Abstract
BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients with iNPH may improve clinically following CSF diversion through shunt surgery, but it remains a challenge to predict which patients respond to shunting. It has been proposed that CSF and blood biomarkers may be used to predict shunt response in iNPH.ObjectiveTo conduct a systematic review and meta-analysis to identify which CSF and venous biomarkers predict shunt-responsive iNPH most accurately.MethodsOriginal studies that investigate the use of CSF and venous biomarkers to predict shunt response were searched using the following databases: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR. Included studies were assessed using the ROBINS-I tool, and eligible studies were evaluated utilising univariate meta-analyses.ResultsThe study included 13 studies; seven addressed lumbar CSF levels of amyloid-β 1–42, nine studies CSF levels of Total-Tau, six studies CSF levels of Phosphorylated-Tau, and seven studies miscellaneous biomarkers, proteomics, and genotyping. A meta-analysis of six eligible studies conducted for amyloid-β 1–42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (− 0.55 SMD, p = 0.04) and Total-Tau (− 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-β 1–42 (− 0.26 SMD, p = 0.55) or the other included biomarkers.ConclusionThis meta-analysis found that lumbar CSF levels of Phosphorylated-Tau and Total-Tau are significantly increased in shunt non-responsive iNPH compared to shunt-responsive iNPH. The other biomarkers, including amyloid-β 1–42, did not significantly differentiate shunt-responsive from shunt-non-responsive iNPH. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins.
Highlights
Idiopathic normal pressure hydrocephalus is a neurodegenerative disease and subtype of dementia incorporating disturbed cerebrospinal fluid (CSF) homeostasis, first described in 1965 [2]
Two ratios of CSF biomarkers were examined for their use as biomarkers (T-Tau/amyloid-β 1–42 and P-Tau/amyloid-β 1–42) to predict shunt response in Idiopathic normal pressure hydrocephalus (iNPH) patients
Upon pooling all study data on P-Tau and T-Tau, respectively, our meta-analysis found that T-Tau and P-Tau levels were significantly increased in shunt-nonresponsive iNPH (p = 0.02 and p = 0.04, respectively)
Summary
Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and subtype of dementia incorporating disturbed cerebrospinal fluid (CSF) homeostasis, first described in 1965 [2]. The clinical symptoms include gait ataxia, cognitive decline (dementia), urinary incontinence, and apathy [67] that may improve following CSF diversion (shunt) surgery It remains an obstacle, that even though affected individuals fulfil the diagnostic criteria of probable iNPH according to the American-European [62] or Japanese [35, 56] guidelines, likely response to shunt surgery cannot be predicted from fulfilling the current diagnostic criteria. A meta-analysis of six eligible studies conducted for amyloid-β 1–42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (− 0.55 SMD, p = 0.04) and Total-Tau (− 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-β 1–42 (− 0.26 SMD, p = 0.55) or the other included biomarkers. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
