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https://www.readbyqxmd.com/read/28653282/therapeutic-targets-for-multiple-sclerosis-current-treatment-goals-and-future-directions
#1
REVIEW
Andrew L Smith, Jeffrey A Cohen, Le H Hua
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, and the most common cause of nontraumatic disability in young adults. Most patients have a relapsing-remitting course, and roughly half of them will eventually enter a degenerative progressive phase, marked by gradual accrual of disability over time in the absence of relapses. Early initiation of treatment has delayed the onset of disability progression. Thus, there is increased interest in treating to target in MS, particularly targeting no evidence of disease activity...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28650601/multiple-sclerosis-in-an-acupuncture-practice
#2
(no author information available yet)
Multiple sclerosis (MS) is a severe autoimmune demyelinating disease that affects nervous system, has high morbidity and mortality and no effective targeted therapies are available. We present a case of 66-year-old female patient who has been treated by both conventional and Chinese traditional medicine after diagnosis was confirmed in 2008 as MS and antiphospholipid syndrome associated with CNS vasculitis. After diagnosis with clinical image confirmed with CT and MRI scan, where demyelinating zones were present, she started pharmacological therapy without major improvement...
May 26, 2017: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28648457/enriched-environment-promotes-remyelination-and-motor-function-recovery-through-modulation-of-hdac1-2-in-mice
#3
Jian Zheng, Weijun Ding, Baoming Li, Youjun Yang
Brain structure and functions are significantly affected by enriched environment (EE). Rodent and rhesus monkeys raised in EE will increase myelination in development, and these increase correlate with improved cognitive functions on learning and memory. However, whether and how EE influences remyelination in the adult remained undefined. Here, we used a cuprizone-induced demyelination mouse model demonstrate that EE significantly enhances remyelination. This EE-regulated remyelination is associated with improved motor skills...
June 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28648091/mediators-go-together-high-production-of-cxcl9-cxcl10-ifn-%C3%AE-and-tnf-%C3%AE-in-ham-tsp
#4
Heytor Victor Pereira da Costa Neco, Vanessa Gabryelle da Silva Teixeira, Ana Carolina Lemos da Trindade, Paula Machado Ribeiro Magalhães, Virgínia Maria Barros de Lorena, Lúcio Roberto Cançado Castellano, Joelma Rodrigues de Souza, Luydson Richardson Vasconcelos, Patrícia Muniz Mendes Freire de Moura, Clarice Neuenschwander Lins de Morais
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic demyelinating and disabling syndrome caused by HTLV-1. Although the pathogenic mechanisms that lead to HAM/TSP outcome have not been elucidated, genetic and immunological factors may be involved in the myelopathy occurrence. The present study aimed to compare cytokines, chemokines and nitric oxide levels in asymptomatic and HAM/TSP HTLV-1 infected patients. The study group consisted of 21 HAM/TSP and 48 asymptomatic HTLV-1 patients...
June 24, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28647707/hepatitis-e-virus-and-neurological-disorders
#5
REVIEW
Brendan N Mclean, James Gulliver, Harry R Dalton
Hepatitis E is the most common cause of hepatitis worldwide. While originally considered a disease of developing countries, it is increasingly recognised in developed countries, probably related to contaminated pork meat, and where infection is often asymptomatic. However, several non-liver manifestations have become apparent, the most important of which are neurological, including Guillain-Barré syndrome (acute inflammatory demyelinating polyradiculoneuropathy (AIDP)), neuralgic amyotrophy and meningoencephalitis...
June 24, 2017: Practical Neurology
https://www.readbyqxmd.com/read/28647405/docosahexaenoic-acid-promotes-oligodendrocyte-differentiation-via-ppar-%C3%AE-signalling-and-prevents-tumor-necrosis-factor-%C3%AE-dependent-maturational-arrest
#6
A Bernardo, M L Giammarco, C De Nuccio, M A Ajmone-Cat, S Visentin, R De Simone, L Minghetti
Docosahexaenoic acid (DHA) is an essential omega-3 fatty acid known to be neuroprotective in several models of human diseases, including multiple sclerosis. The protective effects of DHA are largely attributed to its ability to interfere with the activity of transcription factors controlling immune and inflammatory responses, including the agonist-dependent transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ). In this study, we used primary oligodendrocyte progenitor (OP) cultures from neonatal rat brain to investigate whether DHA could influence OP maturation and directly promote myelination, as previously reported for selective PPAR-γ agonists...
June 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28646890/influence-of-type-i-ifn-signaling-on-anti-mog-antibody-mediated-demyelination
#7
Carsten Tue Berg, Reza Khorooshi, Nasrin Asgari, Trevor Owens
BACKGROUND: Antibodies with specificity for myelin oligodendrocyte glycoprotein (MOG) are implicated in multiple sclerosis and related diseases. The pathogenic importance of anti-MOG antibody in primary demyelinating pathology remains poorly characterized. OBJECTIVE: The objective of this study is to investigate whether administration of anti-MOG antibody would be sufficient for demyelination and to determine if type I interferon (IFN) signaling plays a similar role in anti-MOG antibody-mediated pathology, as has been shown for neuromyelitis optica-like pathology...
June 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28646568/blink-r1-latency-utility-in-diagnosis-and-treatment-assessment-of-poems-and-cidp
#8
Wei Wang, William J Litchy, Michelle L Mauermann, P James B Dyck, Angela Dispenzieri, Jay Mandrekar, Peter J Dyck, Christopher J Klein
INTRODUCTION: In POEMS and CIDP, limb nerve conduction studies (NCS) are limited in identifying demyelination and detecting treatment effects in severely affected patients. Blink R1-latency may improve these assessments. METHODS: POEMS and CIDP patients having undergone NCS and blink reflex were identified. Correlations between R1-latency, limb NCS and neuropathy impairment scores (NIS) were compared. RESULTS: With182 patients (124 POEMS, 58 CIDP) identified, R1-prolongation (>13ms) occurred in 64...
June 23, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28646336/nogo-a-antibodies-enhance-axonal-repair-and-remyelination-in-neuro-inflammatory-and-demyelinating-pathology
#9
Benjamin V Ineichen, Sandra Kapitza, Christiane Bleul, Nicolas Good, Patricia S Plattner, Maryam S Seyedsadr, Julia Kaiser, Marc P Schneider, Björn Zörner, Roland Martin, Michael Linnebank, Martin E Schwab
Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions...
June 23, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28645295/identification-of-the-flotillin-1-2-heterocomplex-as-a-target-of-autoantibodies-in-bona-fide-multiple-sclerosis
#10
S Hahn, G Trendelenburg, M Scharf, Y Denno, S Brakopp, B Teegen, C Probst, K P Wandinger, M Buttmann, A Haarmann, F Szabados, M Vom Dahl, T Kümpfel, P Eichhorn, H Gold, F Paul, S Jarius, N Melzer, W Stöcker, L Komorowski
BACKGROUND: Autoantibodies, in particular those against aquaporin-4 and myelin-oligodendrocyte glycoprotein (MOG), aid as biomarkers in the differential diagnosis of demyelination. Here, we report on discovery of autoantibodies against flotillin in patients with multiple sclerosis (MS). METHODS: The target antigen was identified by histo-immunoprecipitation using the patients' sera and cryosections of rat or pig cerebellum combined with mass spectrometrical analysis...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28643229/progressive-multifocal-leukoencephalopathy-in-a-patient-with-lymphoma-and-presumptive-hyper-ige-syndrome
#11
Rahsan Gocmen, Nazire Pinar Acar, Deniz Cagdas, Asli Kurne
We, herein, report a 23-year-old male with a rare inherited immunodeficiency disease, hyperimmunoglobulin IgE syndrome (HIES), who developed progressive multifocal leukoencephalopathy (PML) and lymphoma simultaneously. Primary immunodeficiency of the patient has remained undiagnosed until adulthood. PML is a severe demyelinating disease of the central nervous system caused by John Cunningham virus. HIES is a rare, inherited immunodeficiency characterized by high serum levels of IgE, recurrent staphylococcal infection, eczema, and hypereosinophilia...
June 22, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28642167/mice-lacking-gpr37-exhibit-decreased-expression-of-the-myelin-associated-glycoprotein-mag-and-increased-susceptibility-to-demyelination
#12
Brilee M Smith, Michelle M Giddens, Jessica Neil, Sharon Owino, TrangKimberly T Nguyen, Duc Duong, Fengqiao Li, Randy A Hall
GPR37 is an orphan G protein-coupled receptor that is predominantly expressed in the brain and found at particularly high levels in oligodendrocytes. GPR37 has been shown to exert effects on oligodendrocyte differentiation and myelination during development, but the molecular basis of these actions is incompletely understood and moreover nothing is known about the potential role(s) of this receptor under demyelinating conditions. To shed light on the fundamental biology of GPR37, we performed proteomic studies comparing protein expression levels in the brains of mice lacking GPR37 and its close relative GPR37-like 1 (GPR37L1)...
June 19, 2017: Neuroscience
https://www.readbyqxmd.com/read/28642160/a-novel-missense-variant-gln220arg-of-gnb4-encoding-guanine-nucleotide-binding-protein-subunit-beta-4-in-a-japanese-family-with-autosomal-dominant-motor-and-sensory-neuropathy
#13
Shiroh Miura, Takuya Morikawa, Ryuta Fujioka, Kazuhito Noda, Kengo Kosaka, Takayuki Taniwaki, Hiroki Shibata
Dominant intermediate Charcot-Marie-Tooth disease F (CMTDIF) is an autosomal dominant hereditary form of Charcot-Marie-Tooth disease (CMT) caused by variations in the guanine nucleotide-binding protein, subunit beta-4 gene (GNB4). We examined two Japanese familial cases with CMT. Case 1 was a 49-year-old male whose chief complaint was slowly progressive gait disturbance and limb dysesthesia that appeared at the age of 47. On neurological examination, he showed hyporeflexia or areflexia, distal limb muscle weakness, and distal sensory impairment with lower dominancy...
June 19, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28642030/cyclic-mog35-55-ameliorates-clinical-and-neuropathological-features-of-experimental-autoimmune-encephalomyelitis
#14
Athanasios Lourbopoulos, George Deraos, Minos-Timotheos Matsoukas, Olga Touloumi, Aggeliki Giannakopoulou, Hubert Kalbacher, Nikolaos Grigoriadis, Vasso Apostolopoulos, John Matsoukas
EAE is induced to susceptible mice using linear peptides of myelin proteins of the central nervous system. Specific peptide motifs within the peptide-binding groove of the MHC peptide-complex determines the affinity of the peptide in each animal and the consequent T-cell receptor recognition and activation of the cell. Altered peptide ligand (APL) vaccination is a novel approach based on an effort to induce T-cell tolerance or alter cytokine profile from pro-inflammatory to anti-inflammatory. In the present study we synthesized the MOG35-55 peptide and altered its 3-dimensional conformation to make it a cyclic one (c-MOG35-55)...
June 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28641774/membranous-nephropathy-with-neuromyelitis-optica-spectrum-disorder
#15
Xiangling Li, YanQiang Wang
Membranous nephropathy (MN) accompanying Neuromyelitis optica spectrum disorders (NMOSD) has rarely been described previously. We recently presented a 45-year-old Chinese male presenting with recurrent lower extremity pitting edema, or eyelid edema, proteinuria and hyperlipidemia. especially intractable hiccup and vomiting, painful tonic spasm (PTS) as the revealing symptom of a demyelinating disorder of central nervous system. The kindey biopsy specimen showed MN stage 2. Serological testing revealed antibodies AQP4, MRI head and spine revealed medulla oblongata and C1-C2 cervical vertebra lesions...
July 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28641766/amyloid-pet-in-pseudotumoral-multiple-sclerosis
#16
Jordi A Matías-Guiu, María Nieves Cabrera-Martín, Ana Cortés-Martínez, Vanesa Pytel, Teresa Moreno-Ramos, Celia Oreja-Guevara, José Luis Carreras, Jorge Matías-Guiu
BACKGROUND: Pseudotumoral multiple sclerosis is a rare form of demyelinating disease of the central nervous system. Positron emission tomography (PET) using amyloid-tracers has also been suggested as a marker of damage in white matter lesions in multiple sclerosis due to the nonspecific uptake of these tracers in white matter. METHOD: We present the case of a 59 year-old woman with a pathological-confirmed pseudotumoral multiple sclerosis, who was studied with the amyloid tracer (18)F-florbetaben...
July 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28640199/the-role-of-peripheral-cns-directed-antibodies-in-promoting-inflammatory-cns-demyelination
#17
REVIEW
Silke Kinzel, Martin S Weber
In central nervous system (CNS) demyelinating disorders, such as multiple sclerosis (MS), neuromyelitis optica (NMO) and related NMO-spectrum disorders (NMO-SD), a pathogenic role for antibodies is primarily projected into enhancing ongoing CNS inflammation by directly binding to target antigens within the CNS. This scenario is supported at least in part, by antibodies in conjunction with complement activation in the majority of MS lesions and by deposition of anti-aquaporin-4 (AQP-4) antibodies in areas of astrocyte loss in patients with classical NMO...
June 22, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28639596/guillain-barre-syndrome-demographics-clinical-profile-seasonal-variation-in-a-tertiary-care-centre-of-central-india
#18
Manisha Shrivastava, Shah Nehal, Navaid Seema
BACKGROUND & OBJECTIVES: Guillain-Barre syndrome (GBS) is an autoimmune disease and a recognized cause of generalized progressive paralysis worldwide. The present study was aimed to document the clinical findings, demographics and seasonal variations amongst the patients with GBS during the hospital stay. METHODS: A retrospective analysis of 66 referred cases diagnosed as GBS was conducted. Medical records and the data related to age, sex, antecedent illness, duration of symptoms before admission, muscle power graded by the Medical Research Council scale, functional scores, details of Intensive Care Unit complications and need for ventilation were obtained...
February 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28638989/parietal-white-matter-lesions-in-alzheimer-s-disease-are-associated-with-cortical-neurodegenerative-pathology-but-not-with-small-vessel-disease
#19
Kirsty E McAleese, Lauren Walker, Sophie Graham, Elisa L J Moya, Mary Johnson, Daniel Erskine, Sean J Colloby, Madhurima Dey, Carmen Martin-Ruiz, John-Paul Taylor, Alan J Thomas, Ian G McKeith, Charles De Carli, Johannes Attems
Cerebral white matter lesions (WML) encompass axonal loss and demyelination, and the pathogenesis is assumed to be small vessel disease (SVD)-related ischemia. However, WML may also result from the activation of Wallerian degeneration as a consequence of cortical Alzheimer's disease (AD) pathology, i.e. hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ) deposition. WML seen in AD have a posterior predominance compared to non-demented individuals but it is unclear whether the pathological and molecular signatures of WML differ between these two groups...
June 21, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28638987/leukodystrophies-a-proposed-classification-system-based-on-pathological-changes-and-pathogenetic-mechanisms
#20
REVIEW
Marjo S van der Knaap, Marianna Bugiani
Leukodystrophies are genetically determined disorders characterized by the selective involvement of the central nervous system white matter. Onset may be at any age, from prenatal life to senescence. Many leukodystrophies are degenerative in nature, but some only impair white matter function. The clinical course is mostly progressive, but may also be static or even improving with time. Progressive leukodystrophies are often fatal, and no curative treatment is known. The last decade has witnessed a tremendous increase in the number of defined leukodystrophies also owing to a diagnostic approach combining magnetic resonance imaging pattern recognition and next generation sequencing...
June 21, 2017: Acta Neuropathologica
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