Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke.Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke.Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023).Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants.Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke.Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, −1; −1.7 to −0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group.Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke.Trial Registration: ClinicalTrials.gov Identifier: NCT03481777

Only a minority of patients with acute ischaemic stroke receive reperfusion treatment, primarily due to prehospital delay. We aimed to investigate predictors of a primary contact to the emergency medical services, arrival at stroke centre within 3 h of symptom onset and initiation of reperfusion therapy in patients with acute stroke. We conducted a cross-sectional study of consecutive patients with acute ischaemic stroke, intracerebral haemorrhage or transient ischaemic attack. Structured interviews of patients and bystanders were performed and combined with clinical information from the Danish Stroke Registry. Eligible patients were aged ≥18 years and were independent in activities of daily living before the stroke. We included 435 patients. Presence of a bystander at symptom onset and knowledge of ≥2 core symptoms of stroke were associated with a primary emergency medical services contact. Higher stroke severity and patients or bystanders perceiving the situation as very serious were associated with a primary emergency medical services contact (OR_patients 2.10; 95% CI 1.12–3.95 and OR_bystanders 22.60; 95% CI 4.98–102.67), <3 h from onset to arrival (OR_patients 3.01; 95% CI 1.46–6.21 and OR_bystanders 4.44; 95% CI 1.37–14.39) and initiation of reperfusion therapy (OR_patients 3.08; 95% CI 1.23–7.75 and OR_bystanders 4.70; 95% CI 1.14–19.5). Conclusion: Having a bystander, knowledge of ≥2 core symptoms and understanding that stroke is a serious event are associated with appropriate help-seeking behaviour, shorter prehospital delay and higher chance of reperfusion therapy in acute stroke patients.

BACKGROUND: When patients with acute ischemic stroke present with suspected large vessel occlusion in the catchment area of a primary stroke center (PSC), the benefit of direct transport to a comprehensive stroke center (CSC) has been suggested. Equipoise remains between transport strategies and the best transport strategy is not well established. METHODS: We conducted a national investigator-driven, multicenter, randomized, assessor-blinded clinical trial. Patients eligible for intravenous thrombolysis (IVT) who were suspected for large vessel occlusion were randomized 1:1 to admission to the nearest PSC (prioritizing IVT) or direct CSC admission (prioritizing endovascular therapy). The primary outcome was functional improvement at day 90 for all patients with acute ischemic stroke, measured as shift towards a lower score on the modified Rankin Scale score. RESULTS: From September 2018 to May 2022, we enrolled 171 patients of whom 104 had acute ischemic stroke. The trial was halted before full recruitment. Baseline characteristics were well balanced. Primary analysis of shift in modified Rankin Scale (ordinal logistic regression) revealed an odds ratio for functional improvement at day 90 of 1.42 (95% CI, 0.72–2.82, P =0.31). Onset to groin time for patients with large vessel occlusion was 35 minutes ( P =0.007) shorter when patients were transported to a CSC first, whereas onset to needle (IVT) was 30 minutes ( P =0.012) shorter when patients were transported to PSC first. IVT was administered in 67% of patients in the PSC group versus 78% in the CSC group and EVT was performed in 53% versus 63% of the patients, respectively. CONCLUSIONS: This trial investigated the benefit of bypassing PSC. We included only IVT-eligible patients presenting <4 hours from onset and with suspected large vessel occlusion. Lack of power prevented the results from showing effect on functional outcome for patients going directly to CSC. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03542188.

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).