Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

Abstract

<jats:p>Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.</jats:p>

The choroid plexus as a site of damage in hemorrhagic and ischemic stroke and its role in responding to injury

“…Increases could aid in the clearance of neurotoxic factors from the brain (CSF sink effect) but might also exacerbate hydrocephalus. With regards to the latter, choroid plexus hyperplasia and choroid plexus papillomas are associated with CSF hypersecretion and hydrocephalus [140]. Decreases in CSF production might serve to decrease the incidence of hydrocephalus and reduce intracranial pressure, and CP cauterization has been used as a treatment for hydrocephalus [141, 142].…”

Choroid Plexus Hyperplasia with Intractable Ascites and a Resulting Communicating Hydrocele following Shunt Operation for Hydrocephalus

“…CSF production in such cases has been reported as 400–5,000 mL/day [1]. Although our patient did not receive external drainage, > 150 mL of CSF were removed daily when he was only 1 month old, following reservoir placement.…”

“…Cerebrospinal fluid (CSF) overproduction can be one of the causes of pediatric hydrocephalus [1]. Previous studies have reported cases of choroid plexus hyperplasia/hypertrophy [2-12] and papilloma [13-18] with hydrocephalus that led to a shunt-related accumulation of ascites after a ventriculoperitoneal (VP) shunting operation.…”

Opportunities in posthemorrhagic hydrocephalus research: outcomes of the Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop

“…Non-surgical methods that alter CSF dynamics could be used at earlier time points in isolation or later in conjunction with temporizing devices. Current targets for these interventions include pharmaceutical reduction of CSF production by the choroid plexus (reviewed in [ 134 , 222 ]), increased CSF absorption (e.g., increase absorption through aquaporin channels [ 223 – 225 ], especially following IVH [ 226 ], as well as cranial nerve lymphatics [ 227 ]), and improved CSF flow (e.g., enhancement of natural processes that repair motile cilia). This list, however, also highlights the need for a better understanding of the choroid plexus response after IVH, alternative routes of CSF production and absorption, and the role of motile cilia in the development of hydrocephalus after hemorrhage.…”