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 250,000 名新生儿患有脑积水，最常见于新生儿感染后， 撒哈拉非洲 (SSA) 每年。大多数人很难获得治疗。我们开发并验证了一部小说 内镜下第三脑室造瘘联合脉络丛手术治疗婴儿脑积水 烧灼（ETV/CPC）可避免大多数人的分流依赖性。我们之前在 CURE 的合作工作 乌干达儿童医院 (CCHU) 支持分流安置和 ETV/CPC 之间的平衡 才能有5年的生存和发展。 ETV/CPC 可以防止那些没有紧急情况的人出现分流依赖 解决分流故障的方法很引人注目，但我们不知道哪种治疗方法可以优化发育。 我们寻求确认最佳的治疗选择范例。使用基于 CT 的测量，我们发现大脑 和脑脊液体积区分神经认知结果，提供了一种有希望的客观测量 脑积水治疗效果。来自我们 R-21 和 R01 资助的随机对照试验的初步数据 ETV/CPC 与分流治疗 PIH 的随机对照试验（ClinicalTrials.gov 注册 NCT01936272）显示没有 一年内安全性、有效性、发育结果或大脑生长方面的重要差异 那些在 1 岁时脑容量达到正常或接近正常的患者，无论术前容量如何，都有最好的表现 结果。当前的提案旨在实现以下目标：1）检验以下假设： 5年内镜下治疗妊娠高血压综合征优于或等于分流术 神经认知发展； 2) 进一步将CCHU发展成为神经科学研究机构； 3）开发 国内可持续超低场 (ULF) MRI 成像的能力； 4) 安装优化的ULF-MRI 在CCHU； 5) 将 MRI 衍生的大脑/CSF 体积指标与长期神经认知相关联 PIH 治疗后的发展。按计划，RCT患者研究队列将进一步进行 使用贝利婴儿发育量表 (BSID-III) 进行 24 个月后的发育评估 与重复基于 CT 的大脑和脑脊液体积指标一起进行操作。在当前的提案中，发展 将在治疗后 5 年使用 Vineland-III 进行评估，并评估 生活质量。将姆巴拉拉科技大学 (MUST) 开发为 ULF-MRI 后 示范和资源中心，ULF-MRI 将安装在 CCHU，用于评估体积和 与 CT 相比的诊断工具。神经认知结果将与术前和术后 MRI 相关 基于脑/脑脊液体积和治疗方式。研究的扩展将确定是否非劣效性 ETV/CPC 的分流与发育结果有关，并且大脑生长在治疗后 5 年持续存在， 基于 MRI 的体积指标是否能有效取代基于 CT 的指标，以及大脑和脑脊液是否有效 事实证明，体积测量对于指导最佳临床管理很有用。拟议的项目将决定是否 ETV/CPC 是首选的初始治疗方法，并将进一步发展 CCHU 的研究能力。