1. The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - A prospective, pilot observational study.
- Author
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Ehler J, Petzold A, Wittstock M, Kolbaske S, Gloger M, Henschel J, Heslegrave A, Zetterberg H, Lunn MP, Rommer PS, Grossmann A, Sharshar T, Richter G, Nöldge-Schomburg G, and Sauer M
- Subjects
- Aged, Aged, 80 and over, Critical Care, Disease-Free Survival, Female, Humans, Male, Middle Aged, Pilot Projects, Prospective Studies, Severity of Illness Index, Survival Rate, Brain Diseases blood, Brain Diseases diagnostic imaging, Brain Diseases mortality, Brain Diseases physiopathology, Electroencephalography, Intermediate Filaments metabolism, Magnetic Resonance Imaging, Shock, Septic blood, Shock, Septic diagnostic imaging, Shock, Septic mortality, Shock, Septic physiopathology
- Abstract
Sepsis-associated encephalopathy (SAE) contributes to mortality and neurocognitive impairment of sepsis patients. Neurofilament (Nf) light (NfL) and heavy (NfH) chain levels as biomarkers for neuroaxonal injury were not evaluated in cerebrospinal fluid (CSF) and plasma of patients with sepsis-associated encephalopathy (SAE) before. We conducted a prospective, pilot observational study including 20 patients with septic shock and five patients without sepsis serving as controls. The assessment of SAE comprised a neuropsychiatric examination, electroencephalography (EEG), magnetic resonance imaging (MRI) and delirium screening methods including the confusion assessment method for the ICU (CAM-ICU) and the intensive care delirium screening checklist (ICDSC). CSF Nf measurements in sepsis patients and longitudinal plasma Nf measurements in all participants were performed on days 1, 3 and 7 after study inclusion. Plasma NfL levels increased in sepsis patients over time (p = 0.0063) and remained stable in patients without sepsis. Plasma NfL values were significantly higher in patients with SAE (p = 0.011), significantly correlated with the severity of SAE represented by ICDSC values (R = 0.534, p = 0.022) and correlated with a poorer functional outcome after 100 days (R = -0.535, p = 0.0003). High levels of CSF Nf were measured in SAE patients. CSF NfL levels were higher in non-survivors (p = 0.012) compared with survivors and correlated with days until death (R = -0.932, p<0.0001) and functional outcome after 100 days (R = -0.749, p<0.0001). The present study showed for the first time that Nf levels provide complementary prognostic information in SAE patients indicating a higher chance of death and poorer functional/cognitive outcome in survivors., Competing Interests: AP is supported by the Moorfields Biomedical Research Centre, and the Dutch MS Research Foundation and received honoraria from Novartis for QC reading (Passos study). MPL is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. HZ is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg (not involved in this study), has served at advisory boards of Roche Diagnostics and Eli Lilly and has received travel support from Teva. The remaining authors (JE, MW, SK, MG, JH, AH, PSR, AG, TS, GR, GNS, MS) declare that there are no competing interests. "This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2019
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