Improving Infant Hydrocephalus Outcomes in Uganda: A Longitudinal Prospective Study Protocol for Predicting Developmental Outcomes and Identifying Patients at Risk for Early Treatment Failure after ETV/CPC.

Taylor A Vadset,Ajay Rajaram,Julia Tatz,Miriah Kemigisha Katungi,Benjamin C Warf,Davis Natukwatsa,Joshua Magombe,Katharine Playter,Marvin Seruwu,Esther Nalule,Rutvi Vyas,Steven J Schiff,Moses Wabukoma,Ronald Mulondo,Chuan-Heng Hsiao,Pei-Yi Lin,Aaron Fenster,Abhaya V Kulkarni,Edith Mbabazi Kabachelor,P Ellen Grant ,Luis E Neri Perez ,Jason Sutin ,Brian Nsubuga Kaaya ,Jennifer Queally

doi:10.3390/metabo12010078

Abstract

Infant hydrocephalus poses a severe global health burden; 80% of cases occur in the developing world where patients have limited access to neurosurgical care. Surgical treatment combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC), first practiced at CURE Children’s Hospital of Uganda (CCHU), is as effective as standard ventriculoperitoneal shunt (VPS) placement while requiring fewer resources and less post-operative care. Although treatment focuses on controlling ventricle size, this has little association with treatment failure or long-term outcome. This study aims to monitor the progression of hydrocephalus and treatment response, and investigate the association between cerebral physiology, brain growth, and neurodevelopmental outcomes following surgery. We will enroll 300 infants admitted to CCHU for treatment. All patients will receive pre/post-operative measurements of cerebral tissue oxygenation (SO2), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO2) using frequency-domain near-infrared combined with diffuse correlation spectroscopies (FDNIRS-DCS). Infants will also receive brain imaging, to monitor tissue/ventricle volume, and neurodevelopmental assessments until two years of age. This study will provide a foundation for implementing cerebral physiological monitoring to establish evidence-based guidelines for hydrocephalus treatment. This paper outlines the protocol, clinical workflow, data management, and analysis plan of this international, multi-center trial.

Highlights

Hydrocephalus is a severe disease where excess cerebral spinal fluid (CSF) accumulates in the brain, and if left untreated will rapidly cause brain damage, severe neurological and developmental disorders, and even death
This is an investigator-initiated, multi-site, prospective, observational study that seeks to characterize the longitudinal evolution of cerebral physiology and brain growth during disease progression, treatment response, and long-term neurodevelopment up to two years of age in children with hydrocephalus
The recruitment period is estimated based on the randomized control clinical trial (NCT01936272) previously conducted at CURE Children’s Hospital of Uganda (CCHU)

Summary

Introduction

Hydrocephalus is a severe disease where excess cerebral spinal fluid (CSF) accumulates in the brain, and if left untreated will rapidly cause brain damage, severe neurological and developmental disorders, and even death. Infants with hydrocephalus are treated with a ventriculoperitoneal shunt (VPS), a permanently-implanted mechanical valve that drains CSF directly from the brain’s ventricles into the abdominal cavity to ease the enlargement of the ventricles [6,7]. In comparison to shunt placement, successful ETV/CPC treatment lowers infection risk and presents a similar mortality or morbidity rate. ETV/CPC avoids life-long shunt dependence with its attendant danger of shunt failure, has a lower risk of treatment failure after six months, and may be more cost-effective [9,10,11,12,13,14,15]. The randomized controlled trial (RCT) at CCHU comparing ETV/CPC vs VPS treatments (NCT01936272)

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