European Stroke Journal

To analyse structural and non-structural modifications of acute stroke care pathways undertaken at healthcare institutions across the regions of Italy due to the coronavirus disease 2019 (COVID-19) pandemic.

Research on National decrees specific for the pandemic was carried out. The stroke pathways of four Italian regions from North to South, such as Lombardy, Veneto, Lazio and Campania, were analysed before and after the pandemic outbreak.

On 29 February 2020, the Italian Minister of Health issued national guidelines on how to address the COVID-19 emergency. Stroke management was affected and required changes, basically resulting in the need to prioritise the ongoing COVID-19 emergency. In the most affected regions, the closure of departments and hospitals led to a complete reorganisation of previously functioning stroke networks. With the closure of several Stroke Units and Stroke Centres, the transportation time to hospital lengthened significantly, especially for the outlying populations.

The COVID-19 pandemic outbreak has been spreading rapidly in Italy and placing an overwhelming burden on healthcare systems. In response to this, political and healthcare decision-makers worked together to develop and implement efforts to sustain the national healthcare system while fighting the pandemic. Stroke care pathways changed during the pandemic and different organisational models were applied in the most affected regions.

Stroke treatment pathways will need to be redesigned so to guarantee that severe and acute disease patients do not lose their rights to the access and delivery of care during the COVID-19 pandemics.

The coronavirus disease 2019 (COVID-19) pandemic has been placing an overwhelming burden on health systems, thus threatening their ability to operate effectively for acute conditions in which treatments are highly time sensitive, such as cerebrovascular disorders and myocardial infarction. As part of an effort to reduce the consequences of this outbreak on health service delivery to stroke patients, the European Stroke Organisation has undertaken a survey aimed at collecting information on the provision of stroke care during the pandemic.

Cross-sectional, web-based survey, conducted from 26 March through 1 April 2020 among stroke care providers, focused on reorganisation of health services, the delivery of acute and post-acute stroke care and the availability of personal protective equipment.

A total of 426 stroke care providers from 55 countries completed the survey, most of whom worked in Europe (n = 375, 88%) and were stroke physicians/neurologists (n = 334, 78%). Among European respondents, 289 (77%) reported that not all stroke patients were receiving the usual care in their centres and 266 (71%) estimated that functional outcomes and recurrence rates of stroke patients would be negatively affected by the organisational changes caused by the pandemic. The areas considered as being most affected were acute care and rehabilitation. Most professionals had to adapt their activities and schedules and more than half reported shortage of protective equipment.

Strategies to maintain availability of stroke care during the COVID-19 outbreak are crucial to prevent indirect mortality and disability due to suboptimal care.

European Stroke Organisation proposes a set of targeted actions for decision makers facing this exceptional situation.

Symptoms of occult brain cancer may mimic stroke. Misdiagnosis may lead to improper treatment and delayed diagnosis. We characterised strokes associated with occult primary brain cancer and determined risk that ischaemic and haemorrhagic strokes are associated with occult primary brain cancer.

All patients with incident stroke in Denmark 2003–2015 were identified through the Danish Stroke Registry (n = 85,893) and matched 1:10 on age and sex to the Danish background population without a stroke history (n = 858,740). This cohort was linked to the Danish Cancer Registry and prevalence of occult primary brain cancer defined as the event of previously unknown primary brain cancer during a one-year follow-up was estimated. We used Cox regression models to study risk of occult primary brain cancer in comparison to the background population.

Of 77,484 patients with ischaemic strokes, 39 (1 in 2000) were associated with primary brain cancer; of 8409 with haemorrhagic strokes, it was 126 (1 in 66). In the background cohort, 205 (1 in 4000) had occult primary brain cancer. The multivariate stroke risk factor analysis showed that patients with occult primary brain cancer differed significantly from those without occult primary brain cancer indicating they might have stroke mimics rather than true strokes.

Discussion and conclusions: Strokes associated with occult primary brain cancer tend to be stroke mimics rather than true strokes. Primary brain cancer is rare in patients with ischaemic stroke (1 in 2000); risk that misdiagnosis results in maltreatment is, therefore, very low. Occult primary brain cancers are mainly found among patients with haemorrhagic stroke; they are not uncommon (1 in 66) and should always be kept in mind.

Atrial fibrillation is an important risk factor for ischemic stroke, and is associated with an increased risk of poor outcome after ischemic stroke. Endovascular thrombectomy is safe and effective in acute ischemic stroke patients with large vessel occlusion of the anterior circulation. This meta-analysis aims to investigate whether there is an interaction between atrial fibrillation and treatment effect of endovascular thrombectomy, and secondarily whether atrial fibrillation is associated with worse outcome in patients with ischemic stroke due to large vessel occlusion.

Individual patient data were from six of the recent randomised clinical trials (MR CLEAN, EXTEND-IA, REVASCAT, SWIFT PRIME, ESCAPE, PISTE) in which endovascular thrombectomy plus standard care was compared to standard care alone. Primary outcome measure was the shift on the modified Rankin scale (mRS) at 90 days. Secondary outcomes were functional independence (mRS 0–2) at 90 days, National Institutes of Health Stroke Scale score at 24 h, symptomatic intracranial hemorrhage and mortality at 90 days. The primary effect parameter was the adjusted common odds ratio, estimated with ordinal logistic regression (shift analysis); treatment effect modification of atrial fibrillation was assessed with a multiplicative interaction term.

Among 1351 patients, 447 patients had atrial fibrillation, 224 of whom were treated with endovascular thrombectomy. We found no interaction of atrial fibrillation with treatment effect of endovascular thrombectomy for both primary (p-value for interaction: 0.58) and secondary outcomes. Regardless of treatment allocation, we found no difference in primary outcome (mRS at 90 days: aOR 1.11 (95% CI 0.89–1.38) and secondary outcomes between patients with and without atrial fibrillation.

We found no interaction of atrial fibrillation on treatment effect of endovascular thrombectomy, and no difference in outcome between large vessel occlusion stroke patients with and without atrial fibrillation.

The global incidence of ischemic stroke among patients with human immunodeficiency virus is increasing. The aim of this controlled case analysis was to study patient characteristics, stroke etiologies, and risk factors in human immunodeficiency virus-positive patients in a medical system with easy access to antiretroviral therapies.

We conducted a retrospective, observational study of human immunodeficiency virus-positive patients treated in our stroke unit and outpatient clinic in Germany between 2012 and 2018. A control group of all patients treated for acute ischemic stroke in 2018 was used to elicit possible differences in stroke localization, etiology, and distribution of risk factors.

Out of 3615 patients with an acute ischemic stroke, 24 (0.7%) were newly or previously diagnosed as human immunodeficiency virus-positive. Strokes in this cohort were caused by large-vessel disease (37.5%), small-vessel disease (20.8%), cryptogenic-embolism (20.8%), vasculitis (16.7%), and cardio-embolism (4.2%). Large-vessel disease-related strokes were more often located in the posterior circulation (77.8%). Compared to the control group, cardio-embolic strokes were less and vasculitis and large-vessel disease more frequent. Human immunodeficiency virus-positive patients were younger at stroke onset (53.7 ± 12.8 vs. 70.2 ± 14.6 years, p = 0.05).

Although the prevalence of human immunodeficiency virus-infection among patients treated for acute ischemic strokes appears low, this collective merits special attention due to a high burden of potentially modifiable risk factors and vasculitis.

Compared to previous studies, age at stroke onset was one of the highest, supporting the hypothesis that as antiretroviral therapy increases the life expectancy of people living with HIV/AIDS, they will be increasingly affected by cardiovascular disease. Human immunodeficiency virus-related cerebral vasculitis was associated with high mortality (75%).

Deficits of emotion recognition after ischemic stroke are often overlooked by clinicians, and are mostly not spontaneously reported by patients. However, impaired emotion recognition after stroke negatively affects the ability to return to work and the quality of life. It is still unknown how often impairments of emotion recognition occur shortly after ischemic stroke. We aimed to estimate the occurrence of impaired emotion recognition after ischemic stroke and to characterise these patients with impaired emotion recognition.

Two hundred thirty patients were included, derived from a prospective study of cognitive recovery. Five weeks after ischemic stroke a neuropsychological assessment was performed, including an emotion recognition task (i.e. Ekman 60-faces test). Emotion recognition was regarded as impaired if the total score was below the fifth percentile for a large independent reference sample.

Emotion recognition was impaired in 33.5% of patients. Patients with impaired emotion recognition were more likely to have an abnormal Montreal Cognitive Assessment during hospitalisation, and 5 weeks after their stroke, a higher proportion of them had a vascular cognitive disorder (VCD). Even 20% of patients without VCD had impaired emotion recognition.

Discussion: Emotion recognition was often impaired after ischemic stroke. This is clinically relevant, since impaired emotion recognition negatively impacts social functioning.

Conclusion: Even when there was no cognitive disorder in traditional cognitive domains, emotion recognition was impaired in 1 out of 5 patients. Clinicians should systematically ask patients and their caregivers about deficits in emotion recognition, and, if needed, test for these deficits.

Literature on prevalence of symptomatic internal carotid artery stenosis is scarce and heterogeneous. Prevalence may have decreased in recent years due to improved management of cardiovascular risk factors. We aim to estimate current prevalence and identify risk factors of ipsilateral internal carotid artery stenosis in patients with recent hemispheric transient ischaemic attack or ischaemic stroke in the Netherlands.

We included consecutive adult patients admitted to two large hospitals in the Netherlands in 2014 who suffered from amaurosis fugax, retinal ischaemia, transient ischaemic attack or ischaemic stroke in the vessel territory of the internal carotid artery. Primary outcome was presence of ipsilateral internal carotid artery stenosis (degree subdivided following NASCET criteria), as assessed with duplex ultrasonography, computed tomography angiography and/or magnetic resonance angiography. We used univariable and multivariable logistic regression to identify risk factors for the presence of a 50–100% internal carotid artery stenosis.

We analysed 883 consecutive patients with recent transient ischaemic attack or ischaemic stroke. Of these, 110 (12.5%) had 50–99% ipsilateral internal carotid artery stenosis. Subgroup analyses showed higher prevalence of any degree of internal carotid artery stenosis for male sex and White patients. In adjusted analyses, higher age (odds ratio 1.4/10 years; 95% confidence interval 1.16–1.63), male sex (odds ratio 2.8; 95% confidence interval 1.83–4.19), retinal ischaemia (odds ratio 2.5; 95% confidence interval 1.32–4.76) and current smoking (odds ratio 1.8; 95% confidence interval 1.09–2.79) were statistically significant risk factors for 50–100% internal carotid artery stenosis.

The prevalence of internal carotid artery stenosis seems to be lower in patients with recent transient ischaemic attack or ischaemic stroke than stated in previous studies. We found that higher age, male sex, White ethnicity, retinal ischaemia and current smoking were important risk factors for symptomatic internal carotid artery stenosis.

While the relationship between hypertension and incident intracerebral haemorrhage is well established, other risk factors are less clear. This study examined risk factors for primary intracerebral haemorrhage, separately for lobar and non-lobar intracerebral haemorrhage.

Incidence of intracerebral haemorrhage was studied among 28,416 individuals from the population-based Malmö Diet and Cancer cohort. Intracerebral haemorrhage cases were ascertained using the Swedish Hospital Discharge Register and the Stroke Register of Malmö, validated by review of hospital records and images, and classified by location by a neuroradiologist. Multivariable Cox regression was used.

Three hundred and thirty-three intracerebral haemorrhages occurred, mean follow-up time was 18.4 years. Systolic blood pressure (hazard ratio per 10 mmHg 1.19 [95% confidence interval 1.13–1.26], diastolic blood pressure (hazard ratio 1.42 [1.27–1.59]), oral anticoagulants (hazard ratio 4.26 [2.17–8.38]), smoking (hazard ratio 1.45 [1.14–1.87]), living alone (hazard ratio 1.32 [1.04–1.69]) and low apolipoprotein B (hazard ratio per 10 mg/dL: 0.94 [0.90–0.99]) were significantly associated with incident intracerebral haemorrhage after multivariable adjustment. Systolic blood pressure, smoking and oral anticoagulants were associated with lobar intracerebral haemorrhage. Systolic blood pressure, diastolic blood pressure, living alone and diabetes were associated with non-lobar intracerebral haemorrhage. Diabetes and diastolic blood pressure showed significantly different relationships with lobar and non-lobar intracerebral haemorrhage. Alcohol, apolipoprotein A1, body mass index, waist circumference, physical activity and education were not independently associated with intracerebral haemorrhage.

Discussion and conclusions: Blood pressure, smoking, low apolipoprotein B, oral anticoagulants and living alone were associated with intracerebral haemorrhage. Diabetes was associated with non-lobar intracerebral haemorrhage only. Further research is required on differences between lobar and non-lobar intracerebral haemorrhage.

While acute treatment and secondary prevention in stroke have undergone major improvements, hospital readmission after index stroke remains high. However, there are few reports on long-term readmission patterns.

For this prospective observational study, data on demographics, functional status and living conditions were obtained from the Swedish Stroke Register (Riksstroke). Data on comorbidity and hospital readmissions up to five years post-index stroke were obtained from the Swedish National Patient Register. Patients were grouped based on number of readmissions: low (0–1) intermediate (2–4), high (5–9) or very high (≥10).

Of the 10,092 patients included, 43.7% had been readmitted within 12 months and 74.0% within 5 years. There was an average of three readmissions per individual during the five-year interval. A small group of patients with a high-comorbidity burden accounted for the majority of readmissions: approximately 20% of patients accounted for 60% of readmissions, and 5% of patients accounted for 25%. Circulatory conditions were the most common cause followed by infectious disease, stroke, trauma and diseases of the nervous system other than stroke. The proportion of readmissions due to stroke decreased sharply in the first six months.

A small number of patients with a high degree of comorbidity accounted for the majority of hospital readmissions after index stroke. Our results highlight the need for further development of strategies to support high-risk comorbid stroke patients in the community setting. Further research describing characteristics and healthcare utilisation patterns in this group is warranted.

Small vessel disease causes a quarter of ischaemic strokes (lacunar subtype), up to 45% of dementia either as vascular or mixed types, cognitive impairment and physical frailty. However, there is no specific treatment to prevent progression of small vessel disease.

We designed the LACunar Intervention Trial-2 (LACI-2) to test feasibility of a large trial testing cilostazol and/or isosorbide mononitrate (ISMN) by demonstrating adequate participant recruitment and retention in follow-up, drug tolerability, safety and confirm outcome event rates required to power a phase 3 trial.

LACI-2 is an investigator-initiated, prospective randomised open label blinded endpoint (PROBE) trial aiming to recruit 400 patients with prior lacunar syndrome due to a small subcortical infarct. We randomise participants to cilostazol v no cilostazol and ISMN or no ISMN, minimising on key prognostic factors. All patients receive guideline-based best medical therapy. Patients commence trial drug at low dose, increment to full dose over 2–4 weeks, continuing on full dose for a year. We follow-up participants to one year for symptoms, tablet compliance, safety, recurrent vascular events, cognition and functional outcomes, Trails B and brain MRI. LACI-2 is registered ISRCTN 14911850, EudraCT 2016–002277-35.

Trial outcome: Primary outcome is feasibility of recruitment and compliance; secondary outcomes include safety (cerebral or systemic bleeding, falls, death), efficacy (recurrent cerebral and cardiac vascular events, cognition on TICS, Trails B) and tolerability.

LACI-2 will determine feasibility, tolerability and provide outcome rates to power a large phase 3 trial to prevent progression of cerebral small vessel disease.

The type of antithrombotic treatment in cervical artery dissection patients is still a matter of debate. Most physicians prefer anticoagulants over antiplatelet agents for stroke prevention. However, this approach is not evidence-based and antiplatelets might be as safe and as effective. The ‘Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection’ (‘TREAT-CAD’) trial (clinicaltrials.gov: NCT02046460) compares Aspirin to oral anticoagulants (vitamin K antagonists) with regard to efficacy and safety by using both clinical and imaging surrogate outcome measures. TREAT-CAD tests the hypothesis, that aspirin is as safe and effective as vitamin K antagonists.

TREAD-CAD is a Prospective, Randomised controlled, Open-labelled, multicentre, non-inferiority trial with Blinded assessment of outcome Events (PROBE-design). Key eligibility criteria are (i) clinical symptoms attributable to cervical artery dissection and (ii) verification of the cervical artery dissection diagnosis by established magnetic resonance imaging criteria. Patients are randomised to receive either Aspirin 300 mg daily or vitamin K antagonists for 90 days.

Primary outcomes are assessed at 14 ± 10 days (magnetic resonance imaging and clinical examination) and at 90 ± 30 days (clinical examinations). The primary endpoint is a composite outcome measure – labelled Cerebrovascular Ischemia, major Hemorrhagic events or Death (CIHD) – and includes (i) occurrence of any stroke (including retinal infarction), (ii) new ischaemic lesions on diffusion-weighted magnetic resonance imaging, (iii) any major extracranial haemorrhage, (iv) any symptomatic intracranial haemorrhage, (v) any new haemorrhagic lesion visible on paramagnetic-susceptible sequences and (vi) death.

After database closure, (i) central verification of cervical artery dissection diagnosis will be done by two experienced raters, (ii) adjudication of outcome events will be performed by independent adjudication committees, separately for clinical and imaging outcomes. The primary analysis will be done on the per protocol data set. The targeted sample size consists of 169 evaluable patients in the per protocol data set.

TREAT-CAD is testing the non-inferiority of Aspirin versus vitamin K antagonists treatment in patients with symptomatic cervical artery dissection by combined clinical and magnetic resonance imaging outcomes.