Neurocognitive outcomes and changes in brain and CSF volume after treatment of post-infectious hydrocephalus in Ugandan infants by shunting or ETV/CPC: a randomized prospective trial

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The goals of this R01 Renewal are driven by the results of our successfully conducted randomized controlled clinical trial comparing endoscopic third ventriculostomy combined with choroid plexus cauterization (ETV/CPC) to shunt treatment for post-infectious hydrocephalus (PIH, the most common hydrocephalus etiology in Uganda) in infants < 6 months of age (ClinicalTrials.gov NCT01936272, R01HD085853, R21HD068213) at the CURE Children’s Hospital of Uganda (CCHU). The interim outcomes of this study are becoming a landmark in children’s medicine, finding that: a) at up to 24 months, there was no significant difference between ETV/CPC and shunt in regard to failure rate, developmental outcome, and brain growth; b) brain volume, not CSF volume, correlated strongly with developmental outcome; c) successful treatment of the hydrocephalus led to improved brain growth in the first year, which stagnated during the second year. Because almost all of the failures of endoscopic treatment occurred early in the first year of life, we anticipate that the longer term outcomes of hydrocephalus treatment may favor endoscopy if we follow these children through primary school age from 5 to 10 years. Furthermore, our ability to perform much more detailed neurocognitive assessments during this further followup will be much more accurate than during our pre-school assessments. Lastly, we can gather all of our data and perform a much more definitive cost-effectiveness analysis if we can follow this unique cohort for a full 10 years. We have engaged in substantial capacity building during the previous 5 years of support during this clinical trial. We have developed a thriving research unit at the CURE Children’s Hospital of Uganda, enabling high-quality research to be conducted in multiple other NIH funded studies unrelated to this clinical trial (DP1HD086071, R01AI145057, and R01HD096693). Furthermore, since all hydrocephalus treatment requires brain imaging, we have developed a thriving center for sustainable low-field MRI engineering at the Mbarara University of Science and Technology. This present project seeks to follow this unique cohort to 10 years of age, seeking to definitively establish whether endoscopic treatment is more sustainable for infants in the developing world, establish low field MRI as a sustainable imaging technology, and establish the capacity of both the medical and engineering sites in Uganda as independent research and technology development centers for Africa.