International Journal of Stroke

Acute stroke care represents a challenge for decision makers. Decisions based on erroneous assessments may generate false expectations of patients and their family members, and potentially inappropriate medical advice. Game theory is the analysis of interactions between individuals to study how conflict and cooperation affect our decisions.

We reviewed principles of game theory that could be applied to medical decisions under uncertainty.

Medical decisions in acute stroke care are usually made under constrains: short period of time, with imperfect clinical information, limit understanding about patients and families’ values and beliefs. Game theory brings some strategies to help us manage complex medical situations under uncertainty. For example, it offers a different perspective by encouraging the consideration of different alternatives through the understanding of patients’ preferences and the careful evaluation of cognitive distortions when applying ‘real-world’ data. The stag-hunt game teaches us the importance of trust to strength cooperation for a successful patient–physician interaction that is beyond a good or poor clinical outcome.

The application of game theory to stroke care may improve our understanding of complex medical situations and help clinicians make practical decisions under uncertainty.

The study of sex differences on stroke incidence, prevalence and mortality is an emerging field of stroke epidemiology and care.

This study sought to determine the information available on stroke epidemiology in women worldwide and possible sex differences in stroke epidemiology, and, if so, describe the nature of these differences and whether they are consistent across countries/groups of countries.

We searched the available literature in English published between 1 January 2008 and 5 May 2015. Out of 17.789 papers only 56 peer-reviewed papers (29 community-based studies, 17 retrospective studies, 6 reviews, and 4 cross-sectional studies) have been included in the study. This review adopted the epidemiologic transition theory, which classifies countries into four stages according to their levels of industrialization and economy. For the first and second stages, reliable registries and health certification are lacking, and therefore our sought after data were very limited.

In the third stage, specifically for Eastern Europe (post-socialist countries), the burden from stroke in women was on the rise, while in the fourth stage, despite an aging population, decreases in stroke incidence, prevalence and mortality have been observed, even in subjects older than 80 years for both sexes. However, regarding studies of US populations, these trends for women were less pronounced for African Americans, and Hispanics as well as Indians. This suggests a “gender-gap” regarding access to treatment and care.

In conclusion, identifying the presence of differing global burden between the sexes will allow us to better understand how to prevent, treat, and manage both men and women.

Documentation of atrial fibrillation is required to initiate oral anticoagulation therapy for recurrent stroke prevention. Atrial fibrillation often goes undetected with traditional electrocardiogram monitoring techniques. We evaluated whether atrial fibrillation detection using continuous long-term monitoring with an insertable cardiac monitor is cost-effective for preventing recurrent stroke in patients with cryptogenic stroke, in comparison to the standard of care.

A lifetime Markov model was developed to estimate the cost-effectiveness of insertable cardiac monitors from a UK National Health Service perspective using data from the randomized CRYSTAL-AF trial and other published literature. We also conducted scenario analyses (CHADS₂ score) and probabilistic sensitivity analyses. All costs and benefits were discounted at 3.5%.

Monitoring cryptogenic stroke patients with an insertable cardiac monitor was associated with fewer recurrent strokes and increased quality-adjusted life years compared to the standard of care (7.37 vs 7.22). Stroke-related costs were reduced in insertable cardiac monitor patients, but overall costs remained higher than the standard of care (£19,631 vs £17,045). The incremental cost-effectiveness ratio was £17,175 per quality-adjusted life years gained, compared to standard of care in the base-case scenario, which is below established quality-adjusted life years willingness-to-pay thresholds. When warfarin replaced non-vitamin-K oral anticoagulants as the main anticoagulation therapy, the incremental cost-effectiveness ratio was £13,296 per quality-adjusted life years gained.

Insertable cardiac monitors are a cost-effective diagnostic tool for the prevention of recurrent stroke in patients with cryptogenic stroke. The cost-effectiveness results have relevance for the UK and across value-based healthcare systems that assess costs relative to outcomes.

Stroke unit care is associated with decrease in mortality and improvement in neurological outcome in patients with acute stroke. Heart rate is a commonly monitored variable in the stroke unit. However, little is known about tachycardia burden in the stroke unit and its association with outcome.

To investigate the effects of tachycardia burden in the stroke unit on functional outcome in patients with acute ischemic stroke.

We collected data from 246 patients with acute ischemic stroke admitted to our stroke unit between July 2013 and June 2014. Tachycardia burden was defined as duration of heart rate over 95 per minute divided by the total monitoring time, using the heart rate data sampled every 1 min. We divided the study population into quartiles of tachycardia burden and analyzed their association with poor three-month functional outcome (modified Rankin Scale score of ≥3).

Among included patients (age, 67.4  ±  12.8; male, 53.7%), tachycardia burden was 0.7% (median, interquartile range [0.1–5.7%]). The patients with higher tachycardia burdens were older, more likely to have higher stroke severity, cardioembolic etiology, atrial fibrillation, fever, pneumonia, higher initial glucose level, and higher white blood cell count. As compared with the lowest quartile (<0.1%), the highest quartile of tachycardia burden (≥6.0%) was significantly associated with poor outcome (adjusted odds ratio, 5.10; 95% confidence interval, 1.38–18.90; p = 0.01) after adjustment for covariates.

Patients with increased tachycardia burden during stroke unit stay have poor functional outcome. Countermeasures against worsening factors might be utilized for patients with increased tachycardia burden.

Prognosis after intracerebral hemorrhage (ICH) is poor and care-limiting decisions may worsen outcomes.

To determine whether in current UK stroke practice, key acute care decisions are associated with stroke subtype (ICH/ischemic) and whether these decisions are independently associated with survival.

We extracted data describing all stroke patients included in a UK quality register between 1 April 2013 and 31 March 2014. Key care decisions in our analyses were transfer to higher level care on admission and palliation in the first 72 h. We used multivariable regression models to test for associations between stroke subtype (ICH/ischemic), key care decisions, and survival.

A total of 65,818 patients were included in the final analysis. After ICH (n = 7020/65,818, 10.7%), 10.5% were palliated on the day of admission and 19.3% by 72 h (vs. 0.7% and 3.3% for ischemic stroke). Although a greater proportion were admitted directly to higher level care after ICH (3.7% vs. 1.5% for ischemic stroke), ICH was not independently associated with the decision to admit to higher level care (adjusted odds ratio (OR): 1.12, 95% confidence interval (95%CI): 0.95–1.31, p = 0.183). However, ICH was strongly associated with the decision to commence palliative care on the day of admission (OR: 7.27, 95%CI: 6.31–8.37, p < 0.001). Palliative care was independently associated with risk of death by 30 days regardless of stroke subtype.

When compared to ischemic stroke, patients with ICH are much more likely to commence palliative care during the first 72 h of their care, independent of level of consciousness, age, and premorbid health.

Education level is considered as an important factor for post-stroke functional outcome. Our previous study confirms the feasibility of SMART program to improve adherence of secondary stroke prevention in China.

We aim to investigate whether this program can influence the impact of educational level on post-stroke functional outcome in this sub-group analysis of SMART study.

We enrolled 3722 patients with acute ischemic stroke from multicenter (n = 47) SMART cohort. Patient’s educational level was categorized as three: illiterate, 6th grade or lower, and 7th grade or higher. Functional outcome at six-month post-stroke was assessed by Modified Rankin Scale (mRS) and categorized as favorable (mRS: 0–2) or poor (mRS: 3–5). Binary logistic model, adjusting for age, gender, stroke history, hypertension, diabetes, hyperlipidemia, educational level, and NIHSS was performed, respectively, in SMART group and usual care group to evaluate the effect of the SMART program on stroke functional outcome among different educated patients.

In both groups, logistic regression analysis showed that poor functional outcome was independently associated with older age [OR(95% CI):1.81(1.41–2.33), p < 0.001(SMART); OR (95% CI):1.38 (1.09–1.73), p = 0.007(usual care)], higher baseline NIHSS [OR (95% CI): 2.90 (2.38–3.53), p < 0.001(SMART); OR (95% CI): 2.82 (2.32–3.44), p < 0.001(usual care)], and diabetes [OR(95% CI):1.88 (1.18–3.00), p = 0.008(SMART); OR (95%CI):1.68 (1.03–2.73), p = 0.037(usual care)]. Compared to illiterate, higher educational levels were independently associated with favorable outcome in usual care group [OR (95% CI): 0.43 (0.20–0.93), p = 0.032 (6th grade or lower) and OR (95% CI): 0.40 (0.19–0.84), p = 0.016 (7th Grade or higher)], but not in SMART group (p = 0.806 and p = 0.889, respectively).

This study demonstrates that implementation of SMART program may improve post-stroke functional outcome among illiterate. This suggests special attention should be paid to illiterate patients with intensive education in order to improve post-stroke disability.

The steep, time-dependent loss of benefit from reperfusion in clinical trials is consistent with loss of penumbra over the early hours of ischemia, as observed in animal models. Human imaging studies, however, show persistent penumbra for up to 48 h. We investigated core and penumbra volumes and collateral status in relation to time after stroke onset within the first 6 h.

Using data from three multimodal computer tomography-based studies in acute ischemic stroke patients <6 h after onset, we measured core and penumbra volumes, collateral status, and target mismatch (defined as core volume < 50 ml, perfusion lesion volume > 15 ml, mismatch ratio > 1.8). Patients were grouped by onset to imaging time (<3, 3–4.5, 4.5–6 h). We explored correlates of penumbra proportion by multivariable linear regression.

Analysis included 144 subjects. Across time epochs, neither proportions of penumbra (59%, 64%, 75% at <3, 3–4.5, >4. 5 h, respectively, p = 0.4) nor poor collaterals (15/56 (27%), 14/47 (30%), 4/15 (27%) at <3, 3–4.5, >4.5 h, p = 0.9) differed significantly. Penumbra proportion was not clearly related to time to imaging (R²= 0.003; p = 0.5) but a trend for divergent effects by collateral status was seen (slight increase in penumbra over time with good collaterals versus reduced with poor, interaction = 0.08). The proportion of patients with target mismatch did not vary by time (56%, 74%, and 67% at <3, 3–4.5, >4.5 h, p = 0.09).

In a cross-sectional sample imaged within 6 h, neither the proportions of penumbral tissue nor “target mismatch” varied by time from onset. A trend for reducing penumbra proportion only among those with poor collaterals may have pathophysiological and therapeutic importance.

Cerebrolysin is a mixture of neuropeptides and free amino acids that is clinically used for the treatment of stroke. To further standardize treatment schemes, we assessed the dose response of Cerebrolysin on sensorimotor outcome in a rat model of ischemic stroke.

This study was a prospective, blinded, placebo-controlled, preclinical experiment. Male and female Wistar rats, subjected to embolic middle cerebral artery occlusion, were randomly treated with Cerebrolysin doses of 0.8, 2.5, 5.0, 7.5 ml/kg or placebo, 4 h after middle cerebral artery occlusion for a total of 10 consecutive days.

The primary outcome was neurologic improvement at day 28, lesion volume, mortality, and animal weight were secondary and safety outcomes, respectively. There was a significant (p < 0.001) dose effect of Cerebrolysin on neurological outcome. Cerebrolysin at a dose of ≥ 2.5 ml/kg significantly (p < 0.001) improved neurological outcome (Mean Estimate (95% CL): 0.8 ml/kg: 6.2 (–6.0/18.4), 2.5 ml/kg: −28.9 (−41.6/−16.2), 5.0 ml/kg: −33.4 (−45.0/−21.7), 7.5 ml/kg: −36.3 (−48.2/−24.4). Higher doses (≥2.5 ml/kg) resulted in better recovery; however, differences between effective doses were not significant. Treatment with 5 ml/kg reduced lesion volume (p = 0.016). No treatment gender interactions were found and there were no differences in death or weight loss.

Collectively, these data on Cerebrolysin efficacy demonstrate the feasibility of a preclinical study setup following a randomized, placebo-controlled, and blinded design with a clinical relevant treatment scheme. Cerebrolysin at doses of ≥ 2.5 ml/kg improved functional outcome and at a dose of 5 ml/kg reduced infarct volume.

Hairdresser-related ischemic cerebrovascular events (HICE) are attributed to compression of vertebral arteries or cervical artery dissections. We determined their frequency, mechanisms, localization and outcome in a pre-specified study.

We prospectively collected ischemic strokes and transient ischemic attacks occurring in relation to a hairdresser visit from 2002 to 2013, using consecutive data from an ischemic stroke registry (ASTRAL). HICE were compared to all other acute ischemic strokes in ASTRAL.

We identified 10 HICE (9 strokes and 1 transient ischemic attack). Age and anterior-posterior distribution were similar with a significantly higher rate of females (90% vs. 43%, p = 0.02) in the HICE group compared to ASTRAL. Patients with HICE had significantly lower incidence of hyperlipidemia (30% vs. 73%) and diabetes (0% vs. 19%). The mechanisms of HICE were diverse: carotid artery dissection (n = 2), cardiac (n = 2), lacunar (n = 2), other determined (n = 2) and unknown etiology (n = 2). Two HICE with atherosclerotic intracranial disease were possibly caused by acute hemodynamic changes related to systemic hypotension during hot air hair drying. Unadjusted favorable outcome at three months seemed to be better in HICE (90% vs. 57%), and 12-month mortality and recurrences were similar.

HICE may occur frequently in females without a predilection for the posterior circulation. Although some HICE may occur by chance (pseudo-HICE), hairdresser visits may have a causal role in some cases, including cervical artery dissection or hemodynamic compromise related to pre-existing arterial disease (true HICE). Available data are insufficient for specific preventive recommendations.

Atrial fibrillation is associated with a high risk of stroke and its prevalence increases in subjects aged ≥65 years. After an ischemic stroke, the use of standard monitoring methods may underestimate the detection rate of atrial fibrillation. Hence, it is very likely that even patients having a first atherothrombotic or lacunar stroke with high burden of vascular risk factors are exposed to increased risk of developing atrial fibrillation in the subsequent years and atrial fibrillation may be the cause underlying possible recurrent strokes

The Silent Atrial Fibrillation aFter Ischemic StrOke (SAFFO) trial has the objective to evaluate the detection of atrial fibrillation or atrial flutter as first diagnosis by implantable loop recorder in patients with first-ever atherothrombotic or lacunar stroke. We hypothesize that the detection will be higher than that observed by using standard cardiac monitoring

SAFFO is a prospective, multicenter, randomized, controlled, open-label trial with blinded assessment of outcome measures. Patients who fulfill inclusion criteria will be randomized to either continuous monitoring using an implantable loop recorder plus standard monitoring (intervention arm) or standard heart rhythm monitoring alone (control arm) with a ratio of 1:1

The primary endpoint is the detection of atrial fibrillation/atrial flutter as first diagnosis in the first 12 months of the study period

If positive, SAFFO trial could have important clinical implications in terms of changing the standard diagnostic protocol in patients with atherothrombotic and lacunar stroke, and of increasing the shift of secondary prevention treatment from antiplatelet to anticoagulant therapy.

Tracheostomy is a common procedure in long-term ventilated critical care patients and frequently necessary in those with severe stroke. The optimal timing for tracheostomy is still unknown, and it is controversial whether early tracheostomy impacts upon functional outcome.

The Stroke-related Early Tracheostomy vs. Prolonged Orotracheal Intubation in Neurocritical care Trial 2 (SETPOINT2) is a multicentre, prospective, randomized, open-blinded endpoint (PROBE-design) trial. Patients with acute ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage who are so severely affected that two weeks of ventilation are presumed necessary based on a prediction score are eligible. It is intended to enroll 190 patients per group (n = 380). Patients are randomized to either percutaneous tracheostomy within the first five days after intubation or to ongoing orotracheal intubation with consecutive weaning and extubation and, if the latter failed, to percutaneous tracheostomy from day 10 after intubation. The primary endpoint is functional outcome defined by the modified Rankin Scale (mRS, 0–4 (favorable) vs. 5 + 6 (unfavorable)) after six months; secondary endpoints are mortality and cause of mortality during intensive care unit-stay and within six months from admission, intensive care unit-length of stay, duration of sedation, duration of ventilation and weaning, timing and reasons for withdrawal of life support measures, relevant intracranial pressure rises before and after tracheostomy.

The necessity and optimal timing of tracheostomy in ventilated stroke patients need to be identified. SETPOINT2 should clarify whether benefits in functional outcome can be achieved by early tracheostomy in these patients.