BackgroundCorrect diagnosis of stroke and its subtypes is pivotal in early stages for optimum treatment.AimsThe aim of this systematic review and meta-analysis is to summarize the published evidenc...

Blood biomarkers for the diagnosis and differentiation of stroke: A systematic review and meta-analysis.

Early or primary injury due to brain aggression, such as mechanical trauma, hemorrhage or is-chemia, triggers the release of damage-associated molecular patterns (DAMPs) in the extracellular space. Some DAMPs, such as S100B, participate in the regulation of cell growth and survival but may also trigger cellular damage as their concentration increases in the extracellular space. When DAMPs bind to pattern-recognition receptors, such as the receptor of advanced glycation end-products (RAGE), they lead to non-infectious inflammation that will contribute to necrotic cell clearance but may also worsen brain injury. In this narrative review, we describe the role and ki-netics of DAMPs and RAGE at the acute phase of brain injury. We searched the MEDLINE database for “DAMPs” or “RAGE” or “S100B” and “traumatic brain injury” or “subarachnoid hemorrhage” or “stroke”. We selected original articles reporting data on acute brain injury pathophysiology, from which we describe DAMPs release and clearance upon acute brain injury, and the implication of RAGE in the development of brain injury. We will also discuss the clinical strategies that emerge from this overview in terms of biomarkers and therapeutic perspectives

https://www.mdpi.com/1422-0067/22/5/2439/pdf

DAMPs and RAGE Pathophysiology at the Acute Phase of Brain Injury: An Overview.

The safety and efficacy of mobile stroke units (MSUs) in prehospital stroke management has recently been investigated in different clinical studies. MSUs are ambulances equipped with a CT scanner, point-of-care lab, telemedicine and are staffed with a stroke specialised medical team. This European Stroke Organisation (ESO) guideline provides an up-to-date evidence-based recommendation to assist decision-makers in their choice on using MSUs for prehospital management of suspected stroke, which includes patients with acute ischaemic stroke (AIS), intracranial haemorrhage (ICH) and stroke mimics. The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and aggregated data meta-analyses of the literature, assessed the quality of the available evidence and made specific recommendations. Expert consensus statements are provided where sufficient evidence was not available to provide recommendations based on the GRADE approach. We found moderate evidence for suggesting MSU management for patients with suspected stroke. The patient group diagnosed with AIS shows an improvement of functional outcomes at 90 days, reduced onset to treatment times and increased proportion receiving IVT within 60 min from onset. MSU management might be beneficial for patients with ICH as MSU management was associated with a higher proportion of ICH patients being primarily transported to tertiary care stroke centres. No safety concerns (all-cause mortality, proportion of stroke mimics treated with IVT, symptomatic intracranial bleeding and major extracranial bleeding) could be identified for all patients managed with a MSU compared to conventional care. We suggest MSU management to improve prehospital management of suspected stroke patients.

https://journals.sagepub.com/doi/pdf/10.1177/23969873221079413

European Stroke Organisation (ESO) guidelines on mobile stroke units for prehospital stroke management

Stroke remains a leading cause of death and disability, with limited therapeutic options and suboptimal tools for diagnosis and prognosis. High throughput technologies such as proteomics generate large volumes of experimental data at once, thus providing an advanced opportunity to improve the status quo by facilitating identification of novel therapeutic targets and molecular biomarkers. Proteomics studies in animals are largely designed to decipher molecular pathways and targets altered in brain tissue after stroke, whereas studies in human patients primarily focus on biomarker discovery in biofluids and, more recently, in thrombi and extracellular vesicles. Here, we offer a comprehensive review of stroke proteomics studies conducted in both animal and human specimen and present our view on limitations, challenges, and future perspectives in the field. In addition, as a unique resource for the scientific community, we provide extensive lists of all proteins identified in proteomic studies as altered by stroke and perform postanalysis of animal data to reveal stroke-related cellular processes and pathways.

Stroke Proteomics: From Discovery to Diagnostic and Therapeutic Applications.

Stroke remains a leading cause of death and disability, with limited therapeutic options and suboptimal tools for diagnosis and prognosis. High throughput technologies such as proteomics generate large volumes of experimental data at once, thus providing an advanced opportunity to improve the status quo by facilitating identification of novel therapeutic targets and molecular biomarkers. Proteomics studies in animals are largely designed to decipher molecular pathways and targets altered in brain tissue after stroke, whereas studies in human patients primarily focus on biomarker discovery in biofluids and, more recently, in thrombi and extracellular vesicles. Here, we offer a comprehensive review of stroke proteomics studies conducted in both animal and human specimen and present our view on limitations, challenges, and future perspectives in the field. In addition, as a unique resource for the scientific community, we provide extensive lists of all proteins identified in proteomic studies as altered by stroke and perform postanalysis of animal data to reveal stroke-related cellular processes and pathways. 

Stroke Proteomics: From Discovery to Diagnostic and Therapeutic Applications

Biomarkers indicative of intracerebral hemorrhage (ICH) may help triage acute stroke patients in the pre-hospital phase. We hypothesized that serum concentration of glial fibrillary acidic protein (GFAP) in combination with ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), measured by a rapid bio-assay, could be used to distinguish ICH from ischemic stroke. This prospective two-center study recruited patients with a clinical diagnosis of acute stroke both in the pre-hospital phase and at hospital admission (within 4 and 6 h after symptom onset, respectively). Blood samples were analyzed for concentrations of GFAP and UCH-L1 using ELISA techniques. The reference standard was the diagnosis of ICH, ischemic stroke, or stroke mimicking condition achieved after clinical workup including brain imaging. A total of 251 patients were included (mean age [± SD] 72 ± 15 years; 5 ICH, 23 ischemic strokes and 14 stroke mimics in the pre-hospital part; and 59 ICH, 148 ischemic strokes and 2 stroke mimics in the in-hospital part). Mean delay (± SD) from symptom onset to blood withdrawal was 130 ± 79 min for the pre-hospital patients and 136 ± 86 min for the in-hospital patients. Both GFAP and UCH-L1 serum concentrations were higher in patients having ICH as compared to other diagnoses (GFAP: median 330 ng/L [interquartile range 64–7060, range 8–56,100] vs. 27.5 ng/L [14–57.25, 0–781], p < 0.001; UCH-L1: 401 ng/L [265–764, 133–1812] vs. 338 ng/L [213–549.5, 0–2950], p = 0.025). Area-under-the-curve values were 0.866 (95% CI 0.809–0.924, p < 0.001) for GFAP, and 0.590 (0.511–0.670, p = 0.033) for UCH-L1. Regarding overall diagnostic accuracy, UCH-L1 did not add significantly to the performance of GFAP. GFAP may differentiate ICH from ischemic stroke and stroke mimics. A point-of-care test to distinguish between ischemic and hemorrhagic strokes might facilitate triage to different treatment pathways or locations, or be used to select patients for trials of ultra-early interventions.

Diagnostic Accuracy of Glial Fibrillary Acidic Protein and Ubiquitin Carboxy-Terminal Hydrolase-L1 Serum Concentrations for Differentiating Acute Intracerebral Hemorrhage from Ischemic Stroke.

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.

Henriette S Jaeger

Papers

Diagnostic Accuracy of Glial Fibrillary Acidic Protein and Ubiquitin Carboxy-Terminal Hydrolase-L1 Serum Concentrations for Differentiating Acute Intracerebral Hemorrhage from Ischemic Stroke.

Ultraearly Thrombolysis by an Anesthesiologist in a Mobile Stroke Unit A prospective, controlled intervention study