Idiopathic normal pressure hydrocephalus may be a "two hit" disease: benign external hydrocephalus in infancy followed by deep white matter ischemia in late adulthood

J Magn Reson Imaging. 2006 Oct;24(4):747-55. doi: 10.1002/jmri.20684.


Purpose: To determine if normal pressure hydrocephalus (NPH) could result from decreased resorption of cerebrospinal fluid (CSF) by the arachnoidal villi, leading to benign external hydrocephalus [BEH] in infancy, followed by deep white matter ischemia (DWMI) in late adulthood (the more hydrophilic environment increasing resistance to CSF flow through the extracellular space (ECS) of the brain).

Materials and methods: CSF outflow via the fourth ventricle and the ECS of the brain was mathematically modeled using a parallel electrical circuit analog. The apparent diffusion coefficient (ADC) was measured as a surrogate of the amount of water in the ECS in normals, patients with symptomatic NPH, and patients with dilated ventricles without symptoms of NPH ("pre-NPH").

Results: The electrical circuit model demonstrates increasing ventricular volume with increasing resistance to flow through the ECS of the brain. ADC measurements performed in the centrum semiovale are significantly higher in patients with NPH and "pre-NPH" than in age-matched controls (P<0.05), controlling for the same degree of DWMI indicating increased fluid in the ECS of the brain.

Conclusion: The electrical circuit analog and finding of increased periventricular ADC support the theory that NPH is a "two hit" disease.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / pathology
  • Brain Ischemia / etiology*
  • Brain Ischemia / pathology
  • Brain Mapping / methods
  • Cerebral Ventricles / pathology
  • Cerebrospinal Fluid / physiology
  • Female
  • Humans
  • Hydrocephalus, Normal Pressure / cerebrospinal fluid*
  • Hydrocephalus, Normal Pressure / complications*
  • Hydrocephalus, Normal Pressure / pathology
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Models, Theoretical
  • Risk Factors