Neurocognitive outcomes and changes in brain and CSF volume after treatment of po

描述（由申请人提供）：我们估计，在撒哈拉以南非洲地区，每年有超过100，000名新生儿发生感染后脑积水（PIH），大多数没有机会接受治疗。我们之前在乌干达CURE儿童医院（CCHU）的合作工作：a）确定新生儿感染是小儿脑积水的最常见原因，也是原发性脑损伤的重要原因; B）确定不动杆菌是妊高征的潜在重要病原体，具有季节性差异; c）证明了使用廉价分流术治疗的一年结局; d）开发了用于治疗婴儿脑积水的联合内窥镜第三脑室造口术和脉络丛烧灼术（ETV/CPC）的新技术，避免了分流依赖的危险; e）开发了预测ETV/CPC结果的评分; f）在脊髓脊膜膨出（MM）婴儿中，分流或ETV/CPC的早期发育结局没有总体差异; g）在8个发展中国家接受过该手术的培训外科医生。ETV/CPC可防止因分流故障而无法紧急接受专科护理的患者出现分流依赖性，这一点很有说服力，但我们不知道哪种治疗可优化给定PIH患者的大脑发育，我们发现两个治疗组间MM脑积水婴儿的5年生存率无差异。我们寻求确认最佳的治疗选择范例。使用CT成像数据，我们发现脑容量和CSF容量（在较小但重要的程度上）是神经认知结果的重要多变量判别因素。该方法有望作为脑积水治疗疗效的客观指标。本R21建议：1）将CCHU作为脑积水研究和临床试验的独立场所; 2）将脑/CSF容量指标与妊高征治疗期间的神经认知发育相关联; 3）通过随机对照试验（RCT）验证ETV/CPC治疗妊高征在神经认知发育方面与分流术一样好或更好的假设;以及4）确定采用术前脑/CSF体积参数来指导治疗的可行性。ETV/CPC在50-70%的PIH婴儿中成功，而CCHU的分流患者中有54%在一年内成功。我们发现两种治疗MM婴儿的5年生存率无差异。将对PIH婴儿进行分流管置入与ETV/CPC的RCT。术前以及术后6个月和12个月时，患者将接受CT成像，以进行脑和CSF体积评估，并使用Bayley婴儿发育量表（BSID）进行神经认知评估。将神经认知结局、术前和术后脑/CSF体积和治疗方式相关联。CCHU将发展全面的患者随访、神经认知评估、脑/CSF体积测定、统计分析和未来脑积水研究的临床试验设计能力。这些初步数据和研究地点的开发将为未来的R 01合作应用奠定基础。 公共卫生相关性：感染后脑积水似乎是整个发展中世界的一个主要公共卫生问题，在国内出现识别和治疗此类儿童的专业护理之前，它没有引起全球卫生界的注意。有两种治疗这些儿童的策略-分流术与内窥镜技术-没有明确的证据支持哪种治疗是最佳的。配备了新的体积图像分析工具，将神经发育结果与大脑生长相关联，我们在这里提出了一个新的随机临床试验在东非，将启动一个循证基础，更好地治疗这些儿童。

DESCRIPTION (provided by applicant): We estimate that more than 100,000 new infants develop post-infectious hydrocephalus (PIH) in sub-Saharan Africa each year, and most have no opportunity for treatment. Our prior collaborative work at CURE Children's Hospital of Uganda (CCHU) has: a) identified neonatal infection as the single most common cause of pediatric hydrocephalus and an important cause of primary brain injury; b) identified acinetobacter as a potentially important pathogen in PIH with seasonal variance; c) demonstrated the one-year outcome of treatment with an inexpensive shunt; d) developed the novel technique of combined endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC) for treating infant hydrocephalus that avoids the danger of shunt-dependence; e) developed a score to predict the outcome for ETV/CPC; f) showed no overall difference in early developmental outcomes for shunting or ETV/CPC in myelomeningocele (MM) infants; and, g) trained surgeons for this procedure in 8 developing countries. That ETV/CPC prevents shunt dependence among those with no urgent access to subspecialty care for shunt malfunction is compelling, but we do not know which treatment optimizes brain development in a given PIH patient, and we found no difference in 5 year survival between treatment groups for MM infants with hydrocephalus. We seek to confirm the optimal treatment selection paradigm. Using data from CT imaging, we have found that both brain volume, and to a lesser but important degree, CSF volume, are significant multivariate discriminators of neurocognitive outcome. This method is promising as an objective measure of hydrocephalus treatment efficacy. This R21 proposes to: 1) develop CCHU as an independent site for hydrocephalus research and clinical trials; 2) correlate brain/CSF volume metrics with neurocognitive development during PIH treament; 3) test the hypothesis that treatment of PIH by ETV/CPC is as good as or better than shunt placement in regard to neurocognitive development with a randomized controlled trial (RCT); and 4) Determine the feasibility of employing preoperative brain/CSF volume parameters to guide therapy. ETV/CPC is successful in 50-70% of infants with PIH, while 54% of shunted patients at CCHU are successful at one year. We found no difference in 5 year survival between the two treatments in MM infants. An RCT of shunt placement vs. ETV/CPC for infants with PIH will be performed. Preoperatively, and at 6 and 12 months postoperatively, patients will have CT imaging for brain and CSF volumetric assessment and neurocognitive assessment with the Bayley Scales of Infant Development (BSID) . Neurocognitive outcome, pre- and post- operative brain/CSF volumes, and treatment modality will be correlated. Capacity at CCHU will be developed for thorough patient follow up, neurocognitive assessment, brain/CSF volume determination, statistical analysis, and clinical trial design for future hydrocephalus research. These preliminary data and research site development will form the basis for future follow-on collaborative R01 applications. PUBLIC HEALTH RELEVANCE: Postinfectious hydrocephalus appears to be a major public health problem throughout the developing world that escaped the attention of the global health community prior to the emergence of in-country specialty care that recognizes and treats such children. There are two strategies for treating these children - shunting versus endoscopic techniques - with no definitive evidence supporting which therapy is optimal. Armed with new volumetric image analysis tools that correlate neurodevelopmental outcome with brain growth, we here propose a novel randomized clinical trial in East Africa that will initiate an evidence-based foundation for better treatment of such children.