European Stroke Journal

Pontine haemorrhage comprises approximately 10% of intracerebral haemorrhages. There is a common presumption that pontine haemorrhage is inherently associated with poor outcome.

The aim of the review was to identify chief predictors of prognosis in (pontine haemorrhage) through systematic review of published literature.

A query of PubMed/MEDLINE was conducted in search of studies in English language since, 1980 focusing specifically on outcome in pontine haemorrhage. References for each publication were reviewed for additional studies not detected by the PubMed/MEDLINE probe. Surgical outcome studies were excluded from the review.

The query identified 7867 titles, after removal of duplicates and irrelevant studies, 20 titles were included in the review. In a total of 1437 pontine haemorrhage patients included in the 20 studies, the overall rate for early all-cause mortality was 48.1%. Level of consciousness on admission and haemorrhage size were the most consistent predictors of mortality in patients with pontine haemorrhage. Haemorrhage localisation within the pons was also a prognostic factor, but not consistently. Age and intraventricular extension were not found to be powerful prognostic predictors.

Based on this review, level of consciousness on admission and haemorrhage size were the most influential prognostic factors in pontine haemorrhage, whereas age, haemorrhage localisation, and intraventricular haemorrhage did not consistently predict prognosis.

The sources of emboli in those with embolic stroke of undetermined source may differ in old and young. We assessed the frequency, features and potential embolic sources of younger vs. older embolic stroke of undetermined source patients in the embolic stroke of undetermined source Global Registry.

Cross-sectional study of consecutive patients over age 18 years, with recent ischaemic strokes at 19 centres conducted in 2013–2014. Characteristics of embolic stroke of undetermined source patients who aged ≤50 years were analysed and compared with embolic stroke of undetermined source patients who aged >50 years.

Among 2144 patients with ischaemic stroke, 323 (15.1%, 95% confidence interval: 13.6–16.7%) were ≤50 years old and, 1821 >50 years. 24% (n = 78) of young vs. 15% (n = 273) of older patients met embolic stroke of undetermined source criteria. The mean age of young embolic stroke of undetermined source patients was 40 years (standard deviation +/−9), 33% were women and the most prevalent vascular risk factor was hypertension (38%). Conventional vascular risk factors were less frequent in younger embolic stroke of undetermined source patients. Fewer young embolic stroke of undetermined source patients (63%) had potential minor risk embolic sources identified vs. older embolic stroke of undetermined source patients (77%) (p = 0.02). Stroke severity on admission was similar in younger vs. older patients (National Institute of Health Stroke Scale (NIHSS) 3 vs. 4, p = 0.06).

Young embolic stroke of undetermined source patients comprise an important subset of ischaemic stroke patients around the world. Severity of stroke on admission and 30-day mortality rates are similar among young and older patients. However, there are important differences between younger vs. older embolic stroke of undetermined source patients with respect to risk factors, and potential embolic sources that could affect response to anticoagulants vs. antiplatelet therapies.

This study provides a benchmark for the global frequency and characteristics of young embolic stroke of undetermined source patients and shows consistent high frequency of embolic stroke of undetermined source in young adults.

Inability to identify stroke warning signs accurately is an important cause of delay in seeking medical attention, leading to potential ineligibility for acute intervention. We report on post-campaign findings (wave 2) of national surveys to estimate changes in population knowledge following a media-based Face, Arm, Speech, Time stroke awareness campaign, comparing findings to those of a pre-campaign population survey (wave 1).

Participants and methods: One thousand and ten randomly selected adults (18+) completed the Stroke Awareness Questionnaire on knowledge of warning signs, risk factors and response to stroke at wave 2 and findings were compared to wave 1 survey results. Logistic regression was used to examine the association between demographic characteristics and self-reported risk factors with knowledge of stroke and emergency response.

No significant differences existed in the ability of respondents to define stroke or to identify two or more stroke risk factors between waves 1 and 2 surveys (71% and 70%, respectively). Respondents to the wave 2 survey were five times more likely (odds ratio 4.9, p < .001) than those responding at wave 1 to know at least two warning signs of stroke (67% vs. 31%, respectively), specifically those targeted by the Face, Arm, Speech, Time campaign. While significant improvement in intention to call an ambulance was noted (odds ratio 1.5, p < .001, 57% at wave 2 compared to 47% at wave 1), for almost half of respondents (43%) this would not have been their first response to stroke. Less than 5% of respondents to both surveys identified thrombolysis as an emergency treatment for stroke (3.9% at wave 2 compared to 1.8% at wave 1).

Although significant improvements were made in several areas of stroke knowledge and intended response, awareness of acute stroke interventions was poor and intended behavioural response was suboptimal.

Findings from this study indicate need for targeted campaigns to improve population understanding of the reasons underlying the importance of rapid emergency response to stroke.

In ischaemic stroke care, fast reperfusion is essential for disability free survival. It is unknown if bypassing thrombolysis centres in favour of endovascular thrombectomy (mothership) outweighs transport to the nearest thrombolysis centre for alteplase and then transfer for endovascular thrombectomy (drip-and-ship). We use conditional probability modelling to determine the impact of treatment times on transport decision-making for acute ischaemic stroke.

Probability of good outcome was modelled using a previously published framework, data from the Irish National Stroke Register, and an endovascular thrombectomy registry at a tertiary referral centre in Ireland. Ireland was divided into 139 regions, transport times between each region and hospital were estimated using Google’s Distance Matrix Application Program Interface. Results were mapped using ArcGIS 10.3.

Using current treatment times, drip-and-ship rarely predicts best outcomes. However, if door to needle times are reduced to 30 min, drip-and-ship becomes more favourable; even more so if turnaround time (time from thrombolysis to departure for the endovascular thrombectomy centre) is also reduced. Reducing door to groin puncture times predicts better outcomes with the mothership model.

This is the first case study modelling pre-hospital transport for ischaemic stroke utilising real treatment times in a defined geographic area. A moderate improvement in treatment times results in significant predicted changes to the optimisation of a national acute stroke patient transport strategy.

Modelling patient transport for system-level planning is sensitive to treatment times at both thrombolysis and thrombectomy centres and has important implications for the future planning of thrombectomy services.

Patients with acute stroke are at high risk for infection. These infections are associated with unfavourable outcome after stroke. A prediction rule can identify the patients at the highest risk for strategies to prevent infection. We aim to develop a prediction rule for post-stroke pneumonia and other infections in patients with acute stroke.

We used data from the Preventive Antibiotics in Stroke Study, a multicentre randomised trial comparing preventive ceftriaxone vs. standard stroke care in patients with acute stroke. Possible predictors for post-stroke pneumonia or infection were selected from the literature. Backward elimination logistic regression analysis was used to construct prediction rules for pneumonia or infection. Internal validation was performed and a risk chart was constructed. We adjusted for preventive antibiotic use.

Pneumonia was diagnosed in 159 of the 2538 included patients, and infection in 348. Pneumonia was predicted by higher age, male sex, pre-stroke disability, medical history of chronic obstructive pulmonary disease, more severe stroke, dysphagia and intracerebral haemorrhage (rather than ischaemic stroke). Infections were predicted by higher age, male sex, history of diabetes, chronic obstructive pulmonary disease, more severe stroke, dysphagia, use of bladder catheter, preventive antibiotic use and intracerebral haemorrhage. With the prediction rule developed, risks for pneumonia ranged from 0.4% to 56.2% and from 1.8% to 88.0% for infection. Discrimination of the score was good (C-statistic, 0.84; 95% CI: 0.81–0.87 and 0.82; 95% CI: 0.79–0.84 for pneumonia and infection).

The Preventive Antibiotics in Stroke Study pneumonia and infection rule identify patients at the highest risk for post-stroke pneumonia or infection and may be used for future studies and novel therapies, after confirmation in an external population.

Cognitive impairment can complicate minor stroke, but there is limited information on risk factors including peak cognitive ability earlier in life.

We recruited patients with clinically-evident lacunar or minor non-lacunar ischaemic stroke, recorded clinical features, vascular risk factors, magnetic resonance imaging-detected stroke sub-type and small vessel disease burden. At 1–3 and 12 months after stroke, we assessed educational attainment (years of education), current cognition (Addenbrooke’s Cognitive Examination–Revised), pre-morbid intelligence (National Adult Reading Test) and dependency (modified Rankin Scale).

We recruited 157 patients (87 lacunar, 64 non-lacunar ischaemic strokes), median age 66 (inter-quartile range 56–74) years, 36/157 (23%) patients had a Addenbrooke’s Cognitive Examination–Revised score < 82 at one to three months, 29/151 (19%) had a Addenbrooke’s Cognitive Examination–Revised < 82 at one year. Lower National Adult Reading Test score (cognitive impairment per point on National Adult Reading Test odds ratio 0.91, 95% confidence interval 0.87, 0.95) and older age (per year of age odds ratio 1.04 (95% confidence interval 1.01, 1.08) predicted one-year cognitive impairment more than stroke severity (per point on National Institute of Health Stroke Scale odds ratio 0.96 (95% confidence interval 0.0.68, 1.31)) or vascular risk factors e.g. hypertension (odds ratio for diagnosis of hypertension 0.52 (95% confidence interval 0.24, 1.15). Cognitive impairment was associated with having more white matter hyper-intensities (odds ratio per point increase in Fazekas score 1.42, 95% confidence interval 1.11, 1.83).

This observational study provides evidence that pre-morbid intelligence quotient and education predict cognition after stroke, and confirms the association between cognitive impairment and small vessel disease.

Pre-morbid intelligence should be considered in future studies of post-stroke cognition.

Information about the impact of functional outcome after stroke is currently missing on health-related quality of life, survival and costs. This information would be valuable for health economic evaluations and for allocation of resources in stroke health care.

Data on 297 Swedish patients included in the Third International Stroke Trial were analysed including functional outcome at six months (measured by Oxford Handicap Scale), health-related quality of life up to 18 months (EQ-5D-3L) and survival up to 36 months. We used record linkage to collect data on costs up to 36 months, using national patient registers.

Patients with a better functional outcome level at six months had a significantly better health-related quality of life at 18 months (p < 0.05), better long-term survival (p < 0.05) and lower costs (p < 0.001), for all time points up to 36 months. The difference in costs was mainly due to differences in days spent in hospital (p < 0.005).

This study showed an association between functional outcome at six months and health-related quality of life up to 18 months, and costs up to 36 months.

Functional outcome six months after stroke is an important determinant of health-related quality of life, survival and costs over 36 months. Effective interventions aimed at reducing short-term disability levels are therefore also expected to reduce the overall burden of stroke.

We aimed to develop and validate a prognostic score for disability at discharge and functional outcome at three months in patients with acute ischemic stroke based on clinical information available on admission.

The Dutch Stroke Score (DSS) was developed in 1227 patients with ischemic stroke included in the Paracetamol (Acetaminophen) In Stroke study. Predictors for Barthel Index (BI) at discharge (‘DSS-discharge’) and modified Rankin Scale (mRS) at three months (‘DSS-3 months’) were identified in multivariable ordinal regression. The models were internally validated with bootstrapping techniques. The DSS-3 months was externally validated in the PRomoting ACute Thrombolysis in Ischemic StrokE study (1589 patients) and the Preventive Antibiotics in Stroke Study (2107 patients). Model performance was assessed in terms of discrimination, expressed by the area under the receiver operating characteristic curve (AUC), and calibration.

At model development, the strongest predictors of Barthel Index at discharge were age per decade over 60 (odds ratio = 1.55, 95% confidence interval (CI) 1.41–1.68), National Institutes of Health Stroke Scale (odds ratio = 1.24 per point, 95% CI 1.22–1.26) and diabetes (odds ratio = 1.62, 95% CI 1.32–1.91). The internally validated AUC was 0.76 (95% CI 0.75–0.79). The DSS-3 months, additionally consisting of previous stroke and atrial fibrillation, performed similarly at internal (AUC 0.75, 95% CI 0.74–0.77) and external validation (AUC 0.74 in PRomoting ACute Thrombolysis in Ischemic StrokE (95% CI 0.72–0.76) and 0.69 in Preventive Antibiotics in Stroke Study (95% CI 0.69–0.72)). Observed outcome was slightly better than predicted.

Discussion: The DSS had satisfactory performance in predicting BI at discharge and mRS at three months in ischemic stroke patients.

If further validated, the DSS may contribute to efficient stroke unit discharge planning alongside patients' contextual factors and therapeutic needs.

We aimed to assess alterations in glucose, blood pressure and temperature in acute ischaemic stroke and investigate their association with early all-cause mortality and functional outcome.

We studied all consecutive acute ischaemic stroke patients admitted in 2001–2010 to the Acute Stroke Unit, at Alexandra University Hospital, in Athens. Serial measurements were performed in the first seven days post-stroke and different parameters have been estimated: mean daily values, variability, subject-specific baseline levels and rate of change in serial measurements. Cox-proportional-hazards-model analysis and logistic-regression analysis were applied to investigate the association between these parameters and all-cause mortality and functional outcome after adjustment for known confounders of stroke outcome.

In 1271 patients (mean age 72.3 ± 11.2 years), after adjusting for confounders, baseline glucose levels (HR: 1.005, 95%CI: 1.001–1.01; p = 0.017), variability of systolic BP (SBP) as estimated by standard deviation (HR: 1.028, 95%CI: 1.01–1.048; p = 0.005), the baseline temperature (HR: 2.758, 95%CI: 2.067–3.68; p < 0.001) and the rate of temperature change (HR: 1.841, 95%CI: 1.616–2.908; p < 0.001) were independently associated with all-cause mortality within three months. Poor functional outcome was associated with subject-specific baseline values of temperature (OR: 1.743; 95%CI: 1.076–2.825; p = 0.024), the rate of SBP (OR: 1.159; 95% CI: 1.047–1.280; p = 0.004) and temperature change (OR: 1.402; 95% CI: 1.061–1.853; p = 0.018).

The main strength of our study is that we analysed simultaneously three parameters and we used four different variables for each parameter of interest.

Baseline glucose levels, variability of SBP and baseline temperature and its rate of change are independent predictors of all-cause mortality. Baseline values of temperature and the rate of changes in SBP and temperature are independent predictors of poor functional outcome.

Mechanical thrombectomy within 6 h after stroke onset improves the outcome in patients with large vessel occlusions. The aim of our study was to establish a model based on diffusion weighted and perfusion weighted imaging to provide an accurate prediction for the 6 h time-window in patients with unknown time of stroke onset.

A predictive model was designed based on data from the DEFUSE 2 study and validated in a subgroup of patients with large vessel occlusions from the AXIS 2 trial.

We constructed the model in 91 patients from DEFUSE 2. The following parameters were independently associated with <6 h time-window and included in the model: interquartile range and median relative diffusion weighted imaging, hypoperfusion intensity ratio, core volume and the interaction between median relative diffusion weighted imaging and hypoperfusion intensity ratio as predictors of the 6 h time-window. The area under the curve was 0.80 with a positive predictive value of 0.90 (95%CI 0.79–0.96). In the validation cohort (N = 90), the area under the curve was 0.73 (P for difference = 0.4) with a positive predictive value of 0.85 (95%CI 0.69–0.95).

After validation in a larger independent dataset the model can be considered to select patients for endovascular treatment in whom stroke onset is unknown.

In patients with large vessel occlusion and unknown time of stroke onset an automated multivariate imaging model is able to select patients who are likely within the 6 h time-window.

Glyceryl trinitrate, a nitric oxide donor, is a candidate treatment for acute stroke; it lowers blood pressure, does not alter cerebral blood flow or platelet function and is neuroprotective in experimental stroke. The ongoing rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial aims to assess the safety and efficacy of paramedic-delivered glyceryl trinitrate in patients with ultra-acute stroke.

Aims and design: The rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial is a multicentre UK-based prospective randomised sham-controlled outcome-blinded parallel-group trial in patients with presumed stroke who present to the ambulance service following a 999 emergency call. The primary outcome is the modified Rankin scale measured by central telephone follow-up at 90 days.

This paper describes the statistical analysis plan for the rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial and was developed prior to unblinding to treatment allocation. The statistical analysis plan includes details of methods for analyses and unpopulated tables and figures to be included in the primary and other secondary publications.

Statistical analysis plan details what analyses will be done prior to unblinding to treatment allocation to avoid bias in the findings. Rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial will determine whether glyceryl trinitrate administered ultra-acutely can improve outcome after stroke. The rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 trial is registered as ISRCTN26986053.