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

特发性常压脑积水（iNPH）是一种由脑积水引起的患者出现痴呆、行走和膀胱控制问题的疾病，其中正常充满液体的脑结构（脑室）的压力增加导致它们变大并压缩关键的脑结构。这是一种常见的严重致残疾病，在65岁以上的老年人中，有3.7%的人罹患此病。与典型的痴呆症不同，iNPH是可以治疗的。有这些症状的患者，如果在脑部扫描中被发现有iNPH的特征，可能会出现“脑脊液分流”，这是一种将脑脊液通过手术转移到低压区域（如腹腔）的过程。如果不进行治疗，iNPH患者会发展为行动不便、精神错乱和大小便失禁状态。由于未知的原因，一些在脑部扫描上具有正确的iNPH特征的患者对脑脊液分流没有反应。有“预测性测试”可以帮助告知哪些人会在手术后好转。这些检查有风险，因为它们涉及评估从脊柱下部大量抽出CSF或用针进入脊髓腔并测量CSF压力动态后症状的改善。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，他们必须支持他们的进行性痴呆，其原因从来没有真正解释过。弥散张量成像是一种磁共振成像（MRI）扫描技术，它可以显示非常详细的脑白质通路，这在传统的MRI脑部扫描中是看不到的。在这项研究中，我们打算使用DTI对正在接受调查的iNPH患者进行白质束造影，并比较30名iNPH患者的扫描结果，并比较那些对脑脊液分流有反应的（分流反应性）和那些没有（分流无反应性）。这将有助于我们理解为什么有些患者对脑脊液分流有反应，也将有助于我们在未来为这些患者开发无创测试。由于白质束造影受神经退行性疾病的影响，因此解释共存的神经退行性疾病将是重要的。我们还假设，具有iNPH影像学特征但对预测检测无反应的患者，其症状可能有其他原因，如神经退行性痴呆（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、脑脊液测试、高级脑成像（淀粉样蛋白- pet扫描）来测试大范围的痴呆症，以开发研究患者的“退行性生物标志物档案”。如果我们在对预测测试没有反应的患者身上找到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个体提供明确的调查和治疗途径。

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.