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PLoS One. 2019 Jan 24;14(1):e0211184. doi: 10.1371/journal.pone.0211184. eCollection 2019.

The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - A prospective, pilot observational study.

Author information

Department of Anesthesiology and Intensive Care Medicine, University Medical Center Rostock, Rostock, Germany.
Department of Neuroimmunology, Institute of Neurology, University College London, London, United Kingdom.
Moorfields Eye Hospital, The National Hospital for Neurology and Neurosurgery, London, United Kingdom.
Department of Neurology, University Medical Center Rostock, Rostock, Germany.
Department of Internal Medicine, Intensive Care Unit, University Medical Center Rostock, Rostock, Germany.
Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom.
UK Dementia Research Institute at University College London, London, United Kingdom.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Neurology, Medical University Vienna, Vienna, Austria.
Institute for Diagnostic and Interventional Radiology, University Medical Center Rostock, Rostock, Germany.
Department of Neuro-anesthesiology and Intensive Care Medicine, Saint-Anne Teaching Hospital, Paris-Decartes University, Paris, France.
Laboratory of Human Histopathology and Animal Models, Institut Pasteur, Paris, France.

Erratum in


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.

Conflict of interest statement

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.

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