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.
Highlights
During the last decades the main focus of sepsis care has been directed towards short- and long-term survival of patients [1]
confusion assessment method for the ICU (CAM-ICU) screening was positive for brain dysfunction in 16 of 20 participants
Immunohistochemistry gave clear evidence for axonal degeneration in sepsis which supports the diagnostic role of neurofilament proteins (Nf) measurements in sepsis-associated encephalopathy (SAE) patients. This is the first study on the relevance of neurofilament heavy (NfH) and neurofilament light chains (NfL) in cerebrospinal fluid (CSF) and plasma to detect SAE and to predict outcome in patients with sepsis
Summary
During the last decades the main focus of sepsis care has been directed towards short- and long-term survival of patients [1]. The need for prolonged registration of EEG to detect abnormalities over time is not practicable in the ICU setting and previous studies showed no association between EEG and brain dysfunction detected by CAM-ICU [18]. In this context body fluid biomarkers may be of diagnostic value [6,19,20]. As a consequence of axonal injury Nf are released into the extracellular fluid and can be measured by ELISA technique [30] This is the first study on the value of neurofilament heavy (NfH) and neurofilament light chains (NfL) in cerebrospinal fluid (CSF) and plasma of patients with SAE. The aim is to evaluate the potential suitability of Nf as biomarkers to detect SAE, septic brain injury and to predict outcome in patients with sepsis
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