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Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus

INTRODUCTION: The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers sele...

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Autores principales: Grønning, Rebecca, Jeppsson, Anna, Hellström, Per, Laurell, Katarina, Farahmand, Dan, Zetterberg, Henrik, Blennow, Kaj, Wikkelsø, Carsten, Tullberg, Mats
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601279/
https://www.ncbi.nlm.nih.gov/pubmed/37880775
http://dx.doi.org/10.1186/s12987-023-00475-8
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author Grønning, Rebecca
Jeppsson, Anna
Hellström, Per
Laurell, Katarina
Farahmand, Dan
Zetterberg, Henrik
Blennow, Kaj
Wikkelsø, Carsten
Tullberg, Mats
author_facet Grønning, Rebecca
Jeppsson, Anna
Hellström, Per
Laurell, Katarina
Farahmand, Dan
Zetterberg, Henrik
Blennow, Kaj
Wikkelsø, Carsten
Tullberg, Mats
author_sort Grønning, Rebecca
collection PubMed
description INTRODUCTION: The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers selected to reflect a range of pathophysiological processes. METHODS: In 119 consecutive patients with iNPH, the iNPH scale was used before and after shunt surgery to quantify outcome. Ventricular CSF was collected perioperatively and analyzed for biomarkers of astrogliosis, axonal, amyloid and tau pathology, and synaptic dysfunction: glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL40/CHI3L1), monocyte chemoattractant protein-1 (MCP-1) neurofilament light (NfL), amyloid beta 38 (Aβ38), Aβ40, Aβ42, amyloid beta 42/40 ratio (Aβ42/40), soluble amyloid precursor protein alfa (sAPPα), sAPPβ, total tau (T-tau), phosphorylated tau (P-tau), growth-associated protein 43 (GAP43), and neurogranin. RESULTS: The neurogranin concentration was higher in improved (68%) compared to unimproved patients (median 365 ng/L (IQR 186–544) vs 330 (205–456); p = 0.046). A linear regression model controlled for age, sex and vascular risk factors including neurogranin, T-tau, and GFAP, resulted in adjusted R(2) = 0.06, p = 0.047. The Aβ42/40 ratio was bimodally distributed across all samples, as well as in the subgroups of improved and unimproved patients but did not contribute to outcome prediction. The preoperative MMSE score was lower within the low Aβ ratio group (median 25, IQR 23–28) compared to the high subgroup (26, 24–29) (p = 0.028). The T-Tau x Aβ40/42 ratio and P-tau x Aβ40/42 ratio did not contribute to shunt response prediction. The prevalence of vascular risk factors did not affect shunt response. DISCUSSION: A higher preoperative ventricular CSF level of neurogranin, which is a postsynaptic marker, may signal a favorable postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers explained only 6% of the variability in outcome. Evidence of amyloid or tau pathology did not affect the outcome.
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spelling pubmed-106012792023-10-27 Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus Grønning, Rebecca Jeppsson, Anna Hellström, Per Laurell, Katarina Farahmand, Dan Zetterberg, Henrik Blennow, Kaj Wikkelsø, Carsten Tullberg, Mats Fluids Barriers CNS Research INTRODUCTION: The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers selected to reflect a range of pathophysiological processes. METHODS: In 119 consecutive patients with iNPH, the iNPH scale was used before and after shunt surgery to quantify outcome. Ventricular CSF was collected perioperatively and analyzed for biomarkers of astrogliosis, axonal, amyloid and tau pathology, and synaptic dysfunction: glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL40/CHI3L1), monocyte chemoattractant protein-1 (MCP-1) neurofilament light (NfL), amyloid beta 38 (Aβ38), Aβ40, Aβ42, amyloid beta 42/40 ratio (Aβ42/40), soluble amyloid precursor protein alfa (sAPPα), sAPPβ, total tau (T-tau), phosphorylated tau (P-tau), growth-associated protein 43 (GAP43), and neurogranin. RESULTS: The neurogranin concentration was higher in improved (68%) compared to unimproved patients (median 365 ng/L (IQR 186–544) vs 330 (205–456); p = 0.046). A linear regression model controlled for age, sex and vascular risk factors including neurogranin, T-tau, and GFAP, resulted in adjusted R(2) = 0.06, p = 0.047. The Aβ42/40 ratio was bimodally distributed across all samples, as well as in the subgroups of improved and unimproved patients but did not contribute to outcome prediction. The preoperative MMSE score was lower within the low Aβ ratio group (median 25, IQR 23–28) compared to the high subgroup (26, 24–29) (p = 0.028). The T-Tau x Aβ40/42 ratio and P-tau x Aβ40/42 ratio did not contribute to shunt response prediction. The prevalence of vascular risk factors did not affect shunt response. DISCUSSION: A higher preoperative ventricular CSF level of neurogranin, which is a postsynaptic marker, may signal a favorable postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers explained only 6% of the variability in outcome. Evidence of amyloid or tau pathology did not affect the outcome. BioMed Central 2023-10-25 /pmc/articles/PMC10601279/ /pubmed/37880775 http://dx.doi.org/10.1186/s12987-023-00475-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Grønning, Rebecca
Jeppsson, Anna
Hellström, Per
Laurell, Katarina
Farahmand, Dan
Zetterberg, Henrik
Blennow, Kaj
Wikkelsø, Carsten
Tullberg, Mats
Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus
title Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus
title_full Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus
title_fullStr Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus
title_full_unstemmed Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus
title_short Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus
title_sort association between ventricular csf biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601279/
https://www.ncbi.nlm.nih.gov/pubmed/37880775
http://dx.doi.org/10.1186/s12987-023-00475-8
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