Abstract
Plasma glial fibrillary acidic protein (GFAP) and tau are promising markers for differentiating acute cerebral ischemia (ACI) and hemorrhagic stroke (HS), but their prehospital dynamics and usefulness are unknown. We performed ultra-sensitivite single-molecule array (Simoa®) measurements of plasma GFAP and total tau in a stroke code patient cohort with cardinal stroke symptoms [National Institutes of Health Stroke Scale (NIHSS) ≥3]. Sequential sampling included 2 ultra-early samples, and a follow-up sample on the next morning. We included 272 cases (203 ACI, 60 HS, and 9 stroke mimics). Median (IQR) last-known-well to sampling time was 53 (35-90) minutes for initial prehospital samples, 90 (67-130) minutes for secondary acute samples, and 21 (16-24) hours for next morning samples. Plasma GFAP was significantly higher in patients with HS than ACI (P < 0.001 for <1 hour and <3 hour prehospital samples, and <3 hour secondary samples), while total tau showed no intergroup difference. The prehospital GFAP release rate (pg/mL/minute) occurring between the 2 very early samples was significantly higher in patients with HS than ACI [2.4 (0.6-14.1)] versus 0.3 (-0.3-0.9) pg/mL/minute, P < 0.001. For cases with <3 hour prehospital sampling (ACI n = 178, HS n = 59), a combined rule (prehospital GFAP >410 pg/mL, or prehospital GFAP 90-410 pg/mL together with GFAP release >0.6 pg/mL/minute) enabled ruling out HS with high certainty (NPV 98.4%) in 68% of patients with ACI (sensitivity for HS 96.6%, specificity 68%, PPV 50%). In comparison to single-point measurement, monitoring the prehospital GFAP release rate improves ultra-early differentiation of stroke subtypes. With serial measurement GFAP has potential to improve future prehospital stroke diagnostics.
Highlights
Emergency medical services (EMS) encountering a patient with acute stroke symptoms are challenged with the difficult task of rapidly triaging the patient to the appropriate hospital with sufficient therapeutic capabilities, a challenge that has become increasingly complicated after the advent of thrombectomy and its expanding time window [1]
We evaluated the diagnostic benefits of combining initial prehospital glial fibrillary acidic protein (GFAP) concentrations and the GFAP release rate
Main comparisons were performed between the acute cerebral ischemia (ACI) and hemorrhagic stroke (HS) groups (n 1⁄4 263)
Summary
Emergency medical services (EMS) encountering a patient with acute stroke symptoms are challenged with the difficult task of rapidly triaging the patient to the appropriate hospital with sufficient therapeutic capabilities, a challenge that has become increasingly complicated after the advent of thrombectomy and its expanding time window [1]. Novel methods for on-scene diagnosis of acute stroke and differentiation of ischemic and hemorrhagic subtypes are needed, and such methods could facilitate selection of patients for future prehospital therapeutic studies [2]. The prospect of rapid and sensitive analysis of brain biomarkers in blood has recently become less elusive aNeurology and Clinical Neurosciences, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; bDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden; cWallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden; dDepartment of Old Age. Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; eNIHR Biomedical Research Centre for Mental Health and Biomedical. Plasma glial fibrillary acidic protein (GFAP) and tau are promising markers for differentiating acute cerebral ischemia (ACI) and hemorrhagic stroke (HS), but their prehospital dynamics and usefulness are unknown
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