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28821874/global-methylation-correlates-with-clinical-status-in-multiple-sclerosis-patients-in-the-first-year-of-ifnbeta-treatment
#3
María Jesús Pinto-Medel, Begoña Oliver-Martos, Patricia Urbaneja-Romero, Isaac Hurtado-Guerrero, Jesús Ortega-Pinazo, Pedro Serrano-Castro, Óscar Fernández, Laura Leyva
The alteration of DNA methylation patterns are a key component of disease onset and/or progression. Our objective was to evaluate the differences in Long Interspersed Nuclear Element-1 (LINE-1) methylation levels, as a surrogate marker of global DNA methylation, between multiple sclerosis (MS) patients and healthy controls. In addition, we assessed the association of LINE-1 methylation with clinical disease activity in patients treated with IFNbeta (IFNβ). We found that individuals with high levels of LINE-1 methylation showed 6-fold increased risk of suffering MS...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814543/loss-of-dual-leucine-zipper-kinase-signaling-is-protective-in-animal-models-of-neurodegenerative-disease
#4
Claire E Le Pichon, William J Meilandt, Sara Dominguez, Hilda Solanoy, Han Lin, Hai Ngu, Alvin Gogineni, Arundhati Sengupta Ghosh, Zhiyu Jiang, Seung-Hye Lee, Janice Maloney, Vineela D Gandham, Christine D Pozniak, Bei Wang, Sebum Lee, Michael Siu, Snahel Patel, Zora Modrusan, Xingrong Liu, York Rudhard, Miriam Baca, Amy Gustafson, Josh Kaminker, Richard A D Carano, Eric J Huang, Oded Foreman, Robby Weimer, Kimberly Scearce-Levie, Joseph W Lewcock
Hallmarks of chronic neurodegenerative disease include progressive synaptic loss and neuronal cell death, yet the cellular pathways that underlie these processes remain largely undefined. We provide evidence that dual leucine zipper kinase (DLK) is an essential regulator of the progressive neurodegeneration that occurs in amyotrophic lateral sclerosis and Alzheimer's disease. We demonstrate that DLK/c-Jun N-terminal kinase signaling was increased in mouse models and human patients with these disorders and that genetic deletion of DLK protected against axon degeneration, neuronal loss, and functional decline in vivo...
August 16, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28812249/long-term-disability-and-progression-in-spinal-onset-multiple-sclerosis
#5
Bedile Irem Tiftikcioglu, Irem Ilgezdi, Yasar Zorlu, Ufuk Sener, Figen Tokucoglu
The aim of this study is to investigate the long-term effects of the initial spinal cord (SC) involvement in MS patients. In this retrospective, single-center study, 824 patients with definite MS were screened. A total of 348 patients were excluded for ambiguous documentation of the initial relapse, pediatric onset, diagnosis of primary progressive disease, irregular assessments or visits causing doubt on the onset of progression time, and clinical follow-up duration less than 12 months. Eventually, 476 MS patients were included...
August 10, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/28812220/sphingosine-1-phosphate-receptor-modulators-for-the-treatment-of-multiple-sclerosis
#6
REVIEW
Burhan Z Chaudhry, Jeffrey A Cohen, Devon S Conway
Sphingosine 1-phosphate receptor (S1PR) modulators possess a unique mechanism of action in the treatment of multiple sclerosis (MS). Subtype 1 of the S1PR is expressed on the surface of lymphocytes and is important in regulating egression from lymph nodes. The S1PR modulators indirectly antagonize the receptor's function leading to sequestration of lymphocytes in the lymph nodes. Fingolimod was the first S1PR modulator to receive regulatory approval for relapsing-remitting MS after 2 phase III trials demonstrated potent efficacy, safety, and tolerability...
August 15, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28812062/clinical-and-experimental-studies-of-a-novel-p525r-fus-mutation-in-amyotrophic-lateral-sclerosis
#7
Lisha Kuang, Marisa Kamelgarn, Alexandra Arenas, Jozsef Gal, Deborah Taylor, Weiming Gong, Martin Brown, Daret St Clair, Edward J Kasarskis, Haining Zhu
OBJECTIVE: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models. METHODS: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions...
August 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28808201/thalamic-paramagnetic-iron-by-t2-relaxometry-correlates-with-severity-of-multiple-sclerosis
#8
Eva Baranovicova, Ema Kantorova, Dagmar Kalenska, Lucia Lichardusova, Michal Bittsan-Sky, Dusan Dobrota
Iron can contribute to the pathogenesis and progression of multiple sclerosis (MS) due to its accumulation in the human brain. We focus on the thalamus as an information transmitter between various subcortical and cortical areas. Thalamic iron seems to follow different rules than iron in other deep gray matter structures and its relation to the clinical outcomes of MS is still indistinct. In our study, we investigated a connection between thalamic iron and patients' disability and course of the disease. The presence of paramagnetic substances in the tissues was tracked by T2* quantification...
July 13, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28808113/lncrna-gas5-inhibits-microglial-m2-polarization-and-exacerbates-demyelination
#9
Dingya Sun, Zhongwang Yu, Xue Fang, Mingdong Liu, Yingyan Pu, Qi Shao, Dan Wang, Xiaolin Zhao, Aijun Huang, Zhenghua Xiang, Chao Zhao, Robin Jm Franklin, Li Cao, Cheng He
The regulation of inflammation is pivotal for preventing the development or reoccurrence of multiple sclerosis (MS). A biased ratio of high-M1 versus low-M2 polarized microglia is a major pathological feature of MS Here, using microarray screening, we identify the long noncoding RNA (lncRNA) GAS5 as an epigenetic regulator of microglial polarization. Gain- and loss-of-function studies reveal that GAS5 suppresses microglial M2 polarization. Interference with GAS5 in transplanted microglia attenuates the progression of experimental autoimmune encephalomyelitis (EAE) and promotes remyelination in a lysolecithin-induced demyelination model...
August 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28806143/whose-preferences-matter-a-patient-centered-approach-for-eliciting-treatment-goals
#10
Nananda F Col, Andrew J Solomon, Vicky Springmann, Calvin P Garbin, Carolina Ionete, Lori Pbert, Enrique Alvarez, Brenda Tierman, Ashli Hopson, Christen Kutz, Idanis Berrios Morales, Carolyn Griffin, Glenn Phillips, Long H Ngo
BACKGROUND: Patients facing a high-stakes clinical decision are often confronted with an overwhelming array of options. High-quality decisions about treatment should reflect patients' preferences as well as their clinical characteristics. Preference-assessment instruments typically focus on pre-selected clinical outcomes and attributes chosen by the investigator. OBJECTIVE: We sought to develop a patient-centered approach to elicit and compare the treatment goals of patients with multiple sclerosis (MS) and healthcare providers (HCPs)...
August 1, 2017: Medical Decision Making: An International Journal of the Society for Medical Decision Making
https://www.readbyqxmd.com/read/28805578/nonmotor-symptoms-in-amyotrophic-lateral-sclerosis-a-systematic-review
#11
Ton Fang, Felix Jozsa, Ammar Al-Chalabi
BACKGROUND: ALS is a progressive neurodegenerative disease with no curative treatment. Nonmotor symptoms presenting in ALS may cause significant distress, worsen prognosis, and affect survival. OBJECTIVE: To systematically review evidence for the prevalence of nonmotor ALS symptoms, and treatment options. METHODS: Multiple medical literature databases were searched and studies screened using predefined inclusion criteria. Of 4580 studies, 44 were eligible for inclusion with 25 relating to treatment and 19 to the prevalence of nonmotor symptoms in ALS...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28803512/heterogeneous-pathological-processes-account-for-thalamic-degeneration-in-multiple-sclerosis-insights-from-7%C3%A2-t-imaging
#12
Céline Louapre, Sindhuja T Govindarajan, Costanza Giannì, Nancy Madigan, Jacob A Sloane, Constantina A Treaba, Elena Herranz, Revere P Kinkel, Caterina Mainero
BACKGROUND: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. OBJECTIVE: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). METHODS: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28801580/immune-responses-against-helicobacter-pylori-specific-antigens-differentiate-relapsing-remitting-from-secondary-progressive-multiple-sclerosis
#13
Georgios Efthymiou, Efthymios Dardiotis, Christos Liaskos, Emmanouela Marou, Vana Tsimourtou, Eirini I Rigopoulou, Thomas Scheper, Alexandros Daponte, Wolfgang Meyer, Lazaros I Sakkas, Georgios Hadjigeorgiou, Dimitrios P Bogdanos
To assess whether Helicobacter pylori (Hp) antibody (ab) reactivity against individual Hp antigens is pathogenetically relevant to multiple sclerosis (MS), we systematically investigated prevalence and clinical significance of abs against 14 immunodominant and subdominant Hp antigens by ELISA and immunoblotting in 139 consecutive MS patients with relapsing-remitting (RRMS, n = 102) or secondary progressive (SPMS, n = 37). Sera from 39 patients with Parkinson's disease (PD), 21 with Alzheimer's disease (ALZ) and 68 healthy controls (HCs), were also tested...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28799222/progression-retinal-ganglion-cell-loss-in-multiple-sclerosis-is-associated-with-new-lesions-in-the-optic-radiations
#14
Alexander Klistorner, Elizabeth C Graham, Con Yiannikas, Michael Barnett, John Parratt, Ray Garrick, Chenyu Wang, Yuyi You, Stuart L Graham
BACKGROUND: The mechanism of retinal ganglion cell (RGC) and retinal nerve fibre layer (RNFL) loss in multiple sclerosis (MS) remains unknown. This study aims to investigate the association between temporal RNFL (tRNFL) thinning and disease activity in the brain determined by T2 lesions on MRI. METHODS: 55 consecutive relapsing-remitting MS (RRMS) patients and 25 controls were enrolled. All patients underwent annual optical coherence tomography (OCT) and high-resolution MRI scans for tRNFL thickness and brain lesion volume analysis, respectively...
August 10, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28797088/csf-profile-in-primary-progressive-multiple-sclerosis-re-exploring-the-basics
#15
Ahmed Abdelhak, Tilman Hottenrott, Christoph Mayer, Gudrun Hintereder, Uwe K Zettl, Oliver Stich, Hayrettin Tumani
OBJECTIVE: The aim of this study was to report the basic cerebrospinal fluid (CSF) profile in patients with primary progressive multiple sclerosis (PPMS). METHODS: The results of CSF analysis from 254 patients with PPMS were collected at four university hospitals in Germany. Routine CSF parameters and different indices of intrathecal immunoglobulin synthesis were evaluated. We assessed possible correlations between the various CSF parameters and the expanded disability status scale (EDSS) both at the time of lumbar puncture and during the course of the disease...
2017: PloS One
https://www.readbyqxmd.com/read/28797086/epigenetic-differences-between-monozygotic-twins-discordant-for-amyotrophic-lateral-sclerosis-als-provide-clues-to-disease-pathogenesis
#16
Paul E Young, Stephen Kum Jew, Michael E Buckland, Roger Pamphlett, Catherine M Suter
Amyotrophic lateral sclerosis (ALS) is a devastating late-onset neurodegenerative disorder in which only a small proportion of patients carry an identifiable causative genetic lesion. Despite high heritability estimates, a genetic etiology for most sporadic ALS remains elusive. Here we report the epigenetic profiling of five monozygotic twin pairs discordant for ALS, four with classic ALS and one with the progressive muscular atrophy ALS variant, in whom previous whole genome sequencing failed to uncover a genetic basis for their disease discordance...
2017: PloS One
https://www.readbyqxmd.com/read/28796432/7t-mri-visualization-of-cortical-lesions-in-adolescents-and-young-adults-with-pediatric-onset-multiple-sclerosis
#17
Ritobrato Datta, Varun Sethi, Sophia Ly, Amy T Waldman, Sona Narula, Blake E Dewey, Pascal Sati, Daniel Reich, Brenda Banwell
BACKGROUND: Cortical pathology in multiple sclerosis (MS) has been associated with prolonged and progressive disease. 7T magnetic resonance imaging (MRI) provides enhanced visualization of cortical lesions (CLs). Hence, we conducted a pilot study to explore whether CLs occur early in MS, as evidenced by pediatric-onset patients. METHODS: A total of 8 pediatric-onset MS patients were imaged using 7T MRI. CLs were annotated on T1-weighted magnetization-prepared rapid acquisition of gradient echoes images as leukocortical (LC), intracortical, or subpial...
August 10, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/28794971/the-relationship-between-cortical-lesions-and-periventricular-nawm-abnormalities-suggests-a-shared-mechanism-of-injury-in-primary-progressive-ms
#18
Matteo Pardini, Maria Petracca, Asaff Harel, Lazar Fleysher, Niels Oesingmann, Giulia Bommarito, Michelle Fabian, Declan Chard, Fred Lublin, Matilde Inglese
In subjects with multiple sclerosis (MS), pathology is more frequent near the inner and outer surfaces of the brain. Here, we sought to explore if in subjects with primary progressive MS (PPMS) cortical lesion load is selectively associated with the severity of periventricular normal appearing white matter (NAWM) damage, as assessed with diffusion weighted imaging. To this aim, twenty-four subjects with PPMS and twenty healthy controls were included in the study. Using diffusion data, skeletonized mean diffusivity (MD) NAWM maps were computed excluding WM lesions and a 2 mm-thick peri-lesional rim...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28794248/anti-inflammatory-disease-modifying-treatment-and-short-term-disability-progression-in-spms
#19
Johannes Lorscheider, Vilija G Jokubaitis, Tim Spelman, Guillermo Izquierdo, Alessandra Lugaresi, Eva Havrdova, Dana Horakova, Maria Trojano, Pierre Duquette, Marc Girard, Alexandre Prat, François Grand'Maison, Pierre Grammond, Eugenio Pucci, Cavit Boz, Patrizia Sola, Diana Ferraro, Daniele Spitaleri, Jeanette Lechner-Scott, Murat Terzi, Vincent Van Pesch, Gerardo Iuliano, Roberto Bergamaschi, Cristina Ramo-Tello, Franco Granella, Celia Oreja-Guevara, Helmut Butzkueven, Tomas Kalincik
OBJECTIVE: To investigate the effect of disease-modifying treatment on short-term disability outcomes in secondary progressive multiple sclerosis (SPMS). METHODS: Using MSBase, an international cohort study, we previously validated a highly accurate definition of SPMS. Here, we identified patients in MSBase who were either untreated or treated with a disease-modifying drug when meeting this definition. Propensity score matching was used to select subpopulations with comparable baseline characteristics...
August 9, 2017: Neurology
https://www.readbyqxmd.com/read/28793364/melatonin-reduces-inflammatory-response-in-peripheral-t-helper-lymphocytes-from-relapsing-remitting-multiple-sclerosis-patients
#20
Nuria Álvarez-Sánchez, Ivan Cruz-Chamorro, María Díaz-Sánchez, Helia Sarmiento-Soto, Pablo Medrano-Campillo, Alicia Martínez-López, Patricia Judith Lardone, Juan Miguel Guerrero, Antonio Carrillo-Vico
Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system in which the immune system plays a central role. In particular, effector populations such as T helper (Th) 1, Th9, Th17 and Th22 cells are involved in disease development, whereas T regulatory cells (Tregs) are associated with the resolution of the disease. Melatonin levels are impaired in MS patients, and exogenous melatonin ameliorates the disease in MS animal models by modulating the Th1/Th17/Treg responses and also improves quality of life and several symptoms in MS patients...
August 9, 2017: Journal of Pineal Research
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