Impaired Retinal Vasoreactivity: An Early Marker of Stroke Risk in Diabetes

Diabetes is a common cause of small vessel disease leading to stroke and vascular dementia. While the function and structure of large cerebral vessels can be easily studied, the brain’s microvasculature remains difficult to assess. Previous studies have demonstrated that structural changes in the retinal vessel architecture predict stroke risk, but these changes occur at late disease stages. Our goal was to examine whether retinal vascular status can predict cerebral small vessel dysfunction during early stages of diabetes. Retinal vasoreactivity and cerebral vascular function were measured in 78 subjects (19 healthy controls, 22 subjects with prediabetes, and 37 with type‐2 diabetes) using a new noninvasive retinal imaging device (Dynamic Vessel Analyzer) and transcranial Doppler studies, respectively. Cerebral blood vessel responsiveness worsened with disease progression of diabetes. Similarly, retinal vascular reactivity was significantly attenuated in subjects with prediabetes and diabetes compared to healthy controls. Subjects with prediabetes and diabetes with impaired cerebral vasoreactivity showed mainly attenuation of the retinal venous flicker response. This is the first study to explore the relationship between retinal and cerebral vascular function in diabetes. Impairment of venous retinal responsiveness may be one of the earliest markers of vascular dysfunction in diabetes possibly indicating subsequent risk of stroke and vascular dementia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/136050/1/jon12412.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/136050/2/jon12412_am.pd

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

Comparison of retinal vasodilator and constrictor responses in type 2 diabetes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93551/1/j.1755-3768.2012.02445.x.pd

Impaired retinal vasodilator responses in prediabetes and type 2 diabetes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99677/1/aos12129.pd

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

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

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

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