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Investigating Shunt-Responsiveness in Idiopathic Normal Pressure Hydrocephalus Using White Matter Tractography and Degenerative Biomarker Profiles

使用白质纤维束成像和退行性生物标志物谱研究特发性正常压力脑积水的分流反应性

基本信息

批准号：
MR/W030098/1
负责人：
Christopher Carswell
金额：
$ 32.08万
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2023
资助国家：
英国
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FW030098%2F1
关键词：
Investigating Shunt Responsiveness Idiopathic Normal

项目摘要

Idiopathic Normal Pressure Hydrocephalus (iNPH) is a disease in which patients develop dementia and problems with walking and bladder control due to hydrocephalus, where pressure increases in the normal fluid filled brain structures (ventricles) result in them getting larger and compressing critical brain structures. It is a common and severely disabling illness which affects between up to 3.7% of over 65 year-olds. Unlike typical dementias iNPH is treatable. Patients with these symptoms who are found to have features of iNPH on brain scans can have "cerebrospinal fluid (CSF) shunting", a process where brain fluid is surgically distracted to an area of lower pressure such as the abdominal cavity. Without treatment patients with iNPH progress to an immobile, demented and incontinent state. For unknown reasons, some patients with the correct features of iNPH on their brain scans do not respond to CSF shunting. There are "predictive tests" which can help inform who will improve with surgery. These tests carry risks as they involve assessing for improvement of symptoms after draining a large volume of CSF from the lower spine or accessing the spinal cavity with a needle and measuring the CSF pressure dynamics. Unfortunately, there is no known treatment for those individuals who do not respond to CSF-shunting and they must be supported with their progressive dementia, the cause of which is never really explained. Diffusion Tensor Imaging is a research Magnetic Resonance Imaging (MRI) scanning technique that can show very detailed white matter pathways in the brain which cannot be seen on conventional MRI brain scans. In this study we intend to perform white matter tractography using DTI in patients being investigated for iNPH and compare the scans from thirty iNPH patients and compare those whorespond to CSF shunting ("shunt-responsive") and those who do not ("shunt-unresponsiveness"). This will help us understand why some patients respond to CSF shunting and will also help us to develop non-invasive tests for these patients in the future. As white matter tractogrphy is influenced by neurodegenerative disease it will be important to account for co-existing neurodegeneration. We also hypothesise that patients with imaging features of iNPH who do not respond to predictive testing may have another cause for their symptoms such as neurodegenerative dementia (e.g. Parkinson's disease or Alzheimer's disease). In this study we also intend to test for a wide-range of dementias using blood tests, CSF tests, advanced brain imaging (amyloid-PET scanning) to develop "degenerative biomarker profiles" on the study patients. If we find evidence of neurodegenerative dementias in patients who do not respond to predictive testing, we will then be able to start work on providing a clear path of investigation and treatment for these unfortunate individuals.

特发性正常压力脑积水（iNPH）是一种疾病，其中患者由于脑积水而发展为痴呆和行走和膀胱控制问题，其中正常液体填充的脑结构（脑室）中的压力增加导致它们变大并压缩关键脑结构。这是一种常见的严重致残性疾病，影响高达3.7%的65岁以上的人。与典型的痴呆不同，iNPH是可以治疗的。具有这些症状的患者在脑部扫描中发现具有iNPH的特征，可以有“脑脊液（CSF）分流”，这是一个脑液被手术分散到低压区域（如腹腔）的过程。如果不治疗，iNPH患者会发展为不动、痴呆和失禁状态。由于未知的原因，一些在脑部扫描上具有正确iNPH特征的患者对CSF分流没有反应。有“预测性测试”可以帮助告知谁将通过手术改善。这些测试具有风险，因为它们涉及评估从下脊柱引流大量CSF后症状的改善或用针进入脊髓腔并测量CSF压力动力学。不幸的是，对于那些对CSF分流没有反应的人没有已知的治疗方法，他们必须支持进行性痴呆，其原因从未真正解释过。扩散张量成像是一种研究磁共振成像（MRI）扫描技术，可以显示大脑中非常详细的白色物质通路，这在常规MRI脑部扫描中无法看到。在这项研究中，我们打算使用DTI对iNPH患者进行白色纤维束成像，比较30例iNPH患者的扫描结果，并比较对CSF分流有反应（“分流反应”）和无反应（“分流无反应”）的患者。这将帮助我们理解为什么有些患者对CSF分流有反应，也将帮助我们在未来为这些患者开发非侵入性测试。由于白色物质纤维束描记术受神经退行性疾病的影响，因此解释共存的神经退行性病变将非常重要。我们还假设，具有iNPH成像特征的患者对预测性测试无反应，可能有其他原因导致其症状，如神经退行性痴呆（例如帕金森病或阿尔茨海默病）。在这项研究中，我们还打算使用血液测试，CSF测试，高级脑成像（淀粉样蛋白PET扫描）来测试各种痴呆症，以开发研究患者的“退行性生物标志物谱”。如果我们在对预测性测试没有反应的患者中发现神经退行性痴呆的证据，那么我们将能够开始为这些不幸的人提供明确的调查和治疗途径。