Department of Neurosurgery, ASUFC "Santa Maria Della Misericordia", Piazzale Santa Maria Della Misericordia 15, 33100, Udine, Italy.
Department of Clinical, Diagnostic and Pediatric Sciences, University of Pavia, Via Alessandro Brambilla 74, 27100, Pavia, Italy.
Fluids Barriers CNS. 2023 Jan 26;20(1):7. doi: 10.1186/s12987-023-00407-6.
Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and partially reversible form of dementia, characterized by impaired interactions between multiple brain regions. Because of the presence of comorbidities and a lack of accurate diagnostic and prognostic biomarkers, only a minority of patients receives disease-specific treatment. Recently, resting-state functional-magnetic resonance imaging (rs-fMRI) has demonstrated functional connectivity alterations in inter-hemispheric, frontal, occipital, default-mode (DMN) and motor network (MN) circuits. Herein, we report our experience in a cohort of iNPH patients that underwent cerebrospinal fluid (CSF) dynamics evaluation and rs-fMRI. The study aimed to identify functional circuits related to iNPH and explore the relationship between DMN and MN recordings and clinical modifications before and after infusion and tap test, trying to understand iNPH pathophysiology and to predict the best responders to ventriculoperitoneal shunt (VPS) implant.
We prospectively collected data regarding clinical assessment, neuroradiological findings, lumbar infusion and tap test of thirty-two iNPH patients who underwent VPS implant. Rs-fMRI was performed using MELODIC-ICA both before and after the tap test. Rs-fMRI data of thirty healthy subjects were also recorded.
At the baseline, reduced z-DMN and z-MN scores were recorded in the iNPH cohort compared with controls. Higher z-scores were recorded in more impaired patients. Both z-scores significantly improved after the tap test except in subjects with a low resistance to outflow value and without a significant clinical improvement after the test. A statistically significant difference in mean MN connectivity scores for tap test responders and non-responders was demonstrated both before (p = 0.0236) and after the test (p = 0.00137). A statistically significant main effect of the tap test on DMN connectivity after CSF subtraction was recorded (p = 0.038).
Our results suggest the presence of a partially reversible plasticity functional mechanism in DMN and MN. Low values compensate for the initial stages of the disease, while higher values of z-DMN were recorded in older patients with a longer duration of symptoms, suggesting an exhausted plasticity compensation. The standardization of this technique could play a role as a non-invasive biomarker in iNPH disease, suggesting the right time for surgery. Trial Registration Prot. IRB 090/2021.
特发性正常压力脑积水（iNPH）是一种进行性和部分可逆转的痴呆形式，其特征是多个脑区之间的相互作用受损。由于存在合并症和缺乏准确的诊断和预后生物标志物，只有少数患者接受了针对该疾病的治疗。最近，静息态功能磁共振成像（rs-fMRI）已经证明了半球间、额部、枕部、默认模式网络（DMN）和运动网络（MN）回路中的功能连接改变。在此，我们报告了我们在一组接受脑脊液（CSF）动力学评估和 rs-fMRI 的 iNPH 患者中的经验。该研究旨在确定与 iNPH 相关的功能回路，并探讨 DMN 和 MN 记录与输注和 taps 试验前后的临床变化之间的关系，试图了解 iNPH 的病理生理学，并预测对脑室-腹腔分流术（VPS）植入反应最好的患者。
我们前瞻性地收集了 32 例接受 VPS 植入的 iNPH 患者的临床评估、神经影像学发现、腰椎输注和 taps 试验的数据。在 taps 试验前后，我们使用 MELODIC-ICA 进行 rs-fMRI 。还记录了 30 名健康受试者的 rs-fMRI 数据。
在基线时，与对照组相比，iNPH 组记录到的 z-DMN 和 z-MN 评分较低。评分较高的患者病情更严重。除了对流出阻力值低且试验后无明显临床改善的患者外，tap 试验后 z 评分均显著改善。在 taps 试验的反应者和非反应者之间，tap 试验的平均 MN 连接评分显示出统计学上的显著差异，无论是在试验前（p=0.0236）还是在试验后（p=0.00137）。CSF 扣除后，tap 试验对 DMN 连接的主效应有统计学意义（p=0.038）。
我们的结果表明 DMN 和 MN 中存在部分可逆的可塑性功能机制。低值代偿了疾病的早期阶段，而 z-DMN 在症状持续时间较长的老年患者中记录到更高的值，表明可塑性补偿已经耗尽。该技术的标准化可能作为 iNPH 疾病的一种非侵入性生物标志物发挥作用，提示手术的最佳时机。试验注册方案 IRB 090/2021。
