title: Elevated CSF neurofilament proteins predict brain atrophy: A 15-year follow-up study.
abstract: Body fluid and structural imaging biomarkers give information on neurodegeneration. The relationship over time is not known in multiple sclerosis.
  
  
  
  To investigate the temporal relationship of elevated cerebrospinal fluid (CSF) neurofilament (Nf) protein levels, a biomarker for axonal loss, with magnetic resonance imaging (MRI) atrophy measures.
  
  
  
  In patients with multiple sclerosis, CSF Nf heavy chain (NfH) phosphoform levels were quantified at baseline and dichotomised into 'normal' and 'high'. Atrophy was assessed by MRI at baseline and 15-year follow-up using SIENAX and FreeSurfer software.
  
  
  
  High baseline CSF NfH(SMI35) levels predicted pronounced atrophy at 15-year follow-up (odds ratio (OR): 36, p < 0.01), in the absence of baseline brain atrophy (OR: 28, p < 0.05), for the averaged MRI normalised brain volume (1.44 L vs 1.33 L, p < 0.05), normalised grey matter volume (0.77 L vs 0.69 L, p < 0.01) and putamen (12.7 mL vs 10.7 mL, p < 0.05). Region-specific calculations including the spinal cord showed that a power of >80% is reached with 14-50 patients.
  
  
  
  These data suggest that high CSF NfH levels are an early predictor of later brain and spinal cord atrophy using structural imaging biomarkers and can be investigated in reasonably sized patient cohorts.
authors.affiliation: Department of Neurology and Ophthalmology, VUmc MS Center Amsterdam, VU University Medical Center, Neuroscience Campus, Amsterdam, The Netherlands/Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK a.petzold@ucl.ac.uk a.petzold@vumc.nl.
authors.forename: Axel
authors.initials: A
authors.lastname: Petzold
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands/Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Martijn D
authors.initials: MD
authors.lastname: Steenwijk
authors.affiliation: Westfriesgasthuis, Hoorn, The Netherlands.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Eikelenboom
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
authors.affiliation: Department of Neurology, VUmc MS Center Amsterdam, VU University Medical Center, Neuroscience Campus, Amsterdam, The Netherlands.
authors.forename: Bernard Mj
authors.initials: BM
authors.lastname: Uitdehaag
mesh_terms: D000328:Adult; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000473:pathology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D011237:Predictive Value of Tests; D012984:Software; D013116:Spinal Cord / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; C051774:neurofilament protein H
keywords: CSF; Neurodegeneration; biomarker; cerebrospinal fluid; multiple sclerosis; neurofilaments