Mechanical thrombectomy in acute ischemic stroke—experience from 6 years of practice

INTRODUCTION: We present our results from the first 6 years with mechanical thrombectomy in the treatment of ischemic stroke. METHODS: Every patient treated with mechanical thrombectomy for acute ischemic stroke from September 2005 to December 2011 was consecutively included in this retrospective analysis. Baseline and outcome data were retrieved from computerized records at the hospital. National Institute of Health Stroke Scale (NIHSS) score and the modified Rankin Scale (mRS) score were used as outcome parameters. Favorable outcome was defined as a mRS score of 0–2, corresponding to independence in activities of daily living. We also evaluated revascularization and severe adverse events, with focus on symptomatic intracranial hemorrhage. RESULTS: Good functional outcome (mRS 0–2) was achieved in 50 % (120/240) of all patients. For patients with no neurological deficit prior to stroke onset (i.e., mRS = 0 before stroke), the proportion with good functional outcome was 54 %. Symptomatic hemorrhages occurred in 4.6 % of the cases (5.7 % in the anterior circulation). CONCLUSION: In summary, our results supports that mechanical thrombectomy is a safe and effective method to restore blood flow in selected patients suffering from an acute ischemic stroke

Predictors for cerebral edema in acute ischemic stroke treated with intravenous thrombolysis

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. 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. 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. 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

Carotid Endarterectomy After Intracranial Endovascular Thrombectomy for Acute Ischaemic Stroke in Patients with Carotid Artery Stenosis

Objective: Recent randomised controlled trials demonstrated the benefit of intracranial endovascular thrombectomy (EVT) in acute ischaemic stroke. There is no consensus, however, on how to treat concomitant extracranial carotid artery stenosis after EVT. The aim of this study was to evaluate the outcome in patients treated with carotid endarterectomy (CEA) after EVT, comparing complication rates among patients undergoing CEA for stroke without previous EVT. Methods: This was a registry study of all patients (n = 3 780) treated with CEA after stroke in Sweden and the capital Helsinki region, Finland, from January 2011 to September 2020. Sixty three patients (1.7%; 0.5% 2011, 4.3% 2019) underwent EVT prior to CEA. The primary outcome was 30 day stroke and death rate. Results: The EVT+CEA group had major stroke as the qualifying neurological event (QNE) in 79%, but just 5.9% had this in the CEA only group (p < .001). Intravenous thrombolysis was administered before EVT in 54% of patients in the EVT+CEA group, but in just 12% in those receiving CEA only (p < .001). The combined stroke and death rate at 30 days for EVT+CEA was 0.0% (95% confidence interval [CI] 0.0 - 5.7). One patient had a post-operative TIA, none had post-operative intracerebral or surgical site haemorrhage. CEA was performed within a median of seven days (interquartile range 4, 15) after QNE, and 75% had CEA Conclusion: These results indicate that CEA is safe to perform after previous successful EVT for acute ischaemic stroke. Results were comparable with those undergoing CEA only, despite the EVT+CEA patients having more severe stroke symptoms prior to surgery, and timing was similar.Peer reviewe

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.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The SITS registry is financed directly and indirectly by grants from Karolinska Institutet, Stockholm County Council, the Swedish Heart-Lung Foundation, as well as from an unrestricted sponsorship from Boehringer-Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, and conducted studies supported by EVER Pharma and Ferrer Internacional, as well as in collaboration with Karolinska Institutet, supported by Stryker, Covidien, and Phenox. SITS is currently conducting studies supported by Boehringer-Ingelheim and Biogen. N Ahmed is supported by Stockholm County Council and Swedish Heart-lung Foundation. Irene Escudero-Martínez has received a grant from “Fundación Progreso y Salud, Junta de Andalucía” (grant EF-0437-2018).Peer reviewe

Global Expression Profiling in Atopic Eczema Reveals Reciprocal Expression of Inflammatory and Lipid Genes

Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood.We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE.Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. We found a significant enrichment of differentially expressed genes in AE with cytobands associated to the disease, and furthermore new chromosomal regions were found that could potentially guide future region-specific linkage mapping in AE. The full data set is available at http://microarray-pubs.stanford.edu/eczema

Mechanisms of thrombosis and restenosis after vascular injury

Atherosclerosis is the underlying cause of about 50% of all deaths in the western world. Peripheral vascular disease commonly affects the arteries supplying the leg and is mostly caused by atherosclerosis. When medical treatment of lower extremity ischemia has failed, percutaneous transluminal angioplasty (PTA) and bypass surgery are two major therapeutic options. The advances in vascular surgery and endovascular techniques over the past half-century have greatly expanded the number of arterial lesions that can be treated. The major limitations of a successful revascularisation are thrombosis and the later development of restenosis. This thesis has explored the mechanisms of thrombosis and restenosis after vascular injury, focusing on the interaction between coagulation, inflammation, and oxidative stress. The long-term outcome of infrainguinal PTA was evaluated in 77 patients. Cumulative primary and secondary patency rates, respectively, were 81% and 86% at 1 year, 65% and 73% at 5 years, and 12% and 17% at 10 years. Patency rates were better for patients with claudication than critical ischemia. Stenoses had better primary patency than occlusions. Generalised femoral artery disease and diabetes mellitus predicted poor survival. Although the overall long-term patency of infrainguinal PTA is poor, the technique has a low morbidity and can be performed in selected patients with a reasonable long-term result. If conservative treatment has failed infrainguinal PTA should be considered, when lesions and patients are suitable, because of its minimal invasive nature. It is also important when treating patients with peripheral arterial disease to give attention to their general cardiovascular condition. In an experimental study a specific direct thrombin inhibitor, inogatran, reduced neointimal hyperplasia after arterial injury in rats. A more prolonged administration of the thrombin inhibitor gave a further reduction of the neointimal hyperplasia. It seems that inhibition of thrombin activity is not only important early after injury, but also later. This could have clinical implications in the treatment of restenosis. Inflammation and oxidative stress in the vessel wall may play important roles in the development of restenosis after angioplasty. In patients with peripheral arterial disease, a much more prolonged inflammatory response than previously noted was observed after angioplasty, but only minor changes in coagulation activity. C-reactive protein was elevated the day after angioplasty and peaked after one week. Coagulation and inflammatory markers were not significantly related to restenosis. The redox-active protein, thioredoxin, was significantly elevated 4 hours after angioplasty and returned to baseline within 24 hours. Circulating thioredoxin could theoretically impair the chemotactic response at local sites of inflammation. An association in patients with elevated levels of thioredoxin after angioplasty and reduced restenosis needs to be further evaluated. This thesis has discussed the intimate relation between thrombosis, inflammation, oxidative stress, and restenosis. Further studies are needed to delineate the molecular mechanisms behind these observations and their involvement in thrombosis and restenosis. It is not only important to be able to understand the individual pathways of these processes, but also the ways they intersect and interact. If these pathways are further defined, improved treatment strategies, including antithrombotic treatments, statins, and thioredoxin, to modulate postprocedure inflammation could be tailored