Ventricular cerebrospinal fluid neurofilament protein levels decrease in parallel with white matter pathology after shunt surgery in normal pressure hydrocephalus

Eur J Neurol. 2007 Mar;14(3):248-54. doi: 10.1111/j.1468-1331.2006.01553.x.


Normal pressure hydrocephalus (NPH) is characterized by disturbed cerebrospinal fluid (CSF) dynamics and white matter lesions (WML). Although the morphology of these lesions is described, little is known about the biochemistry. Our aim was to explore the relationship between ventricular CSF markers, periventricular WML and postoperative clinical outcome in patients with NPH. We analysed lumbar and ventricular concentrations of 10 CSF markers, 12 clinical symptoms and signs, magnetic resonance imaging (MRI) periventricular white matter hyperintensities (PVH) and ventricular size before and 3 months after shunt surgery in 35 patients with NPH. Higher ventricular CSF neurofilament protein (NFL), an axonal marker, correlated with more extensive PVH. A larger postoperative reduction in NFL correlated with larger reduction in PVH and a more pronounced overall improvement. Albumin ratio, HMPG, NPY, VIP and GD3 increased postoperatively whereas NFL, tau and HVA decreased. Variations in ventricular size were not associated with CSF concentrations of any marker. We conclude that NPH is characterized by an ongoing periventricular neuronal dysfunction seen on MRI as PVH. Clinical improvement after shunt surgery is associated with CSF changes indicating a restitution of axonal function. Other biochemical effects of shunting may include increased monoaminergic and peptidergic neurotransmission, breakdown of blood brain barrier function, and gliosis.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Axons / metabolism
  • Axons / pathology
  • Biomarkers / analysis
  • Biomarkers / cerebrospinal fluid
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Cerebrospinal Fluid Pressure / physiology
  • Cerebrospinal Fluid Proteins / analysis
  • Cerebrospinal Fluid Proteins / metabolism
  • Cerebrospinal Fluid Shunts
  • Down-Regulation / physiology
  • Female
  • Humans
  • Hydrocephalus, Normal Pressure / cerebrospinal fluid*
  • Hydrocephalus, Normal Pressure / physiopathology*
  • Hydrocephalus, Normal Pressure / surgery
  • Lateral Ventricles / pathology
  • Lateral Ventricles / physiopathology
  • Lateral Ventricles / surgery
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Fibers, Myelinated / metabolism*
  • Nerve Fibers, Myelinated / pathology
  • Neurofilament Proteins / cerebrospinal fluid*
  • Predictive Value of Tests
  • Treatment Outcome
  • Wallerian Degeneration / cerebrospinal fluid*
  • Wallerian Degeneration / diagnosis*
  • Wallerian Degeneration / physiopathology


  • Biomarkers
  • Cerebrospinal Fluid Proteins
  • Neurofilament Proteins