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; 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.

项目摘要/摘要 婴儿脑积水是一个严重的全球健康问题，估计每年有40万例新病例。几乎 其中一半在撒哈拉以南非洲发生，新生儿感染是那里最常见的原因。未经处理， 脑积水会导致脑损伤甚至死亡。标准治疗长期以来一直是 放置脑室的分流（VPS），但这些设备需要终身维护和几乎所有设备 多次失败。因此，分流依赖性在LMIC中更危险 神经外科护理困难或不可能。治愈乌干达儿童医院（CCHU）开发了一种替代方法 内窥镜第三室术与脉络丛餐饮（ETV/CPC）相结合的治疗 患者无分流的寿命。 ETV/CPC与VPS的NIH资助，随机对照试验，用于患有后婴儿 CCHU的传染性脑积水（PIH）发现大脑后一年治疗没有显着差异 增长或发展结果。治疗失败是两者的重大问题，发生在三分之一中。 发育结果与大脑生长的量有关，但与传统指标无关 头或心室尺寸。治疗一直集中在控制心室大小上，但这几乎没有关联 有结果。大脑生长是一个更好的指标，我们在PIH中假设这部分取决于完整性 感染后的潜在大脑物质，部分是脑循环支持法规的能力。 因此，我们假设脑血流和代谢更代表疾病严重程度 和治疗反应。我们开发了一种新颖的频域近红外和分散 相关光谱（FDNIRS/DCS）技术以测量脑血流（CBF）和氧气 代谢（CMRO2）在床边非侵入性。在BCH和CCHU的试点研究中，我们发现未经治疗 脑积水逐渐阻碍了脑灌注并抑制代谢，而成功治疗 立即恢复CBF和CMRO2。此外，手术后立即更大的CMRO2与 六个月后，大脑生长更好。现在，我们建议在更大的小组中验证这些结果，目的是 领先的脑积水治疗远离靶向通风尺寸而不是将其引导到测量 大脑身体健康的改善。这样的范式转变将对 发展中国家，美国和世界其他地区。