Elevated Serum Glial Fibrillary Acidic Protein (GFAP) is Associated with Poor Functional Outcome After Cardiopulmonary Resuscitation.

BACKGROUND: The neurological prognosis of patients after cardiopulmonary resuscitation (CPR) is difficult to assess. GFAP is an astrocytic intermediate filament protein released into bloodstream in case of cell death. We performed a prospective study aiming to compare the predictive potential of GFAP after resuscitation to the more widely used biomarker neuron-specific enolase (NSE). METHODS: One hundred patients were included at 48 h (tolerance interval ±12 h) after cardiac arrest. A serum sample was collected immediately after study inclusion. We determined serum levels of GFAP and NSE by means of immunoassays. Primary outcome was the modified Glasgow outcome scale at 4 weeks. Values below four were considered as a poor functional outcome. RESULTS: Median GFAP levels in poor outcome (n = 61) and good outcome (n = 39) patients were 0.03 µg/L (interquartile range 0.01-0.07 µg/L) and 0.02 µg/L (0.01-0.03 µg/L; p = 0.014), respectively. GFAP revealed a sensitivity of 60.7% and a specificity of 66.7% to predict a poor functional outcome. All patients having a GFAP level >0.08 µg/L had a poor functional outcome. For NSE, sensitivity was 44.3% and specificity was 100.0% for predicting a poor outcome. Multivariate regression analysis revealed GFAP, NSE, and the Karnofsky index to be independent predictors of outcome. CONCLUSIONS: The release patterns of GFAP and NSE after CPR show differences. GFAP levels above 0.08 µg/L were associated with a poor outcome in all cases, and patients with strongly elevated values (>3 µg/L) consistently had severe brain damage on brain imaging. Both biomarkers independently contribute to outcome prediction after CPR.

Glial Fibrillary Acidic Protein Serum Levels Distinguish between Intracerebral Hemorrhage and Cerebral Ischemia in the Early Phase of Stroke.

BACKGROUND: Recent studies have suggested that glial fibrillary acidic protein (GFAP) serum concentrations distinguish between intracerebral hemorrhage (ICH) and ischemic stroke (IS) shortly after symptom onset. In this prospective multicenter trial we validated GFAP in an independent patient cohort and assessed the quantitative relationship between GFAP release, bleeding size, and localization. METHODS: We included patients with a persistent neurological deficit (NIH Stroke Scale ≥4) suggestive of stroke within 6 h of symptom onset. Blood samples were drawn at hospital admission. GFAP serum concentrations were measured using an electrochemiluminometric immunoassay. Primary endpoint was the final diagnosis established at hospital discharge (ICH, IS, or stroke mimic). RESULTS: 202 patients were included (45 with ICH, 146 with IS, 11 stroke mimics). GFAP concentrations were significantly higher in ICH than in IS patients [median (interquartile range) 0.16 µg/L (0.04-3.27) vs 0.01 µg/L (0.01-0.01), P <0.001]. A GFAP cutoff of 0.03 µg/L provided a sensitivity of 77.8% and a specificity of 94.2% in distinguishing ICH from IS and stroke mimics [ROC analysis area under the curve 0.872 (95% CI, 0.802-0.942), P <0.001]. GFAP serum concentrations were positively correlated with ICH volume. Lobar ICH volumes were larger and thus associated with higher GFAP concentrations as compared to deep ICH. CONCLUSIONS: Serum GFAP was confirmed to be a biomarker indicating ICH in patients presenting with acute stroke symptoms. Very small ICH may be missed owing to less tissue destruction.

Post-cardiac arrest serum levels of glial fibrillary acidic protein for predicting neurological outcome.

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 °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.

Blood levels of glial fibrillary acidic protein (GFAP) in patients with neurological diseases.

BACKGROUND AND PURPOSE: The brain-specific astroglial protein GFAP is a blood biomarker candidate indicative of intracerebral hemorrhage in patients with symptoms suspicious of acute stroke. Comparably little, however, is known about GFAP release in other neurological disorders. In order to identify potential "specificity gaps" of a future GFAP test used to diagnose intracerebral hemorrhage, we measured GFAP in the blood of a large and rather unselected collective of patients with neurological diseases. METHODS: Within a one-year period, we randomly selected in-patients of our university hospital for study inclusion. Patients with ischemic stroke, transient ischemic attack and intracerebral hemorrhage were excluded. Primary endpoint was the ICD-10 coded diagnosis reached at discharge. During hospital stay, blood was collected, and GFAP plasma levels were determined using an advanced prototype immunoassay at Roche Diagnostics. RESULTS: A total of 331 patients were included, covering a broad spectrum of neurological diseases. GFAP levels were low in the vast majority of patients, with 98.5% of cases lying below the cut-off that was previously defined for the differentiation of intracerebral hemorrhage and ischemic stroke. No diagnosis or group of diagnoses was identified that showed consistently increased GFAP values. No association with age and sex was found. CONCLUSION: Most acute and chronic neurological diseases, including typical stroke mimics, are not associated with detectable GFAP levels in the bloodstream. Our findings underline the hypothesis that rapid astroglial destruction as in acute intracerebral hemorrhage is mandatory for GFAP increase. A future GFAP blood test applied to identify patients with intracerebral hemorrhage is likely to have a high specificity.

Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke.

BACKGROUND: Glial fibrillary acidic protein (GFAP) is a biomarker candidate indicative of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. GFAP is released rapidly in the presence of expanding intracerebral bleeding, whereas a more gradual release occurs in ischemic stroke. In this study the diagnostic accuracy of plasma GFAP was determined in a prospective multicenter approach. METHODS: Within a 1-year recruitment period, patients suspected of having acute (symptom onset<4.5 h before admission) hemispheric stroke were prospectively included into the study in 14 stroke centers in Germany and Switzerland. A blood sample was collected at admission, and plasma GFAP was measured by use of an electrochemiluminometric immunoassay. The final diagnosis, established at hospital discharge, was classified as ICH, ischemic stroke, or stroke mimic. RESULTS: The study included 205 patients (39 ICH, 163 ischemic stroke, 3 stroke mimic). GFAP concentrations were increased in patients with ICH compared with patients with ischemic stroke [median (interquartile range) 1.91 µg/L (0.41-17.66) vs 0.08 µg/L (0.02-0.14), P<0.001]. Diagnostic accuracy of GFAP for differentiating ICH from ischemic stroke and stroke mimic was high [area under the curve 0.915 (95% CI 0.847-0.982), P<0.001]. A GFAP cutoff of 0.29 µg/L provided diagnostic sensitivity of 84.2% and diagnostic specificity of 96.3% for differentiating ICH from ischemic stroke and stroke mimic. CONCLUSIONS: Plasma GFAP analysis performed within 4.5 h of symptom onset can differentiate ICH and ischemic stroke. Studies are needed to evaluate a GFAP point-of-care system that may help optimize the prehospital triage and management of patients with symptoms of acute stroke.