Abstract
Background and PurposeThe 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.MethodsWithin 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.ResultsA 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.ConclusionMost 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.
Highlights
The astroglial protein Glial Fibrillary Acidic Protein (GFAP) has been identified as a potential blood biomarker of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. [1,2,3,4] GFAP is released rapidly in case of an expanding parenchymal bleeding in the brain leading to immediate cell destruction, whereas it is detected with delay in case of ischemic stroke (IS), where necrosis and cellular disintegration do not occur before 6–12 h after symptom onset
Apart from a considerable number of acute stroke patients, whose GFAP blood levels are reported in the literature, only little is known about GFAP in patients with other neurological diseases
GFAP was found elevated in the plasma of patients with glioblastoma, whereas other intracranial tumors including metastases were not shown to increase GFAP blood levels. [7,10,11] GFAP blood levels were shown to correlate with severity and outcome after traumatic brain injury. [12,13,14] Sporadically it was reported that patients with neuromyelitis optica show increased GFAP plasma levels [15]
Summary
The astroglial protein GFAP has been identified as a potential blood biomarker of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. [1,2,3,4] GFAP is released rapidly in case of an expanding parenchymal bleeding in the brain leading to immediate cell destruction, whereas it is detected with delay in case of ischemic stroke (IS), where necrosis and cellular disintegration do not occur before 6–12 h after symptom onset. The astroglial protein GFAP has been identified as a potential blood biomarker of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. [1] It is not yet clear, whether the upregulation of GFAP following different pathological events in the CNS, a process commonly known as reactive astrogliosis, may lead to GFAP release and emergence of detectable protein levels in peripheral blood [9]. The brain-specific astroglial protein GFAP is a blood biomarker candidate indicative of intracerebral hemorrhage in patients with symptoms suspicious of acute stroke. 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
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