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https://www.readbyqxmd.com/read/29605155/als-genes-in-the-genomic-era-and-their-implications-for-ftd
#1
REVIEW
Hung Phuoc Nguyen, Christine Van Broeckhoven, Julie van der Zee
Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, characterized genetically by a disproportionately large contribution of rare genetic variation. Driven by advances in massive parallel sequencing and applied on large patient-control cohorts, systematic identification of these rare variants that make up the genetic architecture of ALS became feasible. In this review paper, we present a comprehensive overview of recently proposed ALS genes that were identified based on rare genetic variants (TBK1, CHCHD10, TUBA4A, CCNF, MATR3, NEK1, C21orf2, ANXA11, TIA1) and their potential relevance to frontotemporal dementia genetic etiology...
March 28, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29542376/serum-neurofilament-light-chain-is-a-biomarker-of-acute-and-chronic-neuronal-damage-in-early-multiple-sclerosis
#2
Nelly Siller, Jens Kuhle, Muthuraman Muthuraman, Christian Barro, Timo Uphaus, Sergiu Groppa, Ludwig Kappos, Frauke Zipp, Stefan Bittner
BACKGROUND: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament - a major component of the neuro-axonal cytoskeleton - is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. OBJECTIVE: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. METHODS: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology...
March 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29438265/keep-your-eyes-wide-open-on-visual-and-vision-related-measurements-to-better-understand-multiple-sclerosis-pathophysiology
#3
Yael Backner, Netta Levin
BACKGROUND: Multiple sclerosis (MS), a demyelinating disease of the central nervous system, is multifaceted. It manifests as acute episodes as well as an accumulative chronic disability; myelin involvement as well as axonal damage; local as well as global effects; and disease load elements as well as compensatory mechanisms. The visual system, with its clear structural organization and relatively direct reflection of damage, may serve as an appropriate model to study MS. METHODS: In recent years, we have witnessed a blossoming in the field of visual measures in MS...
March 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/29405761/guided-imagery-improves-mood-fatigue-and-quality-of-life-in-individuals-with-multiple-sclerosis-an-exploratory-efficacy-trial-of-healing-light-guided-imagery
#4
Laura K Case, Paula Jackson, Revere Kinkel, Paul J Mills
Multiple sclerosis is a disabling and progressive neurological disease that has significant negative effects on health-related quality of life. This exploratory efficacy study examined the effects of Healing Light Guided Imagery (HLGI), a novel variant of guided imagery, compared with a wait-list control in patients with relapsing-remitting multiple sclerosis. Changes in the Beck Depression Inventory, Fatigue Severity Scale, and Multiple Sclerosis Quality of Life instrument (physical and mental components) were compared between groups...
January 2018: Journal of evidence-based integrative medicine
https://www.readbyqxmd.com/read/29313812/pathogenic-commonalities-between-spinal-muscular-atrophy-and-amyotrophic-lateral-sclerosis-converging-roads-to-therapeutic-development
#5
REVIEW
Melissa Bowerman, Lyndsay M Murrray, Frédérique Scamps, Bernard L Schneider, Rashmi Kothary, Cédric Raoul
Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are the two most common motoneuron disorders, which share typical pathological hallmarks while remaining genetically distinct. Indeed, SMA is caused by deletions or mutations in the survival motor neuron 1 (SMN1) gene whilst ALS, albeit being mostly sporadic, can also be caused by mutations within genes, including superoxide dismutase 1 (SOD1), Fused in Sarcoma (FUS), TAR DNA-binding protein 43 (TDP-43) and chromosome 9 open reading frame 72 (C9ORF72)...
December 5, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29311122/experimental-autoimmune-encephalomyelitis-eae-as-animal-models-of-multiple-sclerosis-ms
#6
Simon Glatigny, Estelle Bettelli
Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system (CNS) leading to the progressive destruction of the myelin sheath surrounding axons. It can present with variable clinical and pathological manifestations, which might reflect the involvement of distinct pathogenic processes. Although the mechanisms leading to the development of the disease are not fully understood, numerous evidences indicate that MS is an autoimmune disease, the initiation and progression of which are dependent on an autoimmune response against myelin antigens...
January 8, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29147991/the-role-of-the-gut-microbiome-in-multiple-sclerosis-risk-and-progression-towards-characterization-of-the-ms-microbiome
#7
REVIEW
Anne-Katrin Pröbstel, Sergio E Baranzini
Multiple sclerosis (MS) is the prototypic complex disease, in which both genes and the environment contribute to its pathogenesis. To date, > 200 independent loci across the genome have been associated with MS risk. However, these only explain a fraction of the total phenotypic variance, suggesting the possible presence of additional genetic factors, and, most likely, also environmental factors. New DNA sequencing technologies have enabled the sequencing of all kinds of microorganisms, including those living in and around humans (i...
January 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29079686/monitoring-disease-activity-in-multiple-sclerosis-using-serum-neurofilament-light-protein
#8
MULTICENTER STUDY
Lenka Novakova, Henrik Zetterberg, Peter Sundström, Markus Axelsson, Mohsen Khademi, Martin Gunnarsson, Clas Malmeström, Anders Svenningsson, Tomas Olsson, Fredrik Piehl, Kaj Blennow, Jan Lycke
OBJECTIVE: To examine the effects of disease activity, disability, and disease-modifying therapies (DMTs) on serum neurofilament light (NFL) and the correlation between NFL concentrations in serum and CSF in multiple sclerosis (MS). METHODS: NFL concentrations were measured in paired serum and CSF samples (n = 521) from 373 participants: 286 had MS, 45 had other neurologic conditions, and 42 were healthy controls (HCs). In 138 patients with MS, the serum and CSF samples were obtained before and after DMT treatment with a median interval of 12 months...
November 28, 2017: Neurology
https://www.readbyqxmd.com/read/28885372/light-therapy-for-multiple-sclerosis-associated-fatigue-study-protocol-for-a-randomized-controlled-trial
#9
RANDOMIZED CONTROLLED TRIAL
Farrah J Mateen, Natalie C Manalo, Sara J Grundy, Melissa A Houghton, Gladia C Hotan, Hans Erickson, Aleksandar Videnovic
BACKGROUND: Fatigue is the most commonly reported symptom among multiple sclerosis (MS) patients, more than a quarter of whom consider fatigue to be their most disabling symptom. However, there are few effective treatment options for fatigue. We aim to investigate whether supplemental exposure to bright white light will reduce MS-associated fatigue. METHODS: Eligible participants will have clinically confirmed multiple sclerosis based on the revised McDonald criteria (2010) and a score ≥36 on the Fatigue Severity Scale (FSS)...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28724999/x-ray-phase-contrast-tomography-reveals-early-vascular-alterations-and-neuronal-loss-in-a-multiple-sclerosis-model
#10
A Cedola, A Bravin, I Bukreeva, M Fratini, A Pacureanu, A Mittone, L Massimi, P Cloetens, P Coan, G Campi, R Spanò, F Brun, V Grigoryev, V Petrosino, C Venturi, M Mastrogiacomo, Nicole Kerlero de Rosbo, A Uccelli
The degenerative effects of multiple sclerosis at the level of the vascular and neuronal networks in the central nervous system are currently the object of intensive investigation. Preclinical studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapy in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis, but the neuropathology of specific lesions in EAE and the effects of MSC treatment are under debate. Because conventional imaging techniques entail protocols that alter the tissues, limiting the reliability of the results, we have used non-invasive X-ray phase-contrast tomography to obtain an unprecedented direct 3D characterization of EAE lesions at micro-to-nano scales, with simultaneous imaging of the vascular and neuronal networks...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627962/plasma-neurofilament-light-chain-levels-in-patients-with-ms-switching-from-injectable-therapies-to-fingolimod
#11
Fredrik Piehl, Ingrid Kockum, Mohsen Khademi, Kaj Blennow, Jan Lycke, Henrik Zetterberg, Tomas Olsson
BACKGROUND: Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS). OBJECTIVE: To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod. METHODS: A first cohort consisted of MS patients ( n = 39) and neurological disease controls ( n = 27) where CSF and plasma/serum had been collected for diagnostic purposes...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28560740/acutely-damaged-axons-are-remyelinated-in-multiple-sclerosis-and-experimental-models-of-demyelination
#12
Verena Schultz, Franziska van der Meer, Claudia Wrzos, Uta Scheidt, Erik Bahn, Christine Stadelmann, Wolfgang Brück, Andreas Junker
Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage...
August 2017: Glia
https://www.readbyqxmd.com/read/28512753/serum-neurofilament-light-a-biomarker-of-neuronal-damage-in-multiple-sclerosis
#13
COMPARATIVE STUDY
Giulio Disanto, Christian Barro, Pascal Benkert, Yvonne Naegelin, Sabine Schädelin, Antonella Giardiello, Chiara Zecca, Kaj Blennow, Henrik Zetterberg, David Leppert, Ludwig Kappos, Claudio Gobbi, Jens Kuhle
OBJECTIVE: Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single-molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS). METHODS: sNfL levels were measured in healthy controls (HC, n = 254) and two independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow-up = 3...
June 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28444098/the-cerebrospinal-fluid-in-multiple-sclerosis-far-beyond-the-bands
#14
REVIEW
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/28396093/what-s-new-about-oral-treatments-in-multiple-sclerosis-immunogenetics-still-under-question
#15
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...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28360804/affective-temperament-profiles-in-patients-with-multiple-sclerosis-association-with-mood-disorders
#16
Adile Özkan, Kürşat Altinbaş, Emine Rabia Koç, Halil Murat Şen, Handan Işın Özişik Karaman
INTRODUCTION: The aim of the present study was to screen for bipolarity and to investigate the affective temperaments of patients with multiple sclerosis (MS) and the possible association between the clinical and demographic characteristics of MS patients and temperament profiles. METHODS: A total of 65 patients with MS and 66 healthy volunteers completed the 32-item hypomania checklist (HCl-32), the Mood Disorder Questionnaire (MDQ), and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A) tests...
December 2016: Noro Psikiyatri Arsivi
https://www.readbyqxmd.com/read/28321351/bilateral-birdshot-retinochoroiditis-and-retinal-astrocytoma
#17
Sunil Mamtora, Yun Wong, Dugald Bell, Teresa Sandinha
Background. This case highlights the importance of recognising multiple pathologies within the eye which may not necessarily be linked. Both birdshot retinochoroiditis and astrocytoma are rare conditions. The case underlines the need for early identification and treatment of birdshot retinochoroiditis with steroids and disease modifying drugs. Astrocytoma in the absence of tuberous sclerosis is also uncommon. Case Presentation. A 36-year-old male presented with 3-month history of bilateral progressive flashing lights and floaters...
2017: Case Reports in Ophthalmological Medicine
https://www.readbyqxmd.com/read/28116578/innate-immunity-in-systemic-sclerosis
#18
REVIEW
Christopher Dowson, Nathan Simpson, Laura Duffy, Steven O'Reilly
PURPOSE OF REVIEW: Systemic sclerosis (SSc) is a heterogeneous autoimmune disease which has defined three hallmarks: Small vessel vasculopathy, production of autoantibodies and fibroblast dysfunction. The exact aetiology of the disease remains unknown, due to the complex nature of the cellular signalling pathways involved. However, there is strong and consistent evidence that the innate system, in particular toll-like receptor signalling, is contributing to the progression and perhaps onset of systemic sclerosis...
January 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28018358/endothelial-response-to-glucocorticoids-in-inflammatory-diseases
#19
REVIEW
Karolina A Zielińska, Laura Van Moortel, Ghislain Opdenakker, Karolien De Bosscher, Philippe E Van den Steen
The endothelium plays a crucial role in inflammation. A balanced control of inflammation requires the action of glucocorticoids (GCs), steroidal hormones with potent cell-specific anti-inflammatory properties. Besides the classic anti-inflammatory effects of GCs on leukocytes, recent studies confirm that endothelial cells also represent an important target for GCs. GCs regulate different aspects of endothelial physiology including expression of adhesion molecules, production of pro-inflammatory cytokines and chemokines, and maintenance of endothelial barrier integrity...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27904491/intravenous-transplantation-of-mouse-embryonic-stem-cells-attenuates-demyelination-in-an-icr-outbred-mouse-model-of-demyelinating-diseases
#20
Kidsadagon Pringproa, Anucha Sathanawongs, Chananthida Khamphilai, Sarocha Sukkarinprom, Apichart Oranratnachai
Induction of demyelination in the central nervous system (CNS) of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. However, different mouse strains used result in different pathological outcomes. Moreover, because current medicinal treatments are not always effective in multiple sclerosis patients, so the study of exogenous cell transplantation in an animal model is of great importance. The aims of the present study were to establish an alternative ICR outbred mouse model for studying demyelination and to evaluate the effects of intravenous cell transplantation in the present developed mouse model...
October 2016: Neural Regeneration Research
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