S Rossi1, C Motta1, V Studer2, G Macchiarulo2, G Germani2, A Finardi3, R Furlan3, G Martino3, D Centonze4. 1. Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy/IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy. 2. Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy/Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC),Rome, Italy. 3. Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. 4. Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy/Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC),Rome, Italy centonze@uniroma2.it.
Abstract
BACKGROUND: Subtle diffuse intrathecal inflammation is undetectable by conventional neuroimaging, and could influence multiple sclerosis (MS) disease course. OBJECTIVE: To explore the role of subclinical persisting intrathecal inflammation in radiologically isolated syndrome (RIS) or clinically isolated syndrome (CIS) conversion to MS, and in early MS disease reactivation. METHODS: One-hundred ninety-three subjects with RIS, CIS, relapsing-remitting (RR), or primary progressive (PP) MS were included, along with 76 matched controls. Cerebrospinal fluid (CSF) levels of interleukin-8 (IL-8), a major proinflammatory cytokine, were measured as a biomarker of intrathecal inflammation. Patients were followed up for 2 years. Clinical and imaging measures of disease progression were recorded. RESULTS: High central contents of IL-8 were associated to clinical progression in subjects with RIS, and to the risk of conversion to MS in subjects with CIS. Asymptomatic intrathecal inflammation placed subjects at risk for MS conversion, even regardless lesion load. CSF IL-8 levels were higher in RR MS with high disease activity. Higher number of relapses in the first two years since diagnosis and shorter first inter-attack intervals were observed in patients with high levels of IL-8. CONCLUSION: IL-8 might provide utility in determining the presence of active intrathecal inflammation, and could be important in diagnostically undefined cases.
BACKGROUND: Subtle diffuse intrathecal inflammation is undetectable by conventional neuroimaging, and could influence multiple sclerosis (MS) disease course. OBJECTIVE: To explore the role of subclinical persisting intrathecal inflammation in radiologically isolated syndrome (RIS) or clinically isolated syndrome (CIS) conversion to MS, and in early MS disease reactivation. METHODS: One-hundred ninety-three subjects with RIS, CIS, relapsing-remitting (RR), or primary progressive (PP) MS were included, along with 76 matched controls. Cerebrospinal fluid (CSF) levels of interleukin-8 (IL-8), a major proinflammatory cytokine, were measured as a biomarker of intrathecal inflammation. Patients were followed up for 2 years. Clinical and imaging measures of disease progression were recorded. RESULTS: High central contents of IL-8 were associated to clinical progression in subjects with RIS, and to the risk of conversion to MS in subjects with CIS. Asymptomatic intrathecal inflammation placed subjects at risk for MS conversion, even regardless lesion load. CSF IL-8 levels were higher in RR MS with high disease activity. Higher number of relapses in the first two years since diagnosis and shorter first inter-attack intervals were observed in patients with high levels of IL-8. CONCLUSION:IL-8 might provide utility in determining the presence of active intrathecal inflammation, and could be important in diagnostically undefined cases.
Authors: Andres G Barboza; Edgar Carnero Contentti; Maria Celeste Curbelo; Mario Javier Halfon; Juan Ignacio Rojas; Berenice A Silva; Vladimiro Sinay; Santiago Tizio; Maria Celica Ysrraelit; Ricardo Alonso Journal: Neurol Sci Date: 2021-01-25 Impact factor: 3.307
Authors: Mario Stampanoni Bassi; Sara Garofalo; Girolama A Marfia; Luana Gilio; Ilaria Simonelli; Annamaria Finardi; Roberto Furlan; Giulia M Sancesario; Jonny Di Giandomenico; Marianna Storto; Francesco Mori; Diego Centonze; Ennio Iezzi Journal: Front Mol Neurosci Date: 2017-11-21 Impact factor: 5.639
Authors: Hagen H Kitzler; Hannes Wahl; Judith C Eisele; Matthias Kuhn; Henning Schmitz-Peiffer; Simone Kern; Brian K Rutt; Sean C L Deoni; Tjalf Ziemssen; Jennifer Linn Journal: Neuroimage Clin Date: 2018-05-31 Impact factor: 4.881