We estimate that more than 100,000 new infants develop post-infectious hydrocephalus (PIH) in sub-Saharan Africa each year, and most have no opportunity for treatment. Our prior collaborative work at CURE Children's Hospital of Uganda (CCHU) has: a) identified neonatal infection as the single most common cause of pediatric hydrocephalus and an important cause of primary brain injury;b) identified acinetobacter as a potentially important pathogen in PIH with seasonal variance;c) demonstrated the one-year outcome of treatment with an inexpensive shunt;d) developed the novel technique of combined endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC) for treating infant hydrocephalus that avoids the danger of shunt-dependence;e) developed a score to predict the outcome for ETV/CPC;f) showed no overall difference in early developmental outcomes for shunting or ETV/CPC in myelomeningocele (MM) infants;and, g) trained surgeons for this procedure in 8 developing countries. That ETV/CPC prevents shunt dependence among those with no urgent access to subspecialty care for shunt malfunction is compelling, but we do not know which treatment optimizes brain development in a given PIH patient, and we found no difference in 5 year survival between treatment groups for MM infants with hydrocephalus. We seek to confirm the optimal treatment selection paradigm. Using data from CT imaging, we have found that both brain volume, and to a lesser but important degree, CSF volume, are significant multivariate discriminators of neurocognitive outcome. This method is promising as an objective measure of hydrocephalus treatment efficacy. This R21 proposes to: 1) develop CCHU as an independent site for hydrocephalus research and clinical trials;2) correlate brain/CSF volume metrics with neurocognitive development during PIH treament;3) test the hypothesis that treatment of PIH by ETV/CPC is as good as or better than shunt placement in regard to neurocognitive development with a randomized controlled trial (RCT);and 4) Determine the feasibility of employing preoperative brain/CSF volume parameters to guide therapy. ETV/CPC is successful in 50-70% of infants with PIH, while 54% of shunted patients at CCHU are successful at one year. We found no difference in 5 year survival between the two treatments in MM infants. An RCT of shunt placement vs. ETV/CPC for infants with PIH will be performed. Preoperatively, and at 6 and 12 months postoperatively, patients will have CT imaging for brain and CSF volumetric assessment and neurocognitive assessment with the Bayley Scales of Infant Development (BSID) . Neurocognitive outcome, pre- and post- operative brain/CSF volumes, and treatment modality will be correlated. Capacity at CCHU will be developed for thorough patient follow up, neurocognitive assessment, brain/CSF volume determination, statistical analysis, and clinical trial design for future hydrocephalus research. These preliminary data and research site development will form the basis for future follow-on collaborative R01 applications.

Public Health Relevance

Postinfectious hydrocephalus appears to be a major public health problem throughout the developing world that escaped the attention of the global health community prior to the emergence of in-country specialty care that recognizes and treats such children. There are two strategies for treating these children - shunting versus endoscopic techniques - with no definitive evidence supporting which therapy is optimal. Armed with new volumetric image analysis tools that correlate neurodevelopmental outcome with brain growth, we here propose a novel randomized clinical trial in East Africa that will initiate an evidence-based foundation for better treatment of such children.

National Institute of Health (NIH)
Fogarty International Center (FIC)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-BDCN-Z (50))
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Michels, Kathleen M
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Children's Hospital Boston
United States
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Kulkarni, Abhaya V; Schiff, Steven J; Mbabazi-Kabachelor, Edith et al. (2017) Endoscopic Treatment versus Shunting for Infant Hydrocephalus in Uganda. N Engl J Med 377:2456-2464