Department of Neurosurgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
Department of Neurosurgery and Normal Pressure Hydrocephalus Center, Rakuwakai Otowa Hospital, Kyoto, Japan.
Fluids Barriers CNS. 2021 Apr 19;18(1):20. doi: 10.1186/s12987-021-00243-6.
Idiopathic normal pressure hydrocephalus (iNPH) is considered an age-dependent chronic communicating hydrocephalus associated with cerebrospinal fluid (CSF) malabsorption; however, the aetiology of ventricular enlargement in iNPH has not yet been elucidated. There is accumulating evidence that support the hypothesis that various alterations in CSF dynamics contribute to ventricle dilatation in iNPH. This review focuses on CSF dynamics associated with ventriculomegaly and summarises the current literature based on three potential aetiology factors: genetic, environmental and hydrodynamic. The majority of gene mutations that cause communicating hydrocephalus were associated with an abnormal structure or dysfunction of motile cilia on the ventricular ependymal cells. Aging, alcohol consumption, sleep apnoea, diabetes and hypertension are candidates for the risk of developing iNPH, although there is no prospective cohort study to investigate the risk factors for iNPH. Alcohol intake may be associated with the dysfunction of ependymal cilia and sustained high CSF sugar concentration due to uncontrolled diabetes increases the fluid viscosity which in turn increases the shear stress on the ventricular wall surface. Sleep apnoea, diabetes and hypertension are known to be associated with the impairment of CSF and interstitial fluid exchange. Oscillatory shear stress to the ventricle wall surfaces is considerably increased by reciprocating bidirectional CSF movements in iNPH. Increased oscillatory shear stress impedes normal cilia beating, leading to motile cilia shedding from the ependymal cells. At the lack of ciliary protection, the ventricular wall is directly exposed to increased oscillatory shear stress. Additionally, increased oscillatory shear stress may be involved in activating the flow-mediated dilation signalling of the ventricular wall. In conclusion, as the CSF stroke volume at the cerebral aqueduct increases, the oscillatory shear stress increases, promoting motor cilia shedding and loss of ependymal cell coverage. These are considered to be the leading causes of ventricular enlargement in iNPH.
特发性正常压力脑积水（iNPH）被认为是一种与脑脊液（CSF）吸收不良相关的年龄依赖性慢性交通性脑积水；然而，iNPH 中脑室扩大的病因尚未阐明。越来越多的证据支持这样一种假说，即 CSF 动力学的各种改变有助于 iNPH 中脑室的扩张。这篇综述重点关注与脑室扩大相关的 CSF 动力学，并根据三个潜在病因因素：遗传、环境和流体动力学，总结了当前的文献。导致交通性脑积水的大多数基因突变与脑室室管膜细胞上的运动纤毛异常结构或功能障碍有关。衰老、饮酒、睡眠呼吸暂停、糖尿病和高血压是 iNPH 发病风险的候选因素，尽管没有前瞻性队列研究来调查 iNPH 的危险因素。饮酒可能与室管膜纤毛功能障碍有关，由于糖尿病控制不佳导致持续的高 CSF 糖浓度会增加流体粘度，从而增加心室壁表面的剪切力。众所周知，睡眠呼吸暂停、糖尿病和高血压与 CSF 和间质液交换受损有关。iNPH 中 CSF 的往复双向运动使心室壁表面的振荡剪切力大大增加。增加的振荡剪切力阻碍了正常纤毛的跳动，导致纤毛从室管膜细胞上脱落。在纤毛保护缺失的情况下，心室壁直接暴露于增加的振荡剪切力。此外，增加的振荡剪切力可能参与激活心室壁的血流介导的扩张信号转导。总之，由于脑导水管处 CSF 搏动量增加，振荡剪切力增加，从而促进运动纤毛脱落和室管膜细胞覆盖丧失。这些被认为是 iNPH 中脑室扩大的主要原因。
