Improving infant hydrocephalus outcomes in Uganda: Predicting developmental outcomes and identifying patients at risk for early treatment failure after ETV/CPC

改善乌干达婴儿脑积水的结局：预测发育结局并识别 ETV/CPC 后处于早期治疗失败风险的患者

• 批准号: 10192775
• 负责人: Pei-Yi Lin
• 金额: $ 53.69万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-13 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10192775
• 关键词: Africa South of the Sahara; Aftercare; Age-Months; Boston; Brain; Brain Injuries; Caring; Cauterize; Cerebrovascular Circulation; Cerebrum; Cessation of life; Clinical; Collaborations; Combined Modality Therapy; Creation of ventriculo-peritoneal shunt; Custom; Dangerousness; Data Analyses; Dependence; Developing Countries; Development; Devices; Diffuse; Disease; Early treatment; Emergency Situation; Enrollment; Evolution; Failure; Frequencies; Funding; Goals; Growth; Head; Health; Hydrocephalus; Infant; Infection; Infrastructure; Investments; Lead; Length of Stay; Life; Longterm Follow-up; Maintenance; Measurable; Measurement; Measures; Metabolism; Monitor; National Institute of Child Health and Human Development; Neonatal; Operative Surgical Procedures; Optics; Outcome; Oxygen; Patients; Pediatric Hospitals; Perfusion; Physiological; Physiology; Pilot Projects; Postoperative Period; Prediction of Response to Therapy; Property; Randomized Controlled Trials; Resources; Rest; Risk; Scanning; Severities; Severity of illness; Shunt Device; Site; Spectrum Analysis; Structure; Structure of choroid plexus; Technology; Testing; Thick; Time; Toddler; Training; Treatment Failure; Treatment Step; Uganda; United States; United States National Institutes of Health; Ventriculostomy; X-Ray Computed Tomography; base; brain health; global health; high risk; improved; international center; large scale data; longitudinal dataset; low and middle-income countries; neonatal infection; neurodevelopment; novel; peer; prognostic assays; prognostic tool; quality assurance; standard care; treatment response

Project Summary/Abstract Infant hydrocephalus is a serious global health problem, with an estimated 400,000 new cases annually. Nearly half of these occur in sub-Saharan Africa, with neonatal infection being the most common cause there. Untreated, hydrocephalus causes progressive brain injury and even death. The standard treatment has long been placement of a ventriculoperitoneal shunt (VPS) but these devices require life-long maintenance and nearly all fail multiple times. Because of this, shunt-dependence is more dangerous in LMIC where emergency access to neurosurgical care is difficult or impossible. CURE Children’s Hospital of Uganda (CCHU) developed an alternate treatment combining endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) to give patients a shunt-free life. An NIH-funded, randomized controlled trial of ETV/CPC vs VPS for infants with post- infectious hydrocephalus (PIH) at CCHU found no significant difference at one-year post-treatment in brain growth or developmental outcomes. Treatment failure is a significant problem for both, occurring in a third. Developmental outcomes were associated with the amount of brain growth, but not with traditional metrics of head or ventricle size. Treatment has always focused on controlling ventricle size, but this has little association with outcomes. Brain growth is a better indicator, and we hypothesize in PIH it depends in part on the integrity of the underlying brain matter after infection and in part on the cerebral circulation’s ability to support regrowth. Consequently, we hypothesize cerebral blood flow and metabolism are more representative of disease severity and treatment response. We developed a novel, combined frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS/DCS) technology to measure cerebral blood flow (CBF) and oxygen metabolism (CMRO2) non-invasively at the bedside. In pilot studies at BCH and CCHU, we found untreated hydrocephalus progressively impedes cerebral perfusion and depresses metabolism, while successful treatment immediately restores CBF and CMRO2. Moreover, greater CMRO2 immediately after surgery correlated with better brain growth six months later. We now propose validating these results in a larger group with the goal of leading hydrocephalus treatment away from targeting ventricle size and directing it instead towards measurable improvements in the brain’s physiological health. Such a paradigm shift will have substantial clinical impact in developing countries, the United States, and the rest of the world.

项目概要/摘要 婴儿脑积水是一个严重的全球健康问题，估计每年新增病例 40 万例。 其中一半发生在撒哈拉以南非洲，其中新生儿感染是最常见的原因。 脑积水会导致进行性脑损伤，甚至死亡。 放置脑室腹腔分流器 (VPS)，但这些设备需要终生维护，并且几乎所有 因此，在紧急访问的 LMIC 中，分流依赖性更加危险。 神经外科护理很困难或不可能，乌干达 CURE 儿童医院 (CCHU) 开发了替代方案。 内镜下第三脑室造口术与脉络丛烧灼术 (ETV/CPC) 相结合的治疗 NIH 资助的一项关于 ETV/CPC 与 VPS 治疗后婴儿的随机对照试验。 CCHU 的传染性脑积水 (PIH) 在治疗一年后发现大脑没有显着差异 生长或发育结果的治疗失败对两者来说都是一个重大问题，发生在三分之一的情况下。 发育结果与大脑生长量相关，但与传统的生长指标无关 头部或心室大小的治疗始终集中在控制心室大小，但这几乎没有关联。 大脑发育是一个更好的指标，我们在 PIH 中勇敢地说，它部分取决于完整性。 感染后大脑底层物质的变化，部分影响大脑循环支持再生的能力。 脑血流量和代谢更能代表疾病严重程度 我们开发了一种新颖的组合频域近红外和漫射。 相关光谱 (FDNIRS/DCS) 技术测量脑血流量 (CBF) 和氧气 在 BCH 和 CCHU 的试点研究中，我们发现未经治疗的床边非侵入性代谢（CMRO2）。 脑积水逐渐阻碍脑灌注并抑制新陈代谢，而成功的治疗 立即恢复 CBF 和 CMRO2 此外，手术后立即恢复较高的 CMRO2 与相关。 六个月后大脑发育更好，我们现在建议在更大的群体中验证这些结果，目标是 导致脑积水治疗不再以脑室大小为目标，而是转向可测量的 这种范式转变将对大脑的生理健康产生重大的临床影响。 发展中国家、美国和世界其他国家。