Pathophysiological Mechanisms Underlying Idiopathic Normal Pressure Hydrocephalus: A Review of Recent Insights

Phillip A Bonney; Robert G Briggs; Kevin Wu; Wooseong Choi; Anadjeet Khahera; Brandon Ojogho; Xingfeng Shao; Zhen Zhao; Matthew Borzage; Danny J J Wang; Charles Liu; Darrin J Lee

doi:10.3389/fnagi.2022.866313

Pathophysiological Mechanisms Underlying Idiopathic Normal Pressure Hydrocephalus: A Review of Recent Insights

Front Aging Neurosci. 2022 Apr 28:14:866313. doi: 10.3389/fnagi.2022.866313. eCollection 2022.

Authors

Phillip A Bonney¹, Robert G Briggs¹, Kevin Wu², Wooseong Choi², Anadjeet Khahera¹, Brandon Ojogho^{3

4}, Xingfeng Shao³, Zhen Zhao⁵, Matthew Borzage^{2

6}, Danny J J Wang³, Charles Liu^{1

4}, Darrin J Lee^{1

4}

Affiliations

¹ Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
² Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
³ Laboratory of Functional MRI Technology, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
⁴ USC Neurorestoration Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
⁵ Department of Physiology & Neuroscience and the Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
⁶ Division of Neonatology, Department of Pediatrics, Fetal and Neonatal Institute, Children's Hospital Los Angeles, Los Angeles, CA, United States.

Abstract

The pathophysiologic mechanisms underpinning idiopathic normal pressure hydrocephalus (iNPH), a clinically diagnosed dementia-causing disorder, continue to be explored. An increasing body of evidence implicates multiple systems in the pathogenesis of this condition, though a unifying causative etiology remains elusive. Increased knowledge of the aberrations involved has shed light on the iNPH phenotype and has helped to guide prognostication for treatment with cerebrospinal fluid diversion. In this review, we highlight the central role of the cerebrovasculature in pathogenesis, from hydrocephalus formation to cerebral blood flow derangements, blood-brain barrier breakdown, and glymphatic pathway dysfunction. We offer potential avenues for increasing our understanding of how this disease occurs.

Keywords: blood brain barrier (BBB) breakdown; cerebral blood flow; communicating hydrocephalus; dementia; glymphatic circulation; idiopathic normal pressure hydrocephalus (iNPH); ventriculoperitoneal (VP) shunt.

Publication types

Review