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: 9651986
• 负责人: Abhaya V Kulkarni
• 金额: $ 59.13万
• 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 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9651986
• 关键词: Neurocognitive; outcomes; changes; brain; CSF

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25万新生儿发生脑积水，最常见的是新生儿感染， 非洲撒哈拉沙漠（SSA）大多数人难以获得治疗。我们开发并验证了一种新的 内镜下第三脑室底造瘘联合脉络丛手术治疗婴幼儿脑积水 电灼术（ETV/CPC），避免了大多数分流依赖。我们之前在CURE的合作工作 乌干达儿童医院（CCHU）支持分流术与ETV/CPC之间的平衡， 5年的生存和发展。ETV/CPC可以防止那些没有紧急 分流功能障碍的访问是引人注目的，但我们不知道哪种治疗优化发展。 我们寻求确认最佳的治疗选择范例。通过CT测量，我们发现大脑 和CSF容量区分神经认知结果，提供了一个有前途的客观衡量指标， 脑积水治疗效果。来自我们的R-21和R 01资助的随机对照试验的初步数据 (RCT)用于PIH治疗的ETV/CPC与分流术（ClinicalTrials.gov注册NCT 01936272）显示， 1年时安全性、有效性、发育结局或脑生长方面的重要差异 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， 结果。目前的建议旨在实现以下目标：1）测试假设， 就5年随访而言，妊高征的内镜治疗优于或等于分流术 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 国内可持续超低场（ULF）MRI成像能力; 4）安装优化的ULF-MRI 在CCHU; 5）将MRI衍生的脑/CSF体积指标与长期神经认知功能相关 PIH治疗后的发展。按照计划，RCT患者研究队列将接受进一步的 使用Bayley婴儿发育量表（BSID-III）在术后24个月进行发育评估。 可操作地沿着重复的基于CT的脑和CSF体积度量。在目前的提案中， 将在治疗后5年使用Vineland-III进行评估，并评估 生活质量在开发Mbarara科技大学（MUST）作为ULF-MRI之后， 作为一个示范和资源中心，ULF-MRI将安装在CCHU进行评估， 与CT相比，诊断工具。神经认知结局将与术前和术后MRI相关- 基于脑/CSF体积和治疗方式。研究的扩展将确定非劣效性 在治疗后5年，ETV/CPC分流的发育结局和脑生长持续存在， 基于MRI的体积指标是否有效地取代了基于CT的测量，以及脑和CSF是否 容量测定法证明可用于指导最佳临床管理。该项目将确定是否 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。