Biomechanical instability of the brain-CSF interface in hydrocephalus.

Abstract

Hydrocephalus, characterized by progressive expansion of the CSF-filled ventricles (ventriculomegaly), is the most common reason for brain surgery. 'Communicating' (i.e. non-obstructive) hydrocephalus is classically attributed to a primary derangement in CSF homeostasis, such as choroid plexus-dependent CSF hypersecretion, impaired cilia-mediated CSF flow currents, or decreased CSF reabsorption via the arachnoid granulations or other pathways. Emerging data suggest that abnormal biomechanical properties of the brain parenchyma are an under-appreciated driver of ventriculomegaly in multiple forms of communicating hydrocephalus across the lifespan. We discuss recent evidence from human and animal studies that suggests impaired neurodevelopment in congenital hydrocephalus, neurodegeneration in elderly normal pressure hydrocephalus and, in all age groups, inflammation-related neural injury in post-infectious and post-haemorrhagic hydrocephalus, can result in loss of stiffness and viscoelasticity of the brain parenchyma. Abnormal brain biomechanics create barrier alterations at the brain-CSF interface that pathologically facilitates secondary enlargement of the ventricles, even at normal or low intracranial pressures. This 'brain-centric' paradigm has implications for the diagnosis, treatment and study of hydrocephalus from womb to tomb.