Ultra-acute diagnostics for stroke: Large-scale implementation of prehospital biomarker sampling.

OBJECTIVES: Blood-based biomarkers could enable early and cost-effective diagnostics for acute stroke patients in the prehospital setting to support early initiation of treatments. To facilitate development of ultra-acute biomarkers, we set out to implement large-scale prehospital blood sampling and determine feasibility and diagnostic timesavings of this approach. MATERIALS AND METHODS: Emergency medical services (EMS) personnel of the Helsinki metropolitan area were trained to collect prehospital blood samples from thrombolysis candidates using a cannula adapter technique. Time delays, sample quality, and logistics were investigated between May 20, 2013 and May 19, 2014. RESULTS: Prehospital blood sampling and study recruiting were successfully performed for 430 thrombolysis candidates, of which 50% had ischemic stroke, 14.4% TIA, 13.5% hemorrhagic stroke, and 22.1% stroke mimics. A total of 66.3% of all samples were collected during non-office hours. The median (interquartile range) emergency call to prehospital sample time was 33 minutes (25-41), and the median time from reported symptom onset or wake-up to prehospital sample was 53 minutes (38-85; n=394). Prehospital sampling was performed 31 minutes (25-42) earlier than hospital admission blood sampling and 37 minutes (30-47) earlier than admission neuroimaging. Hemolysis rate in serum and plasma samples was 6.5% and 9.3% for EMS samples, and 0.7% and 1.6% for admission samples. CONCLUSIONS: Prehospital biomarker sampling can be implemented in all EMS units and provides a median timesaving of more than 30 minutes to first blood sample. Large prehospital sample sets will enable development of novel ambulance biomarkers to improve early differential diagnosis and treatment of thrombolysis candidates.

A novel combined model of intracerebral and intraventricular hemorrhage using autologous blood-injection in rats.

Intracerebral hemorrhage (ICH) is the least treatable form of stroke and is associated with the worst prognosis. In up to 40% of cases, ICH is further complicated by intraventricular hemorrhage (IVH), which predisposes to hydrocephalus, and increases case-mortality to 80%. However, IVH is not present in widely used preclinical models of ICH. Here, we characterize a novel rat model of combined ICH and IVH. Rats were injected with different volumes of autologous whole blood into the right deep basal ganglia region (100µL, 150µL, 200µL, and 250µL, n=10 per group). MRI was performed immediately, and at 24, 48, 72h, and 1week after blood injection, along with neurological evaluations. Injected blood volume reliably correlated with blood volumes measured from MRI obtained after blood injection. Brain edema was most prominent in the ⩾200µL groups, peaking at 48h in all groups, being statistically different between the ⩾200µL and <200µL groups at all-time points. Presence of hydrocephalus was detected in most of the animals, most clearly in the 200µL and 250µL groups, both being statistically different from the 100µL group at all-time points, with tendency to worsen during the whole follow-up period. Most deteriorating neurological and behavioral outcomes as well as the highest mortality rates were detected in groups injected with 200µL and 250µL of autologous blood, 40% and 70%, respectively. These volumes were most similar to the clinical scenario of combined ICH and IVH, demonstrating that this novel rat model is a promising starting point for future ICH+IVH research.