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.

Hospital comparison of stroke care in Sweden: a register-based study.

Background And Purpose: The objective of this study was to estimate the level of health outcomes and resource use at a hospital level during the first year after a stroke, and to identify any potential differences between hospitals after adjusting for patient characteristics (case mix).

Method: Data from several registries were linked on individual level: seven regional patient administrative systems, Swedish Stroke Register, Statistics Sweden, National Board of Health and Welfare and Swedish Social Insurance Agency. The study population consisted of 14 125 patients presenting with a stroke during 2010.

Elevated plasma homocysteine upon ischemic stroke is associated with increased long-term mortality in women.

Background: Ischemic stroke is a leading cause of death worldwide, despite preventive and therapeutic advances during the last twenty years. Blood-borne biomarkers have been studied in association to short- and long-term outcome, in order to investigate possible modifiable predictors of disability and death. Increased homocysteine has been associated with increased vascular risk and unfavorable outcome, but homocysteine lowering treatment has not consistently been successful in risk reduction.

Impaired endothelial function in patients with cryptogenic stroke and patent foramen ovale is not affected by closure.

Introduction: Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS) and migraine with aura (MA). Endothelial dysfunction (ED) is a risk factor for development of cardiovascular disease, but might also be involved in migraine pathophysiology. Short-term worsening of migraine has been described after closure of PFO.

Electrical Bioimpedance Spectroscopy on Acute Unilateral Stroke Patients: Initial Observations regarding Differences between Sides.

Purpose: Electrical Bioimpedance Cerebral Monitoring is assessment in real time of health of brain tissue through study of passive dielectric properties of brain. During the last two decades theory and technology have been developed in parallel with animal experiments aiming to confirm feasibility of using bioimpedance-based technology for prompt detection of brain damage. Here, for the first time, we show that electrical bioimpedance measurements for left and right hemispheres are significantly different in acute cases of unilateral stroke within 24 hours from onset.

Prevalence of migraine headache in an in-patient stroke population.

Introduction: Migraine, especially with aura, is a risk factor for ischemic stroke. In this study, we investigated descriptive data and prevalence of migraine in an in-patient stroke population.

Materials And Methods: Patients with acute cerebrovascular disease (CVD) admitted to the stroke unit during a 6-month period were recruited.

Idiopathic small fiber neuropathy: phenotype, etiologies, and the search for fabry disease.

Background And Purpose: The etiology of small fiber neuropathy (SFN) often remains unclear. Since SFN may be the only symptom of late-onset Fabry disease, it may be underdiagnosed in patients with idiopathic polyneuropathy. We aimed to uncover the etiological causes of seemingly idiopathic SFN by applying a focused investigatory procedure, to describe the clinical phenotype of true idiopathic SFN, and to elucidate the possible prevalence of late-onset Fabry disease in these patients.

High cholesterol levels are associated with improved long-term survival after acute ischemic stroke.

Background: Prior statin treatment and high admission cholesterol have been associated with favorable outcome after ischemic stroke (IS), a paradox not completely explained. The aim of this study was to investigate the effect of admission cholesterol levels and the impact of statin treatment on short- and long-term survival after IS.

Methods: Consecutive patients admitted in 2006 and 2010 were included in the study.

Migraine-related ischemic stroke?

Introduction: Migraine, especially migraine with aura, has been described to be associated with an increased risk for ischemic stroke. An increased incidence of silent lesions in the posterior circulation has also been described.

Method: Six cases with migraine and stroke in close relation over time were retrospectively reviewed.

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies.

Background: Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.

Methods: We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry.

Evolution of microglial activation in ischaemic core and peri-infarct regions after stroke: a PET study with the TSPO molecular imaging biomarker [((11))C]vinpocetine.

Although there is increasing evidence for microglial activation after an ischaemic stroke in the infarct core and the peri-infarct region, the "evolution" of the process in stroke patients is poorly known. Using PET and [((11))C]vinpocetine, we measured the regional changes of TSPO in the brain of nine ischaemic stroke patients up to 14weeks after the insult. Already a week after stroke there was an increased radioligand uptake, indicating the up-regulation of TSPO and the presence of activated microglia, in both the ischaemic core and the peri-infarct zone.

Ischemic stroke and patent foramen ovale: risk factors and genetic profile.

Background: Patent foramen ovale (PFO) is considered to be a risk factor for ischemic cerebrovascular disease (ICVD), especially in young people. However, the potential pathophysiological relevance in ischemic stroke is controversial and in need of further investigation. In this study, we examined the conventional risk factors and the distribution of 100 polymorphisms in 47 suspected susceptibility genes for ICVD in stroke patients with or without a PFO.

Visualising neuroinflammation in post-stroke patients: a comparative PET study with the TSPO molecular imaging biomarkers [11C]PK11195 and [11C]vinpocetine.

With the main objective of comparing the prospective diagnostic power of two 11C-labelled molecular imaging biomarkers with affinity for TSPO and used for the visualisation of activated microglia after a stroke, we measured with positron emission tomography (PET) in four post-stroke patients the regional brain uptake and binding potential of [11C]vinpocetine and [11C]PK11195. Percentage standard uptake values (%SUV) and binding potential (BPND) were used as outcome measures. The total peak brain uptake value and average global brain uptake value were higher for [11C]vinpocetine than for [11C]PK11195.

Common CCR 5 polymorphism in stroke: the CCR 5 delta32 polymorphism differentiates cardioembolism from other aetiologies of ischaemic cerebrovascular diseases.

Inflammation is involved in the development of atherosclerosis. The CC chemokine receptor 5 (CCR5) initiates chemotaxis and modulates the inflammation secondary to atherosclerosis and related vascular diseases. The CCR5 Delta32 polymorphism influences the expression of CCR5 on the cell surface.

A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke.

We expanded our genome-wide association study on atrial fibrillation (AF) in Iceland, which previously identified risk variants on 4q25, and tested the most significant associations in samples from Iceland, Norway and the United States. A variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated significantly with AF (odds ratio OR = 1.21, P = 1.

Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke.

Objective: To find sequence variants that associate with the risk for ischemic stroke (IS), we performed a genome-wide association study.

Methods: We genotyped 1,661 Icelandic IS patients and 10,815 control subjects using the Infinium HumanHap300 chip (Illumina, San Diego, CA). A total of 310,881 single nucleotide polymorphisms (SNPs) were tested for association with IS, and the most significant signals were replicated in two large European IS sample sets (2,224 cases/2,583 control subjects).

ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma.

Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls.

Genetic profile of ischemic cerebrovascular disease and carotid stenosis.

Objectives: Carotid artery stenosis (CS) is a major risk factor for ischemic cerebrovascular disease (ICVD) and is therefore of interest in genetic investigating. Here we report the distribution of 100 polymorphisms in 47 suspected susceptibility genes for ICVD and its risk factors.

Materials And Methods: Previously published markers in suspected susceptibility genes were genotyped in ICVD patients and controls (928/602).

The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm.

Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.

Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients.

With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [(11)C]vinpocetine and [(11)C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage. However, regional BP values for [(11)C]vinpocetine were markedly higher than those for [(11)C]PK11195.

PDE4D and ALOX5AP genetic variants and risk for Ischemic Cerebrovascular Disease in Sweden.

Background: Genetic variants in Phosphodiesterase 4D (PDE4D) and 5-lipoxygenase activating protein (ALOX5AP) have been shown to confer risk of Ischemic Cerebrovascular Disease (ICVD) in Iceland. We investigated whether these variants associate with ICVD in Sweden.

Methods: Previously published PDE4D and ALOX5AP gene variants were genotyped for cases (685) and controls (751).

Variants conferring risk of atrial fibrillation on chromosome 4q25.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans and is characterized by chaotic electrical activity of the atria. It affects one in ten individuals over the age of 80 years, causes significant morbidity and is an independent predictor of mortality. Recent studies have provided evidence of a genetic contribution to AF.

Increased soluble 4-1BB ligand (4-1BBL) levels in peripheral blood of patients with multiple sclerosis.

4-1BB ligand (4-1BBL; CD137L) is a member of the tumour necrosis factor superfamily expressed primarily on antigen presenting cells such as B cells, macrophages and dendritic cells. Its engagement with the receptor 4-1BB (CD137) has been shown to promote T-cell activation and regulate proliferation and survival of T cells. The role of the costimulatory molecule in multiple sclerosis (MS) remains unclear.