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

描述(由申请人提供)：我们估计撒哈拉以南非洲每年有超过10万名新生婴儿患上感染后脑积水(PIH)，其中大多数没有机会接受治疗。我们先前在乌干达治疗儿童医院(CCHU)的合作工作：a)确定新生儿感染是儿童脑积水最常见的单一原因，也是导致原发脑损伤的重要原因；b)确定不动杆菌是妊高征潜在的重要病原体，具有季节性变化；c)展示了廉价分流治疗的一年结果；d)开发了内窥镜第三脑室造口和脉络丛烧灼联合(ETV/CPC)治疗婴儿脑积水的新技术，避免了分流依赖的危险；e)制定了一种评分来预测ETV/CPC的结果；(F)在脊髓脊膜膨出(MM)婴儿中，分流术或ETV/CPC的早期发育结果总体上没有差异；以及，g)在8个发展中国家，受过这种手术培训的外科医生。ETV/CPC防止那些无法紧急获得分流故障专科护理的人的分流依赖是令人信服的，但我们不知道哪种治疗方法对特定的PIH患者的大脑发育最优，我们发现MM婴儿合并脑积水的治疗组之间5年存活率没有差异。我们寻求确认最佳治疗选择范例。使用来自CT成像的数据，我们发现脑体积和脑脊液体积都是神经认知结果的显著多变量判别器。该方法作为脑积水治疗效果的客观衡量指标具有广阔的应用前景。R21建议：1)将CCHU发展为脑积水研究和临床试验的独立场所；2)将脑/脑脊液体积指标与妊高征治疗期间的神经认知发育相关；3)通过随机对照试验(RCT)检验ETV/CPC治疗妊高征在神经认知发育方面与分流术相同或更好的假设；以及4)确定用术前脑/脑脊液体积参数指导治疗的可行性。ETV/CPC在50-70%的妊高征儿中获得成功，而在CCHU的分流患者中，54%在一年内获得成功。在MM婴儿中，我们发现两种治疗方法在5年存活率上没有差别。对于妊高征儿，将进行RCT分流与ETV/CPC比较。在手术前、术后6个月和12个月，患者将接受CT成像，以进行脑和脑脊液容量评估，并使用贝利婴儿发育量表(BSID)进行神经认知评估。神经认知结果、手术前和手术后的脑/脑脊液体积以及治疗方式将相互关联。CCHU的能力将被开发用于全面的患者随访、神经认知评估、脑/脑脊液容量测定、统计分析以及未来脑积水研究的临床试验设计。这些初步数据和研究站点的开发将为未来R01的后续协作应用奠定基础。 与公共卫生相关：感染后脑积水似乎是整个发展中世界的一个重大公共卫生问题，在出现承认和治疗这类儿童的国内专门护理之前，该问题没有引起全球卫生界的注意。治疗这些儿童有两种策略-分流术和内窥镜技术-没有明确的证据支持哪种疗法是最佳的。借助新的体积图像分析工具，将神经发育结果与脑生长相关联，我们在东非提出了一项新的随机临床试验，将为更好地治疗此类儿童奠定循证基础。

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.