Pathophysiology of Hydrocephalus
Hydrocephalus results from a failure of cerebrospinal fluid (CSF) homeostasis, causing excessive CSF accumulation in the cerebral ventricles with resultant active ventricular expansion, increased intracranial pressure, and progressive brain tissue damage. 1, 2
Core Pathophysiologic Mechanisms
The fundamental pathophysiology involves disruption of normal CSF dynamics through several distinct mechanisms:
CSF Production and Absorption Imbalance
CSF is produced by the choroid plexus in the lateral ventricles at a relatively constant rate, flowing through the third ventricle, aqueduct of Sylvius, fourth ventricle, and into the subarachnoid space where it is normally absorbed. 3, 4
The classic understanding of hydrocephalus as simple obstruction to bulk CSF flow is evolving to incorporate dysfunctional cerebral pulsations, impaired brain compliance, and newly characterized water-transport mechanisms. 5
Impaired CSF absorption occurs primarily at the arachnoid granulations due to fibrosis, meningeal scarring, and subependymal gliosis, leading to ventricular enlargement. 6
Molecular and Cellular Mechanisms
Molecular mediators including TGF-β1 and TGF-β2 stimulate extracellular matrix protein deposition, directly impairing CSF resorption at absorption sites. 6
Elevated aminoterminal propeptide of Type I collagen (PC1NP) and vascular endothelial growth factor levels in CSF reflect the fibrotic process at arachnoid granulations. 6
The brain parenchyma plays an active role in CSF absorption, with ventricular CSF seeping into the parenchyma where it must be efficiently absorbed to prevent sustained ventricular dilatation. 7
Tissue-Level Pathophysiology
Fibrosis of arachnoid granulations, meningeal fibrosis, and subependymal gliosis impair CSF resorption, creating a cycle of progressive ventricular expansion. 1
White matter damage results from compression and ischemia due to increased intracranial pressure, with localized periventricular white matter being particularly vulnerable. 1, 7
Increased periventricular fluid content develops as CSF seeps across the ventricular wall into surrounding brain tissue when absorption mechanisms are overwhelmed. 7
Classification by Mechanism
Non-Communicating (Obstructive) Hydrocephalus
Obstruction of CSF pathways within the ventricular system prevents normal flow, most commonly at the aqueduct of Sylvius or fourth ventricle outlets. 4, 5
Congenital aqueduct stenosis has been linked to genes that regulate brain morphogenesis and alter the biomechanics of the CSF-brain interface. 2, 5
Brain tumors near the fourth ventricle can cause obstruction of CSF flow pathways. 6
Communicating Hydrocephalus
CSF pathways remain patent, but absorption is impaired at the arachnoid granulations or extracranial lymphatic drainage sites. 6, 3
Evidence indicates that extracranial lymphatic vessels in the ethmoid bone region also play a role in CSF absorption, with decreased lymphatic absorption demonstrated in animal models. 3
Post-hemorrhagic mechanisms involve blood products obstructing CSF flow in the subarachnoid space and damaging absorption sites. 6
Post-infectious mechanisms involve inflammation and subsequent fibrosis of the subarachnoid space from bacterial, viral, or fungal meningitis impairing CSF flow and absorption. 6
Etiology-Specific Pathophysiology
Congenital Hydrocephalus
Congenital hydrocephalus is present at or near birth and has been linked to gene mutations that disrupt brain morphogenesis and alter the biomechanics of the CSF-brain interface. 2
Intrauterine infection or maldevelopment of the aqueduct of Sylvius are the usual causes of congenital hydrocephalus. 4
Spina bifida is one of the most common causes, with approximately 80% of children with spina bifida developing hydrocephalus. 1
Acquired Hydrocephalus
Acquired hydrocephalus develops after birth and is often caused by central nervous system infection or hemorrhage, associated with blockage of CSF pathways and inflammation-dependent dysregulation of CSF secretion and clearance. 2
Post-hemorrhagic hydrocephalus in premature infants occurs in approximately 15-20% of infants weighing less than 1500g at birth who develop intraventricular hemorrhage. 1
The mechanism involves fibrosis of arachnoid granulations, meningeal fibrosis, and subependymal gliosis that impair CSF resorption, with elevated TGF-β2 and extracellular matrix proteins in CSF stimulating deposition in perivascular spaces. 1
Meningitis is a leading cause, particularly in lower-middle-income countries where it accounts for 19.2% of pediatric hydrocephalus cases. 6
Clinical Consequences of Pathophysiology
Uncontrolled hydrocephalus leads to macrocephaly, developmental delays, and neurological deficiencies affecting quality of life and survival. 8
Longevity and the severity of neurological deficiencies are dependent on the etiology of hydrocephalus. 8
Progressive ventricular dilatation increases intracranial pressure, potentially causing cerebral herniation syndromes and alterations in level of consciousness. 8