eprintid: 10144104 rev_number: 8 eprint_status: archive userid: 699 dir: disk0/10/14/41/04 datestamp: 2022-02-23 16:04:23 lastmod: 2022-02-23 16:04:23 status_changed: 2022-02-23 16:04:23 type: article metadata_visibility: show sword_depositor: 699 creators_name: Braun, Madelene creators_name: Bjurnemark, Caroline creators_name: Seo, Woosung creators_name: Freyhult, Eva creators_name: Nyholm, Dag creators_name: Niemelä, Valter creators_name: Blennow, Kaj creators_name: Zetterberg, Henrik creators_name: Fällmar, David creators_name: Kultima, Kim creators_name: Virhammar, Johan title: Higher levels of neurofilament light chain and total tau in CSF are associated with negative outcome after shunt surgery in patients with normal pressure hydrocephalus ispublished: pub divisions: C07 divisions: F86 divisions: B02 divisions: UCL divisions: D07 keywords: Amyloid beta, Biomarkers, Cerebrospinal fluid, Lumbar puncture, Neurofilament light chain, Normal pressure hydrocephalus, Tau note: 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/. The Creative Commons Public Domain Dedication waiver (http://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. abstract: BACKGROUND: Lumbar punctures are a common examination in the work-up of patients with idiopathic normal pressure hydrocephalus (iNPH) and cerebrospinal fluid (CSF) biomarkers should therefore be available for use in selection of shunt candidates. The aim of this study was to investigate if CSF biomarkers are associated with outcome after shunt surgery alone or in combination with comorbidity and imaging markers, and investigate associations between CSF biomarkers and symptoms. METHODS: Preoperative CSF biomarkers were analyzed in 455 patients operated with shunt surgery for iNPH at a single center during 2011-2018. Symptoms before and 12 months after shunt surgery were graded with the Swedish iNPH scale. Neurofilament light chain protein (NfL), total tau (T-tau), phosphorylated tau (P-tau) and amyloid beta1-42 (Aβ1-42) CSF levels were measured. Evans' index and disproportionately enlarged subarachnoid space hydrocephalus were measured on preoperative CT-scans. Preoperative evaluation and follow-up 12 months after shunt surgery were available in 376 patients. RESULTS: Higher levels of NfL and T-tau were associated with less improvement after shunt surgery (β = - 3.10, p = 0.016 and β = - 2.45, p = 0.012, respectively). Patients whose symptoms deteriorated after shunt surgery had higher preoperative levels of NfL (1250 ng/L [IQR:1020-2220] vs. 1020 [770-1649], p < 0.001) and T-tau (221 ng/L [IQR: 159-346] vs. 190 [135-261], p = 0.0039) than patients with postoperative improvement on the iNPH scale. Among the patients who improved ≥ 5 levels on the iNPH scale (55%), NfL was abnormal in 22%, T-tau in 14%, P-tau in 6% and Aβ1-42 in 45%, compared with normal reference limits. The inclusion of CSF biomarkers, imaging markers and comorbidity in multivariate predictive Orthogonal Projections to Latent Structures (OPLS) models to did not improve predictability in outcome after shunt surgery. CONCLUSIONS: Higher levels of T-tau and NfL were associated with a less favorable response to shunt surgery, suggesting a more active neurodegeneration in this group of patients. However, CSF levels of these biomarkers can be elevated also in patients who respond to shunt surgery. Thus, none of these CSF biomarkers, alone or used in combination, are suitable for excluding patients from surgery. date: 2022-02-14 date_type: published publisher: Springer Science and Business Media LLC official_url: https://doi.org/10.1186/s12987-022-00306-2 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1940189 doi: 10.1186/s12987-022-00306-2 medium: Electronic pii: 10.1186/s12987-022-00306-2 lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Barczynska, Patrycja actors_id: PBARC91 actors_role: owner full_text_status: public publication: Fluids Barriers of the CNS volume: 19 number: 1 article_number: 15 event_location: England citation: Braun, Madelene; Bjurnemark, Caroline; Seo, Woosung; Freyhult, Eva; Nyholm, Dag; Niemelä, Valter; Blennow, Kaj; ... Virhammar, Johan; + view all <#> Braun, Madelene; Bjurnemark, Caroline; Seo, Woosung; Freyhult, Eva; Nyholm, Dag; Niemelä, Valter; Blennow, Kaj; Zetterberg, Henrik; Fällmar, David; Kultima, Kim; Virhammar, Johan; - view fewer <#> (2022) Higher levels of neurofilament light chain and total tau in CSF are associated with negative outcome after shunt surgery in patients with normal pressure hydrocephalus. Fluids Barriers of the CNS , 19 (1) , Article 15. 10.1186/s12987-022-00306-2 <https://doi.org/10.1186/s12987-022-00306-2>. Green open access document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10144104/1/Zetterberg_s12987-022-00306-2.pdf