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

通过分流或 ETV/CPC 治疗乌干达婴儿感染后脑积水后的神经认知结果以及大脑和脑脊液体积的变化：一项随机前瞻性试验

• 批准号: 9751092
• 负责人: Abhaya V Kulkarni
• 金额: $ 45.91万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-19 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751092
• 关键词: 7 year old; Africa; Africa South of the Sahara; Aftercare; Age-Months; Base of the Brain; Biomedical Engineering; Brain; Brain imaging; Cauterize; Child; Clinical Management; Cohort Studies; Computer software; Country; Coupled; Data; Dependence; Development; Diagnostic; Environment; Equipoise; Etiology; Evaluation; Failure; Foundations; Funding; Goals; Growth; Head; Health Services Accessibility; Human Resources; Hydrocephalus; Image; Image Analysis; Imaging technology; Infant; Infant Development; Infrastructure; Libraries; Magnetic Resonance Imaging; Measurement; Measures; Methods; Modality; Neonatal; Neurocognitive; Neurosciences Research; Noise; Outcome; Patients; Pediatric Hospitals; Physicians; Postoperative Period; Public Health; Quality of life; Quality-of-Life Assessment; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Recovery; Research; Resolution; Resources; Safety; Science; Selection for Treatments; Shunt Device; Signal Transduction; Site; Structure of choroid plexus; Technology; Testing; Training; Treatment Efficacy; Uganda; United States National Institutes of Health; Universities; Ventriculostomy; Work; base; brain volume; clinical research site; cohort; deep learning; design; early childhood; evidence base; follow-up; imaging Segmentation; improved; neonatal infection; novel; optimal treatments; patient subsets; prevent; prospective; prototype; research facility; success; tool; treatment optimization; treatment strategy; trial comparing

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.

我们估计有25万名新婴儿在亚第 - 每年撒哈拉非洲（SSA）。大多数人可以接受治疗。我们开发并验证了一本小说 内窥镜第三室造口术和脉络丛的婴儿脑积水的手术治疗 避开大多数分流依赖性的烧焦（ETV/CPC）。我们先前在治愈方面的合作工作 乌干达儿童医院（CCHU）支持分流放置与ETV/CPC之间的平衡。 到5年的生存和发展。 ETV/CPC可防止没有紧急的人的分流依赖性 访问分流功能是令人信服的，但我们不知道哪种治疗方法优化了开发。 我们试图确认最佳治疗选择范例。使用基于CT的措施，我们发现大脑 和CSF量歧视神经认知结果，提供了有望的客观测量 脑积水治疗效率。来自我们R-21和R01的初步数据，资助的随机对照试验 （RCT）ETV/CPC与分流式治疗的分流（ClinicalTrials.gov登记NCT01936272）尚未显示 关于安全性，效率，发展结果或大脑增长的一年的重要差异 那些在1年之前达到正常或接近正常大脑量的人，无论preop量如何 结果。当前的提议旨在实现以下目的：1）检验以下假设： PIH的内窥镜治疗比五年更好或等于分流的位置 神经认知发展； 2）进一步发展为神经科学研究机构； 3）发展 可持续超低场（ULF）MRI成像的国内能力； 4）安装优化的ULF-MRI 在CCHU; 5）将MRI衍生的大脑/CSF量指标与长期神经认知相关联 PIH处理后的发展。按计划，RCT患者研究队列将进一步进行 使用婴儿发育范围（BSID-III）在24个月后使用Bayley的发育评估 与重复基于CT的大脑和CSF量指标一起操作。在当前的提议中，发展 评估将在治疗后5年使用Vineland-III进行，并评估 生活质量。在开发了Mbarara科学技术大学（必须）为ULF-MRI之后 演示和资源中心，ULF-MRI将在CCHU安装，以评估体积和 与CT相比，诊断工具。神经认知结果将与术前和术后MRI-相关 基于大脑/CSF的体积和治疗方式。研究的扩展将确定是否不及 在治疗后5年，ETV/CPC关于发展结果和大脑生长持续存在的分流， 基于MRI的数量指标是否有效取代了基于CT的措施，以及大脑和CSF是否 事实证明，体积可用于指导最佳临床管理。拟议的项目将确定是否 ETV/CPC是首选的初始治疗方法，将进一步在CCHU上发展研究能力。