Endoscopic versus Shunt Treatment of Hydrocephalus in Infants

婴儿脑积水的内镜与分流治疗

• 批准号: 10706453
• 负责人: Richard Holubkov
• 金额: $ 154.44万
• 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/10706453
• 关键词: 1 year old; Abdomen; Accounting; Affect; Age; Age Years; American; Anisotropy; Brain; Cauterize; 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; 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。脑积水的传统治疗方法是。 脑脊液（CSF）分流术的终身并发症很高且昂贵，每年都会发生。 医院费用近20亿美元，占所有儿科医院费用的3.1%。 并发症也会对生活质量产生不利影响，因此对受并发症影响的家庭进行的调查也就不足为奇了 脑积水表明他们迫切需要无分流治疗方案 最有希望的无分流治疗方案。 婴儿脑积水的治疗方法是内镜下第三脑室造口术和脉络丛烧灼术 (ETV+CPC)，我们的脑积水临床研究网络 (HCRN) 和其他机构已证明其安全 然而，我们的数据表明，ETV+CPC 与分流相比的认知结果尚不清楚。 大多数家庭会接受 ETV+CPC 的风险以获得免分流的机会，但前提是最初 与分流治疗相比，ETV+CPC 治疗不会导致认知结果明显下降。 在此 U01 提案中，我们的目标是： 1. 确定 ≤12 个月校正年龄的婴儿中，脑积水需要 北美三级儿科神经外科中心的治疗，ETV+CPC 与分流术相比 根据婴儿和婴儿贝利量表测量，手术后 12 个月时认知结果不较差 幼儿发展 (Bayley-III) 认知量表的非劣效性为 1.5 确定，在 2a 中。 同一队列，如果 ETV+CPC 与分流结果相比，Bayley-III 运动/语言量表不较差，或者 Vineland-3 量表 2b。 治疗失败、住院天数、重复手术、成像的使用）以及治疗组之间的并发症。 3a. 利用扩散 MR 确定 ETV+CPC 和分流对大脑结构连接的影响 术后 12 个月胼胝体各向异性分数 (FA) 定义关系。 术前脑/心室容量和脑脊液 (CSF) NCAM-1 水平与术后之间的关系 术后 12 个月胼胝体 FA 和 Bayley-III 认知量表 3c。 脑/心室容积的变化（术前至术后 12 个月）与 FA 之间 术后12个月胼胝体和皮质脊髓束以及Bayley-III认知和运动量表。 为此，我们计划在 HCRN 内开展一项随机对照试验，比较 ETV+CPC 和分流术治疗脑积水婴儿， 由 14 个北美领先的儿科神经外科中心组成的忠诚团队，拥有长期的记录 脑积水的成功合作临床研究和随机对照试验，最佳认知结果，主要内容。 因此，家庭的关注将是我们对 dMRI（一种经过验证的非侵入性）的评估的主要结果。 测量发育中白质微观结构完整性和结构连接性的方法 该随机对照试验将进一步深入了解这两种治疗的发育后果。 帮助家庭确定孩子脑积水的最佳治疗方法。

项目成果

Endoscopic third ventriculostomy in previously shunt-treated patients.

对既往接受过分流治疗的患者进行内镜下第三脑室造口术。

• DOI: 10.3171/2022.6.peds22177
• 发表时间: 2022
• 期刊: Journal of neurosurgery. Pediatrics
• 作者: Rocque,BrandonG;Jensen,Hailey;Reeder,RonW;Kulkarni,AbhayaV;Pollack,IanF;Wellons,JohnC;Naftel,RobertP;Jackson,EricM;Whitehead,WilliamE;Pindrik,JonathanA;Limbrick,DavidD;McDonald,PatrickJ;Tamber,MandeepS;Hankinson,Todd
• 通讯作者: Hankinson,Todd