Endoscopic versus Shunt Treatment of Hydrocephalus in Infants

婴儿脑积水的内镜与分流治疗

• 批准号: 10242095
• 负责人: Richard Holubkov
• 金额: $ 149.22万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10242095
• 关键词: 1 year old; Abdomen; Accounting; Affect; Age; Age-Years; American; Anisotropy; Brain; Cauterize; Cerebral Ventricles; Cerebrospinal Fluid; Cerebrospinal fluid shunts procedure; Cerebrum; Child; Childhood; Clinical Research; Cognitive; Corpus Callosum; Corticospinal Tracts; Data; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Family; Hospital Charges; Hydrocephalus; Image; Infant; Language; Length of Stay; Life; Measures; Methods; Motor; NCAM1 gene; Neurologic; North America; Operative Surgical Procedures; Outcome; Pediatric Hospitals; Performance; Postoperative Period; Procedures; Quality of life; Repeat Surgery; Risk; Shunt Device; Structure of choroid plexus; Surveys; Time; Toddler; Treatment Failure; Ventricular; Ventriculostomy; cohort; insight; neurosurgery; optimal treatments; primary outcome; randomized trial; tertiary care; treatment arm; white matter

Hydrocephalus primarily affects infants under one year of age. The traditional treatment for hydrocephalus is cerebrospinal fluid (CSF) shunt. Life-time complications of CSF shunts are high and expensive, with annual hospital charges of nearly $2.0 billion, accounting for 3.1% of all pediatric hospital charges. As shunt complications also adversely impact quality of life, it is not surprising that surveys of families affected by hydrocephalus show that they desperately desire shunt-free treatment options. The most promising shunt-free treatment for infant hydrocephalus is endoscopic third ventriculostomy with choroid plexus cauterization (ETV+CPC), which our Hydrocephalus Clinical Research Network (HCRN) and others have shown to be safe and viable. However, the cognitive outcome of ETV+CPC compared to shunt is not known. Our data suggest that most families would accept the risks of ETV+CPC for the chance to be free of shunt, but only if initial treatment with ETV+CPC will not lead to noticeable sacrifice in cognitive outcome compared to shunting. With this U01 proposal, we aim: 1. To determine, in infants ≤12 months corrected age, with hydrocephalus requiring treatment at tertiary care pediatric neurosurgery centers in North America, does ETV+CPC compared to shunt result in non-inferior cognitive outcome at 12 months from surgery, as measured by Bayley Scales of Infant and Toddler Development (Bayley-III) Cognitive Scale with a non-inferiority margin of 1.5. 2a. To determine, in the same cohort, if ETV+CPC compared to shunt results in non-inferior Bayley-III Motor/Language Scales or Vineland-3 Scales. 2b. To compare other measures of treatment performance (brain/ventricle volume, treatment failure, hospital days, repeat surgery, use of imaging) and complications between treatment arms. 3a. To determine the effect of ETV+CPC and shunt on cerebral structural connectivity, with diffusion MR fractional anisotropy (FA) in the corpus callosum 12 months after surgery. 3b. To define the relationships between pre-operative brain/ventricular volume and cerebrospinal fluid (CSF) NCAM-1 level to post-operative corpus callosum FA and Bayley-III Cognitive Scale 12 months after surgery. 3c. To define the relationships between change in brain/ventricular volume (pre-operatively to 12 months post-operatively) to FA in the corpus callosum and corticospinal tract and Bayley-III Cognitive and Motor Scales 12 months post-operatively. To do this, we plan an RCT comparing ETV+CPC and shunt in infants with hydrocephalus, within the HCRN, a committed group of 14 leading North American pediatric neurosurgical centers with a long track-record of successful collaborative clinical research and RCTs in hydrocephalus. Optimal cognitive outcome, the primary concern of families, will therefore, be our primary outcome. Assessment of dMRI, a validated, non-invasive method of measuring white matter microstructural integrity and structural connectivity in the developing brain, will provide further insight into the developmental consequences of these 2 treatments. This RCT will help families determine the optimal treatment of hydrocephalus for their child.

脑积水主要影响一岁以下的婴儿。传统的脑积水治疗方法是 脑脊液（CSF）分流。 CSF分流的终身并发症高且昂贵，每年 医院收费近20亿美元，占所有儿科医院费用的3.1％。作为分流 并发症也会对生活质量产生不利影响，毫不奇怪，对受影响的家庭的调查 脑积水表明，他们迫切需要无分流的治疗选择。最有前途的无分流 婴儿脑积水的治疗是内窥镜的第三室室造口术，脉络丛餐 （ETV+CPC），我们的脑积水临床研究网络（HCRN）和其他证明是安全的 和可行。然而，与分流相比，ETV+CPC的认知结果尚不清楚。我们的数据暗示 大多数家庭都会接受ETV+CPC的风险，有机会摆脱分流的机会，但前提是初始 与分流相比，用ETV+CPC的治疗不会导致认知结果的明显牺牲。和 该U01提案，我们的目标：1。确定在≤12个月校正年龄的婴儿中，脑积水需要 与关闭相比 通过手术后12个月的贝利尺度衡量的婴儿和 幼儿发展（Bayley-III）认知量表，非效率差为1.5。 2a。确定，在 相同的队列，如果ETV+CPC与非内部bayley-III运动/语言尺度相比，分流率相比 Vineland-3量表。 2b。比较其他治疗性能的度量（大脑/心室体积， 治疗失败，住院日，重复手术，使用成像）和治疗臂之间的并发症。 3a。确定ETV+CPC和分流对脑结构连通性的影响，并扩散MR 手术后12个月的call体call体的分数各向异性（FA）。 3b。定义关系 术前大脑/心室体积和脑脊液（CSF）NCAM-1水平与术后水平 手术后12个月，call体FA和Bayley-III认知量表。 3C。定义关系 在大脑/心室体积的变化（术前至术后12个月）之间 术后12个月的call体和皮质脊髓和贝利 - III认知和运动尺度。 为此，我们计划一个RCT，比较脑积水的婴儿中的ETV+CPC和分流，在HCRN内，A 由14个领先的北美小儿神经外科手术中心组成 成功的合作临床研究和RCT在脑积水中。最佳认知结果，主要 因此，对家庭的关注将是我们的主要结果。评估DMRI，经过验证的，无创的 在发育中测量白质微观结构完整性和结构连接的方法 大脑将进一步了解这两种治疗方法的发展后果。这个RCT会 帮助家庭确定对孩子的最佳治疗方法。