Association of Reperfusion With Brain Edema in Patients With Acute Ischemic Stroke
W. Taylor KimberlyBruna Garbugio DutraAnna M.M. BoersHeitor AlvesOlvert A. BerkhemerLucie van den BergKevin N. ShethYvo B.W.E.M. RoosAad van der LugtLudo F.M. BeenenDiederik W.J. DippelWim H. van ZwamRobert J. van OostenbruggeHester F. LingsmaHenk A. MarqueringCharles B.L.M. Majoie
117
Citation
41
Reference
10
Related Paper
Citation Trend
Abstract:
It is uncertain whether therapeutic reperfusion with endovascular treatment yields more or less brain edema.To elucidate the association between reperfusion and brain edema. The secondary objectives were to evaluate whether brain edema could partially be responsible for worse outcomes in patients with later reperfusion or lower Alberta Stroke Program Early Computed Tomography Score.This was a post hoc analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), which was a prospective, randomized, multicenter clinical trial of endovascular treatment compared with conventional care of patients with acute anterior circulation ischemic stroke. Of 502 patients enrolled from December 2010 to June 2014, 2 patients declined to participate. Additionally, exclusion criteria were absence of follow-up imaging or presence of parenchymal hematoma, resulting in 462 patients included in this study. Brain edema was assessed retrospectively, from December 10, 2016, to July 24, 2017, by measuring midline shift (MLS) in all available follow-up scans. Observers were blinded to clinical data.Midline shift was assessed as present or absent and as a continuous variable. Reperfusion status was assessed by the modified thrombolysis in cerebral infarction score in the endovascular treatment arm. The modified arterial occlusive lesion score was used to evaluate the recanalization status in both arms. The modified Rankin scale score at 90 days was used for functional outcome.Of 462 patients, the mean (SD) age was 65 (11) years, and 41.8% (n = 193) were women. Successful reperfusion and recanalization were associated with a reduced likelihood of having MLS (adjusted common odds ratio, 0.25; 95% CI, 0.12-0.53; P < .001 and adjusted common odds ratio, 0.34; 95% CI, 0.21-0.55; P < .001, respectively). Midline shift was partially responsible for worse modified Rankin scale scores in patients without reperfusion or recanalization (MLS changed the logistic regression coefficients by 30.3% and 12.6%, respectively). In patients with delayed reperfusion or lower Alberta Stroke Program Early Computed Tomography Score, MLS mediated part of the worse modified Rankin scale scores, corresponding to a change in the regression coefficient of 33.3% and 64.2%, respectively.Successful reperfusion was associated with reduced MLS. This study identifies an additional benefit of reperfusion in relation to edema, as well as rescuing ischemic brain tissue at risk for infarction.Netherlands Trial Registry number: NTR1804 and Current Controlled Trials number: ISRCTN10888758.Keywords:
Stroke
Midline shift
Cerebral edema
Brain ischemia
Intravenous (i.v.) recombinant tissue plasminogen activator (rtPA) remains the only approved therapy for acute ischemic stroke. However, the use of i.v. thrombolysis is restricted to a minority of patients by the rigid 3-h time window. Modern imaging-based selection algorithms that can identify penumbra have been proposed as methods to extend the window and to select patients more likely to respond favorably or unfavorably to i.v. thrombolysis.We aim to compare the safety and efficacy of multiparametric computed tomography (CT)-based i.v. thrombolysis after 3-9 h of symptom onset with standard CT-based thrombolysis within 3 h and with CT-based thrombolysis or placebo after 3-6 h from the pooled data of the large stroke rtPA trials.The imaging-based thrombolysis trial in acute ischemic stroke-II study is a prospective, multicenter and assessor-blind controlled study. The primary efficacy outcome will be a favorable outcome at 90 days defined as a modified Rankin Scale and reperfusion improvement 24-36 h after treatment; the primary safety end-point outcome will be intracerebral hemorrhage 24-36 h after treatment. We aim to include 200 patients by 2010. It is registered with IRCTN number: ISRCTN12033002.
Penumbra
Stroke
Cite
Citations (11)
Objective:
To clarify the associated factors and outcomes of very early neurological deterioration (VEND) after thrombolysis.Background:
Early neurological deterioration (END) within 24 hours after thrombolysis for acute ischemic stroke was associated with high mortality and disability. However, no prior studies focused on END within 1 hour after thrombolysis.Design/Methods:
We retrospectively analyzed patients receiving intravenous thrombolysis for acute ischemic stroke at the National Taiwan University Hospital from January 2018 to December 2021. Relevant clinical and radiographical findings were reviewed. VEND was defined as a ≥ 4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within 1 hour after thrombolysis compared with initial score. A Modified Rankin Scale (mRS) score 0–2 at 3 months was defined as good functional outcome.Results:
In the total of 347 patients (mean age 69.6 ± 13.7 years, 57% male) who received thrombolysis for acute ischemic stroke, 29 (8.4%) patients had VEND. Compared with non-VEND group, VEND group had higher NIHSS scores at 1 hour (19.2 ± 7.3 vs. 9.0 ± 7.1, p < 0.001) and 24 hours (14.1 ± 9.8 vs. 7.3 ± 7.5, p = 0.001), more likely to receive endovascular thrombectomy (EVT) (59% vs. 25%, p < 0.001), and less likely to achieve good functional outcome (24% vs. 58%, p < 0.001). VEND was inversely associated with good functional outcome after adjustment of other significant variables (adjusted odds ratio = 0.24, p = 0.006). In patients with initial NIHSS score ≤ 6 who were initially not regarded as candidates for EVT, VEND was significantly associated with intracranial atherosclerotic disease (ICAD), undergoing EVT after deterioration, and less likely to have good functional outcome.Conclusions:
VEND was a negative predictor for good functional outcome after thrombolysis, which was especially important for patients with initial low NIHSS score and associated with ICAD. Disclosure: Dr. Shen has nothing to disclose. Dr. Yeh has nothing to disclose. Sung-Chun Tang has nothing to disclose. Dr. Jeng has nothing to disclose.Stroke
Acute stroke
Cite
Citations (0)
Background and Purpose— The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of safety and outcome of thrombolysis in CAD. Methods— We performed a systematic literature search on intravenous and intra-arterial thrombolysis in CAD. We calculated the rates of pooled symptomatic intracranial hemorrhage and mortality and indirectly compared them with matched controls from the Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register. We applied multivariate regression models to identify predictors of excellent (modified Rankin Scale=0 to 1) and favorable (modified Rankin Scale=0 to 2) outcome. Results— We obtained individual patient data of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%), with a mean±SD age of 46±11 years. Most patients presented with severe stroke (median National Institutes of Health Stroke Scale score=16). Treatment was intravenous thrombolysis in 67% and intra-arterial thrombolysis in 33%. Median follow-up was 3 months. The pooled symptomatic intracranial hemorrhage rate was 3.1% (95% CI, 1.3 to 7.2). Overall mortality was 8.1% (95% CI, 4.9 to 13.2), and 41.0% (95% CI, 31.4 to 51.4) had an excellent outcome. Stroke severity was a strong predictor of outcome. Overlapping confidence intervals of end points indicated no relevant differences with matched controls from the Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register. Conclusions— Safety and outcome of thrombolysis in patients with CAD-related stroke appear similar to those for stroke from all causes. Based on our findings, thrombolysis should not be withheld in patients with CAD.
Stroke
Fibrinolytic agent
Cite
Citations (143)
Stroke patients with diabetes and admission hyperglycaemia have worse outcomes than non-diabetics, with or without intravenous thrombolysis. Poor vessel recanalization was reported in diabetics treated with intravenous thrombolysis.This study aimed to determine the impact of admission glucose and diabetes on recanalization and outcome after intra-arterial thrombolysis.We analysed 389 patients (213 men, 176 women) treated with intra-arterial thrombolysis. The association of diabetes and admission glucose value with recanalization, outcome, mortality, and symptomatic intracranial haemorrhage was determined. Recanalization was classified according to thrombolysis in myocardial infarction grades. Outcome was measured using the modified Rankin Scale at three-months and categorized as favourable (modified Rankin Scale 0-2) or poor (modified Rankin Scale 3-6).The rate of partial or complete recanalization (thrombolysis in myocardial infarction 2-3) did not differ between patients with and without diabetes (67% vs. 66%; P = 1·000). Mean admission glucose values were similar in patients with poor recanalization (thrombolysis in myocardial infarction 0-1) and patients with partial or complete recanalization (thrombolysis in myocardial infarction 2-3; 7·3 vs. 7·3 mmol/l; P = 0·746). Follow-up at three-months was obtained in 388 of 389 patients. Clinical outcome was favourable (modified Rankin Scale 0-2) in 189 patients (49%) and poor (modified Rankin Scale 3-6) in 199 patients (51%). Mortality at three-months was 20%. Diabetics were more likely to have poor outcome (72% vs. 48%; P = 0·001) and to be dead (30% vs. 19%; P = 0·044) at three-months. After multivariable analysis, there remained an independent relationship between diabetes and outcome (P = 0·003; odds ratio 3·033, 95% confidence interval 1·452-6·336), but not with mortality (P = 0·310; odds ratio 1·436; 95% confidence interval 0·714-2·888). Moreover, higher age (P = 0·001; odds ratio 1·039; 95% confidence interval 1·017-1·061), higher baseline National Institutes of Health Stroke Scale score (P < 0·0001; odds ratio 1·130; 95% confidence interval 1·079-1·182), location of vessel occlusion as categorical variable (P < 0·0001), poor collaterals (P = 0·02; odds ratio 1·587; 95% confidence interval 1·076-2·341), poor vessel recanalization (P < 0·0001; odds ratio 4·713; 95% confidence interval 2·627-8·454), and higher leucocyte count (P = 0·032; odds ratio 1·094; 95% confidence interval 1·008-1·188) were independent baseline predictors of poor outcome. Higher admission glucose was associated with poor outcome (P = 0·006) and mortality (P < 0·0001). After multivariate analyses, glucose remained independently associated with poor outcome (P = 0·019; odds ratio 1·150; 95% confidence interval 1·023-1-292) and mortality (P = 0·005; odds ratio 1·183; 95% confidence interval 1052-1·331). The rate of symptomatic intracranial haemorrhage was similar in diabetics and non-diabetics (6·7% vs. 4·6%; P = 0·512). Mean admission glucose was higher in patients with symptomatic intracranial haemorrhage than without (8·58 vs. 7·26 mmol/l; P = 0·010). Multivariable analysis confirmed an independent association between admission glucose and symptomatic intracranial haemorrhage (P = 0·027; odds ratio 1·187; 95% confidence interval 1·020-1·381).Diabetes and glucose value on admission did not influence recanalization after intra-arterial thrombolysis; nevertheless, they were independent predictors of poor outcome after intra-arterial thrombolysis and a higher admission glucose value was an independent predictor of symptomatic intracranial haemorrhage. This indicates that factors on the capillary, cellular, or metabolic level may account for the worse outcome in patients with elevated glucose value and diabetes.
Ischaemic stroke
Stroke
Cite
Citations (67)
Objective
To evaluate the effectiveness and safety of ultrasound-enhanced thrombolysis for acute ischemic stroke.
Methods
Fifty stroke patients with acute middle cerebral artery occlusion were randomly divided into either a ultrasound-enhanced thrombolysis group (recombinant tissue-plasminogen activator [rtPA]+ 2 MHz ultrasound monitoring for 2 h) or a standard thrombolysis group (rtPA alone). The demographic characteristics, vascular risk factors, blood pressure before treatment, thrombolysis in brain ischemia (TIBI) grade before thrombosis, and vascular occlusion site of the patients were collected. The primary outcome endpoint was the good outcome rate (defined as the modified Rankin Scale score 0-1) at 3 months. The secondary outcome endpoints were complete recanalization at 2 h after thrombolysis, sustained complete recanalization, symptomatic intracerebral hemorrhage, and mortality.
Results
The good outcome rate of the ultrasound-enhanced thrombolysis group at 3 months after treatment was significantly higher than that of the standard thrombolysis group (64% vs. 36%; P=0.011). The sustained complete recanalization rate (40%vs. 8%; P=0.018) and complete recanalization rate (48% vs. 12%; P=0.012) of the ultrasound-enhanced thrombolysis group were significantly higher than those of the standard thrombolysis group, but there were no significant differences in the reocclusion rate (8% vs. 12%; P=0.637), incidence of symptomatic intracerebral hemorrhage (4% vs. 4%; P=1.000), and mortality (4% vs. 4%; P=1.000) compared with the standard thrombolysis group.
Conclusions
Ultrasound-enhanced thrombolysis can improve the sustained complete recanalization rate, complete recanalization rate, and good outcome rate after using rtPA within 2 h, and it does not increase the risks of symptomatic cerebral hemorrhage and death. It is a safe and effective adjunctive thrombolytic therapy.
Key words:
Stroke; Brain Ischemia; Thrombolytic Therapy; Tissue Plasminogen Activator; Ultrasonic Therapy; Ultrasonography, Doppler, Transcranial; Treatment Outcome
T-plasminogen activator
Stroke
Fibrinolytic agent
Cite
Citations (0)
Stroke
Cite
Citations (9)
To investigate the safety and efficacy of stroke thrombolysis in a local hospital.Historical cohort study.A tertiary hospital in Hong Kong.The outcome of acute ischaemic stroke patients treated with intravenous tissue plasminogen activator between October 2008 and May 2011 was compared to those admitted during the same period who were thrombolysis-eligible, but treated conservatively due to unavailability of the thrombolysis service after-hours.Intravenous tissue plasminogen activator.Primary outcome was functional independence (modified Rankin Scale score of 2 or below) at 3 months. Safety outcomes were symptomatic intracranial haemorrhage and 3-month mortality. Secondary outcomes were hospital length of stay, direct home discharge, and nursing home discharge.A total of 48 thrombolysis and 63 non-thrombolysis patients were identified. Fifty-two percent of the thrombolysis group achieved functional independence compared to 24% of non-thrombolysis group (P=0.003), without significant increase in mortality (15% vs 13%, P=0.51) or symptomatic intracranial haemorrhage (4% vs 2%, P=0.58). Twenty-nine percent of the thrombolysis group patients were discharged home directly, versus 6% of non-thrombolysis group (P<0.001). Mean length of stay was shorter for the thrombolysis group (25 vs 35 days; P=0.034). A similar percentage from each group was discharged to nursing homes.Implementation of the stroke thrombolysis service in Hong Kong appeared safe and efficacious. Patients who received thrombolysis had better outcomes compared to non-thrombolysis cohort. Further studies are needed to investigate the economics of stroke thrombolysis in Hong Kong, which may help to improve funding for provision of this service.
Stroke
Cite
Citations (4)
Background Recent evidence has suggested that intra-arterial thrombolysis may provide benefit beyond intravenous thrombolysis in ischemic stroke patients. Previous meta-analyses have only compared intra-arterial thrombolysis with standard treatment without thrombolysis. The objective was to review the benefits and harms of intra-arterial thrombolysis in ischemic stroke patients. Methods We undertook a meta-analysis of randomized controlled trials comparing the efficacy and safety of intra-arterial thrombolysis with either standard treatment or intravenous thrombolysis following acute ischemic stroke. Primary outcomes included poor functional outcomes (modified Rankin Scale 3–6), mortality, and symptomatic intracranial hemorrhage. Study quality was assessed, and outcomes were stratified by comparison treatment received. Results Four trials (n = 351) comparing intra-arterial thrombolysis with standard treatment were identified. Intra-arterial thrombolysis reduced the risk of poor functional outcomes (modified Rankin Scale 3–6) [relative risk (RR) = 0·80; 95% confidence interval = 0·67–0·95; P = 0·01]. Mortality was not increased (RR = 0·82; 95% confidence interval = 0·56–1·21; P = 0·32); however, risk of symptomatic intracranial hemorrhage was nearly four times more likely (RR = 3·90; 95% confidence interval = 1·41–10·76; P = 0·006). Two trials (n = 81) comparing intra-arterial thrombolysis with intravenous thrombolysis were identified. Intra-arterial thrombolysis was not found to reduce poor functional outcomes(modified Rankin Scale 3–6) (RR = 0·68; 95% confidence interval = 0·46–1·00; P = 0·05). Mortality was not increased (RR = 1·12; 95% confidence interval = 0·47–2·68; P = 0·79); neither was symptomatic intracranial hemorrhage (RR = 1·13; 95% confidence interval = 0·32–3·99; P = 0·85). Differences in time from symptom onset-to-treatment and type of thrombolytic administered were found across the trials. Conclusions This analysis finds a modest benefit of intra-arterial thrombolysis over standard treatment, although it does not find a clear benefit of intra-arterial thrombolysis over intravenous thrombolysis in acute ischemic stroke patients. However, few trials, small sample sizes, and indirectness limit the strength of evidence.
Stroke
Fibrinolytic agent
Cite
Citations (38)
Dramatic changes of blood pressure (BP) were observed in the peripheral thrombolysis period, however, there is no consensus about BP control targets in the different phases.We retrospectively studied a consecutive sample of 510 patients treated with intravenous thrombolysis and followed-up for 3 months. The peripheral thrombolysis period was divided into these phases: Phase 1 (from onset to thrombolysis), Phase 2 (thrombolysis), Phase 3 (from thrombolysis to 24 h after thrombolysis), and Phase 4 (from 24 h to 7 days after thrombolysis). Patients were divided into quintiles according to mean blood pressure in these phases, respectively. Neurological improvement was evaluated using the modified Rankin Scale score at 3-month after thrombolysis.Lower risk of intracerebral hemorrhage within 7 days was found in lower quintiles of SBP (OR = 0.100, 95% CI 0.011-0.887, P = 0.039 in Phase 1 quintile Q1, OR = 0.110, 95% CI 0.012-0.974, P = 0.047 in Phase 2-3 quintile Q1, and OR, 0.175, 95% CI, 0.035-0.872; P = 0.033 in Phase 4 quintile Q2, respectively). Better neurological improvement was found in SBP quintiles: Q2-Q4 (127.3-155.7 mmHg) in Phase 4 (OR = 3.095, 95% CI 1.524-6.286, P = 0.002 for Q2; OR = 2.697, 95% CI 1.354-5.370, P = 0.005 for Q3; and OR = 2.491, 95% CI 1.263-4.913, P = 0.008 for Q4, respectively). Our results also showed higher average real variability of SBP was negatively associated with better neurological outcome in Phase 1 and Phase 2-3.Maintaining SBP levels (≤148 mmHg) from admission to the first 24 h after thrombolysis, then keeping SBP levels (127-138 mmHg) would be beneficial.
Stroke
Cite
Citations (4)
Optimal treatment strategy in patients with mild ischemic stroke remains uncertain. While functional dependency or death has been reported in up to one-third of non-thrombolyzed mild ischemic stroke patients, intravenous thrombolysis is currently not recommended in this patient group. Emerging evidence suggests two risk factors-rapid early improvement and large vessel occlusion-as main associates of unfavorable outcome in mild ischemic stroke patients not undergoing intravenous thrombolysis.To analyze natural course as well as safety and three-month outcome of intravenous thrombolysis in mild ischemic stroke without rapid early improvement or large vessel occlusion.Mild ischemic stroke was defined by a National Institute of Health Stroke Scale score ≤6. We used the modified Rankin Scale (mRS) to compare three-month functional outcome in 370 consecutive mild ischemic stroke patients without early rapid improvement and without large vessel occlusion, who either underwent intravenous thrombolysis (n = 108) or received best medical treatment (n = 262).Favorable outcome (mRS ≤ 1) was common in both groups (intravenous thrombolysis: 91%; no intravenous thrombolysis: 90%). Although intravenous thrombolysis use was independently associated with a higher risk of asymptomatic hemorrhagic transformation (OR = 4.62, p = 0.002), intravenous thrombolysis appeared as an independent predictor of mRS = 0 at three months (OR = 3.33, p < 0.0001).Mild ischemic stroke patients without rapidly improving symptoms and without large vessel occlusion have a high chance of favorable three-month outcome, irrespective of treatment type. Patients receiving intravenous thrombolysis, however, more often achieved complete remission of symptoms, which particularly in mild ischemic stroke may constitute a meaningful endpoint.
Stroke
Cite
Citations (11)