As we write this editorial, the world has been swept by the corona virus in a way that was unprecedented just a few months earlier. We are again reminded of the importance of health for society, and of its fragility when systems fail. The corona virus pandemic is having multiple indirect effects also on stroke, on patterns of health care admissions as well as stroke services and rehabilitation. Telemedicine for TIA and stroke suddenly got an unheralded impetus for implementation. Scientific events have been cancelled or rescheduled, including the postponement of the ESOC/WSC from May to November 2020. The full effects of the pandemic cannot be estimated but will most likely be profound and long lasting.
The current issue includes an obituary on Eivind Berge, our Norwegian college whose life was recently cut short. Eivind Berge was a superb scientist, highly esteemed for his capabilities and gentle personality. He was a founding board member of the European Stroke Journal, and he contributed as co-author of two manuscripts in the current issue, demonstrating his involvement in several core ESO activities and networks. Eivind Berge will be much missed.
The current issue contains two articles on intracerebral hemorrhage (ICH). Dr Sánchez and colleagues report on the influence of time to admission to a comprehensive stroke center on the outcome of patients with intracerebral hemorrhage. Patients who were admitted early (≤110 minutes) were significantly younger, had higher NIHSS scores, were more likely to have basal ganglia hematoma, and more frequently had neurological deterioration. Based on data from the TICH-2 trial, Dr Law and colleagues analyzed the incidence and predictors of early seizures in intracerebral hemorrhage and the effect of tranexamic acid. Lobar hematoma was the strongest independent predictor of early seizures after ICH. Tranexamic acid did not increase the risk of post-ICH seizures in the first 90 days. Early seizures resulted in worse functional outcome and increased risk of death. Both these studies remind us on the serious prognosis after ICH, and the large need to develop more efficient acute therapies in this stroke subtype.
Whereas antiplatelet drugs are standard treatment in TIA and ischemic stroke, bleeding remains the main safety concern. Based on the Oxford Vascular Study (OXVASC), Dr Hilkens and colleagues report improved predictors for major bleeding by refinements to the S2TOP-BLEED score previously developed by this group. Adding peptic ulcer, cancer, anemia and renal failure improved predictive performance of the S2TOP-BLEED score for major bleeding after stroke. Future external validation studies will be required to confirm the value of the modified score (STOP-BLEED+) in TIA/stroke patients. There is conflicting evidence on the impact of atrial fibrillation (AF) type, i.e. non-paroxysmal (NPAF) or paroxysmal (PAF), on thromboembolic recurrence. The consensus of risk equivalence is greatly based on historical evidence, focusing on initial stroke risks. Dr Mentel and colleagues performed a systematic review and meta-analysis of observational studies, and found that in patients with prior stroke, NPAF was associated with significantly higher risk of thromboembolic recurrence and mortality than PAF. Future guidance and risk stratification tools may need to consider this differential risk.
Many factors may influence the effect and safety of intravenous thrombolytic therapy (IVT), but the implications of hemoglobin levels have been debated. In a prospective, multicenter register-based study, Altersberger and colleagues found that anemia on admission, but not polyglobulia, was a strong and independent predictor of poor outcome and mortality in IVT-treated stroke patients. There are several potential underlying pathophysiological mechanisms, including a hypoxic effect in penumbral lesions of severe anemia, that warrant further study.
Almost all clinical trials face the problem of missing outcome data, but to what extent may this influence the interpretation of the trial results? Dr Fernandez-Ferro and colleagues used the VISTA-Acute database to assess bias and inefficiency of two imputation methods commonly used in stroke trials evaluating the efficacy of IVT. Replacing missing outcome data tended to overestimate outcome differences of thrombolysed versus non-thrombolysed patients but the impact was minimal below a 10% burden of missing data.
In randomized clinical trials, central adjudication of outcome events has been often used, and has been regarded as an important quality control of the data. However, central adjudication is labor intensive and costly. In a modeling study based on data from five randomized stroke trials, Godolphin and colleagues investigated the amount of misclassification needed before adjudication changed the primary trial results. In addition, they simulated hypothetical trials with a binary outcome and varying sample size, overall event rate, and treatment effect. For the five trials, 2.1%-6% of participants needed to be misclassified before the treatment effect was altered. For the hypothetical trials, those with a larger sample size, stronger treatment effect and overall event rate closer to 50% needed a higher proportion of events non- differentially misclassified before the treatment effect became non- significant. Hence, for large blinded trials, central adjudication is of less importance and may not be necessary.
About one-fourth of ischemic strokes are classified as embolic strokes of undetermined source (ESUS). The detective work to reveal the “undetermined sources” is subject to much current study. In this context, Dr Omran and colleagues investigated Lambl’s excrescences, filiform projections of fibrous tissue commonly seen on cardiac valves and thought to result from endothelial degeneration. In their case-control study, they found no association between Lambl’s excrescences and ESUS. Thus, the results do not support the hypothesis that Lambl’s excrescences are an occult cause of ESUS.
With advances in stroke care comes the issue of economic evaluations of new and existing therapies. However, economical evaluations are heterogenous in methodologies and reporting. In this issue, the ESO Health Economics Working Group used a modified Delphi approach to develop a protocol and a guidance document for data collection for economic evaluations of stroke therapies. The protocol will support a more standardized and transparent approach for economic evaluations of stroke care.
The current issue concludes with two protocol articles. Dr Lorenzano is joined by a large number of international researchers on the topic of stroke in pregnancy and postpartum. Though uncommon, the condition may have an important impact on health of both women and fetus or newborn. The multicenter study aims to study pathophysiological mechanisms, clinical profile, management, and outcome. Dr Mikulik is similarly joined by a large group of scientists involved in the ESO EAST program, which is the first pan-Eastern European (and beyond) multifaceted quality improvement intervention putting evidence-informed policies into practice. Program management and leadership infrastructure has been established in 19 countries, and a platform for a quality register (RES-Q) has been established. We look forward to seeing the results in due course of these two initiatives.
Many of our readers are active clinicians, involved in stroke care and many are currently affected by the effects of the corona virus in their practices. Despite the infectious pandemic, strokes continue to occur and need adequate care. The mission on stroke is as important as ever.