title: Idiopathic normal pressure hydrocephalus may be a "two hit" disease: benign external hydrocephalus in infancy followed by deep white matter ischemia in late adulthood.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  The electrical circuit analog and finding of increased periventricular ADC support the theory that NPH is a "two hit" disease.
authors.affiliation: Department of Radiology, University of California, San Diego, San Diego, California 92103-8224, USA. wgbradley@ucsd.edu
authors.forename: William G
authors.initials: WG
authors.lastname: Bradley
authors.forename: Gautam
authors.initials: G
authors.lastname: Bahl
authors.forename: John F
authors.initials: JF
authors.lastname: Alksne
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology* / Q000473:pathology; D001931:Brain Mapping / Q000379:methods; D002552:Cerebral Ventricles / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000502:physiology; D005260:Female; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D012307:Risk Factors