Hydrocephalus primarily affects infants under one year of age. The traditional treatment for hydrocephalus is cerebrospinal fluid (CSF) shunt. Life-time complications of CSF shunts are high and expensive, with annual hospital charges of nearly $2.0 billion, accounting for 3.1% of all pediatric hospital charges. As shunt complications also adversely impact quality of life, it is not surprising that surveys of families affected by hydrocephalus show that they desperately desire shunt-free treatment options. The most promising shunt-free treatment for infant hydrocephalus is endoscopic third ventriculostomy with choroid plexus cauterization (ETV+CPC), which our Hydrocephalus Clinical Research Network (HCRN) and others have shown to be safe and viable. However, the cognitive outcome of ETV+CPC compared to shunt is not known. Our data suggest that most families would accept the risks of ETV+CPC for the chance to be free of shunt, but only if initial treatment with ETV+CPC will not lead to noticeable sacrifice in cognitive outcome compared to shunting. With this U01 proposal, we aim: 1. To determine, in infants ≤12 months corrected age, with hydrocephalus requiring treatment at tertiary care pediatric neurosurgery centers in North America, does ETV+CPC compared to shunt result in non-inferior cognitive outcome at 12 months from surgery, as measured by Bayley Scales of Infant and Toddler Development (Bayley-III) Cognitive Scale with a non-inferiority margin of 1.5. 2a. To determine, in the same cohort, if ETV+CPC compared to shunt results in non-inferior Bayley-III Motor/Language Scales or Vineland-3 Scales. 2b. To compare other measures of treatment performance (brain/ventricle volume, treatment failure, hospital days, repeat surgery, use of imaging) and complications between treatment arms. 3a. To determine the effect of ETV+CPC and shunt on cerebral structural connectivity, with diffusion MR fractional anisotropy (FA) in the corpus callosum 12 months after surgery. 3b. To define the relationships between pre-operative brain/ventricular volume and cerebrospinal fluid (CSF) NCAM-1 level to post-operative corpus callosum FA and Bayley-III Cognitive Scale 12 months after surgery. 3c. To define the relationships between change in brain/ventricular volume (pre-operatively to 12 months post-operatively) to FA in the corpus callosum and corticospinal tract and Bayley-III Cognitive and Motor Scales 12 months post-operatively. To do this, we plan an RCT comparing ETV+CPC and shunt in infants with hydrocephalus, within the HCRN, a committed group of 14 leading North American pediatric neurosurgical centers with a long track-record of successful collaborative clinical research and RCTs in hydrocephalus. Optimal cognitive outcome, the primary concern of families, will therefore, be our primary outcome. Assessment of dMRI, a validated, non-invasive method of measuring white matter microstructural integrity and structural connectivity in the developing brain, will provide further insight into the developmental consequences of these 2 treatments. This RCT will help families determine the optimal treatment of hydrocephalus for their child.

Hydrocephalus is a potentially debilitating neurological condition that primarily affects babies under a year of age and has traditionally been treated by inserting a shunt between the brain and the abdomen. A newer endoscopic procedure offers hope of shunt-free treatment that may reduce complications over a child's life, but it is not clear if the endoscopic procedure results in similar intellectual outcome as shunt. We propose, therefore, a randomized trial to compare intellectual outcome and brain structural integrity between these 2 treatments, to help families make the best treatment decision for their baby.