☆ 4.2 Article

P-Tau as prognostic marker in long term follow up for patients with shunted iNPH

NEUROLOGICAL RESEARCH (2021)

Journal

NEUROLOGICAL RESEARCH

Volume 43, Issue 1, Pages 78-85

Publisher

TAYLOR & FRANCIS LTD

DOI: 10.1080/01616412.2020.1831300

Keywords

Normal pressure hydrocephalus; neurodegenerative disease; CSF protein; shunt; alzheimer disease

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Abstract

This study aimed to assess the correlation between pre-surgical levels of CSF Beta Amyloid protein, Total Tau protein, and Phospho-Tau protein with long-term clinical outcome in iNPH patients. Results showed a significant association between low levels of P-Tau and T-Tau with favorable clinical outcome after surgery. Therefore, these proteins may have potential value in predicting effectiveness in patients post-surgery.

Objective:Diagnosis of idiopathic Normal Pressure Hydrocephalus (iNPH) relies solely on clinical and radiological criteria while, unlike other neurological diseases, the analysis of cerebrospinal fluid markers is not used in clinical practice. Nevertheless, the overlapping of neurodegenerative diseases affects the long-term shunt efficacy and this occurrence should be detected before surgery. Therefore, we performed this study in order to assess the correlation between pre-surgical levels of CSF Beta Amyloid protein, Total Tau protein and Phospho-Tau protein with long-term clinical outcome. Methods:Between March 2012 and May 2016 we prospective evaluated all patients with iNPH according to guidelines criteria and we analysed CSF concentration of these proteins before and during surgery. Two years after surgery we evaluated iNPH score for all patients, grouping them in shunt responders and non-responders. Results:A total of 117 patients were included: Tap Test non-responders were 58 and at two years we had 35 shunt responders and 15 shunt non-responders. We found a significative difference between shunt-responders and shunt non-responders for pre surgical T-Tau (p: 0.02) and for P-Tau (p: 0.01). All the proteins were significantly associated with clinical outcome after surgery with different cut-off values; in particular, having a 'low' value of T-Tau, P-Tau and A beta 1-42 resulted in favourable outcome after surgery. Conclusions:Low level of P-Tau is a useful CSF biochemical prognostic factor for good clinical outcome at least two years after shunt; meanwhile a lower A beta 1-42 might suggest that the pathophysiology of iNPH could have something in common with other neurodegenerative diseases of the elderly.

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Cerebrospinal fluid transcripts may predict shunt surgery responses in normal pressure hydrocephalus

Zachary Levin, Owen P. Leary, Victor Mora, Shawn Kant, Sarah Brown, Konstantina Svokos, Umer Akbar, Thomas Serre, Petra Klinge, Alexander Fleischmann, Maria Grazia Ruocco

Summary: By using genome-wide RNA sequencing of cerebrospinal fluid, researchers identified genes and pathways that correlate with improvement in gait, urinary incontinence, and cognitive symptoms after shunt surgery in patients with normal pressure hydrocephalus. They also developed a machine learning algorithm to predict surgical outcomes based on gene expression profiles. These transcriptomic signatures have important implications for improving diagnosis, treatment, and understanding of the disease.

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