Transport Strategy in Patients With Suspected Acute Large Vessel Occlusion Stroke: TRIAGE-STROKE, a Randomized Clinical Trial.

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.

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial.

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.

The Prehospital Stroke Score and telephone conference: A prospective validation.

OBJECTIVES: The main aim of the study is to investigate the performance of a two-part stroke scale for screening and subsequent severity assessment combined with a telephone conference (teleconference). MATERIALS AND METHODS: During a 6-month period, we prospectively tested the Prehospital Stroke Score (PreSS). PreSS part 1 is designed to identify stroke or TIA in a prehospital setting. PreSS part 2 is a stroke severity scale designed to identify large-vessel occlusion (LVO). PreSS was performed by emergency medical service (EMS) providers prior to a teleconference with a stroke neurologist. RESULTS: Combined teleconference and PreSS part 1 were performed on 79.3% of all patients diagnosed with stroke/TIA, and 99.1% of the patients with positive scores were subsequently PreSS part 2 scored. PreSS part 1 and teleconference had a sensitivity to identify stroke/TIA of 89.3% (95% CI 85.7-92.2), specificity of 64.5% (95% CI 59.3-69.5), and an area under the curve (AUC) of 0.80 (95% CI 0.77-0.83). Regarding LVO, PreSS part 1 with teleconference recognized 96.7% (95% CI 88.7-99.6) of all cases as stroke. PreSS part 2 had a sensitivity of 55.7% (95% CI 42.4-68.5), specificity of 91.5% (95% CI 89.0-93.6), and AUC of 0.86 (95% CI 0.82-0.90) for identification of LVO. CONCLUSIONS: PreSS was feasible and the sensitivity for stroke/TIA and LVO was high to moderate providing an overall high precision. Almost all LVO cases were ensured acute stroke admission. The high specificity for LVO could be useful for determining transfers strategies. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence when evaluating PreSS combined with teleconference.

Effect of urgency level on prehospital emergency transport times: a natural experiment.

Accurate estimation of ambulance transport time from the scene of incident to arrival at the emergency department (ED) is important for effective resource management and emergency care system planning. Further, differences in transport times between different urgency levels highlight the benefits of ambulance transports with highest urgency level in a setting where ambulances are allowed to not follow standard traffic rules. The objective of the study is to compare ambulance urgency level on the differences in estimates of ambulance transport times generated by Google Maps and the observed transport times in a prehospital setting where emergency vehicles have their own traffic laws. The study was designed as a natural experiment and register study. Ambulance transports dispatched with different levels of urgency (Level A and B) were included in the Central Denmark Region (a mixed urban and rural area) from March 10 to June 11, 2021. Ambulance transports for highest urgency level were compared to lowest urgency level with Google Maps estimated transport times as reference. We analyzed 1981 highest urgency level and 8.958 lowest urgency level ambulance transports. Google Maps significantly overestimated the duration of transports operating at highest level of urgency (Level A) by 1.9 min/10 km (95% CI 1.8; 2.0) in average and 4.8 min/10 km (95% CI 3.9; 5.6) for the first driven 10 km. Contrary, Google Maps significantly underestimated the duration of transports operating at lowest level of urgency (Level B) by -1.8 min/10 km (95% CI -2.1; -1.5) in average and -4.4 min/10 km (95% CI -5.4; -3.5) for the first driven 10 km. Google Maps systematically overestimates transport times of ambulance transports driven with Level A, the highest level of urgency in a setting where ambulances are allowed to not follow standard traffic rules. The results highlight the benefit of using urgency Level A and provide valuable information for emergency care management.

Urban-rural inequalities in IV thrombolysis for acute ischemic stroke: A nationwide study.

INTRODUCTION: Rural residency has been associated with lower reperfusion treatment rates for acute ischemic stroke in many countries. We aimed to explore urban-rural differences in IV thrombolysis rates in a small country with universal health care, and short transport times to stroke units. PATIENTS AND METHODS: In this nationwide cohort study, adult ischemic stroke patients registered in the Danish Stroke Registry (DSR) between 2015 and 2020 were included. The exposure was defined by residence rurality. Data from the DSR, Statistics Denmark, and the Danish Health Data Authority, were linked on the individual level using the Civil Registration Number. Adjusted treatment rates were calculated by balancing baseline characteristics using inverse probability of treatment weights. RESULTS: Among the included 56,175 patients, prehospital delays were shortest for patients residing in capital municipalities (median 4.7 h), and longest for large town residents (median 7.1 h). Large town residents were predominantly admitted directly to a comprehensive stroke center (98.5%), whereas 30.9% of capital residents were admitted to a hospital with no reperfusion therapy available (non-RT unit). Treatment rates were similar among all non-rural residents (18.5%-18.7%), but slightly lower among rural residents (17.2% [95% CI 16.5-17.8]). After adjusting for age, sex, immigrant status, and educational attainment, rural residents reached treatment rates comparable to capital and large town residents at 18.5% (95% CI 17.7-19.4). DISCUSSION AND CONCLUSION: While treatment rates varied minimally by urban-rural residency, substantial differences in median prehospital delay and admission to non-RT units underscored marked urban-rural differences in potential obstacles to reperfusion therapies.

Inter-Rater Agreement on Cincinnati Prehospital Stroke Scale (CPSS) and Prehospital Acute Stroke Severity Scale (PASS) Between EMS Providers, Neurology Residents and Neurology Consultants.

Objective: To examine the agreement between emergency medical service (EMS) providers, neurology residents and neurology consultants, using the Cincinnati Prehospital Stroke Scale (CPSS) and the Prehospital Acute Stroke Severity Scale (PASS). Methods: Patients with stroke, transient ischemic attack (TIA) and stroke mimic were included upon primary stroke admission or during rehabilitation. Patients were included from June 2018 to September 2019. Video recordings were made of patients being assessed with CPSS and PASS. The recordings were later presented to the healthcare professionals. To determine relative and absolute interrater reliability in terms of inter-rater agreement (IRA), we used generalisability theory. Group-level agreement was determined against a gold standard and presented as an area under the curve (AUC). The gold standard was a consensus agreement between two neurology consultants. Results: A total of 120 patient recordings were assessed by 30 EMS providers, two neurology residents and two neurology consultants. Using the CPSS and the PASS, a total of 1,800 assessments were completed by EMS providers, 240 by neurology residents and 240 by neurology consultants. The overall relative and absolute IRA for all items combined from the CPSS and PASS score was 0.84 (95% CI 0.80; 0.87) and 0.81 (95% CI 0.77; 0.85), respectively. Using the CPSS, the agreement on a group-level resulted in AUCs of 0.83 (95% CI 0.78; 0.88) for the EMS providers and 0.86 (95% CI 0.82; 0.90) for the neurology residents when compared with the gold standard. Using the PASS, the AUC was 0.82 (95% CI 0.77; 0.87) for the EMS providers and 0.88 (95% CI 0.84; 0.93) for the neurology residents. Conclusion: The high relative and absolute inter-rater agreement underpins a high robustness/generalisability of the two scales. A high agreement exists across individual raters and different groups of healthcare professionals supporting widespread applicability of the stroke scales.

Too risky, too large, too late, or too mild-Reasons for not treating ischemic stroke patients and the related outcomes.

Background: Despite effective treatments, many patients are still not offered reperfusion therapy for acute ischemic stroke. Methods: We present a single-center observational study on acute ischemic stroke patients, who presented as candidates for reperfusion therapy but were deemed ineligible after work-up. Reasons for non-treatment were obtained by studying patient files and subsequently grouped into "too risky" (e.g., anticoagulant use, comorbidities), "too large" (large infarct), "too late" (late presentation of stroke and wake-up strokes), or "too mild" (clinically mild/remitting symptoms). Modified Rankin scale (mRS) score was prospectively collected in all patients by a structured telephone interview. All non-treated patients with a National Institute of Health Stroke Scale (NIHSS) score of 0-5 were compared with a similar cohort that was treated. Results: Of 529 patients with acute ischemic stroke arriving as reperfusion therapy candidates, 198 (37.4%) were not treated. The majority (42%) were not treated due to admission outside the treatment window (too late) and 24% had absolute contraindications (too risky). Only 8% was excluded because their infarct was too large [median Alberta Stroke Program Early CT score 3 (2-4)]. In the "too mild" group (14%) the percentage of patients not being independent at 90 days was 30%. The adjusted odds ratio for a better outcome (lower mRS) among treated patients with NIHSS 0-5 compared with non-treated was 1.93 (95% confidence interval 1.15-3.23). Conclusion: Presenting outside the treatment window is still the most common reason for not receiving therapy. Our study suggests a benefit of thrombolysis for patients with mild symptoms.

Can Helicopters Solve the Transport Dilemma for Patients With Symptoms of Large-Vessel Occlusion Stroke in Intermediate Density Areas? A Simulation Model Based on Real Life Data.

Background: This modeling study aimed to determine if helicopters may optimize the transportation of patients with symptoms of large vessel stroke in "intermediate density" areas, such as Denmark, by bringing them directly to the comprehensive stroke center. Methods: We estimated the time for the treatment of patients requiring endovascular therapy or intravenous thrombolysis under four configurations: "drip and ship" with and without helicopter and "bypass" with and without helicopter. Time delays, stroke numbers per municipality, and helicopter dispatches for four helicopter bases from 2019 were obtained from the Danish Stroke and Helicopter Registries. Discrete event simulation (DES) was used to estimate the capacity of the helicopter fleet to meet patient transport requests, given the number of stroke codes per municipality. Results: The median onset-to-needle time at the comprehensive stroke center (CSC) for the bypass model with the helicopter was 115 min [interquartile range (IQR): 108, 124]; the median onset-to-groin time was 157 min (IQR: 150, 166). The median onset-to-needle time at the primary stroke center (PSC) by ground transport was 112 min (IQR: 101, 125) and the median onset-to-groin time when primary transport to the PSC was prioritized was 234 min (IQR: 209, 261).A linear correlation between travel time by ground and the number of patients transported by helicopter (rho = 0.69, p < 0.001) indicated that helicopters are being used to transport more remote patients. DES demonstrated that an increase in helicopter capture zone by 20 min increased the number of rejected patients by only 5%. Conclusions: Our model calculations suggest that using helicopters to transport patients with stroke directly to the CSC in intermediate density areas markedly reduce onset-to-groin time without affecting time to thrombolysis. In this setting, helicopter capacity is not challenged by increasing the capture zone.

TRIAGE-STROKE: Treatment strategy In Acute larGE vessel occlusion: Prioritize IV or endovascular treatment-A randomized trial.

RATIONALE: For patients with acute ischemic stroke and large vessel occlusions, intravenous thrombolysis and endovascular therapy are standard of care, but the effect of endovascular therapy is superior to intravenous thrombolysis. If a severe stroke with symptoms indicating large vessel occlusions occurs in the catchment area of a primary stroke center, there is equipoise regarding optimal transport strategy. AIM: For patients presenting with suspected large vessel occlusions (PASS ≥ 2) and a final diagnosis of acute ischemic stroke, we hypothesize that bypassing the primary stroke center will result in an improved 90-day functional outcome. SAMPLE SIZE: We aim to randomize 600 patients, 1:1. DESIGN: A national investigator-driven, multi-center, randomized assessor-blinded clinical trial. The Prehospital Acute Stroke Severity Scale has been developed. It identifies most patients with large vessel occlusions in the pre-hospital setting. Patients without a contraindication for intravenous thrombolysis are randomized to either transport directly to a comprehensive stroke centers for intravenous thrombolysis and of endovascular therapy or to a primary stroke center for intravenous thrombolysis and subsequent transport to a comprehensive stroke centers for of endovascular therapy, if needed. OUTCOMES: The primary outcome will be the 90-day modified Rankin Scale score (mRS) for all patients with acute ischemic stroke. Secondary outcomes include 90-day mRS for all randomized patients, all patients with ischemic stroke but without large vessel occlusions, and patients with hemorrhagic stroke. The safety outcomes include severe dependency or death and time to intravenous thrombolysis for ischemic stroke patients. DISCUSSION: Study results will influence decision making regarding transport strategy for patients with suspected large vessel occlusions.

A multicentre, randomised, sham-controlled trial on REmote iSchemic conditioning In patients with acute STroke (RESIST) - Rationale and study design.

RATIONALE: Remote ischaemic conditioning, applied in the prehospital setting and continued in-hospital, may improve functional outcome in patients with acute ischaemic stroke and intracerebral haemorrhage. AIMS: To evaluate whether combined remote ischaemic per- and postconditioning can improve long-term functional outcome in acute ischaemic stroke and intracerebral haemorrhage patients. METHODS AND DESIGN: Danish multicentre, prospective, randomised, patient-assessor blinded, sham-controlled study. Adult patients with a putative stroke identified prehospital with symptom duration <4 h, who are independent in daily activities will be randomised 1:1 to remote ischaemic conditioning or Sham-remote ischaemic conditioning. The treatment protocol will be five cycles, each consisting of 5 min with a blood pressure cuff inflation and 5 min with a deflated cuff placed on the upper extremity. The cuff pressure for remote ischaemic conditioning will be 200 mmHg-285 mmHg according to the individual systolic blood pressure and 20 mmHg sham-remote ischaemic conditioning during inflation. The study is approved as an acute study and consent is waived in the acute phase.Sample size estimation: For a 7% increased odds for a beneficial shift on the modified Rankin Scale at a significance level of 5% and power of 90%, 1000 patients with a target diagnosis of acute ischaemic stroke and intracerebral haemorrhage and a total of 1500 patients with a prehospital presumed stroke will be included.Study outcomes: The primary outcome will be the modified Rankin Scale score measured at three-month follow-up (analysed using ordinal logistic regression). ClinicalTrials.gov Identifier: NCT03481777.

[Superficial siderosis of the central nervous system treated with prednisolone]. / Superficiel siderose i centralnervesystemet behandlet med prednisolon.

Superficial siderosis (SS) of the central nervous system is a rare disorder in which the most common clinical manifestations are gait ataxia, sensorineural deafness and affection of the corticospinal tracts. Knowledge of this disorder is important since early diagnosis and treatment is crucial for the prognosis. Furthermore, new treatment strategies are emerging. The effect of corticosteroids on SS without an identifiable bleeding source has been debated. We present a case with a good clinical effect of steroids.