Letter by Scheitz et al regarding article, "Randomized controlled trial of early versus delayed statin therapy in patients with acute ischemic stroke: ASSORT trial (administration of statin on acute ischemic stroke patient)"

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Are you suffering from a large arterial occlusion? Please raise your arm!

Background and purpose: Triage tools to identify candidates for thrombectomy are of utmost importance in acute stroke. No prognostic tool has yet gained any widespread use. We compared the predictive value of various models based on National Institutes of Health Stroke Scale (NIHSS) subitems, ranging from simple to more complex models, for predicting large artery occlusion (LAO) in anterior circulation stroke. Methods: Patients registered in the SITS international Stroke Register with available NIHSS and radiological arterial occlusion data were analysed. We compared 2042 patients harbouring an LAO with 2881 patients having no/distal occlusions. Using binary logistic regression, we developed models ranging from simple 1 NIHSS-subitem to full NIHSS-subitems models. Sensitivities and specificities of the models for predicting LAO were examined. Results: The model with highest predictive value included all NIHSS subitems for predicting LAO (area under the curve (AUC) 0.77), yielding a sensitivity and specificity of 69% and 76%, respectively. The second most predictive model (AUC 0.76) included 4-NIHSS-subitems (level of consciousness commands, gaze, facial and arm motor function) yielding a sensitivity and specificity of 67% and 75%, respectively. The simplest model included only deficits in arm motor-function (AUC 0.72) for predicting LAO, yielding a sensitivity and specificity of 67% and 72%, respectively. Conclusions: Although increasingly more complex models yield a higher discriminative performance for predicting LAO, differences between models are not large. Assessing grade of arm dysfunction along with an established stroke-diagnosis model may serve as a surrogate measure of arterial occlusion-status, thereby assisting in triage decisions

Early recurrent ischemic lesions in patients with cryptogenic stroke and patent foramen ovale: an observational study

Background: Randomized controlled trials indicate that patent foramen ovate (PFO) closure reduces risk of stroke recurrence in patients with cryptogenic stroke and PFO. However, the optimal time point for PFO closure is unknown and depends on the risk of stroke recurrence. Objective: We aimed to investigate risk of early new ischemic lesions on cerebral magnetic resonance imaging (MRI) in cryptogenic stroke patients with and without PFO. Methods: Cryptogenic stroke patients underwent serial MRI examinations within 1 week after symptom onset to detect early new ischemic lesions. Diffusion-weighted imaging (DWI) lesions were delineated, co-registered, and analyzed visually for new hyperintensities by raters blinded to clinical details. A PFO was classified as stroke-related in patients with PFO and a Risk of Paradoxical Embolism (RoPE) score >5 points. Results: Out of 80 cryptogenic stroke patients, risk of early recurrent DWI lesions was not significantly different in cryptogenic stroke patients with and without PFO. Similar results were observed in patients <= 60 years of age. Patients with a stroke-related PFO even had a significantly lower risk of early recurrent ischemic lesions compared to all other patients with cryptogenic stroke (unadjusted odds ratio 0.23 [95% confidence interval 0.06-0.87], P = 0.030). Conclusion: Our data argue against a high risk of early stroke recurrence in patients with cryptogenic stroke and PFO

Clinical selection strategies to identify ischemic stroke patients with large anterior vessel occlusion: results from SITS-ISTR (Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry)

Background and Purpose—The National Institutes of Health Stroke Scale (NIHSS) correlates with presence of large anterior vessel occlusion (LAVO). However, the application of the full NIHSS in the prehospital setting to select patients eligible for treatment with thrombectomy is limited. Therefore, we aimed to evaluate the prognostic value of simple clinical selection strategies. Methods—Data from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry (January 2012–May 2014) were analyzed retrospectively. Patients with complete breakdown of NIHSS scores and documented vessel status were included. We assessed the association of prehospital stroke scales and NIHSS symptom profiles with LAVO (internal carotid artery, carotid-terminus or M1-segment of the middle cerebral artery). Results—Among 3505 patients, 23.6% (n=827) had LAVO. Pathological finding on the NIHSS item best gaze was strongly associated with LAVO (adjusted odds ratio 4.5, 95% confidence interval 3.8–5.3). All 3 face–arm–speech–time test (FAST) items identified LAVO with high sensitivity. Addition of the item gaze to the original FAST score (G-FAST) or high scores on other simplified stroke scales increased specificity. The NIHSS symptom profiles representing total anterior syndromes showed a 10-fold increased likelihood for LAVO compared with a nonspecific clinical profile. If compared with an NIHSS threshold of ≥6, the prehospital stroke scales performed similarly or even better without losing sensitivity. Conclusions—Simple modification of the face–arm–speech–time score or evaluating the NIHSS symptom profile may help to stratify patients’ risk of LAVO and to identify individuals who deserve rapid transfer to comprehensive stroke centers. Prospective validation in the prehospital setting is required

A Score for Risk of Thrombolysis-Associated Hemorrhage Including Pretreatment with Statins

Background: Symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis with recombinant tissue-plasminogen activator (rt-PA) for acute ischemic stroke is associated with a poor functional outcome. We aimed to develop a score assessing risk of sICH including novel putative predictors—namely, pretreatment with statins and severe renal impairment. Methods: We analyzed our local cohort (Berlin) of patients receiving rt-PA for acute ischemic stroke between 2006 and 2016. Outcome was sICH according to ECASS-III criteria. A multiple regression model identified variables associated with sICH and receiver operating characteristics were calculated for the best discriminatory model for sICH. The model was validated in an independent thrombolysis cohort (Basel). Results: sICH occurred in 53 (4.0%) of 1,336 patients in the derivation cohort. Age, baseline National Institutes of Health Stroke Scale, systolic blood pressure on admission, blood glucose on admission, and prior medication with medium- or high-dose statins were associated with sICH and included into the risk of intracranial hemorrhage score. The validation cohort included 983 patients of whom 33 (3.4%) had a sICH. c-Statistics for sICH was 0.72 (95% CI 0.66–0.79) in the derivation cohort and 0.69 (95% CI 0.60–0.77) in the independent validation cohort. Inclusion of severe renal impairment did not improve the score. Conclusion: We developed a simple score with fair discriminating capability to predict rt-PA- related sICH by adding prior statin use to known prognostic factors of sICH. This score may help clinicians to identify patients with higher risk of sICH requiring intensive monitoring

Cardiovascular MRI Compared to Echocardiography to Identify Cardioaortic Sources of Ischemic Stroke: A Systematic Review and Meta-Analysis

Background: To compare the diagnostic yield of echocardiography and cardiovascular MRI (CMR) to detect structural sources of embolism, in patients with ischemic stroke with a secondary analysis of non-stroke populations. Methods and Results: We searched MEDLINE/Embase (from 01.01.2000 to 24.04.2021) for studies including CMR to assess prespecified sources of embolism. Comparison included transthoracic and/or transesophageal echocardiography. Two authors independently screened studies, extracted data and assessed bias using the QUADAS-2 tool. Estimates of diagnostic yield were reported and pooled. Twenty-seven studies with 2,525 patients were included in a study-level analysis. Most studies had moderate to high risk of bias. Persistent foramen ovale, complex aortic plaques, left ventricular and left atrial thrombus were the most common pathologies. There was no difference in the yield of left ventricular thrombus detection between both modalities for stroke populations (4 studies), but an increased yield of CMR in non-stroke populations (28.1 vs. 16.0%, P < 0.001, 10 studies). The diagnostic yield in stroke patients for detection of persistent foramen ovale was lower in CMR compared to transoesophageal echocardiography (29.3 vs. 53.7%, P < 0.001, 5 studies). For both echocardiography and CMR the clinical impact of the management consequences derived from many of the diagnostic findings remained undetermined in the identified studies. Conclusions: Echocardiography and CMR seem to have similar diagnostic yield for most cardioaortic sources of embolism except persistent foramen ovale and left ventricular thrombus. Randomized controlled diagnostic trials are necessary to understand the impact on the management and potential clinical benefits of the assessment of structural cardioaortic stroke sources. Registration: PROSPERO: CRD42020158787

Can intracranial time-of-flight-MR angiography predict extracranial carotid artery stenosis?

Objectives: Extracranial stenosis of the internal carotid artery (ICA) is an important cause of ischemic stroke and transient ischemic attack (TIA). It can be diagnosed using contrast-enhanced CT or MR angiography (MRA) as well as Doppler ultrasound. In this study, we assessed the diagnostic value of intracranial time-of-flight (TOF) MRA to predict extracranial ICA stenosis (ICAS). Methods: We retrospectively analyzed consecutive patients with acute ischemic stroke or TIA and middle- (50-69%) or high-grade (70-99%) unilateral extracranial ICAS according to NASCET criteria assessed by ultrasound between January 2016 and August 2018. The control group consisted of patients without extracranial ICAS. Intraluminal signal intensities (SI) of the intracranial ICA on the side of the extracranial stenosis were compared to the contralesional side on TOF-MRA source images. SI ratios (SIR) of contralesional:lesional side were compared between groups. Results: In total, 151 patients were included in the main analysis. Contralesional:lesional SIR in the intracranial C4-segment was significantly higher in patients with ipsilateral extracranial ICA stenosis (n = 51, median 74 years, 57% male) compared to the control group (n = 100, median 68 years, 48% male). Mean SIR was 1.463 vs. 1.035 (p < 0.001) for right-sided stenosis and 1.362 vs. 1.000 (p < 0.001) for left-sided stenosis. Receiver-operating characteristic curve demonstrated a cut-off value of 1.086 for right-sided [sensitivity/specificity 75%/81%; area under the curve (AUC) 0.81] and 1.104 for left-sided stenosis (sensitivity/specificity 70%/84%; AUC 0.80) in C4 as a good predictor for high-grade extracranial ICAS. Conclusions: SIR on TOF-MRA can be a marker of extracranial ICAS

Neurological update: use of cardiac troponin in patients with stroke

Cardiac troponin is a specific and sensitive biomarker to identify and quantify myocardial injury. Myocardial injury is frequently detected after acute ischemic stroke and strongly associated with unfavorable outcomes. Concomitant acute coronary syndrome is only one of several possible differential diagnoses that may cause elevation of cardiac troponin after stroke. As a result, there are uncertainties regarding the correct interpretation and optimal management of stroke patients with myocardial injury in clinical practice. Elevation of cardiac troponin may occur as part of a ‘Stroke-Heart Syndrome’. The term ‘Stroke-Heart Syndrome’ subsumes a clinical spectrum of cardiac complications after stroke including cardiac injury, dysfunction, and arrhythmia which may relate to disturbances of autonomic function and the brain–heart axis. In this review, we provide an up-to-date overview about prognostic implications, mechanisms, and management of elevated cardiac troponin levels in patients with acute ischemic stroke

Stroke–Heart Syndrome: Recent Advances and Challenges

After ischemic stroke, there is a significant burden of cardiovascular complications, both in the acute and chronic phase. Severe adverse cardiac events occur in 10% to 20% of patients within the first few days after stroke and comprise a continuum of cardiac changes ranging from acute myocardial injury and coronary syndromes to heart failure or arrhythmia. Recently, the term stroke– heart syndrome was introduced to provide an integrated conceptual framework that summarizes neurocardiogenic mechanisms that lead to these cardiac events after stroke. New findings from experimental and clinical studies have further refined our understanding of the clinical manifestations, pathophysiology, and potential long-term consequences of the stroke– heart syndrome. Local cerebral and systemic mediators, which mainly involve autonomic dysfunction and increased inflammation, may lead to altered cardiomyocyte metabolism, dysregulation of (tissue-resident) leukocyte pop-ulations, and (micro-) vascular changes. However, at the individual patient level, it remains challenging to differentiate between comorbid cardiovascular conditions and stroke-induced heart injury. Therefore, further research activities led by joint teams of basic and clinical researchers with backgrounds in both cardiology and neurology are needed to identify the most relevant therapeutic targets that can be tested in clinical trials

Stroke–Heart Syndrome: Recent Advances and Challenges

After ischemic stroke, there is a significant burden of cardiovascular complications, both in the acute and chronic phase. Severe adverse cardiac events occur in 10% to 20% of patients within the first few days after stroke and comprise a continuum of cardiac changes ranging from acute myocardial injury and coronary syndromes to heart failure or arrhythmia. Recently, the term stroke-heart syndrome was introduced to provide an integrated conceptual framework that summarizes neurocardiogenic mechanisms that lead to these cardiac events after stroke. New findings from experimental and clinical studies have further refined our understanding of the clinical manifestations, pathophysiology, and potential long-term consequences of the stroke-heart syndrome. Local cerebral and systemic mediators, which mainly involve autonomic dysfunction and increased inflammation, may lead to altered cardiomyocyte metabolism, dysregulation of (tissue-resident) leukocyte populations, and (micro-) vascular changes. However, at the individual patient level, it remains challenging to differentiate between comorbid cardiovascular conditions and stroke-induced heart injury. Therefore, further research activities led by joint teams of basic and clinical researchers with backgrounds in both cardiology and neurology are needed to identify the most relevant therapeutic targets that can be tested in clinical trials