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

特发性正常压力性脑积水(INPH)是一种由于脑积水导致患者发展为痴呆、行走和膀胱控制问题的疾病，正常充满液体的脑结构(脑室)中压力的增加导致它们变得更大并压缩关键的脑结构。这是一种常见的严重致残性疾病，在65岁以上的人中，影响高达3.7%。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，可能会有“脑脊液(CSF)分流”，这是一种通过手术将脑液分散到较低压力区域的过程，如腹膜腔。如果不进行治疗，INPH患者会进展到行动不便、精神错乱和大小便失禁的状态。由于未知的原因，一些脑扫描显示INPH特征正确的患者对脑脊液分流术没有反应。有一些“预测性测试”可以帮助告知谁的病情会通过手术改善。这些测试是有风险的，因为它们涉及评估从下脊柱引流大量脑脊液或用针进入脊椎并测量脑脊液压力动态后症状的改善情况。不幸的是，目前还没有已知的治疗方法来治疗那些对脑脊液分流术没有反应的人，他们必须得到进行性痴呆症的支持，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质路径，这在传统的MRI脑部扫描中是看不到的。在这项研究中，我们打算在接受INPH调查的患者中使用DTI进行白质纤维束成像，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患者(“分流反应”)和那些没有分流反应的患者(“分流反应”)。这将帮助我们了解为什么一些患者对脑脊液分流术有反应，也将帮助我们在未来为这些患者开发非侵入性测试。由于白质束成像受到神经退行性疾病的影响，因此考虑到共存的神经退行性变将是很重要的。我们还假设，具有INPH影像特征的患者如果对预测性测试没有反应，他们的症状可能有另一个原因，如神经退行性痴呆(例如帕金森氏病或阿尔茨海默病)。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)对研究患者进行广泛的痴呆症测试，以开发“退行性生物标记物档案”。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一条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.