Interplay between vascular hemodynamics and the glymphatic system in the pathogenesis of idiopathic normal pressure hydrocephalus, exploring novel neuroimaging diagnostics.

ABSTRACT

As the aging population continues to grow, so will the incidence of age-related conditions, including idiopathic normal pressure hydrocephalus (iNPH). The pathogenesis of iNPH remains elusive, and this is due in part to the poor characterization of cerebral spinal fluid (CSF) dynamics within the brain. Advancements in technology and imaging techniques have enabled new breakthroughs in understanding CSF physiology, and therefore iNPH pathogenesis. This includes understanding the hemodynamic and microvascular components involved in CSF influx and flow. Namely, the glymphatic system appears to be the great mediator, facilitating perivascular CSF flow via astrocytic aquaporin channels located along the endothelium of the pial vasculature. The interplay between glymphatics and both arterial pulsatilty and venous compliance has also been recently demonstrated. It appears then that CSF flow, and therefore glymphatic function, are highly dependent on cardiocirculatory and vascular factors. Impairment in any one component, whether it be related to arterial pulsatility, microvascular changes, reduced venous drainage, or astrogliosis, contributes greatly to iNPH, although it is likely a combination thereof. The strong interplay between vascular hemodynamics and CSF flow suggests perfusion imaging and cerebral blood flow quantification may be a useful diagnostic tool in characterizing iNPH. In addition, studies detecting glymphatic flow with magnetic resonance imaging have also emerged. These imaging tools may serve to both diagnose iNPH and help delineate it from other similarly presenting disease processes. With a better understanding of the vascular and glymphatic factors related to iNPH pathogenesis, physicians are better able to select the best candidates for treatment.