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OBJECTIVES: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) peptide, a product of the proteolytic degradation of AMPA receptors in healthy nonathletes and athletes with concussions, is assessed. The detection of AMPAR peptide in conjunction with neuropsychological testing and neuroimaging is undertaken. SUBJECTS: Persons (n = 124, 19-23 years) are enrolled in the pilot-blinded study according to approved Institutional Review Board protocols at Kennesaw State University and DeKalb Medical. METHODS: AMPAR peptide plasma assay was performed using magnetic particles-enzyme-linked immunosorbent assay. All participants had neurocognitive tests (ImPACT); selected subjects with concussions were followed-up with magnetic resonance imaging and neurologic consultations. RESULTS: Athletes (n = 33) with clinically defined single or multiple concussions were compared to 91 age and gender matched controls without a history of concussion. AMPAR peptide values of 0.05-0.40 ng/mL for controls and 1.0-8.5 ng/mL for concussions are found. The biomarker sensitivity of 91% and a specificity of 92% (0.4 ng/mL cut off) to assess concussions are calculated. Poorer ImPACT scores correlated with abnormal levels of the biomarker. In athletes with multiple concussions, increased AMPAR peptide values (2.0-12.0 ng/mL) were associated with minor findings on magnetic resonance imaging. CONCLUSION: AMPAR peptide assay combined with ImPACT and neuroimaging is a promising tool for assessment of concussions. Additional clinical validation studies are required.

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[This corrects the article DOI: 10.1371/journal.pone.0042362.].

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BACKGROUND: The acute assessment of patients with suspected ischemic stroke remains challenging. The use of brain biomarker assays may improve the early diagnosis of ischemic stroke. The main goal of the study was to evaluate whether the NR2 peptide, a product of the proteolytic degradation of N-methyl-D-aspartate (NMDA) receptors, can differentiate acute ischemic stroke (IS) from stroke mimics and persons with vascular risk factors/healthy controls. A possible correlation between biomarker values and lesion sizes was investigated as the secondary objective. METHODS AND FINDINGS: A total of 192 patients with suspected stroke who presented within 72 h of symptom onset were prospectively enrolled. The final diagnosis was determined based on clinical observations and radiological findings. Additionally gender- and age-matched healthy controls (n = 52) and persons with controlled vascular risk factors (n = 48) were recruited to compare NR2 peptide levels. Blinded plasma was assayed by rapid magnetic particles (MP) ELISA for NR2 peptide within 30 min and results for different groups compared using univariate and multivariate statistical analyses. There was a clinical diagnosis of IS in 101 of 192 (53%) and non-stroke in 91 (47%) subjects. The non-stroke group included presented with acute stroke symptoms who had no stroke (n = 71) and stroke mimics (n = 20). The highest NR2 peptide elevations where found in patients with IS that peaked at 12 h following symptom onset. When the biomarker cut off was set at 1.0 ug/L, this resulted in a sensitivity of 92% and a specificity of 96% to detect IS. A moderate correlation (r(s) = 0.73) between NR2 peptide values and acute ischemic cortical lesions (<200 mL) was found. CONCLUSIONS: This study suggests that the NR2 peptide may be a brain specific biomarker to diagnose acute IS and may allow the differentiation of IS from stroke mimics and controls. Additional larger scale clinical validation studies are required.

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BACKGROUND AND PURPOSE: Predicting stroke using biomarkers would enable clinicians to help prevent stroke or mitigate damage. Several stroke biomarkers have been investigated but none has shown near term predictive value. METHODS: We studied patients presenting with a history of stroke or transient ischemic attack (TIA) to determine whether serum levels of autoantibodies to the NMDA receptor NR2 peptide (NR2Ab) reflected the presence of recent stroke compared with controls. Antibody levels were also correlated with clinical risk factors for stroke, including diabetes, hypertension, hyperlipidemia, and history of recent TIA or stroke. RESULTS: Of the 245 patients that presented with acute stroke or TIA, 130 consented to participate and results are available for the 120. Volunteers from the community were recruited as controls. Males and females with multiple recent strokes and females with acute strokes had elevated NR2Ab levels compared to non-stroke patients or controls. Using a multiple regression model, the predictive value for NR2Ab was compared to clinical risk factors. In men, the presence of stroke correlated with hypertension (p<0.001) and NR2Ab levels (p<0.01) and in women the presence of stroke correlated with hypertension (p<0.001), diabetes (p<0.05), atrial fibrillation (p<0.05) and NR2Ab (p<0.01). CONCLUSION: These results suggest that NR2Ab levels reflect a history of multiple strokes and may serve as a predictive factor for stroke.

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