title: Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS.
abstract: OBJECTIVE
  In an ongoing, open-label, phase 1b study on the intrathecal administration of rituximab for progressive multiple sclerosis, an intraventricular catheter was inserted for drug delivery. The objective of this study was to characterize the limited white matter axonal injury evoked by catheter insertion by analyzing a panel of markers for tissue damage in CSF and serum.
  
  
  METHODS
  Lumbar CSF and serum were collected before catheter insertion and at regular intervals during the follow-up period of 1 year. Levels of neurofilament light polypeptide (NF-L), glial fibrillary acidic protein, microtubule-associated protein tau, and S100 calcium binding protein B were measured in the CSF, and NF-L was also quantified in serum at each time point.
  
  
  RESULTS
  One month after neurosurgical trauma, there was a distinct peak in NF-L concentration in both CSF and serum. In contrast, the biomarkers S100 calcium binding protein B, glial fibrillary acidic protein, and microtubule-associated protein tau did not show any significant changes. NF-L levels in both CSF and serum peaked at 1 month post surgery, returning to baseline after 6 to 9 months. A strong correlation was observed between the concentrations of NF-L in CSF and serum.
  
  
  CONCLUSIONS
  The NF-L level, in CSF and serum, appears to be both a sensitive and specific marker for white matter axonal injury. This makes NF-L a valuable tool with which to evaluate acute white matter axonal damage in a clinical setting. Serum analysis of NF-L may become a convenient way to follow white matter axonal damage longitudinally.
  
  
  BACKGROUND
  NCT01719159.
authors.affiliation: Department of Pharmacology and Clinical Neuroscience (J.B., A.D., J.G., T.B., A.S.), Umeå University; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; UmanDiagnostics AB (N.N.), Umeå; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Danderyd Hospital AB, Stockholm, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Bergman
authors.affiliation: Department of Pharmacology and Clinical Neuroscience (J.B., A.D., J.G., T.B., A.S.), Umeå University; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; UmanDiagnostics AB (N.N.), Umeå; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Danderyd Hospital AB, Stockholm, Sweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Dring
authors.affiliation: Department of Pharmacology and Clinical Neuroscience (J.B., A.D., J.G., T.B., A.S.), Umeå University; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; UmanDiagnostics AB (N.N.), Umeå; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Danderyd Hospital AB, Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Pharmacology and Clinical Neuroscience (J.B., A.D., J.G., T.B., A.S.), Umeå University; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; UmanDiagnostics AB (N.N.), Umeå; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Danderyd Hospital AB, Stockholm, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Pharmacology and Clinical Neuroscience (J.B., A.D., J.G., T.B., A.S.), Umeå University; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; UmanDiagnostics AB (N.N.), Umeå; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Danderyd Hospital AB, Stockholm, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Norgren
authors.affiliation: Department of Pharmacology and Clinical Neuroscience (J.B., A.D., J.G., T.B., A.S.), Umeå University; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; UmanDiagnostics AB (N.N.), Umeå; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Danderyd Hospital AB, Stockholm, Sweden.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gilthorpe
authors.affiliation: Department of Pharmacology and Clinical Neuroscience (J.B., A.D., J.G., T.B., A.S.), Umeå University; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; UmanDiagnostics AB (N.N.), Umeå; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Danderyd Hospital AB, Stockholm, Sweden.
authors.forename: Tommy
authors.initials: T
authors.lastname: Bergenheim
authors.affiliation: Department of Pharmacology and Clinical Neuroscience (J.B., A.D., J.G., T.B., A.S.), Umeå University; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; UmanDiagnostics AB (N.N.), Umeå; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Danderyd Hospital AB, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Svenningsson