Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis

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. Standardized 3 T magnetic resonance imaging (MRI) was performed at baseline and 1–3 consecutive follow-ups (42 patients; range: 6–37 months). Results Baseline sNfL correlated significantly with T2 lesion volume (r = 0.555, p < 0.0001). There was no correlation between baseline sNfL and age, Expanded Disability Status Scale (EDSS) score or other calculated MRI measures. However, T2 lesion volume increased (r = 0.67, p < 0.0001) and brain parenchymal volume decreased more rapidly in patients with higher baseline sNfL (r = −0.623, p = 0.0004). Gd-enhancing lesions correlated positively with sNfL levels. Initiation of disease-modifying treatment led to a significant decrease in sNfL levels. Conclusion sNfL indicates acute inflammation as demonstrated by correlation with Gd+ lesions. It is a promising biomarker for neuro-axonal damage in early multiple sclerosis (MS) patients, since higher baseline sNfL levels predicted future brain atrophy within 2 years

Preservation of neuronal function as measured by clinical and MRI endpoints in relapsing-remitting multiple sclerosis: how effective are current treatment strategies?

<p><b>Introduction</b>: Approved medications for relapsing-remitting multiple sclerosis have shown to be effective in terms of their anti-inflammatory potential. However, it is also crucial to evaluate what long-term effects a patient can expect from current MS drugs in terms of preventing neurodegeneration. Here we aim to provide an overview of the current treatment strategies in MS with a specific focus on potential neuroprotective effects.</p> <p><b>Areas covered</b>: Randomized, double-blind and placebo or referral-drug controlled phase 2a/b and phase 3 trials were examined; non-blinded phase 4 studies (extension studies) were included to provide long-term data, if not otherwise available. Endpoints considered were expanded disability status scale, various neuropsychological tests, percent brain volume change and T1-hypointense lesions as well as multiple sclerosis functional composite, confirmed disease progression, and no evidence of disease activity.</p> <p><b>Expert commentary</b>: Overall, neuroprotective functions of classical MS therapeutics are not sufficiently investigated, but available data show limited effects. Thus, further research and development in neuroprotection are warranted. When counselling patients, potential long-term beneficial effects should be presented more conservatively.</p

MSJ765666_supplementary_figure_1 – Supplemental material for Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis

<p>Supplemental material, MSJ765666_supplementary_figure_1 for Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis by Nelly Siller, Jens Kuhle, Muthuraman Muthuraman, Christian Barro, Timo Uphaus, Sergiu Groppa, Ludwig Kappos, Frauke Zipp and Stefan Bittner in Multiple Sclerosis Journal</p

Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis.

BACKGROUND The course of multiple sclerosis (MS) shows substantial inter-individual variability. The underlying determinants of disease severity likely involve genetic and environmental factors. OBJECTIVE The aim of this study was to assess the impact of APOE and HLA polymorphisms as well as smoking and body mass index (BMI) in the very early MS course. METHODS Untreated patients ( n = 263) with a recent diagnosis of relapsing-remitting (RR) MS or clinically isolated syndrome underwent standardized magnetic resonance imaging (MRI). Genotyping was performed for single-nucleotide polymorphisms (SNPs) rs3135388 tagging the HLA-DRB1*15:01 haplotype and rs7412 (Ɛ2) and rs429358 (Ɛ4) in APOE. Linear regression analyses were applied based on the three SNPs, smoking and BMI as exposures and MRI surrogate markers for disease severity as outcomes. RESULTS Current smoking was associated with reduced gray matter fraction, lower brain parenchymal fraction and increased cerebrospinal fluid fraction in comparison to non-smoking, whereas no effect was observed on white matter fraction. BMI and the SNPs in HLA and APOE were not associated with structural MRI parameters. CONCLUSIONS Smoking may have an unfavorable effect on the gray matter fraction as a potential measure of MS severity already in early MS. These findings may impact patients' counseling upon initial diagnosis of MS

Congreso Internacional de Bioeconomía Circular - Fase III 3/3

Moderador: Dr. José de Jesús Brambila (COLPOS) Dr. Salvador Peniche Camps, Lic. Diana Stefania García Valadez, U. de G. Mtra. Carmen Girón Domínguez, Fundación CTA, España Dr. Jorge H. Siller Cepeda, Simplicidad y Enfoque Sostenible Dra. Magdalena Rojas Rojas, UACH Dra. Karina Valencia Sandoval, UAEH Dra. Alejandra Corichi García, UAEH Mtra. Ana Karen Miranda, UACH Dr. Enrique Mendoza Tello, Síntesis AC Mtra Ina Daniela Maza Villalobos Dr. Salvador Arturo Velázquez Crôtte, U. de G.-CUCEA México Moderador: Dr. Mario del Roble Pensado Leglise, IPN CIIEMAD Dra. Miriam Edith García Salazar, Cátedras CONACYT Dr. Sergio Gabriel Ceballos Pérez, COLPOS Psnt. Edgar Corona Zamora, UNAM Psnt. Cristal Antúnez, UNAM Dra. María del Rosario Reyes, ECOSUR Dr. Carlos R. Menéndez G. IICA México M.C. Verónica Estela Ruiz, UACH Ciencias Agrarias Mtra. Nelly López Azuz, IIA - UNAM / México M.C. Carlos Mallén Rivera, INIFAP/México Dr. Pedro Gutiérrez Yurrita, Profepa/MéxicoTemas a tratar: Los senderos de la bioeconomía, logros y retos científicos, institucionales y de gobernanza

MSJ763541_supplementary_material – Supplemental material for Association of smoking but not HLA-DRB1*15:01, <i>APOE</i> or body mass index with brain atrophy in early multiple sclerosis

<p>Supplemental material, MSJ763541_supplementary_material for Association of smoking but not HLA-DRB1*15:01, <i>APOE</i> or body mass index with brain atrophy in early multiple sclerosis by Christiane Graetz, Adriane Gröge, Felix Luessi, Anke Salmen, Daniela Zöller, Janine Schultz, Nelly Siller, Vinzenz Fleischer, Barbara Bellenberg, Achim Berthele, Viola Biberacher, Joachim Havla, Michael Hecker, Reinhard Hohlfeld, Carmen Infante-Duarte, Jan S Kirschke, Tania Kümpfel, Ralf Linker, Friedemann Paul, Steffen Pfeuffer, Philipp Sämann, Gerrit Toenges, Frank Weber, Uwe K Zettl, Antje Jahn-Eimermacher, Gisela Antony, Sergiu Groppa, Heinz Wiendl, Bernhard Hemmer, Mark Mühlau, Carsten Lukas, Ralf Gold, Christina M Lill and Frauke Zipp in Multiple Sclerosis Journal</p