In Vivo CSF Shunt Hydrodynamics in Hydrocephalus

描述（由申请人提供）：由于诊断的不确定性和高治疗风险，正常压力脑积水（NPH）的治疗具有挑战性。迄今为止，尚无针对这种疾病的循证治疗指南。我们的长期目标是通过降低与分流阀相关的并发症以及增加我们对不同分流器设计如何影响脑脊液（CSF）流体动力学的理解来改善NPH的结果。本研究采用三层共享主题研究设计。具体目的是：1)确定两种可调阀设计，一种带虹吸控制装置，一种不带虹吸控制装置，在降低并发症发生率方面，哪一种设计更适合治疗NPH； 2)比较标准差压阀在治疗NPH时，带虹吸控制装置和不带虹吸控制装置的颅内压（ICP）生理反应；3)确定分流手术前后测量的颅内血流/流体动力学变量，支持颅内压动力学的调谐动态吸收器模型。我们假设虹吸控制装置增加分流引流不足的发生率，表现为缺乏神经改善和心室大小缩小。此外，我们假设目前的脑积水模型过于简单，基于ICP波形特征和新动态模型的应用，分流引起的流体动力学可以更好地建模。所有的研究都将作为前瞻性随机临床试验的一部分进行，评估两种现有的fda批准的可调节瓣膜。结果分析将有助于临床医生在NPH管理中应用循证指南。从更好地理解脑脊液分流术的颅内压生理学的角度来看，全面的流体动力学研究将提供有价值的信息，这将有助于为个体患者选择最佳的瓣膜压力或类型。此外，我们预计分流阀制造商将使用这些信息来改进当前的阀门设计。记录调谐动力吸收器模型的明确证据可能对所有ICP疾病具有根本意义。

DESCRIPTION (provided by applicant): The management of normal pressure hydrocephalus (NPH) is challenging due to diagnostic uncertainties and high treatment risks. To date, there are no evidence-based treatment guidelines for this disorder. Our long-term goal is to improve the outcome of NPH by lowering complications related to shunt valves and by increasing our understanding of how different shunt designs influence cerebrospinal fluid (CSF) hydrodynamics. This investigation uses a three-tiered shared-subject study design. The Specific Aims are to 1) determine which of two adjustable valve designs, one with a siphon control device and one without, is superior for the treatment of NPH with regard to lowering the complication rate, 2) compare the intracranial pressure (ICP) physiological response of a standard differential pressure valve, with and without a siphon control device, in the treatment of NPH, and 3) determine whether intracranial hemo/hydrodynamic variables, measured before and after a shunt operation, support the tuned-dynamic absorber model, of intracranial pressure dynamics. We hypothesize that siphon control devices increase the incidence of shunt under-drainage, manifesting as a lack of both neurological improvement and ventricular size reduction. Furthermore, we hypothesize that current hydrocephalus models are over- simplistic and that shunt-induced hydrodynamics are better modeled based on ICP waveform characteristics and the application of novel dynamic models. All of the studies will be performed as part of a prospective, randomized clinical trial assessing two existing, FDA-approved, adjustable valves. The outcome analysis will be useful for clinicians wishing to apply evidence-based guidelines in the management of NPH. From a viewpoint of better understanding the ICP physiology of CSF shunts, the comprehensive hydrodynamic studies will provide valuable information that will be useful in selecting the optimal valve pressure or type for individual patients. In addition, we foresee the information being used by shunt valve manufacturers to improve current valve designs. Documenting definitive evidence of the tuned-dynamic absorber model could have fundamental implications to all ICP disorders.