American Heart Association

Learning the RoPEs of ESUS

Melanie R. F. Greenway, MD

Strambo D, Sirimarco G, Nannoni S, Perlepe K, Ntaios G, Vemmos K, Michel P. Embolic Stroke of Undetermined Source and Patent Foramen Ovale: Risk of Paradoxical Embolism Score Validation and Atrial Fibrillation Prediction. Stroke. 2021;52:1643–1652.

In patients with embolic stroke of undetermined source (ESUS), patent foramen ovale (PFO) is often suspected as a potential mechanism. Recent clinical trials have shown the benefit of PFO closure when patients are properly selected.1-3 Present in 25% of the normal population, when found in the etiology workup for stroke, the most important question to ask is whether this is a pathogenic or incidental finding. The Risk of Paradoxical Embolism (RoPE) score is a commonly used clinical decision tool to estimate the likelihood of PFO as the cause of stroke. The higher the score, the more likely the PFO is the cause of stroke. Using this score, it is also possible to predict whether a patient actually has a PFO. 

In this study, the authors used three independent, international, multicenter stroke registries (ASTRAL, Athens, and Larissa Stroke Outcome Registry) to validate the RoPE score in patients with ESUS to predict both the presence of PFO and the ability to determine if the PFO is the cause of the stroke or not. It is the largest validation cohort of patients with ESUS for the RoPE score to date. They also followed the patients for a period of time to evaluate for incident atrial fibrillation and recurrent stroke. 

The Mind-Controlled Car: A Brain-Computer Interface for Rehabilitation in Pediatric Cerebral Palsy Patients

Jeff Russ, MD, PhD

Jadavji Z, Zhang J, Paffrath B, Zewdie E, Kirton A. Can Children With Perinatal Stroke Use a Simple Brain Computer Interface? Stroke. 2021.

Perinatal stroke is all too common, occurring in up to 1 in 1,100 term infants, considering all-comers with different etiologies and clinical courses.1,2 In particular, perinatal arterial ischemic stroke, which occurs in one out of every 3,000 to 5,000 term births,1,3 or periventricular venous infarction, which occurs in one out of every 6,000 term births,1 typically disrupts unilateral cortical and subcortical motor pathways, often leading to hemiparetic cerebral palsy (CP).4 Since the etiology of these disorders is heterogeneous, prevention remains elusive, and thus treatment strategies rely on harnessing neuroplasticity to regain function through neurorehabilitation. However, novel strategies for rehabilitation are often tested in adult stroke patients, overlooking a young population with enhanced neuroplasticity that would benefit greatly from additional modes of functional recovery.

In their article published in Stroke, Jadavji et al. take a step toward modernizing pediatric neurorehabilitation practices by exploring the feasibility of a non-invasive brain-computer interface (BCI) in pediatric patients with hemiparetic CP. Twenty-one patients between nine and eighteen years old with disabling hemiparetic CP and MRI-confirmed perinatal arterial or venous stroke were recruited to learn and operate an EEG-controlled goal-oriented system. Patients were asked to complete two tasks: either move a mouse on a computer screen toward a red circle or drive a remote-controlled car on the floor toward a finish line. To complete either task, the patients were asked to employ one of two mental imagery strategies: either imagine moving the object toward its target or imagine opening and closing one’s hands. Changes in electrographic signal during these mental imagery epochs were communicated to the BCI-linked mouse or toy car to initiate movement. The patients’ facility with these tasks was compared to that of twenty-four neurotypical control subjects.

Tandem Lesions: Intracranial Preferably, Carotid Stent Always, If Possible

Elena Zapata-Arriaza, MD

Feil K, Herzberg M, Dorn F, Tiedt S, Küpper C, Thunstedt DC, Papanagiotou P, Meyer L, Kastrup A, Dimitriadis K; for the GSR investigators. Tandem Lesions in Anterior Circulation Stroke: Analysis of the German Stroke Registry-Endovascular Treatment. Stroke. 2021 ;52:1265-1275.

Technical management of tandem lesions still raises many questions. With the aim of investigating the safety and efficacy of different technical strategies in tandem lesions, the authors analyzed data from the German Stroke Registry—Endovascular Treatment between June 2015 and December 2019. The registry is an academic, independent, prospective, multicenter, observational registry study with 25 participating stroke centers from all over Germany enrolling consecutive mechanical thrombectomy patients.

Among 6635 analyzed patients, 874 (13.2%) presented with tandem lesions. Of these, 607 (69.5%) underwent acute treatment of the extracranial ICA. Acute treatment of the extracranial ICA lesion led to a higher probability of successful reperfusion (odds ratio, 40.63) compared with patients who did not undergo acute treatment of the extracranial ICA lesion and was associated with good clinical outcome (39.5% versus 29.3%, P<0.001) and a lower rate of mortality (17.1% versus 27.1%, P<0.001) at 3 months. Further significant predictors of successful reperfusion were age and intravenous thrombolysis. Intracranial-first approach compared with extracranial-first approach resulted in a shorter time to flow restoration (53.5 versus 72.0 minutes, P<0.001) and a higher nonsignificant probability of good outcome (45.8% versus 33.0%, P=0.24) without differences in periprocedural complications.

Frequency and Clinical Impact of Procedural Complications During Early Versus Late Endovascular Treatment in Acute Stroke

Tolga D. Dittrich, MD

Maslias E, Nannoni S, Ricciardi F, Bartolini B, Strambo D, Puccinelli F, Hajdu SD, Eskandari A, Saliou G, Michel P. Procedural Complications During Early Versus Late Endovascular Treatment in Acute Stroke: Frequency and Clinical Impact. Stroke. 2021;52:1079–1082.

The efficacy of endovascular treatment (EVT) for patients with acute ischemic stroke due to proximal vessel occlusion is well established. This holds for patients in the early (<6 hours after symptom onset) and radiologically preselected patients in the late time window (6-24 hours). Randomized controlled trials showed a reasonable overall safety profile, with a relatively wide range (2.4-7%) of reported intraprocedural cerebrovascular complications. These complications include embolization in the non-ischemic territory, arterial dissections, and perforations.

In their monocenter retrospective analysis of 695 stroke patients receiving EVT, Maslias and colleagues examined the incidence of intraprocedural complications and their implications for short-term outcomes in the early (N=493) and late time window (N=202). The overall proportion of patients with at least one intraprocedural complication was relatively high across both groups (16.2% in the early, 16.3% in the late window, Padj=0.90). This might be surprising given the intuitive concern of increased intraprocedural complication rates in the late time window (e.g., due to increased permeability of the vessel walls with longer-lasting ischemia). Still, the occurrence of intraprocedural complications was associated with a worse outcome, at least in the short term (i.e., within the first 24 hours), at comparable recanalization rates in the late time window.

Saving the Internal Capsule: Benefits of Early Mechanical Thrombectomy on Deep Brain Tissue

Alejandro Rodríguez-Vázquez, MD

Kaesmacher J, Kaesmacher M, Berndt M, Maegerlein C, Mönch S, Wunderlich S, Meinel TR, Fischer U, Zimmer C, Boeckh-Behrens T, Kleine JF. Early Thrombectomy Protects the Internal Capsule in Patients With Proximal Middle Cerebral Artery Occlusion. Stroke. 2021;52:1570–1579.

As we know, the lenticuloestriate territory is irrigated by terminal, noncollateralized vascularization and thus is often damaged in acute ischemic strokes secondary to proximal middle cerebral artery (MCA) occlusions, even when a complete recanalization via mechanical thrombectomy is achieved. This territory, however, includes both grey and white matter with different susceptibility to ischemia. In this study, the authors tried to determine if early thrombectomy allows to spare the more resistant white-matter fibers in the internal capsule despite the harm on neighboring grey matter deep tissue.

This was a prospective, observational, single-center study which included 92 consecutive patients with isolated MCA occlusion, less than 6 hours from symptoms onset, mechanical thrombectomy, and follow-up diffusion-weighted image magnetic resonance (median time three days). Eighty patients (87%) achieved successful recanalization, and 89 patients (97.7%) had reperfusion of the proximal M1 segment with restoration of complete MCA lenticuloestriate artery flow. All patients showed estriatal ischemia, but only 45 of 92 patients (48.9%) had ischemic damage on the internal capsule, including three patients without M1 reperfusion. Patients with partial perfusion of the MCA perforators before thrombectomy (defined as the visibility of any of the medial or lenticuloestriate artery groups in the pre-thrombectomy arteriography) were less likely to have internal capsule ischemia (56.4% vs. 37.8%). In addition, time from symptom onset to groin puncture and to reperfusion was lower in the patients without internal capsule ischemia (medians 210 vs. 221 min, P=0.033; and 209 vs. 247 min, P<0.001, respectively). Collateral grade did not differ between groups.

Ischemic Stroke in COVID-19 — Is Endotheliopathy the Cause?

Ammad Mahmood, MBChB

McAlpine LS, Zubair AS, Maran I, Chojecka P, Lleva P, Jasne AS, Navaratnam D, Matouk C, Schindler J, Sheth KN, et al. Ischemic Stroke, Inflammation, and Endotheliopathy in COVID-19 Patients. Stroke. 2021.

Ischemic stroke occurring during COVID-19 infection has been the subject of significant interest, though exact mechanisms linking infection to stroke risk are not yet understood and, as such, management of this increased risk is still debated.1 This retrospective observational cohort study compares 2 cohorts of patients with ischemic stroke, one with COVID-19 infection (n=21) and one without (n=168). As well as gathering data on clinical characteristics and etiology, serial laboratory markers of inflammation were examined to ascertain what role inflammation and endothelial damage and activation may play in the pathogenesis of ischemic stroke in COVID-19.

Traditional risk factors between groups were similar with a similar rate of LVO, though COVID-19 patients were less likely to receive intravenous thrombolysis. A correlation between onset of stroke and peak levels of CRP, ferritin and D-dimer was found. An association was found between elevated interleukin-6 and soluble interleukin-2 receptor levels at stroke onset and cases of embolic stroke of undetermined source (ESUS), though the ESUS criteria used is not mentioned. A subset ofD, Matouk C, Schind 8 patients had markers of endotheliopathy measured (von Willebrand factor activity and antigen, Factor VIII), and these were found to be elevated compared with a similar cohort of non-COVID-19 patients.

Statin Use and Intracerebral Hemorrhages

Kevin O’Connor, MD

Sprügel MI, Kuramatsu JB, Volbers B, Saam JI, Sembill JA, Gerner ST, Balk S, Hamer HM, Lücking H, Hölter P, et al. Impact of Statins on Hematoma, Edema, Seizures, Vascular Events, and Functional Recovery After Intracerebral Hemorrhage. Stroke. 2021;52:975-984.

Statin use following recent intracerebral hemorrhage (ICH) has been controversial. Sprügel et al. assessed the effects of statins in patients with ICH based on data from a single center in Germany (n=1275).

The statin group was slightly older (median age 76-years, IQR 69–80) than the non-statin group (72 IQR, 61–80). After excluding those receiving oral anticoagulation (228/1275 [17.9%]) and propensity score matching (n=410), among those with ICH, statin use on hospital admission was associated with higher rates of lobar vs. non-lobar hemorrhages (statin, 71/125 [56.8%] versus 130/285 [45.6%]; p=0.037, OR 1.57 [95% CI 1.03–2.40]; p=0.03). There was no difference between groups with regard to ICH volume, incidence of hematoma enlargement, or intraventricular hemorrhage. There was no difference in peak peri-hemorrhagic edema (PHE) related to statin use at admission (statin n=73 versus 293; p=0.853) or statin continuation after admission (continuation n=123 versus 243; p=0.070). Statin initiation, however, was associated with increased peak PHE (initiated n=50 versus 243; p=0.008).

#StrokeMonth: Covert Infarction — A Silent Stroke Pandemic

Thomas Meinel, MD

A lot of brain MRI scans are performed every day, for example because of headache, seizure, or trauma. Those scans occasionally reveal chronic scars of previous brain tissue damage, but in patients who are unaware of any prior stroke symptoms. In medical terms, those scars represent an incidental finding, meaning the scar tissue does not have association with the indication for the planned MRI.  

The frequency of covert infarction increases with age, and roughly 30% of 70-year-old individuals have covert infarctions. They can be found more frequently when cardiovascular risk factors such as arterial hypertension, diabetes, or smoking are present. It is estimated that brain infarction occurs three to five times more often without causing symptoms than with typical symptoms of stroke. How can this be explained?

#StrokeMonth: More COVID-19, Less Stroke? Lessons to Learn From the Pandemic

Raffaele Ornello, MD

The scientific community has largely investigated the association between COVID-19 and thrombosis, pointing out that COVID-19 may cause large blood clots all over the body. However, this information from science contrasts with clinical practice. Indeed, several reports worldwide have shown that stroke-related hospitalizations declined during the COVID-19 pandemic. Why did the pandemic lead to a decline in stroke-related hospital admissions? It is unlikely that COVID-19 has led to a real decline in stroke incidence, as the infection is associated with a high thrombotic risk. It is more likely that patients’ fear of being admitted to the hospital, coupled with the disruption in emergency care services due to the pandemic emergency, has had a major role in reducing stroke-related admissions.

The ongoing medical emergency has taught us some lessons. The first lesson is to remember that stroke is a medical emergency that needs immediate attention regardless of infectious disease. People from the general population should be educated to seek urgent attention despite the outbreak of other diseases. A second lesson is for the organization of stroke professionals. In territories where stroke patients could be urgently screened for COVID-19 and treated in “clean” wards, the activity and quality of stroke care could be preserved. Establishing and following clear rules led to an effective management of stroke even where the pandemic had large outbreaks. The reorganization of stroke care led to changes in care models; more patients were centralized to centers dedicated to acute stroke care, as demonstrated by the stable number or even increase in endovascular treatments during the pandemic, paralleled by a decline in the use of intravenous thrombolysis, as compared with past years.

MR CLEAN and Mechanical Thrombectomy in Children

Kevin O’Connor, MD

van Es ACGM, Hunfeld MAW, van den Wijngaard I, Kraemer U, Engelen M, van Hasselt BAAM, Fransen PSS, Dippel DWJ, Majoie CBLM, van der Lugt A, et al.; MR CLEAN Registry Investigators. Endovascular Treatment for Acute Ischemic Stroke in Children: Experience From the MR CLEAN Registry. Stroke. 2021;52:781-788.

Although there have been no large, robust, randomized trials of endovascular mechanical thrombectomy (EVT) in children with acute ischemic stroke, there is growing evidence indicating that the approach may be safe and effective.

van Es et al. performed EVT on 9 children between March 2014 and July 2017 (4 boys and 5 girls, aged 13 months-16 years, median 14 years) with an anterior circulation large vessel occlusion. Four of these children had a left ventricular assist device (ages 13 months, 18 months, 3 years, and 10 years). The median initial Pediatric National Institutes of Health Stroke Scale score (PedNIHSS) was 17 (IQR, 9.5-19.5). Four of 9 children received IV alteplase; four children with LVAD did not because they were therapeutically anticoagulated. Younger children with smaller vessels necessitated the use of smaller catheters and stent retrievers. The six children ages >10-year, however, underwent EVT with a stent retriever commonly employed for M1 occlusions in adults.