title: Effects of repeated intrathecal triamcinolone-acetonide application on cerebrospinal fluid biomarkers of axonal damage and glial activity in multiple sclerosis patients.
abstract: OBJECTIVE
  Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults. Over time, the disease progresses and, with accumulating disability, symptoms such as spasticity may occur. Although several treatment options are available, some patients may not respond to first-line therapeutics. However, some of these patients may benefit from intrathecally administered triamcinolone-acetonide (TCA), a derivative of glucocorticosteroids (GCS). GCS may have neurotoxic effects, and cell apoptosis may occur. The aim of this study was to investigate the effects of TCA on biomarkers in the cerebrospinal fluid (CSF) suggestive of neurodegeneration.
  
  
  METHODS
  In order to assess neurotoxic effects of TCA, neurofilament heavy-chain (NfH)(SMI35), tau protein, and S-100B protein levels were determined before and during treatment with TCA in 54 patients with primary progressive MS, as well as relapsing MS (relapsing-remitting and secondary progressive MS).
  
  
  RESULTS
  NfH(SMI35) levels in the CSF of patients treated with TCA intrathecally did not increase significantly during the treatment cycle (p = 0.068). After application of TCA, tau protein levels were increased significantly at day 4 (p = 0.03) and at day 8 (p ≤ 0.001). S-100B protein levels decreased significantly (p ≤ 0.05) during treatment with TCA.
  
  
  CONCLUSIONS
  NfH(SMI35) levels did not change significantly; however, tau protein levels did increase significantly within the reference range. Taking these findings together, the long-term effects of TCA on NfH(SMI35) and tau protein levels need to be investigated further to understand whether levels of both biomarkers will change over repeated TCA applications. Interestingly, S-100B protein levels decreased significantly during the first applications, which may have represented reduced astrocytic activity during TCA treatment.
authors.affiliation: Department of Neurology, Neuroimmunological Section, University of Rostock, Rostock, Germany, paulus.rommer@meduniwien.ac.at.
authors.forename: P S
authors.initials: PS
authors.lastname: Rommer
authors.forename: F
authors.initials: F
authors.lastname: Kamin
authors.forename: A
authors.initials: A
authors.lastname: Petzold
authors.forename: H
authors.initials: H
authors.lastname: Tumani
authors.forename: M
authors.initials: M
authors.lastname: Abu-Mugheisib
authors.forename: W
authors.initials: W
authors.lastname: Koehler
authors.forename: F
authors.initials: F
authors.lastname: Hoffmann
authors.forename: A
authors.initials: A
authors.lastname: Winkelmann
authors.forename: R
authors.initials: R
authors.lastname: Benecke
authors.forename: U K
authors.initials: UK
authors.lastname: Zettl
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000473:pathology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D064568:S100 Calcium Binding Protein beta Subunit / Q000134:cerebrospinal fluid*; D014222:Triamcinolone Acetonide / Q000008:administration & dosage*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C054369:MAPT protein, human; D016900:Neurofilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D016875:tau Proteins; C051774:neurofilament protein H; D014222:Triamcinolone Acetonide