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每年有超过10万的新生儿患上感染后脑积水（PIH），并且大多数没有机会得到治疗。我们之前在乌干达CURE儿童医院（CCHU）的合作工作：a)确定新生儿感染是儿童脑积水最常见的单一原因，也是原发性脑损伤的重要原因；b)确定不动杆菌是PIH中具有季节性变化的潜在重要病原体；C)证明了使用廉价分流器治疗一年的结果；d)开发了内镜下第三脑室造瘘联合脉络膜丛烧灼术（ETV/CPC）治疗婴儿脑积水的新技术，避免了分流依赖的危险；e)制定一个分数来预测ETV/CPC的结果；f)脊髓脊膜膨出（MM）婴儿的分流或ETV/CPC的早期发育结局没有总体差异；g)在8个发展中国家培训外科医生。ETV/CPC可以防止那些没有紧急获得分流管功能障碍亚专科护理的患者对分流管的依赖，这是令人信服的，但我们不知道哪种治疗方法可以优化特定PIH患者的大脑发育，我们发现MM婴儿脑积水的5年生存率在治疗组之间没有差异。我们试图确认最佳治疗选择范式。利用CT成像数据，我们发现脑容量和脑脊液容量是神经认知结果的重要多变量判别因素。该方法有望作为衡量脑积水治疗效果的客观指标。本R21建议：1)将CCHU发展为脑积水研究和临床试验的独立站点；2)将脑/脑脊液容量指标与PIH治疗期间的神经认知发展相关联；3)通过随机对照试验（RCT）验证ETV/CPC治疗PIH在神经认知发展方面与分流器放置一样好或更好的假设；4)确定术前脑/脑脊液容积参数指导治疗的可行性。在50-70%的PIH患儿中，ETV/CPC是成功的，而在CCHU的分流患者中，54%的患者在一年内是成功的。我们发现两种治疗方法在MM婴儿的5年生存率上没有差异。将对PIH患儿进行分流器放置与ETV/CPC的随机对照试验。术前、术后6个月和12个月，患者将接受CT成像，进行脑和脑脊液容量评估，并使用Bayley婴儿发育量表（BSID）进行神经认知评估。神经认知结果、术前和术后脑/脑脊液容量和治疗方式将相互关联。CCHU的能力将发展为彻底的患者随访，神经认知评估，脑/脑脊液容量测定，统计分析和临床试验设计，为未来的脑积水研究。这些初步数据和研究地点的开发将构成未来后续协作R01应用的基础。

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.