Date Published: September 9, 2017
Publisher: Springer Vienna
Author(s): Claudia L. Craven, Irene Baudracco, Henrik Zetterberg, Michael P. T. Lunn, Miles D. Chapman, Neghat Lakdawala, Laurence D. Watkins, Ahmed K. Toma.
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.
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.
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.
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.
Idiopathic normal-pressure hydrocephalus (INPH) is a condition that predominantly affects the elderly population, has a prevalence of 0.02%–5.9% and affects an estimated 2 million people within Europe [6, 10]. INPH presents with a triad of cognitive deficits, impaired mobility and incontinence. The mainstay of treatment is cerebrospinal fluid (CSF) diversion via a ventriculo-peritoneal (VP) shunt [1, 3]. Selection of patients for VP shunt insertion remains a challenge since the triad of symptoms in INPH is common in the elderly population. The surgery for a VP shunt is not without risk and a proportion of those with INPH do not benefit [16, 18]. Whilst prognostic tests are becoming more accurate, INPH still has no reliable biomarker to assist in the selection of patients for a VP shunt or for the monitoring of shunt function [7, 9, 15, 16, 18].
Raised levels of T-tau and being shunt-responsive are not mutually exclusive. This is highly relevant, since many units would have presumed such patients (i.e. those with Alzheimer’s disease and INPH) to be poor surgical candidates. In general, INPH exhibits low levels of CSF T-tau, and levels can be good predictors of outcome. However, we discourage diagnosis and outcome prediction based on T-tau levels alone, as its CSF levels are highly variable between individuals. It is likely that a combined panel of markers, including T-tau, will be a more specific method for aiding selection of patients for VP shunt insertion.