title: Subclinical central inflammation is risk for RIS and CIS conversion to MS.
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.
  
  
  CONCLUSIONS
  IL-8 might provide utility in determining the presence of active intrathecal inflammation, and could be important in diagnostically undefined cases.
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy/IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy/IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Motta
authors.affiliation: 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.
authors.forename: V
authors.initials: V
authors.lastname: Studer
authors.affiliation: 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.
authors.forename: G
authors.initials: G
authors.lastname: Macchiarulo
authors.affiliation: 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.
authors.forename: G
authors.initials: G
authors.lastname: Germani
authors.affiliation: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Finardi
authors.affiliation: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Furlan
authors.affiliation: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Martino
authors.affiliation: 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.
authors.forename: D
authors.initials: D
authors.lastname: Centonze
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid*; D016209:Interleukin-8 / Q000134:cerebrospinal fluid*; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; D016209:Interleukin-8
keywords: Clinically isolated syndrome; IL-8; intrathecal inflammation; progression; radiologically isolated syndrome; relapse