Eide Per Kristian, Lashkarivand Aslan, Hagen-Kersten Åsmund Aleksander, Gjertsen Øivind, Nedregaard Bård, Sletteberg Ruth, Løvland Grethe, Vatnehol Svein Are Sirirud, Pripp Are Hugo, Valnes Lars Magnus, Ringstad Geir
Department of Neurosurgery, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Front Neurol. 2022 Apr 6;13:857328. doi: 10.3389/fneur.2022.857328. eCollection 2022.
Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease, characterized by cerebrospinal fluid (CSF) flow disturbance. Today, the only available treatment is CSF diversion surgery (shunt surgery). While traditional imaging biomarkers typically assess CSF space anatomy, recently introduced imaging biomarkers of CSF dynamics and glymphatic enhancement, provide imaging of CSF dynamics and thereby more specifically reveal elements of the underlying pathophysiology. The biomarkers address CSF ventricular reflux grade as well as glymphatic enhancement and derive from intrathecal contrast-enhanced MRI. However, the contrast agent serving as CSF tracer is administered off-label. In medicine, the introduction of new diagnostic or therapeutic methods must consider the balance between risk and benefit. To this end, we performed a prospective observational study of 95 patients with iNPH, comparing different intrathecal doses of the MRI contrast agent gadobutrol (0.10, 0.25, and 0.50 mmol, respectively), aiming at the lowest reasonable dose needed to retrieve diagnostic information about the novel MRI biomarkers. The present observations disclosed a dose-dependent enrichment of subarachnoid CSF spaces (cisterna magna, vertex, and velum interpositum) with dose-dependent ventricular reflux of tracer in iNPH, as well as dose-dependent glymphatic tracer enrichment. The association between tracer enrichment in CSF and parenchymal compartments were as well dose-related. Intrathecal gadobutrol in a dose of 0.25 mmol, but not 0.10 mmol, was at 1.5T MRI considered sufficient for imaging altered CSF dynamics and glymphatic enhancement in iNPH, even though 3T MRI provided better sensitivity. Tracer enrichment in CSF at the vertex and within the cerebral cortex and subcortical white matter was deemed too low for maintaining diagnostic information from a dose of 0.10 mmol. We conclude that reducing the intrathecal dose of gadobutrol from 0.50 to 0.25 mmol gadobutrol improves the safety margin while maintaining the necessary diagnostic information about disturbed CSF homeostasis and glymphatic failure in iNPH.
特发性正常压力脑积水（iNPH）是一种神经退行性疾病，其特征为脑脊液（CSF）流动紊乱。目前，唯一可用的治疗方法是脑脊液分流手术（分流手术）。传统的成像生物标志物通常评估脑脊液空间解剖结构，而最近引入的脑脊液动力学和类淋巴系统增强成像生物标志物，则可对脑脊液动力学进行成像，从而更具体地揭示潜在病理生理学的要素。这些生物标志物涉及脑脊液脑室反流分级以及类淋巴系统增强，源自鞘内注射对比剂增强MRI。然而，用作脑脊液示踪剂的对比剂是超说明书用药。在医学领域，新诊断或治疗方法的引入必须考虑风险与获益之间的平衡。为此，我们对95例iNPH患者进行了一项前瞻性观察研究，比较了不同鞘内剂量的MRI对比剂钆布醇（分别为0.10、0.25和0.50 mmol），目标是获取有关新型MRI生物标志物诊断信息所需的最低合理剂量。目前的观察结果显示，iNPH患者蛛网膜下腔脑脊液间隙（枕大池、头顶和中间帆）的对比剂富集呈剂量依赖性，示踪剂的脑室反流也呈剂量依赖性，类淋巴示踪剂富集同样呈剂量依赖性。脑脊液和实质间隙中示踪剂富集之间的关联也与剂量相关。在1.5T MRI下，0.25 mmol剂量的鞘内钆布醇被认为足以对iNPH患者改变的脑脊液动力学和类淋巴系统增强进行成像，尽管3T MRI具有更高的灵敏度。头顶以及大脑皮质和皮质下白质内脑脊液中的示踪剂富集被认为过低，无法从0.10 mmol剂量中维持诊断信息。我们得出结论，将鞘内钆布醇剂量从0.50 mmol降至0.25 mmol可提高安全边际，同时保留有关iNPH患者脑脊液稳态紊乱和类淋巴系统功能障碍的必要诊断信息。
