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https://www.readbyqxmd.com/read/28345260/resistance-and-aerobic-training-improve-muscle-strength-and-aerobic-capacity-in-cidp
#1
Lars H Markvardsen, Kristian Overgaard, Karen Heje, Søren H Sindrup, Ingelise Christiansen, John Vissing, Henning Andersen
INTRODUCTION: We investigated the effect of aerobic and resistance exercise in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Eighteen CIDP patients treated with subcutaneous immunoglobulin did 12 weeks of aerobic exercise and 12 weeks of resistance exercise after a run-in period of 12 weeks without exercise. Three times weekly the participants performed aerobic exercise on an ergometer bike or resistance exercise with unilateral training of knee and elbow flexion/extension...
March 27, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28344072/osteopontin-metallothionen-i-ii-interactions-in-experimental-autoimmunune-encephalomyelitis
#2
Hrvoje Jakovac, Tanja Grubić Kezele, Sandra Šućurović, Biserka Mulac-Jeričević, Biserka Radošević-Stašić
Osteopontin (OPN), an extracellular matrix (ECM) glyco-phosphoprotein, plays an important role in autoimmune-mediated demyelinating diseases, including multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). As an integrin and CD44 binding protein it participates in bidirectional communication between the ECM and target cells and affects transduction pathways that maintain neuronal and immune cells homeostasis. Its biological activity is also heavily influenced by microenvironment, which stimulates the cleavage of OPN and changes its functions...
March 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28343188/multimodal-evoked-potentials-in-patients-with-multiple-sclerosis-in-assessment-of-the-course-of-the-disease
#3
Beata Łabuz-Roszak, Magdalena Torbus, Katarzyna Kubicka-Bączyk, Agnieszka Machowska-Majchrzak, Agata Kierber, Katarzyna Borucka, Małgorzata Zellner, Anna Starostak-Tatar, Krystyna Pierzchała
INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system with a multifocal damage. THE AIM: The assessment of the MS course by multimodal evoked potentials (EP). MATERIAL AND METHODS: We evaluated 95 patients (63 female, 32 male) with relapsing-remitting MS in the average age of 36.4±10.4. The average disease duration was 4.6±7.4 year. Among them, 48 patients (50.5%) were treated with immunomodulatory drugs...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28342869/microrna-448-promotes-multiple-sclerosis-development-through-induction-of-th17-response-through-targeting-protein-tyrosine-phosphatase-non-receptor-type-2-ptpn2
#4
Rihan Wu, Qinyu He, Haitao Chen, Miao Xu, Ning Zhao, Ying Xiao, Qian-Qian Tu, Wenjun Zhang, Xiaoying Bi
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system, and its pathogenesis remains largely unclear. Much attention has been paid to the role of microRNAs (miRs) in regulation of autoimmune disease. Here, we found, for the first time, that miR-448 expression was significantly increased in periphery blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) of patients with MS, and its expression positively correlated with the disease severity. We further demonstrated that CD4(+) T cells, especially the Th17 lineage, were the major source of miR-448 expression...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28341402/inhibitors-of-protein-arginine-deiminases-and-their-efficacy-in-animal-models-of-multiple-sclerosis
#5
Amit Sarswat, Ewa Wasilewski, Sai K Chakka, Angelica M Bello, Andrew V Caprariello, Chithra M Muthuramu, Peter K Stys, Shannon E Dunn, Lakshmi P Kotra
Protein arginine deiminases (PAD) are implicated in a variety of inflammatory and neurodegenerative diseases including multiple sclerosis (MS). Following the discovery of an in silico hit containing hydantoin and a piperidine moiety, we hypothesized that a 2-carbon linker on the hydantoin would be necessary for a 5-membered heterocycle for optimal PAD inhibitory activity. We designed thirteen compounds as potential inhibitors of PAD2 and PAD4 enzymes-two important PAD enzymes implicated in MS. Two compounds, one with an imidazole moiety (22) and the other with a tetrazole moiety (24) showed good inhibition of PAD isozymes in vitro and in the EAE mouse model of MS in vivo...
March 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28340598/myelin-specific-multiple-sclerosis-antibodies-cause-complement-dependent-oligodendrocyte-loss-and-demyelination
#6
Yiting Liu, Katherine S Given, Danielle E Harlow, Adeline M Matschulat, Wendy B Macklin, Jeffrey L Bennett, Gregory P Owens
Intrathecal immunoglobulin G (IgG) synthesis, cerebrospinal fluid (CSF) oligoclonal IgG bands and lesional IgG deposition are seminal features of multiple sclerosis (MS) disease pathology. Both the specific targets and pathogenic effects of MS antibodies remain poorly characterized. We produced IgG1 monoclonal recombinant antibodies (rAbs) from clonally-expanded plasmablasts recovered from MS patient CSF. Among these were a subset of myelin-specific MS rAbs. We examined their immunoreactivity to mouse organotypic cerebellar slices by live binding and evaluated tissue injury in the presence and absence of human complement...
March 24, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28340352/human-epistatic-interaction-controls-il7r-splicing-and-increases-multiple-sclerosis-risk
#7
Gaddiel Galarza-Muñoz, Farren B S Briggs, Irina Evsyukova, Geraldine Schott-Lerner, Edward M Kennedy, Tinashe Nyanhete, Liuyang Wang, Laura Bergamaschi, Steven G Widen, Georgia D Tomaras, Dennis C Ko, Shelton S Bradrick, Lisa F Barcellos, Simon G Gregory, Mariano A Garcia-Blanco
Multiple sclerosis (MS) is an autoimmune disorder where T cells attack neurons in the central nervous system (CNS) leading to demyelination and neurological deficits. A driver of increased MS risk is the soluble form of the interleukin-7 receptor alpha chain gene (sIL7R) produced by alternative splicing of IL7R exon 6. Here, we identified the RNA helicase DDX39B as a potent activator of this exon and consequently a repressor of sIL7R, and we found strong genetic association of DDX39B with MS risk. Indeed, we showed that a genetic variant in the 5' UTR of DDX39B reduces translation of DDX39B mRNAs and increases MS risk...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340257/cd8-positive-t-cell-leukoencephalitis-with-astrocytopathy-clinically-presenting-as-neuromyelitis-optica
#8
Diana L Thomas, Jody Manners, Daniel Marker, Joseph Mettenburg, Geoffrey Murdoch, Bryan Stevens, Guoji Wang, Clayton Wiley
We describe a novel disease entity with the clinical and radiologic presentation of neuromyelitis optica (NMO) and widespread CD8-positive T-cell leukoencephalitis and astrocytopathy. The 59-year-old female patient had a complex 2-year neurological history that included early changes in cognition and memory, progressive lower extremity motor dysfunction, and multimodal sensory involvement. MRI of the spinal cord showed increased T2 signal in the central cord extending from C2 through T4. MRI of the brain showed symmetric radial enhancement in periventricular deep white matter without evidence of demyelinating lesions...
March 16, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28337644/cns-demyelination-with-tnf-%C3%AE-blockers
#9
REVIEW
Elissavet Kemanetzoglou, Elisabeth Andreadou
Tumor necrosis factor-α (TNF-α) blockers are a popular therapeutic choice in a number of inflammatory diseases. Thus far, five TNF- α blockers have been approved for clinical use (etanercept, infliximab, adalimumab, golimumab. and certolizumab). Despite being considered relatively safe, serious side effects associated with immune suppression have been reported, including central and peripheral nervous system (CNS) demyelinating disorders. It is still elusive whether these events are mere coincidence or a side effect of anti-TNF-α use...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28337205/high-interferon-%C3%AE-uniquely-in-v%C3%AE-1-t-cells-correlates-with-markers-of-inflammation-and-axonal-damage-in-early-multiple-sclerosis
#10
Avadhesh Kumar Singh, Lenka Novakova, Markus Axelsson, Clas Malmeström, Henrik Zetterberg, Jan Lycke, Susanna L Cardell
We have identified a population of T lymphocytes in peripheral blood, Vδ1 TCRγδ T lymphocytes, which unexpectedly was uniquely expressing high production of interferon-γ in newly diagnosed, untreated multiple sclerosis (MS) patients. IFN-γ production in this population distinctly correlated to parameters of clinical disease activity, inflammation, and neuronal damage. These Vδ1 T lymphocytes belong to a population of innate T lymphocytes that recognize antigen in the context of CD1d/CD1c and which include reactivity to the myelin glycosphingolipid sulfatide...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28336681/accuracy-and-reliability-of-stroke-diagnosis-in-the-pediatric-emergency-department
#11
Mark T Mackay, Adriana Yock-Corrales, Leonid Churilov, Paul Monagle, Geoffrey A Donnan, Franz E Babl
BACKGROUND AND PURPOSE: Access to acute stroke interventions in the emergency department (ED) relies on correct clinical diagnosis. Our aims were to determine the accuracy and reliability of pediatric ED physician diagnosis of childhood stroke and other conditions presenting with brain attack symptoms. METHODS: Prospective study of consecutive children aged 1 month to 18 years presenting to the ED from June 2009 to December 2010 with focal neurological deficits...
March 23, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28336415/sncam-as-a-specific-marker-of-peripheral-demyelination
#12
Adam Niezgoda, Sławomir Michalak, Jacek Losy, Alicja Kalinowska-Łyszczarz, Wojciech Kozubski
Adhesion molecules are involved in nerve growth, synaptic plasticity and myelin formation and maintenance process. Neural cell adhesion molecule (CD56 or NCAM) seems to play a crucial role in all the above-mentioned events. Having found poly-sialylated NCAM increased re-expression on demyelinated axons within multiple sclerosis plaques we assessed soluble NCAM (sNCAM) in sera of patients with various types of peripheral nerve affections - demyelinating, axonal "inflammatory", axonal metabolic polyneuropathies and healthy controls...
March 20, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28334918/adaptive-human-immunity-drives-remyelination-in-a-mouse-model-of-demyelination
#13
Mohamed El Behi, Charles Sanson, Corinne Bachelin, Léna Guillot-Noël, Jennifer Fransson, Bruno Stankoff, Elisabeth Maillart, Nadège Sarrazin, Vincent Guillemot, Hervé Abdi, Isabelle Cournu-Rebeix, Bertrand Fontaine, Violetta Zujovic
One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells...
February 22, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334875/white-matter-changes-in-paediatric-multiple-sclerosis-and-monophasic-demyelinating-disorders
#14
Giulia Longoni, Robert A Brown, Parya MomayyezSiahkal, Colm Elliott, Sridar Narayanan, Amit Bar-Or, Ruth Ann Marrie, E Ann Yeh, Massimo Filippi, Brenda Banwell, Douglas L Arnold
Most children who experience an acquired demyelinating syndrome of the central nervous system will have a monophasic disease course, with no further clinical or radiological symptoms. A subset will be diagnosed with multiple sclerosis, a life-long disorder. Using linear mixed effects models we examined longitudinal diffusion properties of normal-appearing white matter in 505 serial scans of 132 paediatric participants with acquired demyelinating syndromes followed for a median of 4.4 years, many from first clinical presentation, and 106 scans of 80 healthy paediatric participants...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334857/co-cultures-with-stem-cell-derived-human-sensory-neurons-reveal-regulators-of-peripheral-myelination
#15
Alex J Clark, Malte S Kaller, Jorge Galino, Hugh J Willison, Simon Rinaldi, David L H Bennett
Effective bidirectional signalling between axons and Schwann cells is essential for both the development and maintenance of peripheral nerve function. We have established conditions by which human induced pluripotent stem cell-derived sensory neurons can be cultured with rat Schwann cells, and have produced for the first time long-term and stable myelinating co-cultures with human neurons. These cultures contain the specialized domains formed by axonal interaction with myelinating Schwann cells, such as clustered voltage-gated sodium channels at the node of Ranvier and Shaker-type potassium channel (Kv1...
February 15, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28332470/adult-onset-demyelinating-neuropathy-associated-with-fbln5-gene-mutation
#16
Si Cheng, He Lv, Wei Zhang, Zhaoxia Wang, Xin Shi, Wei Liang, Yun Yuan
Rare forms of autosomal-dominant Charcot-Marie-Tooth disease (AD-CMT) may be associated with mutations in Fibulin-5 (FBLN5) as AD-CMT is genetically heterogeneous. Here, we report the first pathological study of an Asian family. The proband was a 46-year-old man with slowly progressive distal numbness and weakness for 12 years. He had a history of diabetes mellitus for 12 years. His mother was 81 years old and had mild polyneuropathy. His 16-year-old daughter was asymptomatic. The nerve conduction velocities (NCVs) and compound muscular action potential (CMAP) amplitudes were moderately to severely reduced in the proband, and moderately reduced in his daughter and mother...
March 23, 2017: Clinical Neuropathology
https://www.readbyqxmd.com/read/28332093/pathogenic-implications-of-distinct-patterns-of-iron-and-zinc-in-chronic-ms-lesions
#17
Bogdan F Popescu, Josa M Frischer, Samuel M Webb, Mylyne Tham, Reginald C Adiele, Christopher A Robinson, Patrick D Fitz-Gibbon, Stephen D Weigand, Imke Metz, Susan Nehzati, Graham N George, Ingrid J Pickering, Wolfgang Brück, Simon Hametner, Hans Lassmann, Joseph E Parisi, Guo Yong, Claudia F Lucchinetti
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neurodegeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis...
March 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28328138/homozygous-mutation-in-ptrh2-gene-causes-progressive-sensorineural-deafness-and-peripheral-neuropathy
#18
Rajech Sharkia, Stavit A Shalev, Abdelnaser Zalan, Milit Marom-David, Nathan Watemberg, Jill E Urquhart, Sarah B Daly, Sanjeev S Bhaskar, Simon G Williams, William G Newman, Ronen Spiegel, Abdussalam Azem, Orly Elpeleg, Muhammad Mahajnah
PTRH2 is an evolutionarily highly conserved mitochondrial protein that belongs to a family of peptidyl-tRNA hydrolases. Recently, patients from two consanguineous families with mutations in the PTRH2 gene were reported. Global developmental delay associated with microcephaly, growth retardation, progressive ataxia, distal muscle weakness with ankle contractures, demyelinating sensorimotor neuropathy, and sensorineural hearing loss were present in all patients, while facial dysmorphism with widely spaced eyes, exotropia, thin upper lip, proximally placed thumbs, and deformities of the fingers and toes were present in some individuals...
April 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28328136/22q11-2q13-duplication-including-sox10-causes-sex-reversal-and-peripheral-demyelinating-neuropathy-central-dysmyelinating-leukodystrophy-waardenburg-syndrome-and-hirschsprung-disease
#19
Nadia Falah, Jennifer E Posey, Willa Thorson, Paul Benke, Mustafa Tekin, Brocha Tarshish, James R Lupski, Tamar Harel
Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations...
April 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28327523/methodological-challenges-in-protein-microarray-and-immunohistochemistry-for-the-discovery-of-novel-autoantibodies-in-paediatric-acute-disseminated-encephalomyelitis
#20
Patrick Peschl, Melanie Ramberger, Romana Höftberger, Karin Jöhrer, Matthias Baumann, Kevin Rostásy, Markus Reindl
Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients...
March 22, 2017: International Journal of Molecular Sciences
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