Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study - the importance of comprehensive clinical evaluation.

BACKGROUND: Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management. METHODS: Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis. RESULTS: After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA2DS2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091). CONCLUSION: Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.

Atrial fibrillation in cryptogenic stroke and TIA patients in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Main results.

Introduction: Secondary stroke prevention depends on proper identification of the underlying etiology and initiation of optimal treatment after the index event. The aim of the NOR-FIB study was to detect and quantify underlying atrial fibrillation (AF) in patients with cryptogenic stroke (CS) or transient ischaemic attack (TIA) using insertable cardiac monitor (ICM), to optimise secondary prevention, and to test the feasibility of ICM usage for stroke physicians. Patients and methods: Prospective observational international multicenter real-life study of CS and TIA patients monitored for 12 months with ICM (Reveal LINQ) for AF detection. Results: ICM insertion was performed in 91.5% by stroke physicians, within median 9 days after index event. Paroxysmal AF was diagnosed in 74 out of 259 patients (28.6%), detected early after ICM insertion (mean 48 ± 52 days) in 86.5% of patients. AF patients were older (72.6 vs 62.2; p < 0.001), had higher pre-stroke CHA2DS2-VASc score (median 3 vs 2; p < 0.001) and admission NIHSS (median 2 vs 1; p = 0.001); and more often hypertension (p = 0.045) and dyslipidaemia (p = 0.005) than non-AF patients. The arrhythmia was recurrent in 91.9% and asymptomatic in 93.2%. At 12-month follow-up anticoagulants usage was 97.3%. Discussion and conclusions: ICM was an effective tool for diagnosing underlying AF, capturing AF in 29% of the CS and TIA patients. AF was asymptomatic in most cases and would mainly have gone undiagnosed without ICM. The insertion and use of ICM was feasible for stroke physicians in stroke units.

Headache, migraine and cardiovascular risk factors: the HUNT study.

BACKGROUND: Migraine with aura (MA) has been found to be a risk factor for cardiovascular disease including ischaemic stroke and myocardial infarction. Studies have also reported a higher prevalence of unfavourable cardiovascular risk factors amongst migraineurs, but results have been conflicting as to whether this is restricted to MA or also holds true for migraine without aura (MO). This study aims to examine the relation between headache and cardiovascular risk factors in a large cross-sectional population-based study. METHODS: A total of 48,713 subjects (age ≥ 20 years) completed a headache questionnaire and were classified according to the headache status in the Nord-Trøndelag Health Study in Norway 1995-1997 (HUNT 2). Framingham 10-year risk for myocardial infarction and coronary death could be calculated for 44,098 (90.5%) of these. Parameters measured were blood pressure, body mass index, serum total and high-density lipoprotein cholesterol. RESULTS: Compared to controls, Framingham risk score was elevated in non-migraine headache sufferers (OR 1.17, 95% CI 1.10-1.26), migraineurs without aura (OR 1.17, 95% CI 1.04-1.32) and most pronounced amongst migraineurs with aura (OR 1.54, 95% CI 1.21-1.95). Framingham risk score consistently increased with headache frequency. For non-migrainous headache and MO, the increased risk was accounted for by the lifestyle factors smoking, high BMI and low physical activity, whilst such factors did not explain the elevated risk associated with MA. CONCLUSIONS: Both MA, MO and non-migrainous headache are associated with an unfavourable cardiovascular risk profile, but different mechanisms seem to underlie the elevated risk in MA than in the other headache types.

European Stroke Organisation (ESO) standard operating procedure for the preparation and publishing of guidelines.

The first European Stroke Organization (ESO) standard operating procedure (SOP) published in 2015 aimed at the implementation the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to provide evidence-based guidelines for stroke management. This second ESO-SOP is aiming at further increase of the practicability of ESO guidelines and its technical implications. Authors comprised of the members of the ESO guideline Board and ESO Executive Committee. The final document was agreed on by several internal reviews. The second SOP comprises of the following aspects: rational for the SOP, the introduction of expert consensus statements, types of guideline documents, structures involved and detailed description of the guideline preparation process, handling of financial and intellectual conflicts of interest (CoI), involvement of ESO members in the guideline process, review process, authorship and publication policy, updating of guidelines, cooperation with other societies, and dealing with falsified data. This second SOP supersedes the first SOP published in 2015.

Imaging of Patients with Suspected Large-Vessel Occlusion at Primary Stroke Centers: Available Modalities and a Suggested Approach.

The overwhelming benefit of endovascular therapy in patients with large-vessel occlusions suggests that more patients will be screened than treated. Some of those patients will be evaluated first at primary stroke centers; this type of evaluation calls for standardizing the imaging approach to minimize delays in assessing, transferring, and treating these patients. Here, we propose that CT angiography (performed at the same time as head CT) should be the minimum imaging approach for all patients with stroke with suspected large-vessel occlusion presenting to primary stroke centers. We discuss some of the implications of this approach and how to facilitate them.

Comorbidity of headache and gastrointestinal complaints. The Head-HUNT Study.

Associations between headache, including migraine, and gastrointestinal (GI) symptoms were studied in a large questionnaire-based cross-sectional study (the Head-HUNT Study). The headache questionnaire was completed by 43,782 individuals, who answered all the questions concerning nausea, reflux symptoms, diarrhoea and constipation. In the multivariate analyses, adjusting for age, sex, educational level, medication use, depression and anxiety, a higher prevalence of headache was found in individuals with much reflux [odds ratio (OR) 2.4, 95% confidence interval (CI) 2.2, 2.6], diarrhoea (OR 2.4, 95% CI 2.1, 2.8), constipation (OR 2.1, 95% CI 1.9, 2.4) and nausea (OR 3.2, 95% CI 2.6, 3.8) compared with those without such complaints. All the GI symptoms investigated seemed to be approximately as common among persons with non-migrainous headache as among migraine sufferers, but the association between headache and GI complaints increased markedly with increasing headache frequency. This may suggest that headache sufferers generally are predisposed to GI complaints.

Headache prevalence related to diabetes mellitus. The Head-HUNT study.

In patients with diabetes mellitus (DM), there are changes in vascular reactivity and nerve conduction that may be relevant for migraine pathophysiology. However, previous studies on the relationship between headache and DM have shown conflicting results. The aim of the present study was to investigate a possible association between headache and DM in a large population-based cross-sectional study. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CIs). Prevalence OR of migraine was lower amongst persons with DM compared with those without DM, the OR being 0.4 (95% CI: 0.2-0.9) for type 1 and 0.7 (95% CI: 0.5-0.9) for type 2 DM. Furthermore, OR of headache were lower amongst those with duration of DM > or = 13 years compared with those who had got DM the last 3 years, OR 0.6 (95% CI: 0.4-0.9). The analyses revealed no clear associations between non-migrainous headache and DM. The reason for the inverse relationship between migraine and DM is unknown, but might be related to pathophysiological abnormalities in patients with DM that protect against migraine.

Headache prevalence related to smoking and alcohol use. The Head-HUNT Study.

The aim of this study was to examine a possible association between smoking, alcohol and headache in a large population-based cross-sectional study. A total of 51,383 subjects completed a headache questionnaire and constituted the 'Head-HUNT' Study. Questionnaire-based information on smoking was available in 95% and on alcohol in 89% of the individuals. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CI). Prevalence rates for headache were higher amongst smokers compared with never smokers, most evident for those under 40 years smoking more than 10 cigarettes per day (OR 1.5, 95% CI 1.3-1.6). Passive smoking was also associated with higher headache prevalence. For alcohol use, there was a tendency of decreasing prevalence of migraine with increasing amounts of alcohol consumption compared with alcohol abstinence. Only with regard to symptoms indicating alcohol overuse, a positive association with frequent headache was found. The association between headache and smoking found in the present study raises questions about a causal relationship, e.g. that smoking causes headache or that it allays stress induced by headache. The observed negative association between migraine and alcohol consumption is probably explained by the headache precipitating properties of alcohol.

Patient selection for intra-arterial cerebral revascularization in acute ischemic stroke.

In acute ischemic stroke, rapid revascularization of the cerebral 'penumbra volume' is the key to better patient outcome. The largest and most proximal cerebral thrombotic artery occlusions can in most cases only be opened by intra-arterial intervention. The use of intra-arterial revascularization is rapidly expanding throughout Europe and North America, despite the risk for serious complications and the fact that the benefit of this treatment has not yet been proven in large, randomized clinical trials. Oslo University Hospital has performed approximately 60 intra-arterial procedures annually in acute ischemic stroke during the last few years. In this paper, we discuss important clinical and ethical aspects learned from our own experience. The future of intra-arterial cerebral revascularization will depend on an accurate preintervention patient selection.

Reproducibility of indoor environment characteristics obtained in a walk through questionnaire. A pilot study.

Walk through questionnaires may be feasible tools to obtain data on the indoor environment in community studies. However, limited information is available regarding the reproducibility of the data obtained through these questionnaires. In this pilot study, two construction engineering students inspected ten dwellings twice by means of a standardized walk through questionnaire. The two engineering students inspected the dwellings independent of each other within two months. Time between the two visits varied between 14 and 40 days. The variables presented were based on information from the residents and inspection. The continuous variables recorded included number of rooms in the dwellings, room volume, length of filled shelves and textile area. The inter- and intra-observed variabilities were poorer for number of rooms and shelf factor than for the other variables. For the 3 of the 9 categorical variables based on inspection, the inter-observer comparison showed complete agreement with a kappa statistics of 1.0, these variables being condition of the window frames and construction of outside walls and roof. One of the categorical variables showed a kappa statistics of < 0.5, these variables being presence of basement and presence of condensation at windows. This study indicates a wide variation in observer variability between various items of a walk through questionnaire. Clear definitions of all the parts of the questionnaire are needed, as well as thorough training of observers.

Headache prevalence related to haemoglobin and ferritin. The HUNT Study.

As clinic-based studies show an association between headache and both high and low levels of haemoglobin, we analysed this relationship in a population-based cross-sectional study (the HUNT Study). A total of 2385 women aged 20-55 years responded to a headache questionnaire and gave blood samples for measuring haemoglobin and ferritin. In the multivariate analyses, adjusting for age and education, there was a linear trend of decreasing prevalence of headache (P = 0.02) and migraine (P = 0.01) with decreasing haemoglobin. In particular, migraine was less likely among women with low haemoglobin (values < 11.5 g/dl) (odds ratio 0.4, confidence interval 0.2, 0.9). There was no correlation between headache prevalence and ferritin. The present findings may be relevant for the headache reported in polycythaemia and chronic altitude sickness.