title: Clinical and biomarker assessment of demyelinating events suggesting multiple sclerosis.
abstract: BACKGROUND
  Initial demyelinating event (IDE) diagnosis and prognosis are not straightforward.
  
  
  OBJECTIVE
  To identify potential diagnostic markers and outcome predictors of IDEs suggestive of multiple sclerosis (MS), that is, clinically isolated syndromes (CISs).
  
  
  METHODS
  Clinically isolated syndrome cases (i.e., subjects with an IDE compatible with MS onset and no alternative explanation) with at least 1.5 years' follow-up were retrospectively identified. All cases underwent clinical, neurophysiological, MRI, and cerebrospinal fluid (CSF) assessment, including exploratory tau, 14-3-3, and cystatin C testing. CIS recovery, conversion to MS, and long-term neurological disability were used as outcome measures. Patients with neuromyelitis optica spectrum disorders, idiopathic acute transverse myelitis (IATM), Creutzfeldt-Jacob disease, and non-inflammatory/non-neurodegenerative disorders served as controls for CSF analysis.
  
  
  RESULTS
  Forty-six CIS cases were included. Severe presentation was associated with incomplete recovery, while presence of at least 3 periventricular lesions on baseline MRI correlated with MS conversion. Initial pyramidal tract involvement, incomplete CIS recovery, and number of relapses predicted neurological disability. CSF tau, 14-3-3, and cystatin C did not correlate with any outcome measure. CIS cases had significantly lower tau and cystatin C levels compared to IATM.
  
  
  CONCLUSIONS
  An extensive diagnostic evaluation of patients with an IDE is worthwhile to make prognostic predictions. More robust molecular biomarkers are needed.
authors.affiliation: Section of Clinical Neurology, Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gajofatto
authors.forename: M
authors.initials: M
authors.lastname: Bongianni
authors.forename: G
authors.initials: G
authors.lastname: Zanusso
authors.forename: M R
authors.initials: MR
authors.lastname: Bianchi
authors.forename: M
authors.initials: M
authors.lastname: Turatti
authors.forename: M D
authors.initials: MD
authors.lastname: Benedetti
authors.forename: S
authors.initials: S
authors.lastname: Monaco
mesh_terms: D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000209:etiology; D004185:Disability Evaluation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications*; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D013223:Statistics as Topic; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D048948:14-3-3 Proteins; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D043025:Oligoclonal Bands; D016875:tau Proteins
keywords: clinical outcome; clinically isolated syndrome; multiple sclerosis