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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.

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 128.5 mg/dL (RR, 1.21), and decreased level of consciousness (RR, 1.14) were associated with moderate/severe CED (for all P

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 hours. 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 hours, 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 Conclusions – 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.

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.

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 P P P 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.

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.

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. 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. 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

About the meeting: The purpose of the European Stroke Organisation (ESO)-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. Several scientific sessions discussed in the meeting and each session produced consensus statements. The meeting started 20 years ago as Karolinska Stroke Update, but since 2014, it is a joint conference with ESO. Importantly, it provides a platform for discussion on the ESO guidelines process and on recommendations to the ESO 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 guidelines 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. The ESO-Karolinska Stroke Update consensus statement and recommendations will be published every 2 years and it will work as implementation of ESO-guidelines Background This year’s ESO-Karolinska Stroke Update Meeting was held in Stockholm on 13–15 November 2016. There were 10 scientific sessions discussed in the meeting and each session produced a consensus statement ( Full version with background, issues, conclusions and references are published as web-material and at http://www.eso-karolinska.org/2016 and http://eso-stroke.org ) and recommendations which were prepared by a writing committee consisting of session chair(s), secretary and speakers and presented to the 312 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.

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 ≥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.

• Carnivory in plants is restricted to nutrient-poor and open habitats presumably because of high benefits and/or low costs of carnivory in these conditions. Carnivory is costly because the plants need specific adaptations to capture prey. Drosera rotundifolia produces sticky substances on its leaf surface to catch prey. These substances are primarily carbon-based, and their production can be expected to be lower in shade. The benefit of carnivory is in terms of the increased nutritional gain which will be low when inorganic nutrients are available in the growth medium. We expected that investment in carnivory would be lower in shade and nutrient-rich conditions. • A factorial experiment involving shading and the addition of inorganic nutrients confirmed these predictions in the carnivorous, perennial herb D. rotundifolia. • Plants growing in shade or in media with nutrients added had less sticky leaves and had reduced their investment in carnivory. • Interestingly, the observed changes in the stickiness of the leaves were in accord with the carbon/nutrient balance theory, whereas a carbon-based secondary compound, 7-methyljuglone, in the leaves did not respond to shading or nutrient addition.

1 The effect of supplementary feeding on growth and reproduction of three carnivorous plants species was investigated over a 6-year period. Pinguicula alpina, P. villosa and P. vulgaris populations growing at two altitudes in a subarctic environment were fed with fruit flies (Drosophila melanogaster). 2 Fed plants increased in size relative to control plants during the first years. Subsequently a stable size difference between feeding levels was established. The weight of the over-wintering part was higher in fed plants than in control plants. 3 The flowering frequency (i.e. proportion of plants in a population carrying flowers) was also higher in the fed plants. The proportion of flowering plants increased in the feeding treatment compared to control plants during more-or-less the whole experimental feeding period (5–6 years). Seed production also increased slowly in response to feeding. 4 No feeding effect on nitrogen and phosphorus concentrations in seeds and over-wintering parts was found. 5 In most characteristics the high-altitude populations were less responsive than populations growing at low altitude. In the high-altitude population reproduction failed repeatedly, suggesting that seed output may be more dependent on abiotic factors than on resource availability in cold environments. 6Pinguicula villosa and P. vulgaris used the new resources the same summer for increased leaf rosette growth and current reproduction, showing these species to be income breeders, while the third species (P. alpina) allocated a larger proportion to storage and future reproduction, characteristic of a capital breeder.

We estimated the cost of reproduction and reproductive effort in three iteroparous plant species, Pinguicula alpina, P. villosa and P. vulgaris, in a subarctic environment. The phenotypic costs of reproduction were quantified by comparing resource pools (dry weight, nitrogen or phosphorus) in reproductive and non-reproductive plants. Two types of non-reproductive plants were used; plants whose reproductive parts had been removed (RR) at the start of the growing season and naturally non-reproductive plants (NR). The reproductive effort was calculated as the resources invested in reproduction in relation to the total resource pool (somatic + reproductive parts). For P. vulgaris the amount of resources available was manipulated by feeding plants with insects and/or by leaf removal in a factorial design. A somatic cost of reproduction was found for all species and treatments since reproductive plants had smaller somatic resource pools than non-reproductive plants (both RR and NR). The total resource pool was higher in reproductive plants than in non-reproductive plants. Due to this difference, the reproductive effort exceeded the somatic cost of reproduction. This suggests that mechanisms may exist for decreasing the cost of reproduction. Mechanisms that potentially could explain the discrepancy between reproductive effort and the somatic cost are discussed.