2.5-Minute Fast Brain MRI with Multiple Contrasts in Acute Ischemic Stroke.

PURPOSE: To assess the performance of a 2.5-minute multi-contrast brain MRI sequence (NeuroMix) in diagnosing acute cerebral infarctions. METHODS: Adult patients with a clinical suspicion of acute ischemic stroke were retrospectively included. Brain MRI at 3 T included NeuroMix and routine clinical MRI (cMRI) sequences, with DWI/ADC, T2-FLAIR, T2-weighted, T2*, SWI-EPI, and T1-weighted contrasts. Three radiologists (R1-3) independently assessed NeuroMix and cMRI for the presence of acute infarcts (DWI ↑, ADC = or ↓) and infarct-associated abnormalities on other image contrasts. Sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) were calculated and compared using DeLong's test. Inter- and intra-rater agreements were studied with kappa statistics. Relative DWI (rDWI) and T2-FLAIR (rT2-FLAIR) signal intensity for infarctions were semi-automatically rendered, and the correlation between methods was evaluated. RESULTS: According to the reference standard, acute infarction was present in 34 out of 44 (77%) patients (63 ± 17 years, 31 men). Other infarct-associated signal abnormalities were reported in similar frequencies on NeuroMix and cMRI (p > .08). Sensitivity for infarction detection was 94%, 100%, and 94% evaluated by R1, R2, R3, for NeuroMix and 94%, 100%, and 100% for cMRI. Specificity was 100%, 90%, and 100% for NeuroMix and 100%, 100%, and 100% for cMRI. AUC for NeuroMix was .97, .95, and .97 and .97, 1, and 1 for cMRI (DeLong p = 1, .32, .15), respectively. Inter- and intra-rater agreement was κ = .88-1. The correlation between NeuroMix and cMRI was R = .73 for rDWI and R = .83 for rT2-FLAIR. CONCLUSION: Fast multi-contrast MRI NeuroMix has high diagnostic performance for detecting acute cerebral infarctions.

Impact of prehospital stroke triage implementation on patients with intracerebral hemorrhage.

Background: Little is known about how prehospital triage using large vessel occlusion (LVO) stroke prediction scales affects patients with intracerebral hemorrhage (ICH). Objectives: We aimed to investigate whether the Stockholm Stroke Triage System (SSTS) implemented in 2017 has affected timing and outcomes of acute ICH neurosurgery, and to assess system triage accuracy for ICH with a neurosurgical indication or LVO thrombectomy. Design: Observational cohort study. Methods: In the Stockholm Region, we compared surgical timing, functional outcome, and death at 3 months in patients transported by code-stroke ground ambulance who had ICH neurosurgery, 2 years before versus 2 years after SSTS implementation. We also calculated triage precision metrics for treatment with either ICH neurosurgery or thrombectomy. Results: A total of 36 patients undergoing ICH neurosurgery were included before SSTS implementation and 30 after. No significant difference was found in timing of neurosurgery [median 7.5 (4.9-20.7) versus 9.1 (6.1-12.5) h after onset], distribution of functional outcomes (median 4 versus 4), and death at 3 months [3/29 (9%) versus 5/35 (17%)] before versus after implementation, respectively. The SSTS routed a larger proportion of patients subsequently undergoing ICH neurosurgery directly to the comprehensive stroke center: 13/36 (36%) before versus 18/30 (60%) after implementation. Overall system triage accuracy for ICH neurosurgery or thrombectomy was high at 90%, with 92% specificity and 65% sensitivity. Conclusion: The SSTS, initially designed for prehospital LVO stroke triage, routed more patients with neurosurgical indication for ICH directly to the comprehensive stroke center. This did not significantly affect surgical timing or outcomes.

Timing of Antithrombotic Secondary Prevention in Patients with Intracranial Hemorrhage after Stroke Thrombolysis and Thrombectomy.

In patients with acute ischemic stroke, hemorrhagic transformation (HT) of infarcted tissue frequently occurs after reperfusion treatment. We aimed to assess whether HT and its severity influences the start of secondary prevention therapy and increases the risk of stroke recurrence. In this retrospective dual-center study, we recruited ischemic stroke patients treated with thrombolysis, thrombectomy or both. Our primary outcome was the time between revascularization and the start of any secondary prevention therapy. The secondary outcome was ischemic stroke recurrence within three months. We compared patients with vs. without HT and no (n = 653), minor (n = 158) and major (n = 51) HT patients using propensity score matching. The delay in the start of antithrombotics or anticoagulants was median 24 h in no HT, 26 h in minor HT and 39 h in major HT. No and minor HT patients had similar rates of any stroke recurrence (3.4% (all ischemic) vs. 2.5% (1.6% ischemic plus 0.9% hemorrhagic)). Major HT patients had a higher stroke recurrence at 7.8% (3.9% ischemic, 3.9% hemorrhagic), but this difference did not reach significance. A total of 22% of major HT patients did not start any antithrombotic treatment during the three-month follow-up. In conclusion, the presence of HT influences the timing of secondary prevention in ischemic stroke patients undergoing reperfusion treatments. Minor HT did not delay the start of antithrombotics or anticoagulants compared to no HT, with no significant difference in safety outcomes. Major HT patients remain a clinical challenge with both a delayed or lacking start of treatment. In this group, we did not see a higher rate of ischemic recurrence; however, this may have been censored by elevated early mortality. While not reaching statistical significance, hemorrhagic recurrence was somewhat more common in this group, warranting further study using larger datasets.

Intravenous thrombolysis + endovascular thrombectomy versus thrombolysis alone in large vessel occlusion mild stroke: a propensity score matched analysis.

BACKGROUND AND PURPOSE: The best reperfusion treatment for patients with mild acute ischaemic stroke harbouring proximal anterior circulation large vessel occlusion (LVO) is unknown. The aim was to compare the safety and efficacy of intravenous thrombolysis (IVT) plus endovascular thrombectomy (EVT) versus IVT alone in LVO patients with mild symptoms. METHODS: From the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis and Thrombectomy Register (SITS-ISTR), were included: (i) consecutive acute ischaemic stroke patients, (ii) treated within 4.5 h from symptoms onset, (iii) baseline National Institutes of Health Stroke Scale (NIHSS) score ≤5 and (iv) intracranial internal carotid artery [ICA], M1 or T occlusion [defined as occlusion of ICA terminal bifurcation]. After propensity score matching, 3-month functional outcomes (modified Rankin Scale [mRS] 0-1 and 0-2) and safety outcomes (symptomatic intracerebral haemorrhage and death) were compared (via univariable and multivariable logistic [and ordinal] regression analyses) in patients treated with IVT + EVT versus IVT alone. RESULTS: In all, 1037 patients were included. After propensity score matching (n = 312 per group), IVT + EVT was independently associated with poor functional outcomes (adjusted odds ratio [aOR] 0.46 for mRS 0-1, 95% confidence interval [CI] 0.30-0.72, p = 0.001; aOR 0.52 for mRS 0-2, 95% CI 0.32-0.84, p = 0.007; aOR 1.61 for 1-point shift in mRS score, 95% CI 1.12-2.32, p = 0.011), with no significant differences in safety outcomes compared to IVT alone, despite numerically higher rates of symptomatic intracerebral haemorrhage (3.3% vs. 1.1%; p = 0.082), a higher rate of any haemorrhagic transformation (17.6% vs. 7.3%; p < 0.001) and subarachnoid haemorrhage (7.9% vs. 1.5%; p = 0.002) in the IVT + EVT group. DISCUSSION: In anterior circulation LVO patients presenting with NIHSS score ≤5, IVT + EVT (vs. IVT alone) was associated with poorer 3-month functional outcome. Randomized controlled trials are needed to elucidate the best treatments in mild LVO patients.

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. METHODS: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). FINDINGS: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64). INTERPRETATION: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. FUNDING: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Prehospital stroke mimics in the Stockholm Stroke Triage System.

Introduction: In 2017, Stockholm implemented a new prehospital stroke triage system (SSTS) directing patients with a likely indication for thrombectomy to the regional comprehensive stroke center (CSC) based on symptom severity and teleconsultation with a physician. In Stockholm, 44% of patients with prehospital code stroke have stroke mimics. Inadvertent triage of stroke mimics to the CSC could lead to inappropriate resource utilization. Aims: To compare the characteristics between (1) triage-positive stroke mimics and stroke (TP mimics and TP stroke) and (2) triage-negative stroke mimics and stroke (TN mimics and TN stroke) and to (3) compare the distribution of stroke mimic diagnoses between triage-positive and triage-negative cases. Methods: This prospective observational study collected data from October 2017 to October 2018, including 2,905 patients with suspected stroke who were transported by code-stroke ambulance to a Stockholm regional hospital. Patients directed to the CSC were defined as triage-positive. Those directed to the nearest stroke center were defined as triage-negative. Results: Compared to individuals with TP stroke (n = 268), those with TP mimics (n = 55, median 64 vs. 75 years, P < 0.001) were younger and had lower NIHSS score (median 7 vs. 15, P < 0.001). Similarly, those with TN mimics (n = 1,221) were younger than those with TN stroke (n = 1,361, median 73 vs. 78 years, P < 0.001) and had lower NIHSS scores (median 2 vs. 4, P < 0.001). Functional paresis was more common in those with TP mimics than in those with TN mimics, 18/55 (32.7%) vs. 82/1,221 (6.7%), P < 0.001. Systemic infection was less common in those with TP mimics than in those with TN mimics, 1/55 (1.8%) vs. 160/1,221 (13.1%), P < 0.011. There was a trend toward "syncope, hypotension, or other cardiovascular diagnosis" being less common in those with TP mimics than in those with TN mimics, 1/55 (1.8%) vs. 118/1,221 (9.7%), P < 0.055. Conclusions: In the SSTS, those with triage-positive and triage-negative stroke mimics were younger and had less severe symptoms than patients with stroke. All patients with TP mimics who had hemiparesis but overall exhibited less severe symptoms against true stroke but more severe symptoms than those with TN mimics were triaged to the nearest hospital. Over-triage of functional paresis to the CSC was relatively common. Meanwhile, a large majority of cases with minor symptoms caused by stroke mimics was triaged correctly by the SSTS to the nearest stroke center.

Dual anti-platelet therapy for secondary prevention in intracranial atherosclerotic disease: a network meta-analysis.

Background: Intracranial arterial stenosis (ICAS) is a non-marginal cause of stroke/transient ischemic attacks (TIAs) and is associated with high stroke recurrence rate. Some studies have investigated the best secondary prevention ranging from antithrombotic therapy to endovascular treatment (ET). However, no direct comparison between all the possible treatments is currently available especially between single and dual anti-platelet therapies (SAPT and DAPT). Aim: To establish whether DAPT is more effective than SAPT in preventing the recurrence of ICAS-related stroke, by means of a network meta-analysis (NMA). Design: Systematic review and NMA in accordance to PRISMA guidelines. Data sources and methods: We performed a systematic review of trials investigating secondary prevention (SAPT or DAPT, anticoagulant treatment or ET) in patients with symptomatic ICAS available in MEDLINE, Scopus and Web of Science from January 1989 to May 2021. We defined our primary efficacy outcome as the recurrence of ischemic stroke/TIA. We analysed the extracted data with Bayesian NMA approach. Results: We identified 815 studies and included 5 trials in the NMA. Sequence generation was adequate in all the selected studies while the allocation concealment method was described in one study. All the included studies reported the pre-specified primary outcomes, and outcome assessment was blinded in all the studies. We used the fixed-effect approach as the heterogeneity was not significant (p > 0.1) according to the Cochran's Q statistic. DAPT was superior to SAPT and DAPT + ET in preventing stroke/TIA recurrence [respectively, odds ratio (OR), 0.59; confidence interval (CI), 0.39-0.9; and OR, 0.49, CI, 0.26-0.88], while no difference was found between DAPT and oral anticoagulant therapy (OAC). DAPT was safer than OAC (OR, 0.48; CI, 0.26-0.89) and DAPT + ET (OR, 0.50; CI, 0.35-0.71), while no difference was found between DAPT and SAPT. Conclusion: DAPT is more effective than SAPT for secondary stroke prevention in patients with symptomatic ICAS, without increasing the risk of haemorrhage. Registration: Prospero/CRD42019140033.

Analysis and modelling of mistriage in the Stockholm stroke triage system.

Introduction: The Stockholm Stroke Triage System (SSTS) is a prehospital triage system for detection of patients eligible for endovascular thrombectomy (EVT). Assessment of hemiparesis combined with ambulance-hospital teleconsultation is used to route patients directly to the thrombectomy centre. Some patients are not identified and require secondary transport for EVT (undertriage) while others taken to the thrombectomy centre do not undergo EVT (overtriage). The aims of this study were to characterize mistriaged patients, model for and evaluate alternative triage algorithms. Patients and methods: Patients with suspected stroke transported by priority 1 ground ambulance between October 2017 and October 2018 (n = 2905) were included. Three triage algorithms were modelled using prehospital data. Decision curve analysis was performed to calculate net benefit (correctly routing patients for EVT without increasing mistriage) of alternative models vs SSTS. Results: Undertriage for EVT occurred in n = 35/2582 (1.4%) and overtriage in n = 239/323 (74.0%). Compared to correct thrombectomy triages, undertriaged patients were younger and had lower median NIHSS (10 vs 18), despite 62.9% with an M1 occlusion. In overtriaged patients, 77.0% had a stroke diagnosis (29.7% haemorrhagic). Hemiparesis and FAST items face and speech were included in all models. Decision curve analysis showed highest net benefit for SSTS for EVT, but lower for large artery occlusion (LAO) stroke. Discussion: Undertriaged patients had lower NIHSS, likely due to better compensated proximal occlusions. SSTS was superior to other models for identifying EVT candidates, but lacked information allowing comparison to other prehospital scales. Conclusion: Using prehospital data, alternative models did not outperform the SSTS in finding EVT candidates.

Intima-Media Thickness and Pulsatility Index of Common Carotid Arteries in Acute Ischaemic Stroke Patients with Diabetes Mellitus.

Ultrasonographic parameters such as the common carotid artery (CCA) pulsatility index (PI) and CCA intima-media thickness (IMT) have been associated with an increased mortality and risk of recurrent stroke, respectively. We hypothesized that these ultrasonographic parameters may be useful for monitoring diabetic patients after an acute stroke. We analysed retrospective data of consecutive acute ischaemic stroke patients from the ASTRAL registry who underwent pre-cerebral ultrasonographic evaluation within 7 days of symptom onset. We compared clinical, demographic, radiological and ultrasonographic parameters in diabetic versus non-diabetic patients (univariable and multivariable analyses) and the association of these parameters with CCA PI and CCA IMT. We analysed 1507 carotid duplex ultrasound examinations from patients with a median age of 74 years. Cardiovascular co-morbidities, including hypertension, hypercholesterolemia, obstructive sleep apnoea syndrome, higher body-mass index (BMI) and peripheral artery disease, were associated with diabetes mellitus (DM). Diabetics were more often under antiplatelet therapy and had atrial fibrillation at admission. Diabetic patients showed an increased CCA PI and IMT in line with more atherosclerotic changes on acute CTA compared to non-diabetic patients. Taking IMT as the dependent variable in a second analysis, DM, higher age, hypertension, smoking and CCA PI were associated with higher IMT. Taking CCA PI as the dependent variable in a third analysis, DM, higher age and higher NIHSS at admission were associated with higher CCA PI values. Increased IMT was also associated with higher PI. We show that CCA PI and IMT are higher in diabetic patients in the first week after an initial stroke.

The Stockholm Stroke Triage Project: Outcomes of Endovascular Thrombectomy Before and After Triage Implementation.

BACKGROUND AND PURPOSE: The Stockholm Stroke Triage System (SSTS) is a prehospital algorithm for detection of endovascular thrombectomy (EVT)-eligible patients, combining symptom severity assessment and ambulance-to-hospital teleconsultation, leading to a decision on primary stroke center bypass. In the Stockholm Region (6 primary stroke centers, 1 EVT center), SSTS implementation in October 2017 reduced onset-to-EVT time by 69 minutes. We compared clinical outcomes before and after implementation of SSTS in an observational study. METHODS: We prospectively recruited patients transported by Code Stroke ambulance within the Stockholm region under the SSTS, treated with EVT during October 2017 to October 2019, and compared to EVT patients from 2 previous years. OUTCOMES: shift in modified Rankin Scale (mRS) scores, mRS score 0 to 1, mRS score 0 to 2, and death (all 3 months), National Institutes of Health Stroke Scale (NIHSS) score change 24-hour post-EVT, recanalization (Thrombolysis in Cerebral Infarction 2b-3), and symptomatic intracranial hemorrhage. mRS outcomes were adjusted for age and baseline NIHSS. RESULTS: Patients with EVT in the SSTS group (n=244) were older and had higher baseline NIHSS versus historical controls (n=187): median age 74 (interquartile range, 63-81) versus 71 (61-78); NIHSS score 17 (11.5-21) versus 15 (10-20). During SSTS, median onset-to-puncture time was 136 versus 205 minutes (P<0.001). Adjusted common odds ratio for lower mRS in SSTS patients was 1.7 (95% CI, 1.2-2.3) versus controls. During SSTS, 83/240 (34.6%) versus 44/186 (23.7%) reached 3-month mRS score 0 to 1 (P=0.014), adjusted common odds ratio 2.3 (95% CI, 1.4-3.6). Median NIHSS change 24-hour post-EVT was 6 versus 4 (P=0.005). Differences in Thrombolysis in Cerebral Infarction, symptomatic intracranial hemorrhage, and death were nonsignificant. CONCLUSIONS: With an onset to arterial puncture time reduction by 69 minutes, outcomes in thrombectomy-treated patients improved significantly after region-wide large artery occlusion triage system implementation. These results warrant replication studies in other geographic and organizational circumstances.

Staff and Facility Utilization in Direct Patient Transfer to the Comprehensive Stroke Center: Testing a Real-Time Location System for Automatic Patient Pathway Characterization.

Introduction: Starting reperfusion therapies as early as possible in acute ischemic strokes are of utmost importance to improve outcomes. The Comprehensive Stroke Centers (CSCs) can use surveys, shadowing personnel or perform journal analysis to improve logistics, which can be labor intensive, lack accuracy, and disturb the staff by requiring manual intervention. The aim of this study was to measure transport times, facility usage, and patient-staff colocalization with an automated real-time location system (RTLS). Patients and Methods: We tested IR detection of patient wristbands and staff badges in parallel with a period when the triage of stroke patients was changed from admission to the emergency room (ER) to direct admission to neuroradiology. Results: In total, 281 patients were enrolled. In 242/281 (86%) of cases, stroke patient logistics could be detected. Consistent patient-staff colocalizations were detected in 177/281 (63%) of cases. Bypassing the ER led to a significant decrease in median time neurologists spent with patients (from 15 to 9 min), but to an increase of the time nurses spent with patients (from 13 to 22 min; p = 0.036). Ischemic stroke patients used the most staff time (median 25 min) compared to hemorrhagic stroke patients (median 13 min) and stroke mimics (median 15 min). Discussion: Time spent with patients increased for nurses, but decreased for neurologists after direct triage to the CSC. While lower in-hospital transport times were detected, time spent in neuroradiology (CT room and waiting) remained unchanged. Conclusion: The RTLS could be used to measure the timestamps in stroke pathways and assist in staff allocation.

Sex Equitable Prehospital Stroke Triage Using Symptom Severity and Teleconsultation.

Objectives: We aimed to determine whether there are sex differences in prehospital accuracy of the Stockholm Stroke Triage System (SSTS) to predict large artery occlusion (LAO) stroke, and endovascular thrombectomy (EVT), and whether clinical characteristics differ between men and women undergoing "code stroke" ambulance transport. Materials and Methods: This prospective observational study collected data between October 2017 and October 2018. We included 2,905 patients, transported as "code stroke," by nurse-staffed ground ambulance, to a Stockholm Region hospital. Exclusion criteria were private or helicopter transport, onset outside Stockholm, and in-hospital stroke. We compared overall accuracy, sensitivity, specificity, positive and negative predictive values, and clinical characteristics between sexes. Results: No significant sex differences in SSTS predictive performance for LAO or EVT were found, overall accuracy for LAO 87.3% in women vs. 86.7% in men. Women were median 4 years older and more frequently had stroke mimics (46.2 vs. 41.8%). Women more commonly had decreased level of consciousness (14.0 vs. 10.2%) and moderate-to-severe motor symptoms (by 2.7-3.8 percentage points), and less commonly limb ataxia (7.2 vs. 9.7%). Conclusions: The SSTS had equal predictive performance for LAO and EVT among men and women, despite minor sex differences in the clinical characteristics in patients undergoing ambulance transport for suspected stroke.

One-Minute Multi-contrast Echo Planar Brain MRI in Ischemic Stroke: A Retrospective Observational Study of Diagnostic Performance.

BACKGROUND: Fast multi-contrast echo planar MRI (EPIMix) has comparable diagnostic performance to standard MRI for detecting brain pathology but its performance in detecting acute cerebral infarctions has not been determined. PURPOSE: To assess the diagnostic performance of EPIMix for the detection of acute cerebral infarctions. STUDY TYPE: Retrospective observational cohort. POPULATION: One hundred and seventy-two consecutive patients with a clinical suspicion of non-hyperacute ischemic stroke (January 2018 to December 2019). FIELD STRENGTH AND SEQUENCE: 1.5 T or 3 T. EPIMix ((echo-planar based: diffusion weighted (DWI), T2*-weighted, T2-weighted, T2- and T1-fluid attenuated inversion recovery (FLAIR) images) vs. standard MRI: echo-planar DWI, echo-planar T2*-weighted or susceptibility weighted, turbo spin-echo T2-weighted, T2- and T1-FLAIR turbo spin-echo sequences. ASSESSMENT: Three neuroradiologists rated EPIMix and standard MRI on two separate occasions. Incongruent assessments were resolved in consensus with the fourth reader. The ratings included the diagnostic category (acute infarct, normal, and other pathology). Congruent diagnoses together with consensus diagnoses served as the reference standard. STATISTICAL TESTS: The diagnostic performance of EPIMix and standard MRI against the reference standard was calculated by the area under the receiver operating characteristic curve (AUC) and compared by DeLong's test. Sensitivity and specificity were determined. Inter-rater agreements were evaluated by Fleiss's kappa. RESULTS: Of 172 patients (61 ± 16 years, 103 men), acute infarcts were present in 80/172 (47%), normal findings in 60/172 (35%), and other pathology in 32/172 (19%). Across readers, the AUCs were .94-.95 for EPIMix and .95-.99 for standard MRI, with overlapping 95% CI (P = .02-.18). Inter-rater agreement for EPIMix was 0.90 and for standard MRI was 0.93. The sensitivity for EPIMix and standard MRI was 88-91% and 91-98%, respectively, while the specificity was 98-100% and 98-99%, both with overlapping 95% CI. CONCLUSION: Multi-contrast echo planar MRI showed a high but marginally lower diagnostic performance compared to standard MRI for the detection and characterization of acute brain infarct. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Prehospital Triage Accuracy in Patients With Stroke Symptoms Assessed Within 6 to 24 Hours or With an Unknown Time of Onset.

BACKGROUND AND PURPOSE: The Stockholm Stroke Triage System, implemented in 2017, identifies patients with high likelihood of large vessel occlusion (LVO) stroke. A previous report has shown Stockholm Stroke Triage System notably reduced time to endovascular thrombectomy (EVT). As the indication for EVT now includes patients up to 24 hours, we aimed to assess Stockholm Stroke Triage System triage accuracy for LVO stroke and EVT treatment for patients presenting late (within 6-24 hours or with an unknown onset), put in contrast to triage accuracy within 0 to 6 hours. METHODS: Between October 2017 and October 2018, we included 2905 patients with suspected stroke, transported by priority 1 ground ambulance to a Stockholm Region hospital. Patients assessed 6 to 24 hours from last known well or with unknown onset were defined as late-presenting; those within <6 hours as early-presenting. Triage positivity was defined as transport to comprehensive stroke center because of suspected stroke, hemiparesis and high likelihood of EVT-eligible LVO per teleconsultation. RESULTS: Overall triage accuracy was high in late-presenting patients (90.9% for LVO, 93.9% for EVT), with high specificity (95.7% for LVO, 94.5% for EVT), and low to moderate sensitivity (34.3% for LVO, 64.7% for EVT), with similar findings in the early-presenting group. CONCLUSIONS: Our results may support using the Stockholm Stroke Triage System for primary stroke center bypass in patients assessed by ambulance up to 24 hours from time of last known well.

Performance of dual layer dual energy CT virtual monoenergetic images to identify early ischemic changes in patients with anterior circulation large vessel occlusion.

BACKGROUND AND PURPOSE: Dual energy CT is increasingly available and used in the standard diagnostic setting of ischemic stroke patients. We aimed to evaluate how different dual energy CT virtual monoenergetic energy levels impact identification of early ischemic changes, compared to conventional polyenergetic CT images. MATERIALS AND METHODS: This retrospective single-center study included patients presenting with acute ischemic stroke caused by an occlusion of the intracranial internal carotid artery or proximal middle cerebral artery. Data was gathered on consecutive patients admitted to our institution who underwent initial diagnostic stroke imaging with dual layer dual energy CT and a subsequent follow-up CT one to three days after admission. Automated ASPECTS results from conventional polyenergetic and different virtual monoenergetic energy level reconstructions at admission were generated and compared to reference standard ASPECTS. Confidence intervals (CI) for sensitivity, specificity, negative and positive predictive value were calculated. RESULTS: A total of 24 patients were included. Virtual monoenergetic reconstructions of 70 keV had the highest region-based ASPECTS accuracy, 0.90 (sensitivity 0.82 (95% CI 0.72-0.93), specificity 0.92 (0.88-0.97), negative predictive value 0.94 (0.90-0.96)), whereas virtual monoenergetic reconstructions of 40 keV had the lowest, 0.77 (sensitivity 0.34 (0.26-0.42), specificity 0.90 (0.89-0.96), negative predictive value 0.80 (0.77-0.83)). CONCLUSIONS: Automated 70 keV ASPECTS had the highest diagnostic accuracy, sensitivity and negative predictive value overall. Our results indicate that virtual monoenergetic energy levels impact the identification of early ischemic changes on CT.

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Dual-Energy CT Follow-Up After Stroke Thrombolysis Alters Assessment of Hemorrhagic Complications.

Background and Purpose: We aimed to determine whether dual-energy CT (DECT) follow-up can differentiate contrast staining (CS) from intracranial hemorrhage (ICH) in stroke patients treated with intravenous thrombolysis (IVT), who had undergone acute stroke imaging using CT angiography (CTA), and CT perfusion (CTP). Materials and Methods: Between November 2012 and January 2018, 168 patients at our comprehensive stroke center underwent DECT follow-up within 36 h after IVT and acute CTA with or without CTP but did not receive intra-arterial imaging or treatment. Two independent readers evaluated plain monochromatic CT (pCT) alone and compared this with a second reading of a combined DECT approach using pCT and water- and iodine-weighted images, establishing and grading the ICH diagnosis, per Heidelberg and Safe Implementation of Treatments in Stroke Monitoring Study (SITS-MOST) classifications. Results: On pCT alone within 36 h, 31/168 (18.5%) patients had findings diagnosed as ICH. Using combined DECT (cDECT) changed ICH diagnosis to "CS only" in 3/168 (1.8%) patients, constituting 3/31 (9.7%) of cases with initially pCT-diagnosed ICH. These three cases had pCT diagnoses of one SAH, one minor, and one more extensive petechial hemorrhage (hemorrhagic infarction types 1 and 2), respectively. pCT alone had a 100% sensitivity, 98% specificity, 90% positive predictive value (PPV), 100% negative predictive value (NPV), and 98% accuracy for any ICH, compared to the cDECT. Inter-reader agreement for ICH classification using pCT compared to DECT was weighted kappa 0.92 (95% CI 0.87-0.98) vs. 0.91 (0.85-0.95). Conclusion: Compared to pCT, DECT within 36 h after IV thrombolysis for acute ischemic stroke, changes the radiological diagnosis of post-treatment ICH to "CS only" in a small proportion of patients. Studies are warranted of whether the altered radiological reports have an impact on patient management, for example initiation timing of antithrombotic secondary prevention.

Implementation of a Prehospital Stroke Triage System Using Symptom Severity and Teleconsultation in the Stockholm Stroke Triage Study.

Importance: To our knowledge, it is unknown whether a prehospital stroke triage system combining symptom severity and teleconsultation could accurately select patients for primary stroke center bypass and hasten delivery of endovascular thrombectomy (EVT) without delaying intravenous thrombolysis (IVT). Objective: To evaluate the predictive performance of the newly implemented Stockholm Stroke Triage System (SSTS) for large-artery occlusion (LAO) stroke and EVT initiation. Secondary objectives included evaluating whether the Stockholm Stroke Triage System shortened onset-to-puncture time for EVT and onset-to-needle time (ONT) for IVT. Design, Setting, and Participants: This population-based prospective cohort study conducted from October 2017 to October 2018 across the Stockholm region (Sweden) included patients transported by first-priority ("code stroke") ambulance to the hospital for acute stroke suspected by an ambulance nurse and historical controls (October 2016-October 2017). Exclusion criteria were in-hospital stroke and helicopter or private transport. Of 2909 eligible patients, 4 (0.14%) declined participation. Exposures: Patients were assessed by ambulance nurses with positive the face-arm-speech-time test or other stroke suspicion and were evaluated for moderate-to-severe hemiparesis (≥2 National Institutes of Health stroke scale points each on the ipsilateral arm and leg [A2L2 test]). If present, the comprehensive stroke center (CSC) stroke physician was teleconsulted by phone for confirmation of stroke suspicion, assessment of EVT eligibility, and direction to CSC or the nearest primary stroke center. If absent, the nearest hospital was prenotified. Main Outcomes and Measures: Primary outcome: LAO stroke. Secondary outcomes: EVT initiation, onset-to-puncture time, and ONT. Predictive performance measures included sensitivity, specificity, positive and negative predictive values, the overall accuracy for LAO stroke, and EVT initiation. Results: We recorded 2905 patients with code-stroke transports (1420 women [49%]), and of these, 323 (11%) had A2L2+ teleconsultation positive results and were triaged for direct transport to CSC (median age, 73 years [interquartile range (IQR), 64-82 years]; 55 women [48%]). Accuracy for LAO stroke was 87% (positive predictive value, 41%; negative predictive value, 93%) and 91% for EVT initiation (positive predictive value, 26%; negative predictive value, 99%). Endovascular thrombectomy was performed for 84 of 323 patients (26%) with triage-positive results and 35 of 2582 patients (1.4%) with triage-negative results. In EVT cases with a known onset time (77 [3%]), the median OPT was 137 minutes (IQR, 118-180; previous year, 206 minutes [IQR, 160-280]; n = 75) (P < .001). The regional median ONT (337 [12%]) was unchanged at 115 minutes (IQR, 83-164; previous year, 115 minutes [IQR, 85-161]; n = 360) (P = .79). The median CSC IVT door-to-needle time was 13 minutes (IQR, 10-18; 116 [4%]) (previous year, 31 minutes [IQR, 19-38]; n = 45) (P < .001). Conclusions and Relevance: The Stockholm Stroke Triage System, which combines symptom severity and teleconsultation, results in markedly faster EVT delivery without delaying IVT.

Safety and Outcomes of Intravenous Thrombolysis in Posterior Versus Anterior Circulation Stroke: Results From the Safe Implementation of Treatments in Stroke Registry and Meta-Analysis.

Background and Purpose- Posterior circulation stroke (PCS) accounts for 5% to 19% of patients with acute stroke receiving intravenous thrombolysis. We aimed to compare safety and outcomes following intravenous thrombolysis between patients with PCS and anterior circulation stroke (ACS) and incorporate the results in a meta-analysis. Methods- We included patients in the Safe Implementation of Treatments in Stroke Thrombolysis Registry 2013 to 2017 with computed tomography/magnetic resonance angiographic occlusion data. Outcomes were parenchymal hematoma, symptomatic intracerebral hemorrhage (SICH) per SITS-MOST (Safe Implementation of Thrombolysis in Stroke Monitoring Study), ECASS II (Second European Co-operative Stroke Study) and NINDS (Neurological Disorders and Stroke definition), 3-month modified Rankin Scale score, and death. Adjustment for SICH risk factors (age, sex, National Institutes of Health Stroke Scale, blood pressure, glucose, and atrial fibrillation) and center was done using inverse probability treatment weighting, after which an average treatment effect (ATE) was calculated. Meta-analysis of 13 studies comparing outcomes in PCS versus ACS after intravenous thrombolysis was conducted. Results- Of 5146 patients, 753 had PCS (14.6%). Patients with PCS had lower median National Institutes of Health Stroke Scale: 7 (interquartile range, 4-13) versus 13 (7-18), P<0.001 and fewer cerebrovascular risk factors. In patients with PCS versus ACS, parenchymal hematoma occurred in 3.2% versus 7.9%, ATE (95% CI): -4.7% (-6.3% to 3.0%); SICH SITS-MOST in 0.6% versus 1.9%, ATE: -1.4% (-2.2% to -0.7%); SICH NINDS in 3.1% versus 7.8%, ATE: -3.0% (-6.3% to 0.3%); SICH ECASS II in 1.8% versus 5.4%, ATE: -2.3% (-5.3% to 0.7%). In PCS versus ACS, 3-month outcomes (70% data availability) were death 18.5% versus 20.5%, ATE: 6.0% (0.7%-11.4%); modified Rankin Scale score 0-1, 45.2% versus 37.5%, ATE: 1.7% (-6.6% to 3.2%); modified Rankin Scale score 0-2, 61.3% versus 49.4%, ATE: 2.4% (3.1%-7.9%). Meta-analysis showed relative risk for SICH in PCS versus ACS being 0.49 (95% CI, 0.32-0.75). Conclusions- The risk of bleeding complications after intravenous thrombolysis in PCS was half that of ACS, with similar functional outcomes and higher risk of death, acknowledging limitations of the National Institutes of Health Stroke Scale for stroke severity or infarct size adjustment.