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

我们估计有250,000名新生婴儿患上脑积水，最常见的是新生儿感染后， 每年的撒哈拉非洲(SSA)。大多数人很难获得治疗。我们开发并验证了一部小说 内窥镜下第三脑室造口术联合脉络丛手术治疗婴幼儿脑积水 烧灼(ETV/CPC)，避免了大多数人的分流依赖。我们之前在CURE的合作工作 乌干达儿童医院(CCHU)在分流安置和ETV/CPC方面支持平衡 到5年的生存和发展。ETV/CPC防止了那些没有紧急情况的人的分流依赖 分流故障的治疗是很有吸引力的，但我们不知道哪种治疗方法能最大限度地促进发展。 我们寻求确认最佳治疗选择范例。使用基于CT的测量方法，我们发现大脑 和脑脊液容量区分神经认知结果，提供了一个有希望的客观衡量标准 治疗脑积水的疗效。R-21和R01资助的随机对照试验的初步数据 ETV/CPC与分流术治疗妊高征的(RCT)(ClinicalTrials.gov注册NCT01936272)显示没有 一年内在安全性、有效性、发育结局或脑发育方面的重要差异 那些在1年内达到正常或接近正常脑容量的患者，无论术前脑容量如何，都是最好的。 结果。目前的提议试图实现以下目标：1)检验以下假设 经内窥镜治疗妊高征优于或等于分流术后5年 神经认知发展；2)进一步发展CCHU作为神经科学研究设施；3)发展 可持续超低场磁共振成像的国内能力；4)安装优化的超低场磁共振成像 在CCHU；5)将MRI得出的脑/脑脊液体积指标与长期神经认知能力相关联 妊高征治疗后的进展。按计划，RCT患者研究队列将进行进一步的 出生后24个月使用贝利婴儿发育量表(BSID-III)进行发育评估 手术配合重复的基于CT的脑和脑脊液体积测量。在目前的提案中，发展 将在治疗后5年使用Vinland-III进行评估，以及评估 生活质量。将姆巴拉拉科技大学(MUST)发展为ULF-MRI后 演示和资源中心，将在CCHU安装ULF-MRI，作为体积和 诊断工具与CT的比较。神经认知结果将与手术前和手术后的MRI相关- 基于脑/脑脊液体积和治疗方式。研究的延长将决定是否非自卑 在治疗后5年，ETV/CPC在发育结局和脑发育方面的分流持续， 基于MRI的体积测量是否有效地取代了基于CT的测量，以及大脑和脑脊液 事实证明，容量计量学在指导最佳临床治疗方面是有用的。提议的项目将决定是否 ETV/CPC是首选的初步治疗方法，并将进一步发展CCHU的研究能力。

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 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) supported equipoise between shunt placement and ETV/CPC in regard to 5-year survival and 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 development. We seek to confirm the optimal treatment selection paradigm. Using CT-based measures we found that brain and CSF volume discriminated neurocognitive outcome, providing a promising objective measure of hydrocephalus treatment efficacy. Preliminary data from our R-21 and R01 funded randomized controlled trial (RCT) of ETV/CPC vs. shunt for PIH treatment (ClinicalTrials.gov registration NCT01936272) have shown no important differences at one year in regard to safety, efficacy, developmental outcome, or brain growth Those achieving normal or near-normal brain volume by 1 year, regardless of preop volume, had the best outcome. The current proposal seeks to accomplish the following aims: 1) test the hypothesis that endoscopic treatment of PIH is better than or equal to shunt placement in regard to five-year neurocognitive development; 2) further develop CCHU as a neuroscience research facility; 3) develop the in-country capacity for sustainable ultra-low-field (ULF) MRI imaging; 4) install optimized ULF-MRI at CCHU; 5) Correlate MRI-derived brain/CSF volume metrics with long-term neurocognitive development following PIH treatment. As planned, the RCT patient study cohort will undergo further developmental assessment using the Bayley Scales of Infant Development (BSID-III) at 24 months post- operatively along with repeat CT-based brain and CSF volume metrics. In the current proposal, developmental assessment will be conducted at 5 years post-treatment using the Vineland-III, as well as an assessment of quality of life. After developing Mbarara University of Science and Technology (MUST) as an ULF-MRI demonstration and resource center, ULF-MRI will be installed at CCHU for evaluation as a volumetric and diagnostic tool compared to CT. Neurocognitive outcome will be correlated with pre- and post-operative MRI- based brain/CSF volumes and treatment modality. Extension of the study will determine whether non-inferiority of ETV/CPC to shunt in regard to developmental outcome and brain growth persists at 5 years post-treatment, whether MRI-based volume metrics effectively supplant CT-based measures, and whether brain and CSF volumetrics prove useful in guiding optimal clinical management. The proposed project will determine whether ETV/CPC is the preferred initial treatment and will further develop research capacity at CCHU.