I Håkansson1, A Tisell2,3, P Cassel4, K Blennow5,6, H Zetterberg5,6,7, P Lundberg2,3,8, C Dahle1,4, M Vrethem1, J Ernerudh4. 1. Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. 2. Radiation Physics, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. 3. Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden. 4. Department of Clinical Immunology and Transfusion Medicine and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. 5. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. 6. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 7. Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK. 8. Radiology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Abstract
BACKGROUND AND PURPOSE: Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. METHODS: Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. RESULTS: In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. CONCLUSIONS: This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity.
BACKGROUND AND PURPOSE: Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. METHODS: Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. RESULTS: In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. CONCLUSIONS: This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity.
Authors: Alan Mejia Maza; Rogger P Carmen-Orozco; Emma S Carter; Danitza G Dávila-Villacorta; Gino Castillo; Jemina D Morales; Javier Mamani; Cesar M Gavídia; Joseph Alroy; Charles R Sterling; Armando E Gonzalez; Héctor H García; Randy L Woltjer; Manuela R Verástegui; Robert H Gilman Journal: Brain Pathol Date: 2018-12-11 Impact factor: 6.508
Authors: Claudia Sestito; Cyra E Leurs; Martijn D Steenwijk; John J P Brevé; Jos W R Twisk; Micha M M Wilhelmus; Benjamin Drukarch; Charlotte E Teunissen; Anne-Marie van Dam; Joep Killestein Journal: Neurol Neuroimmunol Neuroinflamm Date: 2021-04-27