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Discriminative value of glial fibrillar acidic protein (GFAP) as a diagnostic tool in acute stroke. Individual patient data meta-analysis
  1. Juan Antonio Cabezas1,
  2. Alejandro Bustamante2,
  3. Nicola Giannini3,
  4. Emilio Pecharroman2,
  5. Aristeidis H Katsanos4,
  6. Georgios Tsivgoulis5,
  7. Michal Rozanski6,
  8. Heinrich Audebert6,
  9. Stefania Mondello7,
  10. Victor Llombart2,
  11. Joan Montaner8,9
  1. 1 Neurology, Virgen del Rocio University Hospital, Sevilla, Spain
  2. 2 Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain
  3. 3 Neurological Clinic, University of Pisa, Pisa, Italy
  4. 4 Department of Neurology, University of Ioannina School of Medicine, Athens, Greece
  5. 5 Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  6. 6 Department of Neurology, Center for Stroke Research Berlin (CSB), Charité–Universitätsmedizin, Berlin, Germany
  7. 7 Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Messina, Italy
  8. 8 Neurology, Virgen Macarena University Hospital, Sevilla, Spain
  9. 9 Neurovascular Laboratory, Vall d'Hebron Hospital, Barcelona, Spain
  1. Correspondence to Dr Joan Montaner, Neurology, Virgen Macarena University Hospital, Sevilla 41009, Spain; jmontaner-ibis{at}


Glial fibrillar acidic protein (GFAP) in serum has been evaluated as a promising biomarker to differentiate between intracerebral hemorrhage (ICH) and acute ischemic stroke (AIS). We assessed its value as diagnostic and prognostic tool for ICH through a literature systematic review and individual patient data (IPD) meta-analysis.

We performed a systematic search in PubMed database until November 2018 for publications that evaluated GFAP to differentiate AIS and ICH within 4.5 hours after symptoms onset. Thereafter, we invited authors of selected studies to participate in this work by providing IPD from their cohorts. We used standardized individual subject’s data to evaluate the association of GFAP concentrations with stroke subtype, demographics, stroke characteristics and factors related with GFAP measurement.

From 4 selected studies, we collected data of 340 patients (236 AIS and 104 ICH). Standardized GFAP blood levels were significantly elevated in ICH compared with those with AIS (median and IQR: 0.84 (0.781–1.24), 0.79 (0.74–0.81); p<0.0001). In both stroke types, GFAP concentrations correlated with baseline stroke severity (r=0.27, p<0.0001; r=0.36, p<0.001; for AIS and ICH, respectively) but no correlation was found regarding time to sampling. Limited data precluded the evaluation of GFAP levels and functional outcome.

These findings demonstrate substantially different levels of GFAP in the blood of patients with ICH compared with patients with AIS soon after the event, while no association was found with outcome. In summary, GFAP could be a valuable diagnostic tool to assist in medical decision-making and to optimize management of stroke in the acute setting.

  • stroke
  • biomarkers

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  • Contributors AB and JM conceived the study. AB, JAC and NG performed the selection of articles. JAC, AB and JM drafted the manuscript. AB, AHK, GT, MR, HA, SM, and VL collected the data. JAC, AB and EP did the data analysis. All authors reviewed and edited the manuscript and approved the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval We did not obtain ethics approval because our study was based on data from previous studies. These individual studies required informed consent before patient enrollment.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained upon reasonable request to involved investigators.