The predictive value of T-tau and AB1-42 levels in idiopathic normal pressure hydrocephalus

Claudia L Craven, Irene Baudracco, Henrik Zetterberg, Michael P T Lunn, Miles D Chapman, Neghat Lakdawala, Laurence D Watkins, Ahmed K Toma, Claudia L Craven, Irene Baudracco, Henrik Zetterberg, Michael P T Lunn, Miles D Chapman, Neghat Lakdawala, Laurence D Watkins, Ahmed K Toma

Abstract

Background: Idiopathic normal pressure hydrocephalus (INPH) has no reliable biomarker to assist in the selection of patients who could benefit from ventriculo-peritoneal (VP) shunt insertion. The neurodegenerative markers T-tau and Aβ1-42 have been found to successfully differentiate between Alzheimer's disease (AD) and INPH and therefore are candidate biomarkers for prognosis and shunt response in INPH. The aim of this study was to test the predictive value of cerebrospinal fluid (CSF) T-tau and Aβ1-42 for shunt responsiveness. In particular, we pay attention to the subset of INPH patients with raised T-tau, who are often expected to be poor surgical candidates.

Methods: Single-centre retrospective analysis of probable INPH patients with CSF samples collected from 2006 to 2016.

Index test: CSF levels of T-tau and Aβ1-42. Reference standard: postoperative outcome. ROC analysis assessed the predictive value.

Results: A total of 144 CSF samples from INPH patients were analysed. Lumbar T-tau was a good predictor of post-operative mobility (AUROC 0.80). The majority of patients with a co-existing neurodegenerative disease responded well, including those with high T-tau levels.

Conclusion: INPH patients tended to exhibit low levels of CSF T-tau, and this can be a good predictor outcome. However levels are highly variable between individuals. Raised T-tau and being shunt-responsive are not mutually exclusive, and such patients ought not necessarily be excluded from having a VP shunt. A combined panel of markers may be a more specific method for aiding selection of patients for VP shunt insertion. This is the most comprehensive presentation of CSF samples from INPH patients to date, thus providing further reference values to the current literature.

Keywords: AB1-42; Cerebrospinal fluid (CSF); Idiopathic normal pressure hydrocephalus (INPH); Neurodegenerative markers; T-tau.

Conflict of interest statement

Conflicts of Interest

Mr. Watkins has received honoraria from and served on advisory boards for Medtronic, Codman and B. Braun.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study formal consent is not required.

Figures

Fig. 1
Fig. 1
Flow chart of patient participants. A total of 87 samples, 71 primary ventricular and 30 primary lumbar (from 65 patients), were included in the final predictive value analysis. Secondary samples (43) and samples from those with poor or no ELD/LP were included in the longitudinal analysis of markers in CSF drainage and in analysis of rostro-caudal gradients
Fig. 2
Fig. 2
ROC curve demonstrating ability CSF levels of T-tau, Aβ1-42 levels and the ratio T-tau/Aβ1-42 to predict improvement in the triad of symptoms a–c lumbar primary CSF a mobility (n = 21), b cognition (n = 13) and c continence (n = 5). d–f Ventricular primary CSF d mobility (n = 36), e cognition (n = 17) and f continence (n = 9)

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