Circulating Factor Seven Activating Protease (FSAP) in the Hyperacute Phase of Stroke

Background. Factor VII activating protease (FSAP) is a circulating serine protease that could be involved in the pathophysiology of stroke. We analyzed the temporal changes in FSAP antigen and FSAP activity after acute cerebral ischemia (ACI) and tested if FSAP could be used to differentiate between stroke subtypes in the hyperacute phase (<4.5 hours after symptom onset). Methods. Of the 118 suspected stroke patients enrolled, 76 had ACI; of which 20 suffered from large vessel occlusion (LVO), 19 had intracerebral hemorrhage (ICH), and 23 had stroke mimics. Median time from symptom onset to the two plasma sample collections, <4.5 hours, were 66 and 107 minutes for the entire study population. Additional samples were collected up to 90 days post stroke in a subset of ACI patients (). FSAP antigen, FSAP activity, FSAP-α2-antiplasmin-complex (FSAP-AP complex), and nucleosomes were measured by activity assays or ELISA. Results. ACI patients treated with tissue plasminogen activator (tPA) had elevated FSAP hours () that subsequently normalized after 6 hours. FSAP-AP complex levels decreased significantly from <4.5 hours () to 6 hours after symptom onset. tPA did not increase FSAP activity significantly in plasma in vitro. FSAP antigen significantly hours after symptom onset in LVO () and ICH () patients. FSAP could not differentiate ACI from ICH or strokes (ACI and ICH) from stroke mimics. FSAP did not correlate with stroke severity. Conclusion. LVO and ICH seem to influence FSAP levels in the hyperacute phase of stroke, but FSAP does not differentiate between stroke subtypes in a hyperacute setting.publishedVersio

Ultraearly thrombolysis by an anesthesiologist in a mobile stroke unit: A prospective, controlled intervention study

Background Acute stroke treatment in mobile stroke units (MSU) is feasible and reduces time-to-treatment, but the optimal staffing model is unknown. We wanted to explore if integrating thrombolysis of acute ischemic stroke (AIS) in an anesthesiologist-based emergency medical services (EMS) reduces time-to-treatment and is safe. Methods A nonrandomized, prospective, controlled intervention study. Inclusion criteria: age ≥18 years, nonpregnant, stroke symptoms with onset ≤4 h. The MSU staffing is inspired by the Norwegian Helicopter Emergency Medical Services crew with an anesthesiologist, a paramedic-nurse and a paramedic. Controls were included by conventional ambulances in the same catchment area. Primary outcome was onset-to-treatment time. Secondary outcomes were alarm-to-treatment time, thrombolytic rate and functional outcome. Safety outcomes were symptomatic intracranial hemorrhage and mortality. Results We included 440 patients. MSU median (IQR) onset-to-treatment time was 101 (71–155) minutes versus 118 (90–176) minutes in controls, p = 0.007. MSU median (IQR) alarm-to-treatment time was 53 (44–65) minutes versus 74 (63–95) minutes in controls, p < 0.001. Golden hour treatment was achieved in 15.2% of the MSU patients versus 3.7% in the controls, p = 0.005. The thrombolytic rate was higher in the MSU (81% vs 59%, p = 0.001). MSU patients were more often discharged home (adjusted OR [95% CI]: 2.36 [1.11–5.03]). There were no other significant differences in outcomes. Conclusions Integrating thrombolysis of AIS in the anesthesiologist-based EMS reduces time-to-treatment without negatively affecting outcomes. An MSU based on the EMS enables prehospital assessment of acute stroke in addition to other medical and traumatic emergencies and may facilitate future implementation.publishedVersio

Diagnostic performance of Glial Fibrillary Acidic Protein and Prehospital Stroke Scale for identification of stroke and stroke subtypes in an unselected patient cohort with symptom onset &lt; 4.5 h

INTRODUCTION: Rapid identification and treatment of stroke is crucial for the outcome of the patient. We aimed to determine the performance of glial fibrillary acidic protein (GFAP) independently and in combination with the Prehospital Stroke Score (PreSS) for identification and differentiation of acute stroke within 4.5 h after symptom onset. PATIENTS AND METHODS: Clinical data and serum samples were collected from the Treat-Norwegian Acute Stroke Prehospital Project (Treat-NASPP). Patients with suspected stroke and symptoms lasting ≤ 4.5 h had blood samples collected and were evaluated with the National Institutes of Health Stroke Scale prospectively. In this sub study, NIHSS was retrospectively translated into PreSS and GFAP was measured using the sensitive single molecule array (SIMOA). RESULTS: A total of 299 patients with suspected stroke were recruited from Treat-NASPP and included in this study (44% acute ischemic stroke (AIS), 10% intracranial hemorrhage (ICrH), 7% transient ischemic attack (TIA), and 38% stroke mimics). ICrH was identified with a cross-fold validated area under the receiver-operating characteristic curve (AUC) of 0.73 (95% CI 0.62–0.84). A decision tree with PreSS and GFAP combined, first identified patients with a low probability of stroke. Subsequently, GFAP detected patients with ICrH with a 25.0% sensitivity (95% CI 11.5–43.4) and 100.0% specificity (95% CI 98.6–100.0). Lastly, patients with large-vessel occlusion (LVO) were detected with a 55.6% sensitivity (95% CI 35.3–74.5) and 82.4% specificity (95% CI 77.3–86.7). CONCLUSION: In unselected patients with suspected stroke, GFAP alone identified ICrH. Combined in a decision tree, GFAP and PreSS identified subgroups with high proportions of stroke mimics, ICrH, LVO, and AIS (non-LVO strokes)