Posthemorrhagic hydrocephalus development after germinal matrix hemorrhage: Established mechanisms and proposed pathways

Abstract

In addition to being the leading cause of morbidity and mortality in premature infants, germinal matrix hemorrhage (GMH) is also the leading cause of acquired infantile hydrocephalus. The pathophysiology of posthemorrhagic hydrocephalus (PHH) development after GMH is complex and vaguely understood, although evidence suggests fibrosis and gliosis in the periventricular and subarachnoid spaces disrupts normal cerebrospinal fluid (CSF) dynamics. Theories explaining general hydrocephalus etiology have substantially evolved from the original bulk flow theory developed by Dr. Dandy over a century ago. Current clinical and experimental evidence supports a new hydrodynamic theory for hydrocephalus development involving redistribution of vascular pulsations and disruption of Starling forces in the brain microcirculation. In this review, we discuss CSF flow dynamics, history and development of theoretical hydrocephalus pathophysiology, and GMH epidemiology and etiology as it relates to PHH development. We highlight known mechanisms and propose new avenues that will further elucidate GMH pathophysiology, specifically related to hydrocephalus.

Keywords: cerebrospinal fluid; choroid plexus; germinal matrix hemorrhage; glymphatic system; intracerebral hemorrhage; intraventricular hemorrhage; neonatal brain hemorrhage; posthemorrhagic hydrocephalus; posthemorrhagic ventricular dilation; subarachnoid hemorrhage.

Figure 1:

Overview of the glymphatic system. Cerebrospinal fluid enters within para-arterial Virchow-Robin spaces in the brain parenchyma and an astroglia-mediated mechanism exchanges cerebrospinal fluid with interstitial fluid and flushes wastes out within para-venous Virchow-Robin spaces (A). Astrogliosis (B) from brain injury possibly disrupts this astroglia-dependent mechanism.

Figure 2:

Axial non-contrasted adult brain MRI demonstrating perivascular spaces (arrows) that appear hypointense to brain tissue and isointense to CSF in T1-weighted (A) and T2-weighted (B) sequences.

Figure 3:

Know pathways and potential mechanisms disrupting cerebrospinal fluid dynamics and contributing to post-hemorrhagic hydrocephalus development after germinal matrix hemorrhage.