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
Published: 2022-02-15
Formatted citation
Braun M, Bjurnemark C, Seo W, Freyhult E, Nyholm D, Niemelä V, Blennow K, Zetterberg H, Fällmar D, Kultima K, Virhammar J..
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 CNS.
(2022).
DOI: 10.1186/s12987-022-00306-2
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 12xa0months 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 12xa0months after shunt surgery were available in 376 patients. RESULTS: Higher levels of NfL and T-tau were associated with less improvement after shunt surgery (βu2009=u2009-xa03.10, pu2009=u20090.016 and β =xa0-xa02.45, pu2009=u20090.012, respectively). Patients whose symptoms deteriorated after shunt surgery had higher preoperative levels of NfL (1250xa0ng/L [IQR:1020-2220] vs. 1020 [770-1649], pu2009<u20090.001) and T-tau (221xa0ng/L [IQR: 159-346] vs. 190 [135-261], pu2009=u20090.0039) than patients with postoperative improvement on the iNPH scale. Among the patients who improvedu2009≥u20095 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.