<scp>GFAP</scp> and antibodies against <scp>NMDA</scp> receptor subunit <scp>NR</scp>2 as biomarkers for acute cerebrovascular diseases

Stanca, D.; Mărginean, Ioan; Şoriţău, Olga; Dragoș, Cristian Mihai; Mărginean, Mariana; Mureșanu, Dafin F.; Vester, Johannes; Rafilă, Alexandru

doi:10.1111/jcmm.12614

Cited by 34 publications

(18 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results are partially in accordance with the findings of Foerch et al [15] and Stanca et al [29] . However, sensitivity in our cohort was lower than that reported by their evaluation (36% compared to 84 and 94%, respectively).…”

Section: Discussionsupporting

confidence: 83%

“…The results suggest that achieving higher levels of sensitivity in detection of ICH in a very early time window may require additional biomarker or clinical information. This approach was recently investigated by Stanca et al [29] who added the assessment of antibodies against NMDA receptor subunit NR2 to GFAP and found a sensitivity of 94% and specificity of 91% for discrimination between ischemic and hemorrhagic stroke. However, the 2 biomarkers were taken at 12 h after stroke, which is clearly too late for making treatment decisions in the hyperacute phase.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Glial Fibrillary Acidic Protein for Prehospital Diagnosis of Intracerebral Hemorrhage

Różański¹,

Waldschmidt

Kunz³

et al. 2016

Cerebrovasc Dis

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Glial Fibrillary Acidic Protein for Prehospital Diagnosis of Intracerebral Hemorrhage

Różański¹,

Waldschmidt

Kunz³

et al. 2016

Cerebrovasc Dis

View full text Add to dashboard Cite

show abstract

“…We included 11 studies involving 1297 participants (350 with ICH and 947 with either AIS or mimic). [10][11][12][13][21][22][23][24][25][26][27] The sensitivity and specificity reported in included studies ranged from 0.36 (95% CI 0.18-0.57) to 0.96 (95% CI 0.78-1.00) and 0.64 (95% CI 0.53-0.74) to 1.00 (95% CI 0.93-1.00), respectively (Figure 2(a)). Information on type of GFAP assay, minimum detectable concentration of GFAP, whether positivity thresholds were pre-defined, and risk of bias were available; other pre-defined covariates were either not reported or reported heterogeneously and were therefore not included in the meta-regression.…”

Section: Search Resultsmentioning

confidence: 99%

Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: Systematic review and meta-analysis of diagnostic test accuracy

Perry

Lucarelli

Penny-Dimri

et al. 2018

International Journal of Stroke

View full text Add to dashboard Cite

Background and aims: Glial fibrillary acidic protein (GFAP) has shown promise in several studies for its ability to diagnose intracerebral hemorrhage (ICH). We evaluated the diagnostic accuracy of blood GFAP level to differentiate (ICH) from acute ischemic stroke (AIS) and stroke mimics, both overall, and in the first three hours after symptom onset. Methods: We searched multiple databases, without language restriction, from inception until December 2017. Hierarchical summary receiver operating characteristic (HSROC) modeling was used to meta-analyze results. We conducted subgroup analyses restricted to blood samples collected within 0-60, 60-120, and 120-180 min time groups after symptom onset, to evaluate diagnostic accuracy in the early pre-hospital phase. Between and within study heterogeneity was explored using meta-regression. Results: The search identified 199 potentially relevant citations from which 11 studies involving 1297 participants (350 ICH, 947 AIS, or mimic) were included. The pooled sensitivity, specificity, and area under the HSROC curve were 0.756 (95% CI 0.630-0.849), 0.945 (95% CI 0.858-0.980), and 0.904 (95% CI 0.878-0.931), respectively. Differences in assays used, but not the other covariates, partially explained between-study heterogeneity (p ¼ 0.034). The summary estimates for the 0-60, 60-120, and 120-180 min subgroups were comparable to the primary analysis and there was no statistically significant difference in diagnostic accuracy between subgroups. Conclusions: GFAP is a promising diagnostic biomarker for ICH diagnosis in the early pre-hospital phase. Test accuracy is affected by assay subtype, but there are still unexplained sources of heterogeneity. High quality, international multicenter trials are warranted to develop and validate a point-of-care GFAP assay for the rapid triage and evaluation of acute stroke in the pre-hospital setting.

show abstract

“…[ 47 ] Furthermore, a recent study suggested that GFAP used in combination with NR2 can differentiate between ischemic stroke and ICH at a time point extended to 12 h after the ictus with a sensitivity of 94% and specificity of 91%. [ 46 ] Another study showed that plasma concentrations of retinol binding protein 4 and GFAP at concentrations >61 μg/mL and <0.07 ng/mL, respectively, demonstrated 100% specificity, and these biomarkers might be independent predictors to discriminate stroke subtype, improving discrimination by 29% ( P < 0.0001). [ 48 ]…”

Section: Use Of Blood Glial Fibrillary Acidic Protein Levels For Earlmentioning

confidence: 99%

Biomarkers for acute diagnosis and management of stroke in neurointensive care units

et al. 2016

View full text Add to dashboard Cite

The effectiveness of current management of critically ill stroke patients depends on rapid assessment of the type of stroke, ischemic or hemorrhagic, and on a patient's general clinical status. Thrombolytic therapy with recombinant tissue plasminogen activator (r-tPA) is the only effective treatment for ischemic stroke approved by the Food and Drug Administration (FDA), whereas no treatment has been shown to be effective for hemorrhagic stroke. Furthermore, a narrow therapeutic window and fear of precipitating intracranial hemorrhage by administering r-tPA cause many clinicians to avoid using this treatment. Thus, rapid and objective assessments of stroke type at admission would increase the number of patients with ischemic stroke receiving r-tPA treatment and thereby, improve outcome for many additional stroke patients. Considerable literature suggests that brain-specific protein biomarkers of glial [i.e. S100 calcium-binding protein B (S100B), glial fibrillary acidic protein (GFAP)] and neuronal cells [e.g., ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE), αII-spectrin breakdown products SBDP120, SBDP145, and SBDP150, myelin basic protein (MBP), neurofilament light chain (NF-L), tau protein, visinin-like protein-1 (VLP 1), NR2 peptide] injury that could be detected in the cerebrospinal fluid (CSF) and peripheral blood might provide valuable and timely diagnostic information for stroke necessary to make prompt management and decisions, especially when the time of stroke onset cannot be determined. This information could include injury severity, prognosis of short-term and long-term outcomes, and discrimination of ischemic or hemorrhagic stroke. This chapter reviews the current status of the development of biomarker-based diagnosis of stroke and its potential application to improve stroke care.

show abstract

GFAP and antibodies against NMDA receptor subunit NR2 as biomarkers for acute cerebrovascular diseases

Cited by 34 publications

References 31 publications

Glial Fibrillary Acidic Protein for Prehospital Diagnosis of Intracerebral Hemorrhage

Glial Fibrillary Acidic Protein for Prehospital Diagnosis of Intracerebral Hemorrhage

Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: Systematic review and meta-analysis of diagnostic test accuracy

Biomarkers for acute diagnosis and management of stroke in neurointensive care units

Contact Info

Product

Resources

About