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

本次R01续订的目标是由我们成功进行的随机调查的结果驱动的 内窥镜下第三脑室造瘘术联合脉络丛术的临床对照研究 电灼术(ETV/CPC)分流治疗感染后脑积水(PIH)最常见 乌干达的脑积水病因学)对6个月大的婴儿(ClinicalTrials.gov NCT01936272， R01HD085853，R21HD068213)，在乌干达治愈儿童医院(CCHU)。过渡时期 这项研究的结果正在成为儿童医学的里程碑，发现：a)最多24岁 3个月后，ETV/CPC组与分流组的失败率无显著差异。 发育结果和脑生长；b)脑体积，而不是脑脊液体积，与 发育结果；c)脑积水的成功治疗改善了#年的脑发育 第一年，第二年停滞不前。因为几乎所有内窥镜检查的失败 治疗发生在生命的第一年，我们预计， 如果我们跟踪观察这些儿童直到小学年龄，脑积水的治疗可能有利于内窥镜检查。 从5年到10年不等。此外，我们进行更详细的神经认知评估的能力 在此期间，进一步的跟踪将比我们的学前评估更准确。最后， 如果可以，我们可以收集所有数据并执行更明确的成本效益分析 跟随这一独特的队列整整10年。 在过去5年的支持期间，我们进行了大量的能力建设 临床试验。我们在乌干达治愈儿童医院建立了一个蓬勃发展的研究单位， 使高质量的研究能够在NIH资助的多个与此无关的其他研究中进行 临床试验(DP1HD086071、R01AI145057和R01HD096693)。此外，由于所有的脑积水 治疗需要脑成像，我们已经为可持续低场磁共振开发了一个蓬勃发展的中心 他在姆巴拉拉科技大学学习工程学。 本项目旨在跟踪这一独特的队列至10岁，寻求最终确定 确定内窥镜治疗对发展中国家的婴儿是否更可持续，建立 低场磁共振作为一种可持续的成像技术，建立了医疗和医疗两方面的能力 乌干达的工程地点，作为非洲的独立研究和技术开发中心。

The goals of this R01 Renewal are driven by the results of our successfully conducted randomized controlled clinical trial comparing endoscopic third ventriculostomy combined with choroid plexus cauterization (ETV/CPC) to shunt treatment for post-infectious hydrocephalus (PIH, the most common hydrocephalus etiology in Uganda) in infants < 6 months of age (ClinicalTrials.gov NCT01936272, R01HD085853, R21HD068213) at the CURE Children’s Hospital of Uganda (CCHU). The interim outcomes of this study are becoming a landmark in children’s medicine, finding that: a) at up to 24 months, there was no significant difference between ETV/CPC and shunt in regard to failure rate, developmental outcome, and brain growth; b) brain volume, not CSF volume, correlated strongly with developmental outcome; c) successful treatment of the hydrocephalus led to improved brain growth in the first year, which stagnated during the second year. Because almost all of the failures of endoscopic treatment occurred early in the first year of life, we anticipate that the longer term outcomes of hydrocephalus treatment may favor endoscopy if we follow these children through primary school age from 5 to 10 years. Furthermore, our ability to perform much more detailed neurocognitive assessments during this further followup will be much more accurate than during our pre-school assessments. Lastly, we can gather all of our data and perform a much more definitive cost-effectiveness analysis if we can follow this unique cohort for a full 10 years. We have engaged in substantial capacity building during the previous 5 years of support during this clinical trial. We have developed a thriving research unit at the CURE Children’s Hospital of Uganda, enabling high-quality research to be conducted in multiple other NIH funded studies unrelated to this clinical trial (DP1HD086071, R01AI145057, and R01HD096693). Furthermore, since all hydrocephalus treatment requires brain imaging, we have developed a thriving center for sustainable low-field MRI engineering at the Mbarara University of Science and Technology. This present project seeks to follow this unique cohort to 10 years of age, seeking to definitively establish whether endoscopic treatment is more sustainable for infants in the developing world, establish low field MRI as a sustainable imaging technology, and establish the capacity of both the medical and engineering sites in Uganda as independent research and technology development centers for Africa.