title: Increased albumin quotient (QAlb) in patients after first clinical event suggestive of multiple sclerosis is associated with development of brain atrophy and greater disability 48 months later.
abstract: The utility of blood-brain barrier (BBB) biomarkers for clinical and magnetic resonance imaging progression in multiple sclerosis (MS) has not been extensively investigated.
  
  
  
  To determine whether cerebrospinal fluid (CSF) measures of BBB at clinical onset predict radiological and clinical deterioration over 48 months.
  
  
  
  This longitudinal study included 182 patients after first clinical event suggestive of MS treated with weekly intramuscular interferon beta-1a. CSF and serum samples were analyzed for leukocytes, total protein, albumin, immunoglobulins, and oligoclonal bands. Optimal thresholds for the albumin quotient (QAlb) were determined. Mixed-effect model analyses, adjusted for age, gender, and treatment escalation, were used to analyze relationship between CSF measures and disease activity outcomes over 48 months of follow-up.
  
  
  
  Increased QAlb at clinical onset was associated with enlargement of lateral ventricles (p = .001) and greater whole brain (p = .003), white matter (p < .001), corpus callosum (p < .001), and thalamus (p = .003) volume loss over 48 months. Higher QAlb was associated with higher Expanded Disability Status Scale score over 48 months (p = .002).
  
  
  
  Increased QAlb at clinical onset is associated with increased brain atrophy and greater disability in patients after first clinical event suggestive of MS.
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic/Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Uher
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Horakova
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Tyblova
authors.affiliation: Department of Neurology, University Hospital, Ostrava, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Zeman
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Krasulova
authors.affiliation: Department of Clinical Biochemistry, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Mrazova
authors.affiliation: Department of Radiology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Seidl
authors.affiliation: Department of Radiology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic.
authors.forename: Manuela
authors.initials: M
authors.lastname: Vaneckova
authors.affiliation: Department of Radiology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Krasensky
authors.affiliation: Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.affiliation: Department of Neurology, State University of New York, Buffalo, NY, USA/Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA/MR Imaging Clinical Translational Research Center, State University of New York, Buffalo, NY, USA rzivadinov@bnac.net.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
mesh_terms: D000328:Adult; D000418:Albumins / Q000134:cerebrospinal fluid*; D001284:Atrophy / Q000473:pathology; D015415:Biomarkers; D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000503:physiopathology*; D012709:Serum Albumin; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000418:Albumins; D015415:Biomarkers; D012709:Serum Albumin
keywords: MRI; Multiple sclerosis; blood–brain barrier; brain atrophy; clinically isolated syndrome; disability