Darrow Jacqueline A, Lewis Alexandria, Gulyani Seema, Khingelova Kristina, Rao Aruna, Wang Jiangxia, Zhang Yifan, Luciano Mark, Yasar Sevil, Moghekar Abhay
Department of Neurology (JAD, AL, SG, KK, AR, AM), Johns Hopkins University School of Medicine; Department of Biostatistics (JW, YZ), Johns Hopkins University Bloomberg School of Public Health; Department of Neurosurgery (ML), and Department of Medicine (SY), Johns Hopkins University School of Medicine, Baltimore, MD.
Neurol Clin Pract. 2022 Apr;12(2):91-101. doi: 10.1212/CPJ.0000000000001156.
The assessment of biomarkers in selecting patients with idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery has been limited to small cohort studies and those with limited follow-up. We assessed the potential for CSF biomarkers in predicting immediate response to CSF tap test (TT) and long-term response after shunt surgery.
CSF was obtained from patients with iNPH referred for CSF TT after baseline assessment of cognition and gait. CSF neurofilament light (NfL), β-amyloid 42 (Aβ), β-amyloid 40 (Aβ), total tau (tTau), and phosphorylated tau 181 (pTau181) and leucine-rich alpha-2-glycoprotein-1 (LRG1) were measured by ELISA. The ability of these measures to predict immediate improvement following CSF TT and long-term improvement following shunt surgery was compared by univariate and adjusted multivariate regression.
Lower NfL, pTau181, tTau, and Aβ were individually predictive of long-term improvement in gait outcomes after shunt surgery. A multivariate model of these biomarkers and MRI Evans index, adjusted for age, improved prediction (area under the receiver operating curve 0.76, 95% confidence interval 0.66-0.86). tTau, pTau181, and Aβ levels were statistically different in those whose gait improved after CSF TT compared with those who did not. Using a multivariate model, combining these markers with Evans index and transependymal flow did not significantly improve prediction of an immediate response to CSF TT.
A combination of CSF biomarkers can predict improvement following shunt surgery for iNPH. However, these measures only modestly discriminate responders from nonresponders following CSF TT. The findings further suggest that abnormal CSF biomarkers in nonresponders may represent comorbid neurodegenerative pathology or a predegenerative phase that presents with an iNPH phenotype.
在选择特发性正常压力脑积水（iNPH）患者进行分流手术时，生物标志物的评估仅限于小型队列研究以及随访有限的研究。我们评估了脑脊液生物标志物在预测脑脊液引流试验（TT）即时反应及分流手术后长期反应方面的潜力。
在对认知和步态进行基线评估后，从因脑脊液TT而转诊的iNPH患者中获取脑脊液。通过酶联免疫吸附测定法（ELISA）测量脑脊液中的神经丝轻链（NfL）、β-淀粉样蛋白42（Aβ）、β-淀粉样蛋白40（Aβ）、总tau蛋白（tTau）、磷酸化tau蛋白181（pTau181）以及富含亮氨酸的α-2-糖蛋白-1（LRG1）。通过单变量和校正多变量回归比较这些指标预测脑脊液TT后即时改善及分流手术后长期改善的能力。
较低的NfL、pTau181、tTau和Aβ各自可预测分流手术后步态结果的长期改善。这些生物标志物与MRI埃文斯指数的多变量模型，经年龄校正后，改善了预测效果（受试者操作特征曲线下面积为0.76，95%置信区间为0.66 - 0.86）。与未改善者相比，脑脊液TT后步态改善者的tTau、pTau181和Aβ水平存在统计学差异。使用多变量模型，将这些标志物与埃文斯指数和经室管膜流动相结合，并未显著改善对脑脊液TT即时反应的预测。
脑脊液生物标志物的组合可预测iNPH分流手术后的改善情况。然而，这些指标在区分脑脊液TT后的反应者与无反应者方面效果有限。研究结果进一步表明，无反应者中异常的脑脊液生物标志物可能代表合并的神经退行性病变或呈现iNPH表型的神经退变前期。
