Circulating endothelial cells as potential diagnostic biomarkers in primary central nervous system vasculitis.

OBJECTIVE: Histological evidence is considered the only proof of primary central nervous system vasculitis (PCNSV). However, brain biopsy is often omitted or delayed because of the invasiveness and possible complications of the procedure. Circulating endothelial cells (CEC) were shown to be elevated in patients with active antineutrophil cytoplasmic antibody-associated vasculitis. We hypothesise that CEC are also elevated in patients with active PCNSV and may contribute to the diagnosis. METHODS: CEC were assessed in 18 patients, 3 of whom had biopsy-proven PCNSV and 15 clinical, cerebrospinal fluid and imaging data, highly suggestive of PCNSV. In 3 of these 15 patients CEC assessment was performed after initiation of successful immunosuppressive therapy. CEC numbers of all patients were compared to those of 16 healthy volunteers and 123 subjects with cerebrovascular risk factors and/or ischaemic stroke, who had been studied in our group before. CEC were assessed by immunomagnetic isolation from peripheral blood. RESULTS: In patients with proven and suspected active PCNSV, CEC were extremely elevated (>400 cells/ml in most of the patients) and significantly higher than in healthy and disease controls (p≤0.01 for each group). CEC significantly decreased with immunosuppressive treatment. CONCLUSIONS: For the first time it is shown that CEC are significantly elevated in patients with active PCNSV in contrast to other pathologies associated with brain infarction and correlate with disease activity. Sensitivity and specificity of the method for diagnosing PCNSV and the use of the method for treatment monitoring should be addressed in future prospective studies with a larger patient group.

Growth differentiation factor 15 plasma levels and outcome after ischemic stroke.

BACKGROUND: Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that is induced after experimental brain injury. We hypothesized that the circulating levels of GDF-15 are increased and associated with neurological outcome in patients with ischemic stroke. METHODS: Serial blood samples were obtained between 6 h and 7 days after symptom onset in 57 consecutive patients with acute ischemic stroke (n = 51) or transient ischemic attack (n = 6). GDF-15 was measured by immunoradiometric assay. Neurological outcome using the modified Rankin Scale (mRS) at 7 and 90 days was classified as favorable (mRS 0 or 1) or unfavorable (mRS >1). RESULTS: Six hours after symptom onset, GDF-15 levels were abnormally high (>1,200 ng/l) in 68% of the patients. They declined by 8% over the course of 7 days (p < 0.001). GDF-15 levels were correlated with the circulating levels of the inflammatory marker interleukin-6 and the glial protein S100 calcium binding protein B, and with carotid intima-media thickness. Ischemic stroke patients with an mRS score >1 at 7 or 90 days had higher circulating levels of GDF-15 at all preceding sampling time points compared to patients with an mRS score of 0 or 1 (p ≤ 0.002). Similarly, in a logistic regression analysis, GDF-15 levels measured between 6 h and 7 days after symptom onset were associated with mRS at 7 and 90 days. CONCLUSIONS: These data show for the first time that the circulating levels of GDF-15 are elevated and associated with neurological outcome in patients with ischemic stroke.

The focus of attention at the virtual cocktail party--electrophysiological evidence.

The width of the attentional focus during the selection of one of two concurrent normal human participants was investigated using event-related potentials. Two stories were presented from virtual locations located 15° to the left and right azimuth by convolving the speech message by the appropriate head-related transfer function determined for each individual participant. Task irrelevant probe stimuli (phoneme/da/uttered by the same speaker as the story) were presented in rapid sequence from the same virtual locations. Occasionally, probes were presented at locations 15 or 30° lateral of the standard probes. Probes coinciding with the attended message gave rise to a fronto-central negativity relative to the phoneme probes coinciding with the unattended speech message. This was similar to the typical ERP attention effect. On the attended side probes deviating from the standard location by 30° elicited a different type of negative response, tentatively identified as a reorienting negativity, whereas probes deviating by 15° did not. These results are taken to suggest that spatial information is used for message selection in a cocktail-party situation but that the focus of spatial attention is relatively wide.