Intracranial Pulsatility, Cerebrospinal Fluid Flow, and Glymphatic Function in Idiopathic Normal Pressure Hydrocephalus

Abstract

Several cerebrospinal fluid (CSF) disorders, including hydrocephalus, may be accompanied with changes in the pulsatile intracranial pressure (ICP). Altered pressure pulsatility provides information about intracranial pressure-volume reserve capacity, usually referred to as intracranial compliance (ICC). Impaired ICC may be associated with neuronal dysfunction and causes the intracranial compartment to be more responsive to intracranial volume changes. The temporary intracranial volume load provided by every heart beat will therefore result in increased pulsatile ICP, which can be diagnosed by ICP monitoring with single ICP wave analysis. Another consequence of impaired ICC is altered CSF flow within the intracranial CSF spaces, e.g. within the Sylvian aqueduct and along large arteries within the subarachnoid space, and altered clearance of molecules from CSF. In humans, the glymphatic function capacity of the brain may be examined by magnetic resonance imaging (MRI) utilizing a MRI contrast agent administered to the CSF space (e.g. intrathecally) to serve as a CSF tracer (gMRI). Using this approach, evidence has been given that individuals with impaired ICC may have reduced clearance of CSF tracer from CSF and brain parenchyma. Since the brain is a highly active metabolic organ, CSF circulation compromise and reduced clearance of waste products may impair neurological function and contribute to neurodegeneration.