Normal pressure hydrocephalus: an analysis of aetiology and response to shunting based on mathematical modeling

The dynamics which maintain the state of enlarged cerebral ventricles and normal intracranial pressures (normal pressure hydrocephalus) are not completely understood, making the response to cerebrospinal fluid diversion difficult to predict. Using our previously described mathematical model of intracranial physiology which allows nonlinear relationships of pressure, volume, and flow in 7 distinct compartments, we desired to determine factors which could be responsible for the development and maintenance of the steady state of normal pressure hydrocephalus. Using typical starting values for CSF volume, pressure, and flow, the model indicates that this condition cannot be sustained, in spite of high CSF outflow resistance, unless capillary flow resistance is elevated. This condition can be the result of arterial hypertension. The additional modeling of a CSF diversion device demonstrates predicted time courses for ventricular size reduction which are consistent with clinical observations. We conclude that certain vascular conditions may allow for the maintenance of an enlarged ventricular size, and that mathematical modeling can assist in identifying factors for clinical study that may maintain normal pressure hydrocephalus even after treatment by CSF diversion.