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

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 Ͻ 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.

Intracranial Pressure versus Phase-Contrast MR Imaging for Normal Pressure Hydrocephalus

“…In regard to using patients without enlarged ventricles to determine the normal ASV, patients who eventually develop NPH often have had enlarged ventricles for many years before symptom onset. 6 We call this "pre-NPH," 6 while Kato et al 7 labeled it "asymptomatic ventricular enlargement with features of idiopathic NPH on MR imaging. "…”

The importance of the cortical subarachnoid space in understanding hydrocephalus

“…Essentially, the causes of idiopathic NPH would be the same as for secondary NPH except that they are unrecognized and probably begin early in life. 3 Head circumference in many of these patients is greater than the 98th percentile, and their outcome is particularly good. Idiopathic NPH is not a single-disease process; nonetheless, it can be studied.…”

“…Assuming that the internal circumference of the skull is 50 cm and that the thickness of the skull is 1 cm, the radius of the intracranial compartment would be 7 cm and the internal volume would be 1372 cm 3 . If the mean thickness of the CSAS is 3 mm, the volume of the brain and ventricles would be 1204 cm 3 . The volume remaining for the CSAS is 168 cm 3 .…”

“…If the mean thickness of the CSAS is 3 mm, the volume of the brain and ventricles would be 1204 cm 3 . The volume remaining for the CSAS is 168 cm 3 . If the normal volume of the sphere representing the ventricles is 30 cm 3 , the radius of the sphere would be 1.9 cm.…”

“…If the normal volume of the sphere representing the ventricles is 30 cm 3 , the radius of the sphere would be 1.9 cm. If sufficient volume is lost from the CSAS to decrease the thickness of the space from 3 to 1 mm while the volume of the brain is unchanged, the volume of the ventricle would be 134 cm 3 and the radius would be 3.2 cm (Fig. 2).…”