Safe Implementation Of Thrombolysis In Stroke-Monitoring Study Research Articles

Patterns and Clinical Implications of Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke: Results From the ENCHANTED Study.

Hemorrhagic transformation may be a potentially devastating complication of IV thrombolysis (IVT) in acute ischemic stroke, but what degree of hemorrhage indicates the greatest negative effect is not known. We aimed to define the associations between hemorrhagic transformation patterns, classified according to clinical and imaging categories, and clinical outcomes after IVT. We conducted a post hoc analysis from the international Enhanced Control of Hypertension and Thrombolysis Stroke Study. Symptomatic intracerebral hemorrhage (sICH) was defined based on established criteria, such as the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. Asymptomatic intracerebral hemorrhage (aICH) was defined as any intracerebral hemorrhage that did not meet the criteria for sICH. Imaging subtypes of hemorrhagic transformation were assessed using the Heidelberg Bleeding Classification system. The primary outcome was death or major disability, defined by modified Rankin scale (mRS) scores 3-6 at 90 days. Secondary outcomes included death, death or disability (mRS 2-6), and poor health-related quality of life (HRQoL), defined as an overall heath utility score ≤0.7 (mean). Of the 4,370 participants, 779 (17.8%) developed any intracranial hemorrhage (ICH), with a median time from randomization to hemorrhage of 23.5 hours (interquartile range 18.92-26.07). According to the SITS-MOST criteria, 62 patients (1.4% of 4,370) were classified as sICH, and 717 patients (16.4% of 4,370) were classified as aICH. sICH per SITS-MOST criteria was associated with death or major disability (odds ratio [OR] 23.05, 95% CI 8.97-59.23), death (OR 20.14, 95% CI 11.32-35.84), death or disability (OR 61.36, 95% CI 8.40-448.01), and poor HRQoL (OR 17.87, 95% CI 7.47-42.71). Similarly, aICH per SITS-MOST criteria was also associated with death or major disability (OR 2.23, 95% CI 1.84-2.70), death (OR 1.82, 95% CI 1.39-2.38), death or disability (OR 2.29, 95% CI 1.87-2.80), and poor HRQoL (OR 1.81, 95% CI 1.50-2.18). Comparable associations were observed for sICH and aICH defined by other criteria, as well as for imaging subtypes based on Heidelberg Bleeding Classification system. All forms of post-IVT hemorrhagic transformation in acute ischemic stroke are associated with increased odds of poor clinical outcomes. Of note, aICH after IVT should not be considered clinically innocuous. ClinicalTrials.gov (NCT01422616).

Decompressive craniectomy in symptomatic intracerebral hemorrhage after ischemic stroke: a multicenter retrospective cohort study.

Symptomatic intracerebral hemorrhage (sICH) after stroke is a devastating neurological complication. Current guidelines support a "possible benefit" of decompressive craniectomy (DC) for large supratentorial sICH with significant mass effect. The authors conducted a retrospective study of 8 comprehensive stroke centers. They included all patients who sustained an sICH after acute ischemic stroke (AIS), as defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), from January 2016 to December 2020. They compared patients who underwent DC to those who were treated with standard medical treatment to measure functional outcome at 90 days, primarily as defined by the modified Rankin Scale (mRS) and secondarily by the Glasgow Outcome Scale-Extended (GOS-E). Eighty-five patients were identified, 26 of whom (30.5%) underwent DC. Patients who underwent DC were younger (58 years [DC] vs 76 years [no DC], p < 0.001). No patient with a previous history of cancer underwent DC (n = 14, p = 0.004). Twenty-five patients (96.2%) in the DC group underwent thrombectomy versus 54 (91.5%) in the non-DC group (p = 0.443). Patients who underwent DC had a longer ICU stay (median [IQR] 240 [38-408] hours vs 24 [5-96] hours in non-DC patients, p = 0.002). At 90 days, 3 patients (4.1%) had obtained an mRS score of 0-2 and 10 patients (11.7%) an mRS score of 0-3. Patients who had improved functional outcome were younger (mRS score, OR 1.06, 95% CI 1.01-1.10, p = 0.012). Patients with a history of cancer had worse 90-day mRS scores (OR 8.49, 95% CI 1.54-159, p = 0.046). The rate of in-hospital mortality or discharge to hospice was significantly higher in the non-DC cohort (10 [38.5%] patients in the DC cohort vs 38 [64.4%] in the non-DC cohort, p = 0.026). Ninety days later, patients who underwent DC were more likely to have improved outcome (mRS mean rank 30.0 vs 40.0, p = 0.027). In multivariable analysis, history of cancer (OR 12.2, 95% CI 1.26-118, p = 0.031) and older age (OR 1.07, 95% CI 1.02-1.13, p = 0.011) increased the odds of worse mRS outcomes while DC did not (OR 1.34, 95% CI 0.357-5.03, p = 0.665). DC after sICH did not improve functional outcome at 90 days according to multivariable analysis, although younger age and absence of previous cancer history were associated with improved outcomes.

Thrombolytic Therapy in Strokes: A Retrospective Clinical Data Analysis of 40 Patients in a 7-Year Period: The Experience of a Greek Internal Medicine Department

Stroke is one of the main causes of mortality and disability in developed countries. In acute ischemic stroke, the standard treatment is recombinant tissue plasminogen activator (rt-PA). The benefits of the treatment depend on the time of administration, the earlier it is administered, the greater its benefit. There are limited studies on the retrospective outcome of thrombolytic therapy in patients with acute ischemic stroke outside of clinical trials. The present retrospective study aimed to analyze the clinical data of 40 patients over 7 years who were hospitalized with acute ischemic stroke at the AHEPA University Hospital in Greece. From January 2013 to December 2020, 40 patients with acute ischemic stroke were admitted and treated. Computed tomography (CT) was performed at 24 h after thrombolytic treatment or earlier in case of neurological worsening. The hospital had 3 months follow-up at the stroke clinic and data consisting of the National Institute of Health Stroke Scale (NIHSS), functional outcome assessed by modified Rankin Scale (mRS) and mortality were reviewed in the medical records from the stroke clinic. The clinical outcome of functional independence defined by the modified Rankin Scale (mRS) ≤ 2 at 3 months was evaluated. Safety outcomes were in-hospital mortality, mortality at 3 months, and symptomatic intracerebral hemorrhage (sICH) defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. The main finding of the present study, that there was an overall reduction in the NIHSS scale after thrombolysis, proves that the patients showed improvement after performing thrombolysis. Consequently, from the total of 40 thrombolysis performed at the clinic, it can be concluded that most patients had a good outcome.

A Comparative Study of Hemorrhagic Conversion Patterns After Stroke Thrombolysis With Alteplase Versus Tenecteplase.

Tenecteplase is the thrombolytic drug of choice for acute ischemic stroke (AIS) as it has unique pharmacologic properties, along with results demonstrating its non-inferiority compared to alteplase. However, there are contradictory data concerning the risk of intracranial hemorrhage. The purpose of the study was to report the rate and patterns of symptomatic intracranial hemorrhage (sICH) in AIS patients after thrombolysis with tenecteplase compared to alteplase. This is a retrospective cohort study with data collected 90 days before and after the change from alteplase to tenecteplase from 15 Texas stroke centers. The primary endpoint is the incidence of sICH according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) and European Cooperative Acute Stroke Study III (ECASS-3) criteria. The secondary endpoints are the radiographic pattern of hemorrhagic conversion according to the Heidelberg bleeding classification (HBC). A total of 431 patients were eligible for thrombolytic therapy. Half of the cohort received alteplase (n=216), and the other half received tenecteplase (n=215). The average age of the alteplase group was 62.94 years old (SD=15.12) and 64.45 years old (SD=14.51) for the tenecteplase group. Seven patients in the alteplase group (3.2%) and 14 (6.5%) in the tenecteplase group had sICH, with an odds ratio of 1.44 (95% CI 0.60-3.43; P=0.41). An increased National Institutes of Health Stroke Scale (NIHSS) score on arrival (1.06; 95% CI 1.0004-1.131; P=0.04) was a statistically significant predictor of sICH. Tenecteplase was associated with a statistically significant increase in HBC-3 (P=0.040) over alteplase. Compared with alteplase, our study revealed a higher rate of sICH with tenecteplase that was not statistically significant and a higher rate of HBC-3 hemorrhages that was statistically significant. The proposed mechanism of bleeding is hemorrhagic conversion in clinically silent infarcts and contusions underlying the lesions. Further studies are needed to confirm our findings and determine predictive risk factors.

Endovascular treatment for acute ischemic stroke in patients with tandem lesion in the anterior circulation: analysis from the METRICS study

BackgroundAcute ischemic stroke (AIS) due to anterior circulation tandem lesion (TL) remains a technical and clinical challenge for endovascular treatment (EVT). Conflicting results from observational studies and missing evidence from...

Blood Pressure Changes During Mechanical Thrombectomy for Acute Ischemic Stroke Are Associated With Serious Early Treatment Complications: Symptomatic Intracerebral Hemorrhage and Malignant Brain Edema.

BackgroundSymptomatic intracranial hemorrhage (sICH) and malignant brain edema (MBE) are well-known deleterious endovascular treatment (EVT) complications that some studies found to be associated with postprocedural blood pressure (BP) variability. We aimed to evaluate their association with periprocedural BP changes, including its intraprocedural decrease.MethodsWe retrospectively analyzed the data of 132 consecutive patients that underwent EVT between 1 December 2018 and 31 December 2019, for anterior circulation ischemic stroke. Analyzed predictors of sICH and MBE included non-invasively obtained BP before and 5-min after treatment, intraprocedural relative decreases of BP from baseline, and its post-treatment increases. SICH was defined in accordance with the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria and MBE as brain edema with midline shift on the follow-up imaging. We used binary logistic regression analysis to investigate the association of BP parameters and the incidence of sICH and MBE.ResultsAmong the included patients, 11 (8.3%) developed sICH and 31 (23.5%) MBE. The intraprocedural decrease of mean arterial blood pressure (MAP) was independently associated with MBE occurrence (aOR per 10 mmHg drop from baseline 1.27; 95% CI 1.01–1.60; P = 0.040). Over 40% MAP drop was associated with a higher risk of sICH in the entire cohort (aOR 4.24; 95% CI 1.33–13.51; P = 0.015), but not in the subgroup with successful reperfusion (aOR 2.81; 95% CI 0.64–12.23; P = 0.169). Post-treatment systolic blood pressure (SBP) and MAP elevation above their minimal values during MT are significantly associated with the development of sICH (aOR per 10 mmHg SBP increase 1.78; 95% CI 1.15–2.76; P = 0.010 and aOR per 10 mmHg MAP increase 1.78; 95% CI 1.04–3.03; P = 0.035).ConclusionsIn the anterior circulation ischemic stroke patients relative MAP decrease during EVT is associated with a higher risk of MBE occurrence, and over 40% MAP drop with a higher incidence of both MBE and sICH. Post-treatment elevation of SBP and MAP increased the risk of sICH.

Asymptomatic Intracranial Hemorrhage Is Associated With Poor Outcomes After Mechanical Thrombectomy for Large Vessel Occlusion

Asymptomatic Intracranial Hemorrhage Is Associated With Poor Outcomes After Mechanical Thrombectomy for Large Vessel Occlusion

Comparison of risk scores in predicting symptomatic intracerebral hemorrhage after endovascular thrombectomy

Several risk scores have been developed to predict symptomatic intracerebral hemorrhage (SICH) after acute reperfusion therapy for ischemic stroke. We compared the performance of established risk scores in predicting SICH after EVT under different SICH criteria. A total of 258 patients with anterior circulation large vessel occlusion who received EVT in two medical centers of Taiwan were recruited. Three definitions of SICH, the European Collaborative Acute Stroke Study II (ECASS II), ECASS III, and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), were used. The HAT, SITS-SICH, SEDAN, and TAG risk scores were applied. Logistic regression and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of each risk model. In the 258 included patients (mean age, 71.9±11.8 years; men, 48.1%), the observed rates of SICH according to ECASS II, ECASS III, and SITS-MOST criteria were 10.1%, 5.0%, and 4.7%, respectively. Higher glucose level (>160mg/dL) and unsuccessful recanalization independently predicted SICH under all criteria. Among the different risk scores, only SEDAN and TAG consistently predicted SICH. SEDAN and TAG scores exhibited the highest AUC in predicting SICH for ECASS III (SEDAN 0.72, TAG 0.72) and SITS-MOST (SEDAN 0.73, TAG 0.70) criteria. Among various risk scores, the TAG and SEDAN scores best predict SICH after EVT. Higher glucose level and unsuccessful recanalization, which are included in the TAG and SEDAN scores, are independent risk factors of SICH in the present cohort, highlighting their detrimental effects.

Initial experience with dual-layer detector spectral CT for diagnosis of blood or contrast after endovascular treatment for ischemic stroke.

To determine whether spectral detector CT (SDCT) with a plain non-enhanced monochromatic CT, a water-weighted image after iodine removal, an iodine map, and Mono energetic images changes the diagnosis and classification of intracranial hemorrhage based on single energy CT after endovascular treatment (EVT) for ischemic stroke. Two readers evaluated single energy and SD CT data collected from 63 patients within one week after EVT. They diagnosed ICH or contrast staining, and graded ICH according to the Heidelberg and Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) classification. Differences in diagnosis between single energy and SD CT were tested with Pearson's chi-squared test. Diagnostic values of single energy CT were calculated. Interrater agreement was based on Cohen's Kappa. When spectral data were added to single energy CT, the diagnosis of ICH changed in 8 CT scans (13%): in 4, the diagnosis of ICH was rejected and in 4, initially undetected ICH was diagnosed. In an additional 3 patients, the ICH grade was modified. CT alone had 88% sensitivity, 87% specificity, 88% positive diagnostic value, 87% negative diagnostic value, and 87% overall accuracy for ICH compared to SDCT. Interreader agreement on the presence of ICH was 0.84 (95% CI 0.51-0.86) for spectral CT and 0.84 (95% CI 0.73-0.97) for single energy CT. SD CT after endovascular treatment contributes to the distinction between intracranial hemorrhage and contrast staining.

Early NT-ProBNP (N-Terminal Probrain Natriuretic Peptide) Elevation Predicts Malignant Edema and Death After Reperfusion Therapy in Acute Ischemic Stroke Patients.

We aimed to investigate the relationship between early NT-proBNP (N-terminal probrain natriuretic peptide) and all-cause death in patients receiving reperfusion therapy, including intravenous thrombolysis and endovascular thrombectomy (EVT). This study included 1039 acute ischemic stroke patients with early NT-proBNP data at 2 hours after the beginning of alteplase infusion for those with intravenous thrombolysis only or immediately at the end of EVT for those with EVT. We performed natural log transformation for NT-proBNP (Ln(NT-proBNP)). Malignant brain edema was ascertained by using the SITS-MOST (Safe Implementation of Thrombolysis in Stroke-Monitoring Study) criteria. Median serum NT-proBNP level was 349 pg/mL (interquartile range, 89-1250 pg/mL). One hundred twenty-one (11.6%) patients died. Malignant edema was observed in 78 (7.5%) patients. Ln(NT-proBNP) was independently associated with 3-month mortality in patients with intravenous thrombolysis only (odds ratio, 1.465 [95% CI, 1.169-1.836]; P=0.001) and in those receiving EVT (odds ratio, 1.563 [95% CI, 1.139-2.145]; P=0.006). The elevation of Ln(NT-proBNP) was also independently associated with malignant edema in patients with intravenous thrombolysis only (odds ratio, 1.334 [95% CI, 1.020-1.745]; P=0.036), and in those with EVT (odds ratio, 1.455 [95% CI, 1.057-2.003]; P=0.022). An early increase in NT-proBNP levels was related to malignant edema and stroke mortality after reperfusion therapy.

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.

Dual energy CT after stroke thrombectomy alters assessment of hemorrhagic complications.

To determine whether dual energy CT with a combined approach (cDECT) using a plain noncontrast monochromatic CT (pCT), a water-weighted image after iodine removal, and an iodine-weighted image changes the diagnosis and classification of intracranial hemorrhage (ICH) after endovascular thrombectomy (EVT) in acute ischemic stroke compared to a pCT image alone without separate water and iodine weighting. During 2012 to 2016, 372 patients at our comprehensive stroke center underwent DECT scans within 36 hours after EVT. Two readers evaluated pCT compared to a second reading with cDECT, establishing the diagnosis of ICH and grading it per the Heidelberg and Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) classifications. Using cDECT changed the ICH diagnosis to contrast staining only in 34% (52 of 152), modified the ICH grade in 10% (15 of 152), and diagnosed initially undetected ICH in 2% (5 of 220). pCT alone had 95% sensitivity, 80% specificity, 66% positive predictive value, 98% negative predictive value, and 85% accuracy for ICH compared to cDECT. Interreader agreement on the presence of ICH increased with cDECT compared to pCT (Cohen κ = 0.77 [95% confidence interval 0.69-0.84] vs 0.68 [0.61-0.76]). cDECT within 36 hours after EVT changes the radiologic report regarding posttreatment ICH in a considerable proportion of patients undergoing EVT compared to pCT alone. This could affect decision-making regarding monitoring, secondary prevention, and prognostication. The cDECT scan could improve the interpretation consistency of high-attenuating changes on post-EVT images.

Intravenous thrombolysis in stroke mimics: results from the SITS International Stroke Thrombolysis Register.

Patients with stroke mimics (SM), i.e. conditions with stroke-like symptoms, may risk harm if treated with intravenous thrombolysis (IVT). Current guidelines state low risk of intracerebral hemorrhage based on studies comprising a total of <400 SM cases. We aimed to compare safety and outcomes following IVT between patients with acute ischaemic stroke and mimicking conditions. We included IVT-treated ischaemic stroke patients in the SITS International Stroke Thrombolysis Register 2003-2017, examined with magnetic resonance imaging 22-36h after treatment. Outcomes were parenchymal hematoma (PH) after treatment, symptomatic intracerebral hemorrhage (SICH) per Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST), Second European Co-operative Stroke Study (ECASS II) and National Institutes of Neurological Disorders and Stroke Study (NINDS) criteria, death and modified Rankin Scale score (mRS) at 3months. Of 10436 patients, 429 mimics (4.1%) were identified. The most common types were functional (30.8%), migraine (17.5%) and seizure (14.2%). Patients with mimics had fewer cerebrovascular risk factors and lower median National Institutes of Health Stroke Scale score [7 (interquartile range, 5-10) vs. 8 (5-14), P<0.001]. Among mimics versus stroke patients, PH was seen in 1.2% vs. 5.1% (P<0.001), SICH NINDS in 0.5% vs. 3.9% (P<0.001), SICH ECASS II in 0.2% vs. 2.1% (P=0.007) and SICH SITS-MOST in 0% vs. 0.5% (P=0.28). Modified Rankin Scale score 0-1 at 3months was present in 84.1% vs. 57.7% (P<0.001) and death within 3months in 2.6% vs. 5.4% (P=0.028) of mimics and stroke patients, respectively. This large observational study indicated that PH and SICH following IVT in patients with SM are uncommon.

Intravenous Thrombolysis in Patients with Acute Ischemic Stroke after a Reversal of Dabigatran Anticoagulation with Idarucizumab: A Real-World Clinical Experience

Intravenous thrombolysis (IVT) is contraindicated in patients with acute ischemic stroke (AIS) using oral anticoagulants. A specific human monoclonal antibody was introduced to reverse immediately the anticoagulation effect of the direct inhibitor of thrombin, dabigatran. Until now, mostly individual cases presenting with successful IVT after a reversal of dabigatran anticoagulation in patients with AIS were published. Thus, we aimed to report real-world data from clinical practice. Patients with AIS on dabigatran treated with IVT after antidote reversal were enrolled in the retrospective nationwide study. Neurological deficit was scored using the National Institutes of Health Stroke Scale (NIHSS) and 90-day clinical outcome using modified Rankin scale (mRS) with a score 0-2 for a good outcome. Intracerebral hemorrhage (ICH) was defined as a presence of any sign of bleeding on control imaging after IVT, and symptomatic intracerebral hemorrhage (SICH) was assessed according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. In total, 13 patients (7 men, mean age 70.0 ± 9.1 years) with a median NIHSS admission score of 7 points were analyzed. Of these patients, 61.5% used 2 × 150 mg of dabigatran daily. Antidote was administrated 427 ± 235 minutes after the last intake of dabigatran, with a mean activated prothrombin time of 38.1 ± 27.8 seconds and a mean thrombin time of 72.2 ± 56.1 seconds. Of the 13 patients, 2 had ICH and 1 had SICH, and no other bleeding complications were observed after IVT. Of the total number of patients, 76.9% had a good 3-month clinical outcome and 3 patients (23.1%) died. Recurrent ischemic stroke occurred in 2 patients (15.4%). The data presented in the study support the safety and efficacy of IVT after the reversal of the anticoagulation effect of dabigatran with antidote in a real-world clinical practice.

Thrombolysis for stroke in Ireland: increasing access and maintaining safety in a challenging environment.

In the setting of a national audit of acute stroke services, we examined the delivery of thrombolytic therapy for ischaemic stroke and whether current practice was achieving safe outcomes and consistent delivery for patients. Data obtained from the recent national stroke audit was compared against previous Irish audit, the most recent SSNAP UK stroke audit and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) study. Thrombolysis was provided in 27 acute hospitals throughout Ireland during the period assessed with 82% (22/27) providing 24/7 access, the remaining sites using redirect policies. Decision to thrombolyse was made by stroke trained consultants in 63% (17/27) of units, with general physicians and emergency medicine consultants covering the other units. Thrombolysis rate for non-haemorrhagic stroke was 11% (n=80/742, CI 95% ±2.23) versus a 1% rate in the 2008 audit. Sites receiving patients through a redirect policy had the highest thrombolysis rate, an average of 24%. Nearly 30% of cases were thrombolysed on the weekend. Eighty-three percent of cases were managed in a stroke unit at some time during admission versus 54% of the national total cases. Thirty-seven percent of patients were ≥80years old. The mortality rate was 11.3% versus the national mortality rate for non-thrombolysed ischaemic strokes of 10% (p>0.5), and this is comparable to the SITS-MOST 2007 study 3-month mortality rate of 11.3% (p>0.5). Stroke thrombolysis is being effectively and safely provided in acute stroke services in Ireland despite regular involvement of non-specialist staff. There is still potential to improve thrombolysis rate.

Inflammatory and metalloproteinases profiles predict three-month poor outcomes in ischemic stroke treated with thrombolysis

Inflammatory mediators and metalloproteinases are altered in acute ischemic stroke (AIS) and play a detrimental effect on clinical severity and hemorrhagic transformation of the ischemic brain lesion. Using data from the Italian multicenter observational MAGIC (MArker bioloGici nell’Ictus Cerebrale) Study, we evaluated the effect of inflammatory and metalloproteinases profiles on three-month functional outcome, hemorrhagic transformation and mortality in 327 patients with AIS treated with intravenous thrombolys in according to SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy) criteria. Circulating biomarkers were assessed at baseline and 24 h after thrombolysis. Adjusting for age, sex, baseline glycemia and National Institute of Health Stroke Scale, history of atrial fibrillation or congestive heart failure, and of inflammatory diseases or infections, baseline alpha-2macroglobulin (A2M), baseline serum amyloid protein (SAP) and pre-post tissue-plasminogen activator (tPA) variations (Δ) of metalloproteinase 9, remained significantly and independently associated with three-month death [OR (95% CI):A2M:2.99 (1.19–7.53); SAP:5.46 (1.64–18.74); Δmetalloproteinase 9:1.60 (1.12–2.27)]. The addition of baseline A2M and Δmetalloproteinase 9 or baseline SAP and Δmetalloproteinase 9 (model-2 or model-3) to clinical variables (model-1) significantly improved the area under curve for prediction of death [model-2 with A2M: p = 0.0205; model-3 with SAP: p = 0.001]. In conclusion, among AIS patients treated with thrombolysis, circulating A2M, SAP and Δmetalloproteinase 9 are independent markers of poor outcome. These results may prompt controlled clinical research about agents antagonizing their effect.

Treatment and Outcome of Thrombolysis-Related Hemorrhage: A Multicenter Retrospective Study.

Treatments for symptomatic intracerebral hemorrhage (sICH) are based on expert opinion, with limited data available on efficacy. To better understand the natural history of thrombolysis-related sICH, with a focus on the efficacy of various treatments used. Multicenter retrospective study between January 1, 2009, and April 30, 2014, at 10 primary and comprehensive stroke centers across the United States. Participants were all patients with sICH, using the definition by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), which included a parenchymal hematoma type 2 and at least a 4-point increase in the National Institutes of Health Stroke Scale score. The primary outcome was in-hospital mortality, and the secondary outcome was hematoma expansion, defined as a 33% increase in the hematoma volume on follow-up imaging. Of 3894 patients treated with intravenous recombinant tissue plasminogen activator (rtPA) within 4½ hours after symptom onset of ischemic stroke, 128 (3.3%) had sICH. The median time from initiation of rtPA therapy to sICH diagnosis was 470 minutes (range, 30-2572 minutes), and the median time from diagnosis to treatment of sICH was 112 minutes (range, 12-628 minutes). The in-hospital mortality rate was 52.3% (67 of 128), and 26.8% (22 of 82) had hematoma expansion. In the multivariable models, code status change to comfort measures after sICH diagnosis was the sole factor associated with increased in-hospital mortality (odds ratio, 3.6; 95% CI, 1.2-10.6). Severe hypofibrinogenemia (fibrinogen level, <150 mg/dL) was associated with hematoma expansion, occurring in 36.3% (8 of 22) of patients without hematoma expansion vs in 25.0% (15 of 60) of patients with hematoma expansion (P = .01), highlighting a role for cryoprecipitate in reversing rtPA coagulopathy. In this study, treatment of postthrombolysis sICH did not significantly reduce the likelihood of in-hospital mortality or hematoma expansion. Shortening the time to diagnosis and treatment may be a key variable in improving outcomes of patients with sICH.

Development of a decision analytic model to support decision making and risk communication about thrombolytic treatment.

BackgroundIndividualised prediction of outcomes can support clinical and shared decision making. This paper describes the building of such a model to predict outcomes with and without intravenous thrombolysis treatment following ischaemic stroke.MethodsA decision analytic model (DAM) was constructed to establish the likely balance of benefits and risks of treating acute ischaemic stroke with thrombolysis. Probability of independence, (modified Rankin score mRS ≤ 2), dependence (mRS 3 to 5) and death at three months post-stroke was based on a calibrated version of the Stroke-Thrombolytic Predictive Instrument using data from routinely treated stroke patients in the Safe Implementation of Treatments in Stroke (SITS-UK) registry. Predictions in untreated patients were validated using data from the Virtual International Stroke Trials Archive (VISTA). The probability of symptomatic intracerebral haemorrhage in treated patients was incorporated using a scoring model from Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) data.ResultsThe model predicts probabilities of haemorrhage, death, independence and dependence at 3-months, with and without thrombolysis, as a function of 13 patient characteristics. Calibration (and inclusion of additional predictors) of the Stroke-Thrombolytic Predictive Instrument (S-TPI) addressed issues of under and over prediction. Validation with VISTA data confirmed that assumptions about treatment effect were just. The C-statistics for independence and death in treated patients in the DAM were 0.793 and 0.771 respectively, and 0.776 for independence in untreated patients from VISTA.ConclusionsWe have produced a DAM that provides an estimation of the likely benefits and risks of thrombolysis for individual patients, which has subsequently been embedded in a computerised decision aid to support better decision-making and informed consent.

National Institutes of Health Stroke Scale Item Profiles as Predictor of Patient Outcome: External Validation on Safe Implementation of Thrombolysis in Stroke-Monitoring Study Data.

National Institutes of Health Stroke Scale (NIHSS) item profiles that were recently proposed and validated may prove useful for clinical prognostication and research studies. We aimed to validate the NIHSS item profiles in hyper-acute stroke patients who received thrombolysis treatment (tissue-type plasminogen activator). We applied the latent class analysis probabilities of the profile membership generated from the derivation study onto NIHSS data from the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST). We separately considered NIHSS data collected within 3 hours and at ≈24 hours after stroke onset to obtain 2 sets of symptom groupings. The discrimination and calibration of both sets of symptom profiles were assessed from their association with outcomes. The outcome measures included modified Rankin Scale (mRS; using full distribution and dichotomized, mRS 0-1 or back to baseline) at day 90 and mortality by 90 days. We obtained data for 6843 patients. Ordinal analysis of mRS showed odds of better outcome across the profiles, for each set of symptom profiles, adjusted for age, sex, and prestroke mRS. Dichotomized outcomes mirrored the ordinal findings. There were significant differences in prognostic discrimination ability for the dichotomized outcome measures between the 2 sets of symptom profiles, with the latter set (ie, 24-hour symptom profiles) performing better. The NIHSS item profiles are individually associated with functional outcome and mortality in acute stroke patients treated with tissue-type plasminogen activator. Considering profiles of NIHSS subscores rather than only the total score is informative for prognostication, particularly for assessments collected 24 hours after stroke onset.

Symptomatic Intracerebral Hemorrhage after Intravenous Thrombolysis in Chinese Patients: Comparison of Prediction Models

To assess the performance of risk scores in predicting symptomatic intracranial hemorrhage (SICH) after intravenous thrombolysis (IVT). A multicenter prospective study was performed in 811 patients who underwent IVT with standard-dose recombinant tissue plasminogen activator within 4.5hours of acute ischemic stroke (AIS) onset in 67 stroke centers involved in the Thrombolysis Implementation and Monitor of acute ischemic Stroke in China program from May 2007 to April 2012. SEDAN (blood sugar, early infarct signs, [hyper]dense cerebral artery sign, age) score, Safe Implementation of Thrombolysis in Stroke (SITS)-SICH score, Glucose Race Age Sex Pressure Stroke Severity (GRASPS) score, Multicenter Stroke Survey (MSS) score, and Stroke Prognostication using Age and National Institutes of Health Stroke Scale (SPAN)-100 index were calculated in selected patients, and their predictive performance for SICH was compared according to the National Institute of Neurological Disorders and Stroke (NINDS), Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), and European Cooperative Acute Stroke Study (ECASS)-II criteria. For predicting the risk of SICH (NINDS definition) after IVT, the area under the receiver operating characteristic (ROC) curve of MSS score was the highest (.71, P<.0001). For predicting the risk of SICH (SITS-MOST definition) after IVT, the area under the ROC curve of GRASPS score was the highest (.73, P=.005). For predicting SICH (ECASS-II definition) after IVT, the area under the ROC curve of MSS score was the highest (.73, P<.0001). SITS-SICH, GRASPS, and MSS scores predicted the risk of SICH after IVT in patients with AIS, but only the latter 2 were better in the Chinese population. MSS score had the best predictive performance for SICH using NINDS and ECASS-II definitions, whereas GRASPS score was the best for SICH using the SITS-MOST definition.