William Guerin Bradley MD, Presenter: Nothing to Disclose

Francis Safar MD, Abstract Co-Author: Nothing to Disclose

Gautam Bahl BS, Abstract Co-Author: Nothing to Disclose

Idiopathic NPH has been previously shown to be associated with deep white matter ischemia (DWMI). This study examines the hypothesis that NPH is actually a “two hit” disease which begins in infancy as Benign External Hydrocephalus (BEH). Since this occurs before the sutures have fused, the intracranial volumes of NPH patients should be larger than normal.

The intracranial volumes of 51 elderly patients with clinically suspected NPH were compared to age and sex-matched controls. All patients had quantitative phase contrast CSF velocity MR imaging studies with aqueductal CSF stroke volumes of at least 60 microliters which is 50% higher than normal. The mild ventricular enlargement in BEH indicates increased resistance to CSF outflow through the usual ventricular pathways and increased flow of CSF via the extracellular space of the brain into the subarachnoid space. A simple mathematical model was constructed to determine if increased resistance to CSF flow through the extracellular space would lead to additional ventricular enlargement.

The average intracranial volume for NPH men was 1682 ml (n=22), compared to 1565 for male controls (n=55). The NPH volume in men averaged 118 cc (7.5%) larger than the control volume which was statistically significant (p=.003). The average intracranial volume for NPH women (n=29) was 1493 ml, compared to 1405 for female controls (n=55). The NPH volumes in women averaged 88 ml (6.3%) larger than the control volume and this was again statistically significant (p=.002). These larger volumes are consistent with an initial “hit” of BEH. Since DWMI (the second “hit") demonstrates myelin pallor histologically, the increasingly hydrophilic environment increases the resistance to the peripheral migration of CSF through the extracellular space of the brain. The mathematical model confirms that increased resistance to this CSF flow leads to increased ventricular enlargement.

NPH is a “two hit” process as demonstrated by larger intracranial volumes and a model showing continuing ventricular enlargement due to the effect of DMWI on the flow of CSF through the extracellular space.

W.G.B.: William G. Bradley, MD, PhD, receives research support from GE and Siemens and owns stock in Vital Images.

Bradley, W, Safar, F, Bahl, G, Idiopathic Normal Pressure Hydrocephalus Is a “Two Hit” Disease: Benign External Hydrocephalus in Infancy Followed by Deep White Matter Ischemia in Late Adulthood.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4416155.html