We estimate 250,000 new infants develop hydrocephalus, most commonly following neonatal infection, in sub- Saharan Africa (SSA) each year. Most have poor access to treatment. We have developed and validated a novel operative treatment for infant hydrocephalus combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC) that avoids shunt dependence in the majority. Our prior collaborative work at CURE Children's Hospital of Uganda (CCHU) supports equipoise between shunt placement and ETV/CPC in regard to 5-year survival and neurocognitive development. That ETV/CPC prevents shunt dependence among those with no urgent access for shunt malfunction is compelling, but we do not know which treatment optimizes brain development. Going forward with humanitarian efforts to improve access to care for PIH infants in SSA, we seek to confirm the optimal treatment selection paradigm. Using data from CT imaging, we have found that both brain and CSF volume are significant multivariate discriminators of neurocognitive outcome. This method is promising as an objective measure of hydrocephalus treatment efficacy. Preliminary data from our R-21 funded (1R21TW009612) randomized controlled trial (RCT) of ETV/CPC vs. shunt for PIH treatment (ClinicalTrials.gov registration NCT01936272) have shown no important differences (either by intention-to-treat or actual treatment received) at this point in regard to safety, efficacy, or developmental outcome, thereby supporting completion of the study and extension of the follow up through the period of maximal brain growth at 24 months of age. This R01 proposes to accomplish the following aims: 1) further develop CCHU as an independent site for clinical hydrocephalus research; 2) test the hypothesis that treatment of PIH by ETV/CPC is better than or equal to shunting in regard to neurocognitive development; 3) correlate brain/CSF volume metrics with neurocognitive development; 4) assess the utility of preoperative brain/CSF volume metrics to guide treatment selection. The RCT initiated in the R- 21 study will be extended and completed. Of 100 required patients, 77 have been enrolled thus far with 6- month follow-up in 40 and none lost to follow-up. For all 100 patients, CT imaging preoperatively and at 6, 12, and 24 months postoperatively will be completed for brain and CSF volumetric assessment. Neurocognitive assessment with the Bayley Scales of Infant Development (BSID-III) will also be completed preoperatively, and at 6, 12, and 24 months post-operatively. Neurocognitive outcome will be correlated with pre- and post- operative brain/CSF volumes and treatment modality. Changes in brain and CSF volumes will also be correlated with treatment modality. Completion of the study will determine whether there is an important difference in developmental outcome between these two treatments. Significantly, demonstrating superiority of ETV/CPC or no important difference will lead to selecting ETV/CPC as the preferred initial treatment. Research capacity at CCHU will be further developed.

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 completion and extension of 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)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BDCN-N (55))
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Russo, Denise
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Children's Hospital Boston
United States
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Obungoloch, Johnes; Harper, Joshua R; Consevage, Steven et al. (2018) Design of a sustainable prepolarizing magnetic resonance imaging system for infant hydrocephalus. MAGMA 31:665-676
Peterson, Mallory; Warf, Benjamin C; Schiff, Steven J (2018) Normative human brain volume growth. J Neurosurg Pediatr 21:478-485
Cherukuri, Venkateswararao; Ssenyonga, Peter; Warf, Benjamin C et al. (2018) Learning Based Segmentation of CT Brain Images: Application to Postoperative Hydrocephalic Scans. IEEE Trans Biomed Eng 65:1871-1884
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