Abstract
Background and Objectives The assessment of biomarkers in selecting patients with idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery has been limited to small cohort studies and those with limited follow-up. We assessed the potential for CSF biomarkers in predicting immediate response to CSF tap test (TT) and long-term response after shunt surgery.
Methods CSF was obtained from patients with iNPH referred for CSF TT after baseline assessment of cognition and gait. CSF neurofilament light (NfL), β-amyloid 42 (Aβ1–42), β-amyloid 40 (Aβ1–40), total tau (tTau), and phosphorylated tau 181 (pTau181) and leucine-rich alpha-2-glycoprotein-1 (LRG1) were measured by ELISA. The ability of these measures to predict immediate improvement following CSF TT and long-term improvement following shunt surgery was compared by univariate and adjusted multivariate regression.
Results Lower NfL, pTau181, tTau, and Aβ1–40 were individually predictive of long-term improvement in gait outcomes after shunt surgery. A multivariate model of these biomarkers and MRI Evans index, adjusted for age, improved prediction (area under the receiver operating curve 0.76, 95% confidence interval 0.66–0.86). tTau, pTau181, and Aβ1–40 levels were statistically different in those whose gait improved after CSF TT compared with those who did not. Using a multivariate model, combining these markers with Evans index and transependymal flow did not significantly improve prediction of an immediate response to CSF TT.
Discussion A combination of CSF biomarkers can predict improvement following shunt surgery for iNPH. However, these measures only modestly discriminate responders from nonresponders following CSF TT. The findings further suggest that abnormal CSF biomarkers in nonresponders may represent comorbid neurodegenerative pathology or a predegenerative phase that presents with an iNPH phenotype.
Footnotes
Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.
↵* These authors contributed equally to this work as co–first authors.
The Article Processing Charge was funded by the authors.
- Received August 24, 2021.
- Accepted January 10, 2022.
- Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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