title: Hexosylceramides as intrathecal markers of worsening disability in multiple sclerosis.
abstract: BACKGROUND
  Sphingolipids are important components of neurons and the myelin sheath whose levels are altered in multiple sclerosis (MS).
  
  
  OBJECTIVE
  We aimed to determine if cerebrospinal fluid (CSF) sphingolipids can be used as markers of MS disease progression.
  
  
  METHODS
  Using liquid chromatography tandem mass spectrometry, we analysed sphingolipids in CSF from 134 individuals. The MS group included 65 patients divided into 41 relapsing-remitting MS (RRMS) and 24 progressive MS (ProgMS). In addition, a group of 13 early MS/clinically isolated syndrome (EarlyMS) and two control groups consisting of 38 individuals with other neurological diseases (OND) and 18 OND with signs of inflammation (iOND) were analysed. A follow-up study included 17 additional RRMS patients sampled at two time points 4.7±1.7 years apart.
  
  
  RESULTS
  Levels of sphingomyelin (SM)- and hexosylceramide (HexCer)-derived sphingolipids increased in the CSF of patients with MS independently of the fatty acid chain length in RRMS (p<0.05). Levels of palmitic acid (16:0)-containing HexCer (HexCer16:0) increased significantly in ProgMS compared with the OND (p<0.001), iOND (p<0.05) and EarlyMS (p<0.01) groups and correlated with Expanded Disability Status Scale in RRMS in both studies (p=0.048; p=0.027).
  
  
  CONCLUSIONS
  HexCer16:0 is a promising candidate marker of disease progression in MS, especially in RRMS.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Antonio
authors.initials: A
authors.lastname: Checa
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Sar
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jesper Z
authors.initials: JZ
authors.lastname: Haeggström
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden craig.wheelock@ki.se.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Wheelock
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002518:Ceramides / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D008297:Male; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D002518:Ceramides
keywords: Multiple sclerosis; axonal damage; cerebrospinal fluid; demyelination; inflammation; mass spectrometry