Predictive Value of Cerebrospinal Fluid Biomarkers for Tap Test Responsiveness in Patients With Suspected Idiopathic Normal Pressure Hydrocephalus

Rongrong Hua, Chunyan Liu, Xing Liu, Jinwu Zhu, Jie Zhang, Lidong Wang, Zhe Shi, Jian Li, Shuangyan Kong, Chenhui Yang, Nan Liu, Lijuan Liu, Jie Sun, Qiong Yang, Yubing Wu, Ying Zhou, Yanfeng Li, Yan Xing, Rongrong Hua, Chunyan Liu, Xing Liu, Jinwu Zhu, Jie Zhang, Lidong Wang, Zhe Shi, Jian Li, Shuangyan Kong, Chenhui Yang, Nan Liu, Lijuan Liu, Jie Sun, Qiong Yang, Yubing Wu, Ying Zhou, Yanfeng Li, Yan Xing

Abstract

Background: The value of cerebrospinal fluid (CSF) biomarkers for assessing idiopathic normal pressure hydrocephalus (iNPH) must be determined. This prospective study aimed to reveal the correlation between CSF biomarkers and clinical symptoms of iNPH and the predictive value of these biomarkers for tap test responsiveness. Methods: Thirty-nine patients with suspected iNPH were recruited, contributed qualified CSF, and underwent a tap test and unified pre- and post-test evaluations of the neurological function. Results: The analysis of biomarkers from the patients' CSF showed decreased levels of tau and its phosphorylated form, especially in the tap test (+) group. The responsiveness of the tap test was also related to the number of combined symptoms (p < 0.01), and a correlation was found between the end pressure or pressure difference in CSF and tap test responsiveness (p < 0.05). The results of the binary logistic regression analysis showed that P (tap test responsiveness) = 1/1 + e∧ - (-5.505 + 55.314 * ratio of p/T-tau - 1.586 * numbers of combined symptoms). The combined indicators (-5.505 + 0.553 * percentage of p/T-tau - 1.586 * numbers of combined symptoms) resulted in the highest sensitivity and specificity of 94.12% and 72.73%, respectively. Conclusions: CSF biomarkers may be assessed to judge tap test responsiveness, which is beneficial for the feasibility of a clinical application.

Keywords: Aβ; cerebrospinal fluid biomarkers; idiopathic normal pressure hydrocephalus; tap test; tau.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Hua, Liu, Liu, Zhu, Zhang, Wang, Shi, Li, Kong, Yang, Liu, Liu, Sun, Yang, Wu, Zhou, Li and Xing.

Figures

Figure 1
Figure 1
Flow chart of participating patients. Thirty-nine patients with suspected idiopathic normal pressure hydrocephalus (iNPH) were included in the final predictive value analysis. Secondary samples that underwent a tap test (+) (n = 17) or (−) (n = 22) were included in the longitudinal analysis of biomarkers in lumbar cerebrospinal fluid (CSF).
Figure 2
Figure 2
Aβ1–42 and tau levels and their relationships with tap test responsiveness or combined symptoms in patients with iNPH. (A) Comparison of CSF levels of Aβ1–42, T-tau, and p-tau between the tap test (+) and (−) groups (* p < 0.05 and **p < 0.01 compared with the corresponding group). (B) Comparison of the ratio of 181p/T-tau in the tap test (+) and (−) groups (***p < 0.001 compared with the corresponding group). (C) Comparison of the ratio of 181p-tau/Aβ1–42 between the tap test (+) and (−) groups. (D–H) Correlation analyses between the actual levels of Aβ1–42, T-tau, p-tau, p/T-tau, and p-tau/Aβ1–42 with the numbers of combined symptoms.
Figure 3
Figure 3
Differences in CSF biomarkers and tap test responsiveness between subgroups with different numbers of combined symptoms. (A–E) Differences in the levels of Aβ1–42, T-tau, 181p/T-tau, and 181p-tau/Aβ1–42 between the subgroups with different numbers of combined symptoms. (F) The relationship of the tap test responsiveness with number of combined symptoms (*p < 0.05 and **p < 0.01 compared with the corresponding group. The data in (B) are presented as the medians with interquartile ranges).
Figure 4
Figure 4
The distribution of combined symptoms and the correlated factors. (A) The distribution of hypertension in patients with one/two/three combined symptoms. (B–D) The CSF initial pressure, end pressure and, pressure difference in patients with one/two/three combined symptoms (*p < 0.05 and **p < 0.01 compared with the corresponding group).
Figure 5
Figure 5
The responsiveness to the tap test and its correlated factors. (A) The differences in the initial and end pressure of CSF in patients with differences in tap test responsiveness. (B) The pressure difference in CSF in patients with differences in tap test responsiveness. (C) ROC curves of T-tau, 181p-tau, and 181p/T-tau levels in assessing tap test responsiveness. (D) ROC curves of combined indicators (−5.505 + 0.553 * percentage of p/T-tau − 1.586 * numbers of combined symptoms) in assessing tap test responsiveness (*p < 0.05 compared with the corresponding group. The data in (B) are presented as the medians with interquartile ranges).

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