Normal pressure hydrocephalus as a failure of ICP homeostasis mechanism: the hidden role of Monro-Kellie doctrine in the genesis of NPH.

OBJECTIVE: The theme of this paper is to outline that the genesis of normal pressure hydrocephalus (NPH) is governed by the intracranial pressure (ICP) homeostatic principle. The development of this new concept is based mainly on rethinking the well-known Monro-Kellie doctrine in the way that ICP homeostasis mechanism is not only a mechanism that works to prevent pathologically high ICP but also a mechanism that aims to protect from pathologically low ICP.

METHODS: The NPH-related literatures are reviewed and reinterpreted to generate a new paradigm for the cascade of pathophysiological events that leads to the genesis NPH, as well as the mechanism of clinical beneficial effects and complications of the shunting procedure.

RESULTS: According to this new paradigm, the suboptimal cerebral perfusion that is associated with the impairment of the cerebral autoregulation is the initial step in the genesis of NPH. When the overall volume of blood that circulates intracranially is diminished, a chronic low ICP with episodes of pathologically low ICP occurs. Since the cranial vault is not collapsible, those episodes of low ICP are compensated by the accumulation of cerebrospinal fluid (CSF) to keep the ICP in normal ideal range. The impairment of brain toxin-flushing mechanism because of CSF pooling combined with the already-established suboptimal cerebral perfusion leads to functional disinhibition of the cerebral cortex.

CONCLUSION: Recognizing the importance of ICP homeostatic mechanisms in the genesis of the NPH is a simple yet novel view that could change the way we look at NP and can give a basic and fundamental theoretical frame work to achieve better understanding of NPH.