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multiple sclerosis + light

J-L Bayart, N Muls, V van Pesch
OBJECTIVES: The detection of cerebrospinal fluid (CSF)-specific IgG oligoclonal bands (OCB) by isoelectric focusing (IEF) is widely used to help diagnose inflammatory neurological disorders (IND), including multiple sclerosis. However, the quantification of free light chains (FLC) is increasingly evaluated as a surrogate method to determine the presence of an intrathecal inflammatory process. The objective of this study was to evaluate the diagnostic performance of kappa (κ) FLC measurement in comparison with OCB detection by IEF...
June 13, 2018: Acta Neurologica Scandinavica
M León Ruiz, M Sospedra, S Arce Arce, J Tejeiro-Martínez, J Benito-León
INTRODUCTION: A growing number of studies have evaluated the effects of transcranial magnetic stimulation (TMS) for the symptomatic treatment of multiple sclerosis (MS). METHODS: We performed a PubMed search for articles, recent books, and recommendations from the most relevant clinical practice guidelines and scientific societies regarding the use of TMS as symptomatic treatment in MS. CONCLUSIONS: Excitatory electromagnetic pulses applied to the affected cerebral hemisphere allow us to optimise functional brain activity, including the transmission of nerve impulses through the demyelinated corticospinal pathway...
June 10, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Giuseppe Felice Mangiatordi, Tatiana Guzzo, Eugenio Claudio Rossano, Daniela Trisciuzzi, Domenico Alberga, Giovanni Fasciglione, Massimiliano Coletta, Alessandra Topai, Orazio Nicolotti
Targeting matrix metalloproteinases (MMPs) is a pursued strategy for treating several pathological conditions, such as multiple sclerosis and cancer. Herein, a series of novel tetrahydro-β-carboline derivatives with outstanding inhibitory activity toward MMPs are present. In particular, compounds 9 f, 9 g, 9 h and 9 i show sub-nanomolar IC50 values. Interestingly, compounds 9 g and 9 i also provide remarkable selectivity toward gelatinases; IC50 =0.15 nm for both toward MMP-2 and IC50 =0.63 and 0...
June 12, 2018: ChemMedChem
Martine Uittenbogaard, Christine A Brantner, ZiShui Fang, Lee-Jun Wong, Andrea Gropman, Anne Chiaramello
Little is known about the molecular mechanism of the rare coexistence of Leber's Hereditary Optic Neuropathy (LHON) and multiple sclerosis (MS), also known as the Harding's syndrome. In this study, we provide novel evidence that the m.11778A > G variant causes a defective metabolic interplay between mitochondrial oxidative phosphorylation and glycolysis. We used dermal fibroblasts derived from a female proband exhibiting clinical symptoms compatible with LHON-MS due to the presence of the pathogenic m...
June 8, 2018: Mitochondrion
Amit Berson, Raffaella Nativio, Shelley L Berger, Nancy M Bonini
Mechanisms of epigenetic regulation, including DNA methylation, chromatin remodeling, and histone post-translational modifications, are involved in multiple aspects of neuronal function and development. Recent discoveries have shed light on critical functions of chromatin in the aging brain, with an emerging realization that the maintenance of a healthy brain relies heavily on epigenetic mechanisms. Here, we present recent advances, with a focus on histone modifications and the implications for several neurodegenerative diseases including Alzheimer's disease (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)...
June 6, 2018: Trends in Neurosciences
Yongbo Kang, Yue Cai
Human immunodeficiency virus (HIV) infection progressively destroys CD4+ mononuclear cells leading to profound cellular immune deficiency that manifests as life threatening opportunistic infections and malignancies, i.e., the acquired immune deficiency syndrome (AIDS). Gut microbiota play key roles in the modulation of host metabolism and gene expression, maintenance of epithelial integrity, and mediation of inflammatory and immunity. Hence, the normal intestinal microbiota plays a major role in the maintenance of health and disease prevention...
June 7, 2018: AIDS Research and Human Retroviruses
Catarina M Abreu, Ricardo Soares-Dos-Reis, Pedro N Melo, João B Relvas, Joana Guimarães, Maria José Sá, Andrea P Cruz, Inês Mendes Pinto
Neuroinflammation plays a critical role in the onset and progression of many neurological disorders, including Multiple Sclerosis, Alzheimer's and Parkinson's diseases. In these clinical conditions the underlying neuroinflammatory processes are significantly heterogeneous. Nevertheless, a common link is the chronic activation of innate immune responses and imbalanced secretion of pro and anti-inflammatory mediators. In light of this, the discovery of robust biomarkers is crucial for screening, early diagnosis, and monitoring of neurological diseases...
2018: Frontiers in Molecular Neuroscience
Christian Barro, Pascal Benkert, Giulio Disanto, Charidimos Tsagkas, Michael Amann, Yvonne Naegelin, David Leppert, Claudio Gobbi, Cristina Granziera, Özgür Yaldizli, Zuzanna Michalak, Jens Wuerfel, Ludwig Kappos, Katrin Parmar, Jens Kuhle
Neuro-axonal injury is a key factor in the development of permanent disability in multiple sclerosis. Neurofilament light chain in peripheral blood has recently emerged as a biofluid marker reflecting neuro-axonal damage in this disease. We aimed at comparing serum neurofilament light chain levels in multiple sclerosis and healthy controls, to determine their association with measures of disease activity and their ability to predict future clinical worsening as well as brain and spinal cord volume loss. Neurofilament light chain was measured by single molecule array assay in 2183 serum samples collected as part of an ongoing cohort study from 259 patients with multiple sclerosis (189 relapsing and 70 progressive) and 259 healthy control subjects...
May 30, 2018: Brain: a Journal of Neurology
O Yildiz, Z Mao, A Adams, N Dubuisson, K Allen-Philbey, G Giovannoni, A Malaspina, D Baker, S Gnanapavan, K Schmierer
BACKGROUND: Evidence suggests people with non-relapsing deteriorating ("progressive") multiple sclerosis (pwPMS) may benefit from disease-modifying immune therapy (DMT). However, only one such treatment (ocrelizumab) has been licensed and is highly restricted to pwPMS suffering from the primary progressive phenotype. The difficulties assessing treatment outcome in pwPMS is one important reason for the lack of respective DMT. The concentration of neurofilaments in the cerebrospinal fluid (CSF) provides a biomarker of neuro-axonal damage, and both neurofilament light (NfL) and heavy chain (NfH) levels have been used as outcome indices and to guide treatment choices...
May 31, 2018: Multiple Sclerosis and related Disorders
E Quintana, C Coll, J Salavedra-Pont, M Muñoz-San Martín, R Robles-Cedeño, J Tomàs-Roig, M Buxó, C Matute-Blanch, L M Villar, X Montalban, M Comabella, H Perkal, J Gich, L L Ramió-Torrentà
BACKGROUND/OBJECTIVE: Chitinase 3-like 1 (CHI3L1) and neurofilament light chain (NF-L) are promising biomarkers of disability in multiple sclerosis (MS); however, their role in cognitive dysfunction remains elusive. Here, we aimed to correlate cerebrospinal fluid (CSF) levels of CHI3L1 and NF-L with cognitive status in MS. METHODS/RESULTS: Fifty one recently diagnosed patients were cognitively evaluated and CSF was collected. Levels of CHI3L1 and NF-L were determined by ELISA...
May 24, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Johanna Breuer, Karin Loser, Nadine Mykicki, Heinz Wiendl, Nicholas Schwab
Multiple sclerosis (MS) is a disease of presumed auto-immune origin. Long-standing observations such as the correlation between MS incidence and geographical latitude or the levels of Vitamin D (Vit D) in the serum have implicated the environmental factors UVB radiation and diet in the etiology of the disease. Clinical trials have been conducted and are currently underway to elucidate whether a Vit D enriched diet or treatment with UVB can influence MS incidence, -severity, and -progression, as well as the ideal time point for treatment...
May 18, 2018: Journal of Neuroimmunology
Jeppe Romme Christensen, Mika Komori, Marina Rode von Essen, Rikke Ratzer, Lars Börnsen, Bibi Bielekova, Finn Sellebjerg
BACKGROUND: Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. OBJECTIVE: To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. METHODS: CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS...
May 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Roos M van der Vuurst de Vries, Yu Yi M Wong, Julia Y Mescheriakova, E Daniëlle van Pelt, Tessel F Runia, Naghmeh Jafari, Theodora Am Siepman, Marie-José Melief, Annet F Wierenga-Wolf, Marvin M van Luijn, Johnny P Samijn, Rinze F Neuteboom, Rogier Q Hintzen
BACKGROUND: A promising biomarker for axonal damage early in the disease course of multiple sclerosis (MS) is neurofilament light chain (NfL). It is unknown whether NfL has the same predictive value for MS diagnosis in children as in adults. OBJECTIVE: To explore the predictive value of NfL levels in cerebrospinal fluid (CSF) for MS diagnosis in paediatric and adult clinically isolated syndrome (CIS) patients. METHODS: A total of 88 adult and 65 paediatric patients with a first attack of demyelination were included and followed (mean follow up-time in adults: 62...
May 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Paul L Wood, Erdal Erol, Glen F Hoffsis, Margaret Steinman, Jeroen DeBuck
Objectives: Bovine paratuberculosis is a devastating infection with Mycobacterium avium subspecies paratuberculosis that ultimately results in death from malnutrition. While the infection is characterized by a long (2-4 years) subclinical phase with immune activation, ultimately host defense mechanisms fail and the bacteria spread from the small intestine to other organs. Since both the gastrointestinal tract and liver are essential for the biosynthesis of structural glycerophospholipids, we investigated the circulating levels of these lipids in field infections and experimentally infected cattle...
2018: SAGE Open Medicine
Emma Rathbone, Lindsay Durant, James Kinsella, Antony R Parker, Ghaniah Hassan-Smith, Michael R Douglas, S John Curnow
OBJECTIVE: To determine whether the ratio of cerebrospinal fluid (CSF) immunoglobulin kappa to lambda light chains at time of multiple sclerosis (MS) diagnosis predicts disease progression and whether this was intrinsic to CSF plasmablasts. METHODS: CSF and peripheral blood were obtained from patients undergoing elective diagnostic lumbar puncture and included clinically isolated syndrome (CIS) (n=43), relapsing remitting MS (RRMS; n=50), primary progressive MS (PPMS; n=20) and other neurological disease controls, both inflammatory (ONID; n=23) and non-inflammatory (OND; n=114)...
May 9, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
Maria Donata Benedetti, Antonio Marangi, Silvia Bozzetti, Francesca Gobbin, Marco Turatti, Maurizio Pea, Alberto Gajofatto, Stelio Mocella
Fingolimod is a commonly used treatment for highly active relapsing-remitting multiple sclerosis (MS). We describe the case of a 50-year old man on fingolimod since 2011 who presented, in April 2017, with a voluminous swelling of the left tonsil. A left tonsillectomy was performed, and histological exam disclosed a papillary squamous cell carcinoma of the palatine tonsil, with an in situ hybridization positive for human papillomavirus (HPV)-16 DNA. Neither lymph nodes involvement nor other metastases were detected...
May 2, 2018: Multiple Sclerosis and related Disorders
Vassilis Bourganis, Olga Kammona, Aleck Alexopoulos, Costas Kiparissides
Central nervous system (CNS) disorders (e.g., multiple sclerosis, Alzheimer's disease, etc.) represent a growing public health issue, primarily due to the increased life expectancy and the aging population. The treatment of such disorders is notably elaborate and requires the delivery of therapeutics to the brain in appropriate amounts to elicit a pharmacological response. However, despite the major advances both in neuroscience and drug delivery research, the administration of drugs to the CNS still remains elusive...
July 2018: European Journal of Pharmaceutics and Biopharmaceutics
Alyria Teixeira Dias, Sandra Bertelli Ribeiro de Castro, Caio César de Souza Alves, Marcilene Gomes Evangelista, Luan Cristian da Silva, Daniele Ribeiro de Lima Reis, Marco Antonio Machado, Maria Aparecida Juliano, Ana Paula Ferreira
OBJECTIVE AND DESIGN: The present work investigates the modulation of experimental autoimmune encephalomyelitis (EAE) using genistein before the EAE induction. MATERIAL: Female C57BL/6 mice (n = 96 mice/experiment), 4-6 weeks old, were used to induce the EAE. The mice were divided into three experimental groups: non-immunized group, immunized group (EAE), and immunized and treated with genistein group (Genistein). TREATMENT: Genistein was used at a dose of 200 mg/kg s...
April 23, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
M Süße, M Hannich, A Petersmann, S Zylla, M Pietzner, M Nauck, A Dressel
BACKGROUND AND PURPOSE: The gold standard for detection of intrathecal immunoglobulin synthesis is the measurement of oligoclonal bands (OCB). In the diagnosis of multiple sclerosis, the kappa free light chains (KFLC) index has a similar sensitivity and specificity as OCB. This study investigated whether determination of the KFLC index could be used to predict the presence of OCB. METHODS: The KFLC index was determined prospectively from 295 paired serum and cerebrospinal fluid samples...
April 23, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Richa Tripathi, Evanthia Bernitsas
Background: Autonomic dysfunction is common in Multiple Sclerosis (MS) patients. Most spinal cord lesions entail some degree of autonomic nervous system dysfunction. MS patients may develop autonomic dysfunction later in their disease course. Methods: We report a patient with no prior history of MS presenting with orthostatic symptoms and diagnosed initially with postural orthostatic tachycardia syndrome (POTS). Four months later, she was diagnosed with radiologically isolated syndrome (RIS)...
2018: Case Reports in Neurological Medicine
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