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.

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.

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.

Minor stroke in large vessel occlusion: A matched analysis of patients from the German Stroke Registry-Endovascular Treatment (GSR-ET) and patients from the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register (SITS-ISTR).

BACKGROUND AND PURPOSE: Reperfusion treatment in patients presenting with large vessel occlusion (LVO) and minor neurological deficits is still a matter of debate. We aimed to compare minor stroke patients treated with endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) or IVT alone. METHODS: Patients enrolled in the German Stroke Registry-Endovascular Treatment (GSR-ET) and the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) between June 2015 and December 2019 were analyzed. Minor stroke was defined as National Institutes of Health Stroke Scale (NIHSS) score ≤5, and LVO as occlusion of the internal carotid, carotid-T, middle cerebral, basilar, vertebral or posterior cerebral arteries. GSR-ET and SITS-ISTR IVT-treated patients were matched in a 1:1 ratio using propensity-score (PS) matching. The primary outcome was good functional outcome at 3 months (modified Rankin Scale score 0-2). RESULTS: A total of 272 GSR-ET patients treated with EVT and IVT (age 68.6 ± 14.0 years, 43.4% female, NIHSS score 4 [interquartile range 2-5]) were compared to 272 IVT-treated SITS-ISTR patients (age 69.4 ± 13.7, 43.4% female, NIHSS score 4 [2-5]). Good functional outcome was seen in 77.0% versus 82.9% (p = 0.119), mortality in 5.9% versus 7.9% (p = 0.413), and intracranial hemorrhage in 8.8% versus 12.5% (p = 0.308) of patients in the GSR-ET versus the SITS-ISTR IVT group, respectively. In a second PS-matched analysis, 624 GSR-ET patients (IVT rate 56.7%) and 624 SITS-ISTR patients (IVT rate 100%), good outcome was more often observed in the SITS-ISTR patients (68.2% vs. 80.9%; p < 0.001), and IVT independently predicted good outcome (odds ratio 2.16, 95% confidence interval 1.43-3.28). CONCLUSIONS: Our study suggests similar effectiveness of IVT alone compared to EVT with or without IVT in minor stroke patients. There is an urgent need for randomized controlled trials on this topic.

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.

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.

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.

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.

Blood Pressure After Endovascular Thrombectomy: Modeling for Outcomes Based on Recanalization Status.

Background and Purpose- The optimal level for blood pressure after endovascular thrombectomy in acute ischemic stroke is not well established. We sought to evaluate the association of post-endovascular thrombectomy systolic blood pressure (SBP) levels with clinical outcomes. Methods- We included endovascular thrombectomy-treated patients registered from 2014 to 2017 in the Safe Implementation of Treatments in Stroke International Thrombectomy Registry. The mean 24-hour SBP after endovascular thrombectomy treatment was analyzed both as a continuous variable and in intervals. The primary outcome was 3-month functional independence (modified Rankin Scale score of 0-2). The secondary outcomes were symptomatic intracerebral hemorrhage (SICH) and 3-month mortality. The SBP interval with the highest proportion of functional independence was chosen as reference. All analyses were performed for successful or unsuccessful recanalization (modified Treatment in Cerebral Ischemia score ≥2b or <2b, respectively). The results were adjusted for known confounders in logistic regression models. Results- In the multivariable analyses, a higher SBP value as a continuous variable was associated unfavorably with all outcomes in patients with successful recanalization (n=2920) and with more SICH in patients with unsuccessful recanalization (n=711). SBP interval ≥160 mm Hg was associated with less functional independence (adjusted odds ratio, 0.28 [95% CIs, 0.15-0.53]) and more SICH (adjusted odds ratio, 6.82 [95% CIs, 1.53-38.09]) compared with reference 100 to 119 mm Hg in patients with successful recanalization. SBP ≥160 mm Hg was associated with more SICH (adjusted odds ratio, 6.62 [95% CIs, 1.07-51.05]) compared with reference 120 to 139 mm Hg in patients with unsuccessful recanalization. Conclusions- Higher SBP values were associated with less functional independence at 3 months in patients with successful recanalization and with more SICH regardless of recanalization status.

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.

Radiological evaluation in patients with clinical suspicion of cerebral venous sinus thrombosis presenting with nontraumatic headache - a retrospective observational study with a validation cohort.

BACKGROUND: Clinical suspicion of cerebral venous sinus thrombosis (CVST) is imprecise due to non-specific symptoms such as headache. The aim was to retrospectively assess the diagnostic value of nonenhanced CT (neCT) in patients with nontraumatic headache and clinically suspected CVST. METHODS: A retrospective consecutive series of patients referred 2013-2015 for radiology were evaluated. Eligible patients had nontraumatic headache and suspicion of CVST stated in the referral, investigated with CT venography (CTV) and nonenhanced CT (neCT). neCT scans were re-evaluated for the presence of CVST or other pathology. All CTVs were checked for the presence of CVST. The validation cohort consisted of 10 patients with nontraumatic CVT (2017-2019). RESULTS: Less than 1% (1/104) had a suspected thrombus on neCT, confirmed by subsequent CTV. The remaining 99% had a CTV excluding CVST. Eleven percent had other imaging findings explaining their symptoms. In the patient with CVST, the thrombosed dural sinus was high attenuating (maximum HU 89) leading to the suspicion of CVST confirmed by CTV. The validation cohort (n = 10) confirmed the presence of a high attenuating (HU > 65) venous structure in the presence of a confirmed thrombus in all patients presenting within 10 days (suspicion written in referral, 10%). CONCLUSIONS: Despite clinical suspicion, imaging findings of CVST in nontraumatic headache are uncommon. Evaluating neCT for high attenuation in dural sinuses, followed by CTV for confirmation in selected cases seems reasonable. CVST should be recognized by all radiologists and requires a high level of awareness when reading neCT for other indications.

Safety and Outcome of Intravenous Thrombolysis in Stroke Patients on Prophylactic Doses of Low Molecular Weight Heparins at Stroke Onset.

Background and Purpose- There are limited data on intravenous thrombolysis treatment in patients with ischemic stroke who have received prophylactic doses of low molecular weight heparins (LMWHs). We aimed to evaluate the safety and outcomes of intravenous thrombolysis treatment in stroke patients taking thromboprophylactic doses of LMWH. Methods- We analyzed 109 291patients treated with intravenous thrombolysis, recorded in the Safe Implementation of Treatments in Stroke International Thrombolysis Register between 2003 and 2017 not taking oral anticoagulants or therapeutic doses of heparin at stroke onset. One thousand four hundred eleven patients (1.3%) were on prophylactic LMWH for deep venous thrombosis prevention. Outcome measures were symptomatic intracerebral hemorrhage, parenchymal hematoma, death within 7 days and 3 months, and functional dependency at 3 months. Results- Patients on LMWH were older, had more severe strokes, more prestroke disability, and comorbidities than patients without LMWH. There was no significant increase in adjusted odds ratios (aOR) for symptomatic intracerebral hemorrhage (aOR, 1.02 [95% CI, 0.48-2.17] as per Safe Implementation of Treatments in Stroke -MOST, aOR, 0.95 [0.59-1.53] per ECASS II]), nor for 7-day mortality (aOR, 1.14 [0.82-1.59]), in the prophylactic LMWH group. The LMWH group had a higher aOR for 3-month mortality (aOR, 1.94 [1.49-2.53]) and functional dependency, aOR, 1.44 (1.10-1.90). Propensity score analysis matching patients on baseline characteristics removed differences between groups on all outcomes except 3-month mortality. Conclusions- Intravenous thrombolysis in patients with acute ischemic stroke on treatment with prophylactic doses of LMWH at stroke onset is not associated with an increased risk of symptomatic intracerebral hemorrhage or early death.

Stroke Care and Application of Thrombolysis in Ibero-America: Report From the SITS-SIECV Ibero-American Stroke Register

Background and Purpose: Standardized registries may provide valuable data to further improve stroke care. Our aim was to obtain updated information about characteristics of stroke patients and management of stroke across the Ibero-American countries, using a common in-hospital registry (Safe Implementation of Treatments in Stroke­Sociedad Iberoamericana de Enfermedades Cerebrovasculares) as a basis for further quality improvement. Methods: Data for this study were entered into the Safe Implementation of Treatments in Stroke registry from September 2009 to December 2013 by 58 centers in 14 countries. Data included demographics, risk factors, onset-to-door time, National Institutes of Health Stroke Scale score, stroke subtype, ischemic stroke etiology, treatments, 3-month mortality, and modified Rankin Scale score. Time to treatment was also recorded for patients treated with thrombolysis. Results: Five thousand four hundred one patients were registered; median age, 65 years; 46% women; 3915 (72.5%) ischemic strokes; 686 (13.7%) hemorrhagic strokes; 213 (4.3%) subarachnoid hemorrhages; 414 (8.3%) transient ischemic attacks; and 31 (0.6%) cerebral vein thrombosis. The most prevalent risk factors were hypertension (71.3%), dyslipidemia (35.2%), and diabetes mellitus (23.6%). Atrial fibrillation was present in 15.1%. Three hundred one ischemic strokes were treated with intravenous thrombolysis (IVT; 7.7%). Patients undergoing IVT were more severely affected (median baseline National Institutes of Health Stroke Scale score, 11 versus 6). The rate of symptomatic intracerebral hemorrhages after IVT was 5.7%. At 3 months, 60.3% of IVT-treated patients and 59.1% of untreated patients were independent (modified Rankin Scale score, 0­2). Mortality was 11.4% in treated and 12.8% in untreated patients. Conclusions: Safe Implementation of Treatments in Stroke­Sociedad Iberoamericana de Enfermedades Cerebrovasculares is the largest registry of a general stroke population and the first study to evaluate the level of IVT use in Ibero-America. It provides valuable information that may help to improve the quality of stroke care in the Ibero-American region.

Impact of Transcranial Doppler Ultrasound on Logistics and Outcomes in Stroke Thrombolysis: Results From the SITS-ISTR.

BACKGROUND AND PURPOSE: Diagnostic transcranial Doppler ultrasound (TCD) is commonly used in patients with acute stroke before or during treatment with intravenous thrombolysis (IVT). We aimed to assess how much TCD delays IVT initiation and whether TCD influences outcomes. METHODS: We analyzed data from the SITS-ISTR (Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register) collected from December 2002 to December 2011. Outcomes were door-to-needle time, symptomatic intracerebral hemorrhage, functional outcome per the modified Rankin Scale, and mortality at 3 months. RESULTS: In hospitals performing any TCD pre-IVT, 1701 of 11 265 patients (15%) had TCD before IVT initiation. Door-to-needle time was higher in patients with pre-IVT TCD (74 versus 60 minutes; P<0.001). At hospitals performing any TCD during IVT infusion, of 9044 patients with IVT, 747 were examined with TCD during IVT. No treatment delay was seen with TCD during IVT. After multivariate adjustment, TCD during IVT was independently associated with modestly increased excellent functional outcome (modified Rankin Scale, 0-1; adjusted odds ratio, 1.28; 95% confidence interval, 1.06-1.55; P=0.012) and lower mortality (adjusted odds ratio, 0.73; 95% confidence interval, 0.55-0.95; P=0.022). CONCLUSIONS: We recommend that TCD, if performed, should be done during IVT infusion, to avoid treatment delay. The association of hyperacute TCD with beneficial outcomes suggests potential impact on patient management, which warrants further study.

Applying openEHR's Guideline Definition Language to the SITS international stroke treatment registry: a European retrospective observational study.

BACKGROUND: Interoperability standards intend to standardise health information, clinical practice guidelines intend to standardise care procedures, and patient data registries are vital for monitoring quality of care and for clinical research. This study combines all three: it uses interoperability specifications to model guideline knowledge and applies the result to registry data. METHODS: We applied the openEHR Guideline Definition Language (GDL) to data from 18,400 European patients in the Safe Implementation of Treatments in Stroke (SITS) registry to retrospectively check their compliance with European recommendations for acute stroke treatment. RESULTS: Comparing compliance rates obtained with GDL to those obtained by conventional statistical data analysis yielded a complete match, suggesting that GDL technology is reliable for guideline compliance checking. CONCLUSIONS: The successful application of a standard guideline formalism to a large patient registry dataset is an important step toward widespread implementation of computer-interpretable guidelines in clinical practice and registry-based research. Application of the methodology gave important results on the evolution of stroke care in Europe, important both for quality of care monitoring and clinical research.

External Validation of the ASTRAL and DRAGON Scores for Prediction of Functional Outcome in Stroke.

BACKGROUND AND PURPOSE: ASTRAL (Acute Stroke Registry and Analysis of Lausanne) and DRAGON (includes dense middle cerebral artery sign, prestroke modified Rankin Scale score, age, glucose, onset to treatment, National Institutes of Health Stroke Scale score) are 2 recently developed scores for predicting functional outcome after acute stroke in unselected acute ischemic stroke patients and in patients treated with intravenous thrombolysis, respectively. We aimed to perform external validation of these scores to assess their predictive performance in the large multicentre Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. METHODS: We calculated the ASTRAL and DRAGON scores in 36 131 and 33 716 patients, respectively, registered in Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register between 2003 and 2013. The proportion of patients with 3-month modified Rankin Scale scores of 3 to 6 was observed for each score point and compared with the predicted proportion according to the risk scores. Calibration was assessed using calibration plots, and predictive performance was assessed using area under the curve of the receiver operating characteristic. Multivariate logistic regression coefficients for the variables in the 2 scores were compared with the original derivation cohorts. RESULTS: The ASTRAL showed an area under the curve of 0.790 (95% confidence interval, 0.786-0.795) and the DRAGON an area under the curve of 0.774 (95% confidence interval, 0.769-0.779). All ASTRAL parameters except range of visual fields and all DRAGON parameters were significantly associated with functional outcome in multivariate analysis. CONCLUSIONS: The ASTRAL and DRAGON scores show an acceptable predictive performance. ASTRAL does not require imaging-data and therefore may have an advantage for the use in prehospital patient assessment. Prospective studies of both scores evaluating the impact of their use on patient outcomes after intravenous thrombolysis and endovascular therapy are needed.

Summary of Evidence on Early Carotid Intervention for Recently Symptomatic Stenosis Based on Meta-Analysis of Current Risks.

BACKGROUND AND PURPOSE: This study aimed to assess the evidence on the periprocedural (<30 days) risks of carotid intervention in relation to timing of procedure in patients with recently symptomatic carotid stenosis. METHODS: A systematic literature review of studies published in the past 8 years reporting periprocedural stroke/death after carotid endarterectomy (CEA) and carotid stenting (CAS) related to the time between qualifying neurological symptoms and intervention was performed. Pooled estimates of periprocedural risk for patients treated within 0 to 48 hours, 0 to 7 days, and 0 to 15 days were derived with proportional meta-analyses and reported separately for patients with stroke and transient ischemic attack as index events. RESULTS: Of 47 studies included, 35 were on CEA, 7 on CAS, and 5 included both procedures. The pooled risk of periprocedural stroke was 3.4% (95% confidence interval [CI], 2.6-4.3) after CEA and 4.8% (95% CI, 2.5-7.8) after CAS performed <15 days; stroke/death rates were 3.8% and 6.9% after CEA and CAS, respectively. Pooled periprocedural stroke risk was 3.3% (95% CI, 2.1-4.6) after CEA and 4.8% (95% CI, 2.5-7.8) after CAS when performed within 0 to 7 days. In hyperacute surgery (<48 hours), periprocedural stroke risk after CEA was 5.3% (95% CI, 2.8-8.4) but with relevant risk differences among patients treated after transient ischemic attack (2.7%; 95% CI, 0.5-6.9) or stroke (8.0%; 95% CI, 4.6-12.2) as index. CONCLUSIONS: CEA within 15 days from stroke/transient ischemic attack can be performed with periprocedural stroke risk <3.5%. CAS within the same period may carry a stroke risk of 4.8%. Similar periprocedural risks occur after CEA and CAS performed earlier, within 0 to 7 days. Carotid revascularization can be safely performed within the first week (0-7 days) after symptom onset.

Remote or extraischemic intracerebral hemorrhage--an uncommon complication of stroke thrombolysis: results from the safe implementation of treatments in stroke-international stroke thrombolysis register.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage after treatment with intravenous recombinant tissue-type plasminogen activator for ischemic stroke can occur in local relation to the infarct, as well as in brain areas remote from infarcted tissue. We aimed to describe risk factors, 3-month mortality, and functional outcome in patients with the poorly understood complication of remote intracerebral hemorrhage, as well as local intracerebral hemorrhage. METHODS: In this study, 43 494 patients treated with intravenous recombinant tissue-type plasminogen activator, with complete imaging data, were enrolled in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) during 2002 to 2011. Baseline data were compared among 970 patients (2.2%) with remote parenchymal hemorrhage (PHr), 2325 (5.3%) with PH, 438 (1.0%) with both PH and PHr, and 39 761 (91.4%) without PH or PHr. Independent risk factors for all hemorrhage types were obtained by multivariate logistic regression. RESULTS: Previous stroke (P=0.023) and higher age (P<0.001) were independently associated with PHr, but not with PH. Atrial fibrillation, computed tomographic hyperdense cerebral artery sign, and elevated blood glucose were associated with PH, but not with PHr. Female sex had a stronger association with PHr than with PH. Functional independence at 3 months was more common in PHr than in PH (34% versus 24%; P<0.001), whereas 3-month mortality was lower (34% versus 39%; P<0.001). CONCLUSIONS: Differences between risk factor profiles indicate an influence of previous vascular pathology in PHr and acute large-vessel occlusion in PH. Additional research is needed on the effect of pre-existing cerebrovascular disease on complications of recanalization therapy in acute ischemic stroke.

Safety of intravenous thrombolysis for ischemic stroke in patients treated with warfarin.

OBJECTIVE: Controversy surrounds the safety of intravenous (IV) tissue plasminogen activator (tPA) in ischemic stroke patients treated with warfarin. The European tPA license precludes its use in anticoagulated patients altogether. American guidelines accept IV tPA use with an international normalized ratio (INR) ≤ 1.7. The influence of warfarin on symptomatic intracerebral hemorrhage (SICH), arterial recanalization, and long-term functional outcome in stroke thrombolysis remains unclear. METHODS: We analyzed data from 45,074 patients treated with IV tPA enrolled in the Safe Implementation of Thrombolysis in Stroke (SITS) International Stroke Thrombolysis Register. A total of 768 patients had baseline warfarin treatment with INR ≤ 1.7. Outcome measures were SICH, arterial recanalization, mortality, and functional independence at 3 months. RESULTS: Patients on warfarin with INR ≤ 1.7 were older, had more comorbidities, and had more severe strokes compared to patients without warfarin. There were no significant differences between patients with and without warfarin in SICH rates (adjusted odds ratio [aOR] = 1.23, 95% confidence interval [CI] = 0.72-2.11 per SITS-MOST; aOR = 1.26, 95% CI = 0.82-1.70 per European Cooperative Acute Stroke Study II) after adjustment for age, stroke severity, and comorbidities. Neither did warfarin independently influence mortality (aOR = 1.05, 95% CI = 0.83-1.35) or functional independence at 3 months (aOR = 1.01, 95% CI = 0.81-1.24). Arterial recanalization by computed tomography/magnetic resonance angiography trended higher in warfarin patients (62% [37 of 59] vs 55% [776/1,475], p = 0.066). Recanalization approximated by disappearance at 22 to 36 hours of a baseline hyperdense middle cerebral artery sign was increased (63% [124 of 196] vs 55% [3,901 of 7,099], p = 0.022). INTERPRETATION: Warfarin treatment with INR ≤ 1.7 did not increase the risk for SICH or death, and had no impact on long-term functional outcome in patients treated with IV tPA for acute ischemic stroke.