Glial Fibrillary Acidic Protein for Prehospital Diagnosis of Intracerebral Hemorrhage

Abstract

Background: Both, acute ischemic stroke (AIS) and hemorrhage stroke (intracerebral hemorrhage, ICH) require early attention but different treatment strategies. Plasma glial fibrillary acidic protein (GFAP) levels were found to be elevated in ICH patients after they arrived in the hospital. Because treatment options differed, we sought to determine whether GFAP can be used to accurately differentiate between of AIS and ICH in the prehospital setting. Methods: We assessed acute stroke patients in the Stroke Emergency Mobile (STEMO). STEMO is a stroke ambulance staffed by a specialized team including a neurologist and equipped with a computed tomography scanner plus a point-of-care laboratory. The STEMO ambulance is integrated in the emergency medical system of Berlin, Germany. Following prehospital stroke diagnosis, blood was drawn and subsequently analysed using research assays from Roche diagnostics. The clinical accuracy of plasma GFAP was tested using a cut-off value of 0.29 ng/ml. Results: Blood samples of 74 patients were analysed. Twenty-five patients had ICH (mean age 69 ± 11 years, median National Institutes of Health Stroke Scale (NIHSS) 15) and 49 IS (mean age 75 ± 10 years, median NIHSS 6). Nine ICH (0 IS patients) had GFAP-levels above 0.29 ng/ml. The sensitivity and specificity of GFAP for differentiating between ICH and AIS were 36.0 and 100%. The sensitivity for ICH volume >15 ml was 61.5%. ICH patients without GFAP elevation had significantly smaller hemorrhage volumes (median 4.5 vs. 37.6 ml, p = 0.004) and were less likely to deteriorate (19 vs. 56%, p = 0.087). Conclusions: GFAP levels >0.29 ng/ml were seen only in ICH, thus confirming the diagnosis of ICH during prehospital care. However, sensitivity is low particularly in smaller hemorrhages.

A scoping review of pre-hospital technology to assist ambulance personnel with patient diagnosis or stratification during the emergency assessment of suspected stroke

“…Blood sampling for biomarkers in the pre-hospital setting appears feasible [41]; however, there is currently no published evidence on diagnostic accuracy and patient outcomes for the studies identified: Helsinki Ultra-acute Stroke Biomarker Study [22] and PRISM [23]. The Helsinki study examines GFAP which appears promising for identifying haemorrhage at an early time point [47][48][49]; however, this biomarker may not be robust and, as it does not identify small haemorrhages with the same performance as large ones, many not be useful to inform IVT decisions [50]. The other Helsinki biomarker, NR2 peptide, has potential for diagnosing ischaemia but data within the first 6 h is limited [51,52].…”

A Systematic Review and Meta-Analysis of Molecular Biomarkers Associated with Early Neurological Deterioration Following Acute Stroke

“…Very early or late sampling for biomarker identification of stroke may lead to false negative cases: for example, Rozanski et al [64] pre-hospital study of Glial Fibrillary Acidic Protein as a biomarker of ICH, with a median onset-to-sampling time of 63 min, had poorer sensitivity than hospital-based studies (median onset-to-sampling time > 120 min). The same may apply to the use of biomarkers to detect END as levels may not yet have risen or have already fallen.…”

“…For example, plasma glial fibrillary acidic protein shows > 90% specificity as a biomarker for haemorrhagic stroke, and concentrations are positively correlated with the risk of subsequent clinical deterioration [64]. Neurofilaments are released during neuroaxonal injury [68], including following traumatic brain injury [69], but are also elevated in active cerebral small vessel disease [70] and acute ischaemic stroke [71], particularly in those with higher severity of primary injury [72] and recurrent ischaemic lesions [71].…”

How Development of Blood Biomarkers Could Benefit Prehospital Management of Acute Stroke

“…For example, Foerch et al found sensitivity and specificity values of 84.2 and 96.3% respectively. Recently, Rozanski et al extended these findings to the prehospital setting, collecting ambulance plasma samples from 25 ICH and 49 ischemic stroke patients, and reporting a sensitivity and specificity of 36 and 100% for identifying ICH using a GFAP cutoff of 0.29 ng/ml [12]. The high specificity suggests that GFAP-based algorithms could be developed to initiate treatment in a significant portion of ICH patients, but larger studies are needed to determine optimal cutoff values for prehospital use.…”