Evidence map›Paper›PMID 35164790›Full record

ArticleFluids and barriers of the CNS2022

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.

Madelene Braun, Caroline Bjurnemark, Woosung Seo, Eva Freyhult, Dag Nyholm, Valter Niemelä, Kaj Blennow, Henrik Zetterberg, David Fällmar, Kim Kultima and 1 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05915000 (Alterations of CSF Protein Markers as Prognostic Indicator of the Response to Cerebrospinal Fluid Shunting in Chronic Hydrocephalus in Adults), which is not on this map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05915000 recruitingnot on this map

Alterations of CSF Protein Markers as Prognostic Indicator of the Response to Cerebrospinal Fluid Shunting in Chronic Hydrocephalus in Adults

TypeobservationalSponsorUniversity of ValenciaRan2019 to 2029Enrolled150ConditionsBeta-amiloid and Phospho-tau Proteins in CSF, Ventricular Size After CSF Shunt, Cognitive Impairment and CSF Shunt, Motor Impairment Evolution After CSF ShuntArmsLumbar CSF protein marker determination
3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Association between p-tau181 in cerebrospinal fluid and shunt response in patients with normal-pressure hydrocephalus.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  2. Article
  3. Observational
  4. Article
  5. Inflammatory protein profiles and shunt response in iNPH.Fluids and barriers of the CNS · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Madelene BraunDepartment of Neuroscience, Neurology, Uppsala University, Akademiska sjukhuset, ing 85, 751 85, Uppsala, Sweden.
Caroline BjurnemarkDepartment of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
Woosung SeoDepartment of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
Eva FreyhultDepartment of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Dag NyholmDepartment of Neuroscience, Neurology, Uppsala University, Akademiska sjukhuset, ing 85, 751 85, Uppsala, Sweden.
Valter NiemeläDepartment of Neuroscience, Neurology, Uppsala University, Akademiska sjukhuset, ing 85, 751 85, Uppsala, Sweden.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
David FällmarDepartment of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
Kim KultimaDepartment of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
Johan VirhammarDepartment of Neuroscience, Neurology, Uppsala University, Akademiska sjukhuset, ing 85, 751 85, Uppsala, Sweden. johan.virhammar@neuro.uu.se.ORCID http://orcid.org/0000-0001-9901-2949

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLumbar 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.

methodsPreoperative 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.

resultsHigher 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.

conclusionsHigher 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.

Indexed as

Hydrocephalus, Normal PressureAmyloid beta-PeptidesBiomarkersCerebrospinal Fluid ShuntsHumansIntermediate Filamentstau ProteinsAmyloid beta-PeptidesBiomarkerstau ProteinsAmyloid betaBiomarkersCerebrospinal fluidLumbar punctureNeurofilament light chainNormal pressure hydrocephalusTau

Identifiers

PMID35164790
PMCPMC8845290

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.