Idiopathic normal pressure hydrocephalus: associations between CSF biomarkers, clinical symptoms, and outcome after shunt surgery.

IF 5.9 1区医学 Q1 NEUROSCIENCES

Fluids and Barriers of the CNS Pub Date : 2025-05-19 DOI:10.1186/s12987-025-00661-w

Majd Saadaldeen, Anna Jeppsson, Per Hellström, Kaj Blennow, Henrik Zetterberg, Carsten Wikkelsø, Mats Tullberg

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引用次数: 0

Abstract

Background: The neurochemical alterations in cerebrospinal fluid (CSF) associated with the typical symptomatology in idiopathic normal pressure hydrocephalus (iNPH) and their association with outcome after shunt surgery are unsettled.

Aim: To explore associations between concentrations of CSF biomarkers reflecting amyloid- and tau pathology, neuronal degeneration as well as astrocytic activation and the characteristic symptomatology in iNPH and to examine whether these biomarkers can predict the postoperative outcome in all patients and in patients without evidence of Alzheimer's disease (AD) pathology.

Methods: This explorative study included 81 patients diagnosed with iNPH at the Hydrocephalus research unit, Sahlgrenska. Symptoms were assessed using the iNPH-scale and standardized clinical tests measuring gait, balance, cognition and urinary incontinence before and median 8 months after shunt surgery. Pre-operative lumbar CSF concentrations of Aβ38, Aβ40, Aβ42, ratio Aβ42/Aβ40, sAPPα, sAPPβ, T-tau, P-tau, MCP-1, and NFL were analyzed. A low Aβ42/Aβ40 ratio defined patients with AD pathology. Correlation and regression analyses between biomarker concentrations and clinical symptoms at baseline as well as postoperative change in symptoms after surgery, were performed.

Results: Higher NFL correlated with more pronounced impairment in all clinical tests, i.e. included measures of gait, balance, cognition and urinary incontinence (r_p=0.25-0.46, p < 0.05). Higher T-tau and P-tau correlated with poorer performance in cognitive tests (r_p=0.26-0.39, p < 0.05). No biomarker could differentiate between improved and unimproved patients in the whole sample or in AD-pathology negative patients. Low ratio Aβ42/Aβ40 lacked predictive value. A higher preoperative P-tau was weakly correlated with less pronounced overall clinical improvement (r_p = -0.238, p = 0.036).

Conclusions: Axonal degeneration, as indicated by elevated NFL, is probably involved in the generation of the full iNPH tetrade of symptoms and tau pathology more specifically with iNPH cognitive impairment. No CSF biomarker could identify shunt responders. CSF evidence of Alzheimer pathology should not be used to exclude patients from shunt surgery.

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特发性常压脑积水：脑脊液生物标志物、临床症状和分流手术后预后之间的关系

背景：与特发性常压脑积水（iNPH）典型症状相关的脑脊液（CSF）神经化学改变及其与分流手术后预后的关系尚不清楚。目的：探讨反映淀粉样蛋白和tau病理、神经元变性和星形细胞活化的脑脊液生物标志物浓度与iNPH的特征性症状之间的关系，并研究这些生物标志物是否可以预测所有患者和无阿尔茨海默病（AD）病理证据的患者的术后预后。方法：本探索性研究纳入了81例在Sahlgrenska脑积水研究单位诊断为iNPH的患者。采用inph量表和标准化临床测试评估患者在分流手术前和术后中位8个月的步态、平衡、认知和尿失禁。分析术前腰椎脑脊液a - β38、a - β40、a - β42浓度、a - β42/ a - β40比值、sAPPα、sAPPβ、T-tau、P-tau、MCP-1、NFL浓度。低A - β42/A - β40比值定义AD病理患者。进行生物标志物浓度与基线临床症状以及术后症状变化之间的相关性和回归分析。结果：在所有临床试验中，高NFL与更明显的损害相关，包括步态、平衡、认知和尿失禁的测量（rp=0.25-0.46, p=0.26-0.39, p= -0.238, p= 0.036）。结论：轴突变性，如升高的NFL所示，可能参与了iNPH症状和tau病理的产生，更具体地说，与iNPH认知障碍有关。没有脑脊液生物标志物可以识别分流反应者。脑脊液证据的阿尔茨海默病不应用于排除患者分流手术。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fluids and Barriers of the CNS Neuroscience-Developmental Neuroscience

CiteScore

10.70

自引率

8.20%

发文量

审稿时长

14 weeks

期刊介绍： "Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease. At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).