Background Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models. Methods We used a compartment model to estimate pressure in the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate and the glymphatic circulation, resistances were calculated and used to estimate pressure and flow before and during an infusion test. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters. Results At baseline intracranial pressure (ICP), we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, 80% of the fluid left through the arachnoid granulations, 20% through the cribriform plate and flow in the PVS was stagnant. Resistance through the glymphatic system was computed to be 2.73 mmHg/(mL/min), considerably lower than other fluid pathways, giving non-realistic ICP during infusion if combined with a lymphatic drainage route. Conclusions The relative distribution of CSF flow to different clearance pathways depends on ICP, with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space. Our results suggest that the glymphatic resistance is too high to allow for pressure driven flow by arterial pulsations and at the same time too small to allow for a direct drainage route from PVS to cervical lymphatics.

中文翻译：

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颅内压升高改变脑脊液清除途径

背景 输液测试是确定分流术是否对正常压力脑积水患者有益的常用程序。该方法具有完善的理论基础和相应的数学模型，可以描述从脉络丛到蛛网膜颗粒的 CSF 循环。在这里，我们调查了所提出的类淋巴或血管旁通路（或类似通路）在多大程度上修改了传统数学模型的结果。方法 我们使用隔室模型来估计蛛网膜下腔和血管旁间隙的压力。对于蛛网膜颗粒、筛板和淋巴循环，计算阻力并用于在输注试验之前和期间估计压力和流量。最后，对模型的不同变化进行了测试，以评估所选参数的敏感性。结果在基线颅内压 (ICP) 时，我们发现非常小的血管旁血流直接进入蛛网膜下腔，而 60% 的液体通过蛛网膜颗粒留下，40% 的液体通过筛板留下。然而，在输注过程中，80% 的液体通过蛛网膜颗粒流出，20% 的液体通过筛板和 PVS 中的流动停滞。通过 glymphatic 系统的阻力计算为 2.73 mmHg/(mL/min)，远低于其他流体通路，如果与淋巴引流途径相结合，在输注过程中会产生不真实的 ICP。结论 CSF 流向不同清除途径的相对分布取决于 ICP，蛛网膜颗粒是流出的主要贡献者。因此，在确定蛛网膜下腔注射物质的途径时，ICP 增加是一个应该解决的重要因素。我们的结果表明，淋巴管阻力太高，无法通过动脉搏动压力驱动流动，同时又太小，无法从 PVS 直接引流到颈部淋巴管。