Objective: To predict long-term clinical outcome of iNPH patients through a panel of neurodegeneration-related CSF biomarkers.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative condition characterized by diagnostic ambiguity and challenging therapeutic choices, such as the shunt surgery¹. Cerebrospinal fluid (CSF) biomarkers mirror brain neuropathology, helping the diagnosis and the prognostic predictions. iNPH doesn’t have a disease-specific CSF biomarker²; however, a panel of neurodegeneration-related CSF biomarkers might facilitate patients stratification and subsequently the therapeutic strategies.

Method: We conducted a single-centre retrospective study over an 8 year-long period, analyzing 32 iNPH patients with CSF biomarkers (amyloid-β-42, phosphorylated-181-tau, total-tau). Nineteen had a long-term follow-up (5 years at least). The clinical assessment was done at baseline through the iNPH grading scale (INPHGS)³ and the modified Ranking Scale (mRS)⁴. At follow-up patients were evaluated with the mRS and divided into “poor outcome” (mRS≥5) and “good outcome” (mRS<5).

Results: “Poor outcome” iNPH group presented CSF total-tau levels higher than “good outcome” patients (mean ± st.dev.:300.58 ± 114.10pg/ml vs.175.69 ± 94.57pg/ml, p=0.041), also in a model adjusted for age (p=0.037). There were no significant differences in the amyloid-β-42(mean ± st.dev.: 719.86 ± 354.16pg/ml vs. 618.64 ±240.51pg/ml, p=0.717), and phosphorylated-181-tau (mean ± st.dev.:42,48 ± 20,63pg/ml vs. 33,52 ±26,73pg/ml, p=0.237) concentrations. Receiver operating characteristic analysis produced for CSF total-tau an area under the curve of 0.778 with the cut-off value of 202.5 pg/mL permitting discriminating the clinical outcome with a sensitivity of 75% and a specificity of 72.7%. At baseline CSF t-tau levels directly correlated with iNPHGS cognitive subscore (Spearman Rho 0.508, p=0.026).

Conclusion: CSF levels of total-tau reflect brain neuronal loss⁵. Despite nonspecific for iNPH pathology, CSF total-tau seems to support the identification of frailer iNPH patients. Higher total-tau levels might predict a long-term poor clinical outcome (severe disability or death) independently from the surgery, helping physicians in therapeutic management of iNPH patients.

References: 1. Giordan E, Palandri G, Lanzino G, Murad MH, Elder BD. Outcomes and complications of different surgical treatments for idiopathic normal pressure hydrocephalus: A systematic review and meta-analysis. J Neurosurg. 2019;131(4):1024-1036. doi:10.3171/2018.5.JNS1875;

2. Blennow K. Cerebrospinal Fluid Protein Biomarkers for Alzheimer’s Disease. NeuroRx. 2004;1(2). doi:10.1602/neurorx.1.2.213;

3. Kubo Y, Kazui H, Yoshida T, et al. Validation of grading scale for evaluating symptoms of idiopathic normal-pressure hydrocephalus. Dement Geriatr Cogn Disord. 2007;25(1). doi:10.1159/000111149;

4. Banks JL, Marotta CA. Outcomes validity and reliability of the modified rankin scale: Implications for stroke clinical trials – A literature review and synthesis. Stroke. 2007;38(3). doi:10.1161/01.STR.0000258355.23810.c6;

5. Migliorati K, Panciani PP, Pertichetti M, et al. P-Tau as prognostic marker in long term follow up for patients with shunted iNPH. Neurol Res. 2021;43(1):78-85. doi:10.1080/01616412.2020.1831300.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/csf-tau-reflects-long-term-outcome-of-patients-with-idiopathic-normal-pressure-hydrocephalus-a-longitudinal-retrospective-study/