Diagnostic Potential of the NMDA Receptor Peptide Assay for Acute Ischemic Stroke

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 (rs = 0.73) between NR2 peptide values and acute ischemic cortical lesions (\u3c200 \u3emL) 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

Biomarkers for Traumatic Brain Injury

Due to injuries sustained in sports and in combat, interest in TBI has never been greater. Biomarkers for Traumatic Brain Injury will fulfil a gap in our understanding of what is occurring in the brain following injury that can subsequently be detected in biological fluids and imaging. This knowledge will be useful for all researchers and clinicians interested in the biochemical and structural sequelae underpinning clinical manifestations of TBI and help guide appropriate patient management. Current and prospective biomarkers for the assessment of traumatic brain injury (TBI), particularly mild TBI, are examined using a multidisciplinary approach involving biochemistry, molecular biology, and clinical chemistry. The book incorporates presentations from outstanding researchers and clinicians in the area and describes advanced proteomic and degradomic technologies in the development of novel biomarker assays. For practical purposes, the focus of this volume is on detection of blood-based biomarkers to improve diagnostic certainty of mild TBI in conjunction with radiological and clinical findings. It represents contributions from internationally-recognized researchers at the forefront of traumatic brain injury many of whom are recipients of grants and contracts from the United States Department of Defense for research specifically on developing diagnostic tests for TBI. The book will be essential reading for scientists, pharmacologists, chemists, medical and graduate students

AMPAR Peptide Values in Blood of Nonathletes and Club Sport Athletes With Concussions

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

Correction: Diagnostic Potential of the NMDA Receptor Peptide Assay for Acute Ischemic Stroke.

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

Flow diagram of study population: (i) patients with definite acute ischemic stroke (IS) and TIA, (ii) the non-stroke group included patients presented with acute stroke symptoms and had no stroke and stroke mimics, (iii) control group comprising healthy volunteers and persons with controlled vascular risk factors (hypertension, diabetes mellitus, and heart disease).

<p>Flow diagram of study population: (i) patients with definite acute ischemic stroke (IS) and TIA, (ii) the non-stroke group included patients presented with acute stroke symptoms and had no stroke and stroke mimics, (iii) control group comprising healthy volunteers and persons with controlled vascular risk factors (hypertension, diabetes mellitus, and heart disease).</p

Characteristics of the study population.

<p>Characteristics of the study population.</p

Operating characteristics of different cutoff points for NR2 peptide concentrations in all study groups.

<p>Operating characteristics of different cutoff points for NR2 peptide concentrations in all study groups.</p

Distribution of plasma NR2 peptide concentrations in (A) healthy controls (n = 52), persons with controlled vascular risk factors (n = 48), non-stroke (n = 99) and acute ischemic stroke (n = 101).

<p>Distribution of NR2 peptide in plasma of patients with acute IS depending on time of symptom onset: n = 10 at 1–3 h, n = 8 at 3–6 h, n = 15 at 6–12 h, n = 17 at 12–24 h, and n = 51 at 24–72 h (<b>B</b>). Correlation of NR2 peptide concentrations with new cortical lesion (<b>C</b>). ROC curves for plasma NR2 peptide depended comparison group (<b>D</b>). Areas under the each curve are 0.930 calculated for the biomarker potential to distinguish acute IS vs certain control group, 0.914 for acute IS vs non-stroke, and 0.920 for acute IS vs combined control and non-stroke groups.</p