Article Abstract

New concepts in the pathogenesis of hydrocephalus

Authors: Satish Krishnamurthy, Jie Li

Abstract

Hydrocephalus is a central nervous system disorder characterized by excessive accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain. Cognitive and physical handicap can occur as a result of hydrocephalus. The disorder can present at any age as a result of a wide variety of different diseases. The pathophysiology of hydrocephalus is unclear. While circulation theory is widely accepted as a hypothesis for the development of hydrocephalus, there is a lack of adequate proof in clinical situations and in experimental settings. However, there is growing evidence that osmotic gradients are responsible for the water content of the ventricles of the brain, similar to their presence in other water permeable organs in the body. Therefore, brain disorders that results in excess macromolecules in the ventricular CSF will change the osmotic gradient and result in hydrocephalus. This review encompasses several key findings that have been noted to be important in the genesis of hydrocephalus, including but not limited to the drainage of CSF through the olfactory pathways and cervical lymphatics, the paravascular pathways and the role of venous system. We propose that as osmotic gradients play an important role in the water transport into the ventricles, the transport of osmotically active macromolecules play a critical role in the genesis of hydrocephalus. Therefore, we can view hydrocephalus as a disorder of macromolecular clearance, rather than circulation. Current evidence points to a paravascular and/or lymphatic clearance of these macromolecules out of the ventricles and the brain into the venous system. There is substantial evidence to support this theory, and further studies may help solidify the merit of this hypothesis.