Article

Serial soluble neurofilament heavy chain in plasma as a marker of brain injury after cardiac arrest

Department of Intensive-and Perioperative Care, Skåne University Hospital
Critical care (London, England) (Impact Factor: 5.04). 03/2012; 16(2):R45. DOI: 10.1186/cc11244
Source: PubMed

ABSTRACT Introduction
Induced hypothermia has been shown to improve outcome after cardiac arrest, but early prognostication is hampered by the need for sedation. Here we tested whether a biomarker for neurodegeneration, the neurofilament heavy chain (NfH), may improve diagnostic accuracy in the first days after cardiac arrest.

Methods
This prospective study included 90 consecutive patients treated with hypothermia after cardiac arrest. Plasma levels of phosphorylated NfH (SMI35) were quantified using standard ELISA over a period of 72 h after cardiac arrest. The primary outcome was the dichotomized Cerebral Performance Categories scale (CPC). A best CPC 1-2 during 6 months follow-up was considered a good outcome, a best CPC of 3-4 a poor outcome. Receiver operator characteristics and area under the curve were calculated.

Results
The median age of the patients was 65 years, and 63 (70%) were male. A cardiac aetiology was identified in 62 cases (69%). 77 patients (86%) had out-of-hospital cardiac arrest. The outcome was good in 48 and poor in 42 patients. Plasma NfH levels were significantly higher 2 and 36 hours after cardiac arrest in patients with poor outcome (median 0.28 ng/mL and 0.5 ng/mL, respectively) compared to those with good outcome (0 ng/mL, p = 0.016, p < 0.005, respectively). The respective AUC were 0.72 and 0.71.

Conclusions
Plasma NfH levels correlate to neurological prognosis following cardiac arrest. In this study, 15 patients had neurological co-morbidities and there was a considerable overlap of data. As such, neurofilament should not be used for routine neuroprognostication until more data are available.

0 Bookmarks
 · 
135 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Early diagnosis of intensive care unit - acquired weakness (ICU-AW) using the current reference standard, that is, assessment of muscle strength, is often hampered due to impaired consciousness. Biological markers could solve this problem but have been scarcely investigated. We hypothesized that plasma levels of neurofilaments are elevated in ICU-AW and can diagnose ICU-AW before muscle strength assessment is possible. For this prospective observational cohort study, neurofilament levels were measured using ELISA (NfHSMI35 antibody) in daily plasma samples (index test). When patients were awake and attentive, ICU-AW was diagnosed using the Medical Research Council scale (reference standard). Differences and discriminative power (using the area under the receiver operating characteristic curve; AUC) of highest and cumulative (calculated using the area under the neurofilament curve) neurofilament levels were investigated in relation to the moment of muscle strength assessment for each patient. Both the index test and reference standard were available for 77 ICU patients. A total of 18 patients (23%) fulfilled the clinical criteria for ICU-AW. Peak neurofilament levels were higher in patients with ICU-AW and had good discriminative power (AUC: 0.85; 95% CI: 0.72 to 0.97). However, neurofilament levels did not peak before muscle strength assessment was possible. Highest or cumulative neurofilament levels measured before muscle strength assessment could not diagnose ICU-AW (AUC 0.59; 95% CI 0.37 to 0.80 and AUC 0.57; 95% CI 0.32 to 0.81, respectively). Plasma neurofilament levels are raised in ICU-AW and may serve as a biological marker for ICU-AW. However, our study suggests that an early diagnosis of ICU-AW, before muscle strength assessment, is not possible using neurofilament levels in plasma.
    Critical care (London, England) 01/2014; 18(1):R18. DOI:10.1186/cc13699 · 5.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Early prognostication after successful cardiopulmonary resuscitation is difficult and there is a need for novel methods to estimate the extent of brain injury and predict outcome. In this study, we evaluate the impact of the cardiac arrest syndrome on the plasma levels of selected tissue-specific microRNAs (miRNAs) and assess their ability to prognosticate death and neurological disability. We included 65 patients treated with hypothermia after cardiac arrest in the study. Blood samples were obtained at 24 hours and at 48 hours. For miRNA-screening purposes, custom quantitative polymerase chain reaction (qPCR)-panels were first used. Thereafter, individual miRNAs were assessed at 48 hours with qPCR. miRNAs successful at predicting prognosis at 48 hours were further analyzed at 24 hours. Outcome was measured according to the Cerebral Performance Categories scale (CPC) at 6 months after cardiac arrest and stratified into good (CPC 1-2) or poor (CPC 3-5). At 48 hours, miR-146a, miR-122, miR-208b, miR-21, miR-9 and miR-128 did not differ between the good and poor neurological outcome groups. In contrast, miR-124 was significantly elevated in patients with poor outcome compared to those with a favorable outcome (P <0.0001) at 24 hours and 48 hours after cardiac arrest. Analysis of receiver operating curves showed an area under the curve of 0.87 (95% confidence interval (CI) 0.79 to 0.96) at 24 hours and of 0.89 (95% CI 0.80 to 0.97) at 48 hours after cardiac arrest. The brain-enriched miRNA miR-124 is a promising novel biomarker for prediction of neurological prognosis following cardiac arrest.
    Critical care (London, England) 03/2014; 18(2):R40. DOI:10.1186/cc13753 · 5.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim of the study: To investigate serum levels of glial fibrillary acidic protein (GFAP) for evaluation of neurological outcome in cardiac arrest (CA) patients and compare GFAP sensitivity and specificity to that of more studied biomarkers neuron-specific enolas (NSE) and S100B. Method: A prospective observational study was performed in three hospitals in Sweden during 2008-2012. The participants were 125 CA patients treated with therapeutic hypothermia (TH) to 32-34 degrees C for 24 hours. Samples were collected from peripheral blood (n = 125) and the jugular bulb (n = 47) up to 108 hours post-CA. GFAP serum levels were quantified using a novel, fully automated immunochemical method. Other biomarkers investigated were NSE and S100B. Neurological outcome was assessed using the Cerebral Performance Categories scale (CPC) and dichotomized into good and poor outcome. Results: GFAP predicted poor neurological outcome with 100% specificity and 14-23% sensitivity at 24, 48 and 72 hours post-CA. The corresponding values for NSE were 27-50% sensitivity and for S100B 21-30% sensitivity when specificity was set to 100%. A logistic regression with stepwise combination of the investigated biomarkers, GFAP, did not increase the ability to predict neurological outcome. No differences were found in GFAP, NSE and S100B levels when peripheral and jugular bulb blood samples were compared. Conclusion: Serum GFAP increase in patients with poor outcome but did not show sufficient sensitivity to predict neurological outcome after CA. Both NSE and S100B were shown to be better predictors. The ability to predict neurological outcome did not increased when combining the three biomarkers.
    Resuscitation 09/2014; 85(12). DOI:10.1016/j.resuscitation.2014.09.007 · 3.96 Impact Factor

Full-text (3 Sources)

Download
30 Downloads
Available from
May 29, 2014