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Stroke is the second leading cause of death and dependency in Europe and costs the European Union more than €30bn, yet significant gaps in the patient pathway remain and the cost‐effectiveness of comprehensive stroke care to meet these needs is unknown. The European Brain Council Value of Treatment Initiative combined patient representatives, stroke experts, neurological societies and literature review to identify unmet needs in the patient pathway according to Rotterdam methodology. The cost‐effectiveness of comprehensive stroke services was determined by a Markov model, using UK cost data as an exemplar and efficacy data for prevention of death and dependency from published systematic reviews and trials, expressing effectiveness as quality‐adjusted life‐years (QALYs). Model outcomes included total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost‐effectiveness ratio (ICER). Key unmet needs in the stroke patient pathway included inadequate treatment of atrial fibrillation (AF), access to neurorehabilitation and implementation of comprehensive stroke services. In the Markov model, full implementation of comprehensive stroke services was associated with a 9.8% absolute reduction in risk of death of dependency, at an intervention cost of £9566 versus £6640 for standard care, and long‐term care costs of £35 169 per 5.1251 QALYS vs. £32 347.40 per 4.5853 QALYs, resulting in an ICER of £5227.89. Results were robust in one‐way and probabilistic sensitivity analyses. Implementation of comprehensive stroke services is a cost‐effective approach to meet unmet needs in the stroke patient pathway, to improve acute stroke care and support better treatment of AF and access to neurorehabilitation. [ABSTRACT FROM AUTHOR]

Background and purpose: Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. Methods: This was a post hoc analysis of the randomized, placebo‐controlled WAKE‐UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0–1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. Results: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64 years; p < 0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p = 0.0007). A comorbidity load defined by a CCI score ≥ 2 was more frequent in patients with polypharmacy (48% vs. 8%; p < 0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30–0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29). Conclusion: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase. [ABSTRACT FROM AUTHOR]

Background and purpose Acute lesions in patients with transient ischaemic attack (TIA) are important as they are associated with increased risk for recurrence. Characteristics associated with acute lesions in young TIA patients were therefore investigated. Methods The sifap1 study prospectively recruited a multinational European cohort ( n = 5023) of patients aged 18-55 years with acute cerebrovascular event. The detection of acute ischaemic lesions was based on diffusion-weighted imaging (DWI). The frequency of DWI lesions was assessed in 829 TIA patients who met the criteria of symptom duration <24 h and their association with demographic, clinical and imaging variables was analysed. Results The median age was 46 years (interquartile range 40-51 years); 45% of the patients were female. In 121 patients (15%) ≥1 acute DWI lesion was detected. In 92 patients, DWI lesions were found in the anterior circulation, mostly located in cortical-subcortical areas ( n = 63). Factors associated with DWI lesions in multiple regression analysis were left hemispheric presenting symptoms [odds ratio (OR) 1.92, 95% confidence interval (CI) 1.27−2.91], dysarthria (OR 2.17, 95% CI 1.38−3.43) and old brain infarctions on MRI (territories of the middle and posterior cerebral artery: OR 2.43, 95% CI 1.42−4.15; OR 2.41, 95% CI 1.02−5.69, respectively). Conclusions In young patients with a clinical TIA 15% demonstrated acute DWI lesions on brain MRI, with an event pattern highly suggestive of an embolic origin. Except for the association with previous infarctions there was no clear clinical predictor for acute ischaemic lesions, which indicates the need to obtain MRI in young individuals with TIA. [ABSTRACT FROM AUTHOR]

Background and purpose Our aim was to investigate whether pulsatile tinnitus ( PT) in cervical artery dissection (Ce AD) has prognostic significance. Methods All Ce AD patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study with documentation of PT were analysed. The presence of PT was systematically assessed using a standardized questionnaire. Stroke severity at admission was defined according to the National Institutes of Health Stroke Scale ( NIHSS). Excellent outcome after 3 months was defined as a modified Rankin Scale of 0-1. Results Sixty-three of 778 patients (8.1%) reported PT. PT+ patients presented less often with ischaemic stroke (41.3% vs. 63.9%, P < 0.001), more often with dissection in the internal carotid artery (85.7% vs. 64.2%, P = 0.001), less often with vessel occlusion (19.0% vs. 34.1%, P = 0.017) and more often with excellent outcome at 3 months (92.1% vs. 75.4%, P = 0.002). Logistic regression analysis identified PT as an independent predictor of excellent outcome after 3 months [odds ratio ( OR) 3.96, 95% confidence interval ( CI) 1.22-12.87] adjusted to significant outcome predictors NIHSS on admission ( OR 0.82, 95% CI 0.79-0.86), Horner syndrome ( OR 1.95, 95% CI 1.16-3.29) and vessel occlusion ( OR 0.62, 95% CI 0.40-0.94) and to non-significant predictors age, sex, pain and location of Ce AD. Conclusion The presence of PT in Ce AD is associated with a benign clinical course and predicts a favourable outcome. [ABSTRACT FROM AUTHOR]

Background and purpose To investigate the association of anemia on admission with ischaemic stroke ( IS), stroke severity and early functional outcome in patients with cervical artery dissection (Ce AD) or with IS of other causes (non-Ce AD- IS patients). Methods The study sample comprised all patients from the Cervical Artery Dissection and Ischaemic Stroke Patients ( CADISP) study without pre-existing disability and with documentation of stroke severity and hemoglobin (Hb) concentration on admission. Anemia was classified as mild (Hb < 12 g/dl in women and Hb < 13 g/dl in men) or moderate to severe (Hb < 10 g/dl in women and Hb < 11 g/dl in men). Stroke severity on admission was assessed with the National Institutes of Health Stroke Scale ( NIHSS). Outcome after 3 months was assessed with the modified Rankin Scale ( mRS-3mo). Unfavorable outcome was defined as mRS-3mo ≥ 3. Results Amongst 1206 study patients (691 Ce AD and 515 non-Ce AD), 87 (7.2%) had anemia, which was moderate to severe in 18 (1.5%) patients. Anemia was associated with female sex in both study samples, but no further associations with risk factors or comorbidities were observed. In Ce AD patients, anemia was associated with occurrence of stroke ( P = 0.042). In both study samples, anemic patients had more severe strokes (Ce AD, P = 0.023; non-Ce AD, P = 0.005). Functional outcome was not associated with anemia in general, but moderate to severe anemia was significantly associated with unfavorable outcome ( P = 0.004). Conclusion Anemia on admission was associated with stroke in Ce AD patients and with more severe strokes in both study samples. Moderate to severe anemia may predict unfavorable outcome. [ABSTRACT FROM AUTHOR]

Background and purpose Patients with ischaemic stroke ( IS) caused by a spontaneous cervical artery dissection ( Ce AD) worry about an increased risk for stroke in their families. The occurrence of stroke in relatives of patients with Ce AD and in those with ischaemic stroke attributable to other (non- Ce AD) causes were compared. Methods The frequency of stroke in first-degree relatives (family history of stroke, FHS) was studied in IS patients ( Ce AD patients and age- and sex-matched non- Ce AD patients) from the Cervical Artery Dissection and Ischemic Stroke Patients ( CADISP) database. FHS ≤ 50 and FHS > 50 were defined as having relatives who suffered stroke at the age of ≤50 or >50 years. FHS ≤ 50 and FHS > 50 were studied in Ce AD and non-Ce AD IS patients and related to age, sex, number of siblings, hypertension, hypercholesterolemia, smoking and body mass index ( BMI). Results In all, 1225 patients were analyzed. FHS ≤ 50 was less frequent in Ce AD patients (15/598 = 2.5%) than in non-Ce AD IS patients (38/627 = 6.1%) ( P = 0.003; odds ratio 0.40, 95% confidence interval 0.22-0.73), also after adjustment for age, sex and number of siblings ( P = 0.005; odds ratio 0.42, 95% confidence interval 0.23-0.77). The frequency of FHS > 50 was similar in both study groups. Vascular risk factors did not differ between patients with positive or negative FHS ≤ 50. However, patients with FHS > 50 were more likely to have hypertension and higher BMI. Conclusion Relatives of Ce AD patients had fewer strokes at a young age than relatives of non-Ce AD IS stroke patients. [ABSTRACT FROM AUTHOR]

Background and purpose It has been suggested that inflammation may play a role in the development of cervical artery dissection ( Ce AD), but evidence remains scarce. Methods A total of 172 patients were included with acute (< 24 h) Ce AD and 348 patients with acute ischaemic stroke (IS) of other (non- Ce AD) causes from the Cervical Artery Dissection and Ischemic Stroke Patients ( CADISP) study, and 223 age- and sex-matched healthy control subjects. White blood cell ( WBC) counts collected at admission were compared across the three groups. Results Compared with healthy control subjects, Ce AD patients and non- Ce AD stroke patients had higher WBC counts ( P < 0.001). Patients with Ce AD had higher WBC counts and were more likely to have WBC > 10 000/μl than non- Ce AD stroke patients (38.4% vs. 23.0%, P < 0.001) and healthy controls (38.4% vs. 8.5%, P < 0.001). WBC counts were higher in Ce AD (9.4 ± 3.3) than in IS of other causes (large artery atherosclerosis, 8.7 ± 2.3; cardioembolism, 8.2 ± 2.8; small vessel disease, 8.4 ± 2.4; undetermined cause, 8.8 ± 3.1; P = 0.022). After adjustment for age, sex, stroke severity and vascular risk factors in a multiple regression model, elevated WBC count remained associated with Ce AD, as compared with non- Ce AD stroke patients [odds ratio (OR) = 2.56; 95% CI 1.60-4.11; P < 0.001) and healthy controls ( OR = 6.27; 95% CI 3.39-11.61; P < 0.001). Conclusions Acute Ce AD was associated with particularly high WBC counts. Leukocytosis may reflect a pre-existing inflammatory state, supporting the link between inflammation and Ce AD. [ABSTRACT FROM AUTHOR]

Objective: To examine whether thrombolysis for stroke attributable to cervical artery dissection (CeADStroke) affects outcome and major haemorrhage rates. Methods: We used a multicentre CeADStroke database to compare CeADStroke patients treated with and without thrombolysis. Main outcome measures were favourable 3-month outcome (modified Rankin Scale 0-2) and 'major haemorrhage' [any intracranial haemorrhage (ICH) and major extracranial haemorrhage]. Adjusted odds ratios [OR (95% confidence intervals)] were calculated on the whole database and on propensity-matched groups. Results: Among 616 CeADStroke patients, 68 (11.0%) received thrombolysis; which was used in 55 (81%) intravenously. Thrombolyzed patients had more severe strokes (median NIHSS score 16 vs. 3; P < 0.001) and more often occlusion of the dissected artery (66.2% vs. 39.4%; P < 0.001). After adjustment for stroke severity and vessel occlusion, the likelihood for favourable outcome did not differ between the treatment groups [ORadjusted 0.95 (95% CI 0.45-2.00)]. The propensity matching score model showed that the odds to recover favourably were virtually identical for 64 thrombolyzed and 64 non-thrombolyzed-matched CeADStroke patients [OR 1.00 (0.49-2.00)]. Haemorrhages occurred in 4 (5.9%) thrombolyzed patients, all being asymptomatic ICHs. In the non-thrombolysis group, 3 (0.6%) patients had major haemorrhages [asymptomatic ICH ( n = 2) and major extracranial haemorrhage ( n = 1)]. Conclusion: As thrombolysis was neither independently associated with unfavourable outcome nor with an excess of symptomatic bleedings, our findings suggest thrombolysis should not be withheld in CeADStroke patients. However, the lack of any trend towards a benefit of thrombolysis may indicate the legitimacy to search for more efficient treatment options including mechanical revascularization strategies. [ABSTRACT FROM AUTHOR]

The outcome of cerebral venous thrombosis (CVT) has been studied infrequently. We assessed the frequency of recurrence of cerebral or systemic thromboembolism and factors influencing recurrence. We performed a retrospective study of consecutive patients with CVT in the period 1985–2002 who were admitted to the University Hospital Gasthuisberg. We performed a chart review and a semi-standardized telephone interview that focused on recurrent CVT or systemic thromboembolism. Fifty-four CVT patients with a mean age of 42 years were followed up for a mean of 3.5 years. Eighty percent were women. Coagulation disorders were found in 17 patients (31%). One patient (1.9%) had recurrent CVT and seven patients (12.9%) suffered systemic thromboembolism after a median of 2.5 months. Patients with recurrent thromboembolism more often had coagulopathies ( P = 0.04) or a history of deep venous thrombosis ( P = 0.007). Patients with early recurrent venous thromboembolism often were not treated with oral anticoagulants ( P < 0.001). It was evident from the above study that a substantial number of patients suffer recurrent thromboembolism after CVT. [ABSTRACT FROM AUTHOR]

Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) are common treatments for carotid artery stenosis. Several randomized controlled trials (RCTs) have compared CEA to CAS in the treatment of carotid artery stenosis. These studies have suggested that CAS is more strongly associated with periprocedural stroke; however, CEA is more strongly associated with myocardial infarction. Published long-term outcomes report that CAS and CEA are similar. A reduction in complications associated with CAS has also been demonstrated over time. The symptomatic status of the patient and history of previous CEA or cervical radiotherapy are significant factors when deciding between CEA or CAS. Numerous carotid artery stents are available, varying in material, shape and design but with minimal evidence comparing stent types. The role of cerebral protection devices is unclear. Dual antiplatelet therapy is typically prescribed to prevent in-stent thrombosis, and however, evidence comparing periprocedural and postprocedural antiplatelet therapy is scarce, resulting in inconsistent guidelines. Several RCTs are underway that will aim to clarify some of these uncertainties. In this review, we summarize the development of varying techniques of CAS and studies comparing CAS to CEA as treatment options for carotid artery stenosis., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Diabetes mellitus is a major risk factor for ischemic stroke. Rising hemoglobin A 1c (HbA 1c ) levels are associated with microvascular diabetes mellitus complication development; however, this relationship has not been established for stroke risk, a macrovascular complication., Methods and Results: We conducted a systematic review and meta-analysis of observational cohort and nested case-control cohort studies assessing the association between rising HbA 1c levels and stroke risk in adults (≥18 years old) with and without type 1 or type 2 diabetes mellitus. Random-effects model meta-analyses were used to calculate pooled adjusted hazard ratios (HRs) and their precision. The systematic review yielded 36 articles, of which 29 articles (comprising n=532 779 participants) were included in our meta-analysis. Compared to non-diabetes mellitus range HbA 1c (<5.7%), diabetes mellitus range HbA 1c (≥6.5%) was associated with an increased risk of first-ever stroke with average HR (95% confidence interval) of 2.15 (1.76, 2.63), whereas pre-diabetes mellitus range HbA 1c (5.7-6.5%) was not (average HR [95% confidence interval], 1.19 [0.87, 1.62]). For every 1% HbA 1c increment (or equivalent), the average HR (95% confidence interval) for first-ever stroke was 1.12 (0.91, 1.39) in non-diabetes mellitus cohorts and 1.17 (1.09, 1.25) in diabetes mellitus cohorts. For every 1% HbA 1c increment, both non-diabetes mellitus and diabetes mellitus cohorts had a higher associated risk of first-ever ischemic stroke with average HR (95% confidence interval) of 1.49 (1.32, 1.69) and 1.24 (1.11, 1.39), respectively., Conclusions: A rising HbA 1c level is associated with increased first-ever stroke risk in cohorts with a diabetes mellitus diagnosis and increased risk of first-ever ischemic stroke in non-diabetes mellitus cohorts. These findings suggest that more intensive HbA 1c glycemic control targets may be required for optimal ischemic stroke prevention., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: New-onset atrial fibrillation (NOAF) after coronary artery bypass graft is related to an increased short-term risk of stroke and mortality. We investigated whether the long-term risk of stroke is increased., Methods and Results: We performed a systematic review and meta-analysis of studies that included patients who had coronary artery bypass graft and who afterwards developed NOAF during their index admission; these patients did not have previous atrial fibrillation. The primary outcome was risk of stroke at 6 months or more in patients who developed NOAF compared with those who did not. Odds ratios, relative risk, and hazard ratios were considered equivalent; outcomes were pooled on the log-ratio scale using a random-effects model and reported as exponentiated effect-sizes. We included 16 studies, comprising 108 711 participants with a median follow-up period of 2.05 years. Average participant age was 66.8 years, with studies including an average of 74.8% males. There was an increased long-term risk of stroke in the presence of NOAF (unadjusted studies effect-sizes=1.36, 95% confidence interval, 1.12-1.65, P =0.001, adjusted studies effect-sizes=1.25, 95% confidence interval, 1.09-1.42, P =0.001). There was evidence of moderate effect variation because of heterogeneity in studies reporting unadjusted ( P =0.021, I 2 =49.8%) and adjusted data ( P =0.081, I 2 =49.1%), and publication bias in the latter group (Egger's test, P =0.031). Sensitivity analysis on unadjusted data by study quality, design, and surgery did not alter the effect direction., Conclusions: Presence of NOAF in patients post-coronary artery bypass graft is associated with increased long-term risk of stroke compared with patients without NOAF. Further studies may show whether the increased risk is mediated by atrial fibrillation and whether anticoagulation reduces risk., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: A patent foramen ovale (PFO) with atrial septal aneurysm (ASA) has been identified as a risk factor for cryptogenic stroke. Patients with migraine with aura (MA) appear to be at risk for silent brain infarction, which might be related to the presence of a PFO. However, the association between MA and PFO with ASA has never been reported. We examined this association in a large observational study., Methods and Results: Patients (>18 years) who underwent an agitated saline transesophageal echocardiography (cTEE) at our outpatient clinics within a timeframe of 4 years were eligible to be included. Before cTEE they received a validated headache questionnaire. Two neurologists diagnosed migraine with or without aura according to the International Headache Criteria. A total of 889 patients (mean age 56.4±14.3 years, 41.7% women) were included. A PFO was present in 23.2%, an isolated ASA in 2.7%, and a PFO with ASA in 6.9%. The occurrence of migraine was 18.9%; the occurrence of MA was 8.1%. The prevalence of PFO with ASA was significantly higher in patients with MA compared to patients without migraine (18.1% vs 6.1%; OR 3.72, 95% CI 1.86-7.44, P<0.001). However, a PFO without ASA was not significantly associated with MA (OR 1.50, 95% CI 0.79-2.82, P=0.21). Interestingly, a PFO with ASA was strongly associated with MA (OR 2.71, 95% CI 1.23-5.95, P=0.01)., Conclusion: In this large observational study, PFO with ASA was significantly associated with MA only. PFO closure studies should focus on this specific intra-atrial anomaly., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Stroke is among the leading causes of morbidity and mortality worldwide. Without reliable prediction models and outcome measurements, comparison of care systems is impossible. We analyzed prospectively collected data from 4 countries to explore the importance of stroke severity in outcome prediction., Methods and Results: For 2 months, all acute ischemic stroke patients from the hospitals participating in the Global Comparators Stroke GOAL (Global Outcomes Accelerated Learning) collaboration received a National Institutes of Health Stroke Scale (NIHSS) score on admission and a modified Rankin Scale score at 30 and 90 days. These data were added to the administrative data set, and risk prediction models including age, sex, comorbidity index, and NIHSS were derived for in-hospital death within 7 days, all in-hospital death, and death and good outcome at 30 and 90 days. The relative importance of each variable was assessed using the proportion of explained variation. Of 1034 admissions for acute ischemic stroke, 614 had a full set of NIHSS and both modified Rankin Scale values recorded; of these, 507 patients could be linked to administrative data. The marginal proportion of explained variation was 0.7% to 4.0% for comorbidity index, and 11.3 to 25.0 for NIHSS score. The percentage explained by the model varied by outcome (16.6-29.1%) and was highest for good outcome at 30 and 90 days. There was high agreement between 30- and 90-day modified Rankin Scale scores (weighted κ=0.82)., Conclusions: In this prospective pilot study, the baseline NIHSS score was essential for prediction of acute ischemic stroke outcomes, followed by age; whereas traditional comorbidity index contributed little to the overall model. Future studies of stroke outcomes between different care systems will benefit from including a baseline NIHSS score., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Aims: We studied whether baseline body temperature and temperature increases after stroke adversely affect outcome after thrombolysis with intravenous tissue plasminogen activator (IV tPA)., Methods: The evolution of body temperature in the first 24 h after treatment with IV tPA was described by calculating the area under the curve of the temperature over time plot relative to temperature at admission (AUCBL) and relative to a standard value of 37 degrees C (AUC37). Temperature parameters were related to functional outcome., Results: The median baseline National Institutes of Health Stroke Scale of 100 consecutive patients was 16 (interquartile range 11-21) and 34 patients had a favourable response to tPA. Patients with an unfavourable outcome had a more important temperature elevation than patients who had a favourable outcome after tPA (+1 degrees C vs +0.6 degrees C, P=0.02), despite similar baseline T and had a higher AUCBL (9.79 vs 5.36, P=0.027) and more frequently showed hyperthermia relative to baseline (82% vs 56%, P=0.011). After adjustment for baseline characteristics, the presence of hyperthermia relative to baseline was associated with a reduced odds of good outcome after thrombolysis (OR 0.34, 95% CI 0.10-0.95, P=0.040)., Conclusion: Hyperthermia relative to baseline temperature in the 24 h after intravenous thrombolysis is associated with an unfavourable outcome.