Reperfusion by endovascular thrombectomy and early cerebral edema in anterior circulation stroke: Results from the SITS-International Stroke Thrombectomy Registry.

BACKGROUND: A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. There is still conflicting evidence whether reperfusion is associated with a lower risk for CED in acute ischemic stroke. AIM: To investigate the association of reperfusion with development of early CED after stroke thrombectomy. METHODS: From the SITS-International Stroke Thrombectomy Registry, we selected patients with occlusion of the intracranial internal carotid or middle cerebral artery (M1 or M2). Successful reperfusion was defined as mTICI ⩾ 2b. Primary outcome was moderate or severe CED, defined as focal brain swelling ⩾1/3 of the hemisphere on imaging scans at 24 h. We used regression methods while adjusting for baseline variables. Effect modification by severe early neurological deficits, as indicators of large infarct at baseline and at 24 h, were explored. RESULTS: In total, 4640 patients, median age 70 years and median National Institutes of Health Stroke Score (NIHSS) 16, were included. Of these, 86% had successful reperfusion. Moderate or severe CED was less frequent among patients who had reperfusion compared to patients without reperfusion: 12.5% versus 29.6%, p < 0.05, crude risk ratio (RR) 0.42 (95% confidence interval (CI): 0.37-0.49), and adjusted RR 0.50 (95% CI: 0.44-0.57). Analysis of effect modification indicated that severe neurological deficits weakened the association between reperfusion and lower risk of CED. The RR reduction was less favorable in patients with severe neurological deficits, defined as NIHSS score 15 or more at baseline and at 24 h, used as an indicator for larger infarction. CONCLUSION: In patients with large artery anterior circulation occlusion stroke who underwent thrombectomy, successful reperfusion was associated with approximately 50% lower risk for early CED. Severe neurological deficit at baseline seems to be a predictor for moderate or severe CED also in patients with successful reperfusion by thrombectomy.

Association of cholesterol levels with hemorrhagic transformation and cerebral edema after reperfusion therapies.

Background: The association between cholesterol levels and cerebral edema (CED) or hemorrhagic transformation (HT) as an expressions of blood-brain barrier (BBB) dysfunction after ischemic stroke is not well established. The aim of this study is to determine the association of total cholesterol (TC) levels with the incidence of HT and CED after reperfusion therapies. Methods: We analyzed SITS Thrombolysis and Thrombectomy Registry data from January 2011 to December 2017. We identified patients with data on TC levels at baseline. TC values were categorized in three groups (reference group ⩾200 mg/dl). The two primary outcomes were any parenchymal hemorrhage (PH) and moderate to severe CED on follow up imaging. Secondary outcomes included death and functional independence (mRS 0-2) at 3 months. Multivariable logistic regression analysis adjusted for baseline factors including statin pretreatment was used to assess the association between TC levels and outcomes. Results: Of 35,314 patients with available information on TC levels at baseline, 3372 (9.5%) presented with TC levels ⩽130 mg/dl, 8203 (23.2%) with TC 130-200 mg/dl and 23,739 (67.3%) with TC ⩾ 200 mg/dl. In the adjusted analyses, TC level as continuous variable was inversely associated with moderate to severe CED (OR 0.99, 95% CI 0.99-1.00, p = 0.025) and as categorical variable lower TC levels were associated with a higher risk of moderate to severe CED (aOR 1.24, 95% CI 1.10-1.40, p = 0.003). TC levels were not associated with any PH, functional independence, and mortality at 3 months. Conclusions: Our findings indicate an independent association between low levels of TC and higher odds of moderate/severe CED. Further studies are needed to confirm these findings.

Cerebral Edema in Patients with severe Hemispheric Syndrome: Incidence, Risk Factors, and Outcomes-Data from SITS-ISTR.

BACKGROUND AND PURPOSE: Cerebral edema (CED) in ischemic stroke can worsen prognosis and about 70% of patients who develop severe CED die if treated conservatively. We aimed to describe incidence, risk factors and outcomes of CED in patients with extensive ischemia. METHODS: Oservational study based on Safe Implementation of Treatments in Stroke-International Stroke Treatment Registry (2003-2019). Severe hemispheric syndrome (SHS) at baseline and persistent SHS (pSHS) at 24 hours were defined as National Institutes of Health Stroke Score (NIHSS) >15. Outcomes were moderate/severe CED detected by neuroimaging, functional independence (modified Rankin Scale 0-2) and death at 90 days. RESULTS: Patients (n=8,560) presented with SHS and developed pSHS at 24 hours; 82.2% received intravenous thrombolysis (IVT), 10.5% IVT+thrombectomy, and 7.3% thrombectomy alone. Median age was 77 and NIHSS 21. Of 7,949 patients with CED data, 3,780 (47.6%) had any CED and 2,297 (28.9%) moderate/severe CED. In the multivariable analysis, age <50 years (relative risk [RR], 1.56), signs of acute infarct (RR, 1.29), hyperdense artery sign (RR, 1.39), blood glucose >128.5 mg/dL (RR, 1.21), and decreased level of consciousness (RR, 1.14) were associated with moderate/severe CED (for all P<0.05). Patients with moderate/severe CED had lower odds to achieve functional Independence (adjusted odds ratio [aOR], 0.35; 95% confidence interval [CI], 0.23 to 0.55) and higher odds of death at 90 days (aOR, 2.54; 95% CI, 2.14 to 3.02). CONCLUSIONS: In patients with extensive ischemia, the most important predictors for moderate/ severe CED were age <50, high blood glucose, signs of acute infarct, hyperdense artery on baseline scans, and decreased level of consciousness. CED was associated with worse functional outcome and a higher risk of death at 3 months.

Effect of Recanalization on Cerebral Edema in Ischemic Stroke Treated With Thrombolysis and/or Endovascular Therapy.

Background and Purpose- A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. Reperfusion may cause blood-brain barrier disruption and a risk for cerebral edema and secondary parenchymal hemorrhage (PH). We aimed to investigate the effect of recanalization on development of early CED and PH after recanalization therapy. Methods- From the SITS-International Stroke Treatment Registry, we selected patients with signs of artery occlusion at baseline (either Hyperdense Artery Sign or computed tomography/magnetic resonance imaging angiographic occlusion). We defined recanalization as the disappearance of radiological signs of occlusion at 22 to 36 hours. Primary outcome was moderate to severe CED and secondary outcome was PH on 22- to 36-hour imaging scans. We used logistic regression with adjustment for baseline variables and PH. Results- Twenty two thousand one hundred eighty-four patients fulfilled the inclusion criteria (n=18 318 received intravenous thrombolysis, n=3071 received intravenous thrombolysis+thrombectomy, n=795 received thrombectomy). Recanalization occurred in 64.1%. Median age was 71 versus 71 years and National Institutes of Health Stroke Scale score 15 versus 16 in the recanalized versus nonrecanalized patients respectively. Recanalized patients had a lower risk for CED (13.0% versus 23.6%), adjusted odds ratio (aOR), 0.52 (95% CI, 0.46-0.59), and a higher risk for PH (8.9% versus 6.5%), adjusted odds ratio, 1.37 (95% CI, 1.22-1.55), than nonrecanalized patients. Conclusions- In patients with acute ischemic stroke, recanalization was associated with a lower risk for early CED even after adjustment for higher rate for PH in recanalized patients.

Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018.

The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at www.eso-karolinska.org and http://eso-stroke.org) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.

Predictors for Cerebral Edema in Acute Ischemic Stroke Treated With Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: Cerebral edema (CED) is a severe complication of acute ischemic stroke. There is uncertainty regarding the predictors for the development of CED after cerebral infarction. We aimed to determine which baseline clinical and radiological parameters predict development of CED in patients treated with intravenous thrombolysis. METHODS: We used an image-based classification of CED with 3 degrees of severity (less severe CED 1 and most severe CED 3) on postintravenous thrombolysis imaging scans. We extracted data from 42 187 patients recorded in the SITS International Register (Safe Implementation of Treatments in Stroke) during 2002 to 2011. We did univariate comparisons of baseline data between patients with or without CED. We used backward logistic regression to select a set of predictors for each CED severity. RESULTS: CED was detected in 9579/42 187 patients (22.7%: 12.5% CED 1, 4.9% CED 2, 5.3% CED 3). In patients with CED versus no CED, the baseline National Institutes of Health Stroke Scale score was higher (17 versus 10; P<0.001), signs of acute infarct was more common (27.9% versus 19.2%; P<0.001), hyperdense artery sign was more common (37.6% versus 14.6%; P<0.001), and blood glucose was higher (6.8 versus 6.4 mmol/L; P<0.001). Baseline National Institutes of Health Stroke Scale, hyperdense artery sign, blood glucose, impaired consciousness, and signs of acute infarct on imaging were independent predictors for all edema types. CONCLUSIONS: The most important baseline predictors for early CED are National Institutes of Health Stroke Scale, hyperdense artery sign, higher blood glucose, decreased level of consciousness, and signs of infarct at baseline. The findings can be used to improve selection and monitoring of patients for drug or surgical treatment.

Predictive factors for decompressive hemicraniectomy in malignant middle cerebral artery infarction.

BACKGROUND: The mortality rate of patients with brain oedema after malignant middle cerebral artery (MCA) infarction approaches 80 % without surgical intervention. Surgical treatment with ipsilateral decompressive hemicraniectomy (DHC) has been shown to dramatically improve survival rates. DHC currently lacks established inclusion criteria and additional research is needed to assess the impact of prognostic factors on functional outcome. The aim of this study was to assess the impact of prognostic factors on functional outcome. METHOD: A retrospective cohort study was carried out including 46 patients who underwent DHC at the Karolinska University Hospital between 2004 and 2014. The maximum time to surgery was 5 days after symptom debut. The primary endpoint was a dichotomised score on the modified Rankin Scale (mRS) 3 months after surgery, with favourable outcome defined as mRS ≤ 4. RESULTS: When the study population was dichotomised according to the primary endpoint, a significant difference between the groups was seen in preoperative Glasgow Coma Score (GCS), blood glucose levels and the infarction's involvement of the basal ganglia (p < 0.05). In a logistic regression model, preoperative GCS contributed significantly with a 59.6 % increase in the probability of favourable outcome for each point gained in preoperative GCS (p = 0.035). CONCLUSIONS: The results indicate that preoperative GCS, blood glucose and the infarction's involvement of the basal ganglia are strong predictors of clinical outcome. These factors should be considered when assessing the probable outcome of DHC, and additional research based on these factors may contribute to improved inclusion criteria for DHC.

Hyperdense middle cerebral artery sign on admission CT scan--prognostic significance for ischaemic stroke patients treated with intravenous thrombolysis in the safe implementation of thrombolysis in Stroke International Stroke Thrombolysis Register.

BACKGROUND: Hyperdense middle cerebral artery sign (HMCAS) on CT scan before stroke thrombolysis is associated with increased risk for haemorrhage and unfavourable outcome in several small studies. METHODS: We examined baseline characteristics, intracranial haemorrhage and outcomes of intravenous thrombolysis in patients with and without HMCAS using the internet-based Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. Symptomatic intracerebral haemorrhage (SICH) was defined as a National Institute of Health Stroke Scale (NIHSS) score decrease of >or=4 points plus type 2 parenchymal haemorrhage on imaging [Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST) definition], or any haemorrhage on follow-up imaging combined with a decrease of at least 1 point on the NIHSS [randomized controlled trial (RCT) definition]. Three-month outcomes were mortality and independence (modified Rankin scale score = 0-2). RESULTS: 1,905 of 10,023 (19.0%) patients had HMCAS. Patients with HMCAS (vs. no HMCAS) were younger (median age 68 vs. 70 years, p < 0.001), had severer stroke (baseline NIHSS score 17 vs. 11, p < 0.05), higher mortality [23% (95% CI 20.0-25.1) vs. 13% (95% CI 12.1-13.7)] and lower independence [31% (95% CI 28.5-33.0) vs. 56% (95% CI 54.8-57.2)]. SICH rates per the SITS-MOST were 1.3% (95% CI 0.8-1.9) versus 1.8% (95% CI 1.5-2.1) and per the RCT definition 10.3% (95% CI 9.0-11.8) versus 6.8% (95% CI 6.2-7.3). In multivariable analysis, HMCAS was not an independent predictor of SICH but of mortality and independence per the SITS-MOST. CONCLUSIONS: HMCAS patients had severer stroke and a worse 3-month outcome. The risk for SICH per the SITS-MOST definition was similar compared to non-HMCAS patients, although increased per the RCT definition. There is not sufficient evidence to exclude these patients from intravenous thrombolysis. Combined treatment approaches might be considered in the perspective of the severe outcome and evaluated in RCTs.