Assessment of 'on-treatment platelet reactivity' and relationship with cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis.

INTRODUCTION: The relationship between on-treatment platelet reactivity and cerebral micro-embolic signals (MES) is unknown, and has not been previously simultaneously assessed in asymptomatic and symptomatic carotid stenosis patients. METHODS: Consecutive eligible patients with ≥50% asymptomatic or recently symptomatic carotid stenosis (≤4weeks following TIA/ischaemic stroke) were recruited to this pilot study. Symptomatic patients were followed up to the 'late' phase (≥3months) following symptom onset or carotid intervention; longitudinal data were analysed from symptomatic patients with data available at both time-points. Platelet function/reactivity was assessed with the PFA-100® to measure collagen-ADP (C-ADP) and collagen-epinephrine (C-EPI) closure times in citrate-anticoagulated whole blood. Bilateral simultaneous 1-hour transcranial Doppler ultrasound (TCD) monitoring of the middle cerebral arteries was performed to classify patients as MES +ve or MES -ve. RESULTS: 31 patients with ≥50% asymptomatic and 46 with early symptomatic carotid stenosis or occlusion were included. 35 symptomatic patients were followed up to the late phase (23 following carotid intervention). Prevalence of 'high on-treatment platelet reactivity' (HTPR) on the C-EPI cartridge did not differ between asymptomatic and symptomatic patients overall, but was lower in 'symptomatic post-intervention' than asymptomatic patients on aspirin monotherapy (10% vs. 50%; p=0.03). The prevalence of HTPR on the C-EPI cartridge decreased between the early and late phases in symptomatic patients (63% vs. 34%; p=0.017), including those on aspirin monotherapy (p=0.016). There were no significant differences in HTPR status between asymptomatic vs. early or late symptomatic MES +ve or MES -ve patients. DISCUSSION: Carotid interventional treatment, presumably in combination with resolution of the acute phase response, may decrease the prevalence of HTPR in patients with recently symptomatic carotid stenosis over time. Preliminary subgroup analysis suggests that successful intervention may reduce the prevalence of aspirin-HTPR in symptomatic patients to lower levels than asymptomatic medically-treated patients on aspirin monotherapy. Larger, longitudinal studies are warranted to reassess the impact of more intensive secondary preventive treatment on ex vivo platelet function at different levels of shear stress in carotid stenosis patients.

Stroke vision, aphasia, neglect (VAN) assessment-a novel emergent large vessel occlusion screening tool: pilot study and comparison with current clinical severity indices.

BACKGROUND: Identification of emergent large vessel occlusion (ELVO) stroke has become increasingly important with the recent publications of favorable acute stroke thrombectomy trials. Multiple screening tools exist but the length of the examination and the false positive rate range from good to adequate. A screening tool was designed and tested in the emergency department using nurse responders without a scoring system. METHODS: The vision, aphasia, and neglect (VAN) screening tool was designed to quickly assess functional neurovascular anatomy. While objective, there is no need to calculate or score with VAN. After training participating nurses to use it, VAN was used as an ELVO screen for all stroke patients on arrival to our emergency room before physician evaluation and CT scan. RESULTS: There were 62 consecutive code stroke activations during the pilot study. 19 (31%) of the patients were VAN positive and 24 (39%) had a National Institutes of Health Stroke Scale (NIHSS) score of ≥6. All 14 patients with ELVO were either VAN positive or assigned a NIHSS score ≥6. While both clinical severity thresholds had 100% sensitivity, VAN was more specific (90% vs 74% for NIHSS ≥6). Similarly, while VAN and NIHSS ≥6 had 100% negative predictive value, VAN had a 74% positive predictive value while NIHSS ≥6 had only a 58% positive predictive value. CONCLUSIONS: The VAN screening tool accurately identified ELVO patients and outperformed a NIHSS ≥6 severity threshold and may best allow clinical teams to expedite care and mobilize resources for ELVO patients. A larger study to both validate this screening tool and compare with others is warranted.

Computational Assessment of the Relation Between Embolism Source and Embolus Distribution to the Circle of Willis for Improved Understanding of Stroke Etiology.

Stroke caused by an embolism accounts for about a third of all stroke cases. Understanding the source and cause of the embolism is critical for diagnosis and long-term treatment of such stroke cases. The complex nature of the transport of an embolus within large arteries is a primary hindrance to a clear understanding of embolic stroke etiology. Recent advances in medical image-based computational hemodynamics modeling have rendered increasing utility to such techniques as a probe into the complex flow and transport phenomena in large arteries. In this work, we present a novel, patient-specific, computational framework for understanding embolic stroke etiology, by combining image-based hemodynamics with discrete particle dynamics and a sampling-based analysis. The framework allows us to explore the important question of how embolism source manifests itself in embolus distribution across the various major cerebral arteries. Our investigations illustrate prominent numerical evidence regarding (i) the size/inertia-dependent trends in embolus distribution to the brain; (ii) the relative distribution of cardiogenic versus aortogenic emboli among the anterior, middle, and posterior cerebral arteries; (iii) the left versus right brain preference in cardio-emboli and aortic-emboli transport; and (iv) the source-destination relationship for embolisms affecting the brain.

[Is necessary to perform a transthoracic echocardiogram in all the patients with cryptogenic stroke during hospitalization?]. / Es necesaria la realizacion de un ecocardiograma transtoracico a todos los pacientes con ictus isquemico indeterminado durante el ingreso?

INTRODUCTION: From 15 to 30% of all ischemic strokes are cardioembolic. Transthoracic echocardiography plays a key role in the evaluation, diagnosis and management of the embolic source. The absence of official recommendations for the use of echocardiography in patients with ischemic stroke leads to a universal application showing low diagnostic efficiency. AIM: To analyze the diagnostic accuracy of echocardiograpm in patients with ischemic stroke in two situations: with universal indication and after the application of risk clinical criteria. PATIENTS AND METHODS: Analysis of the echocardiograms performed on patients with acute ischemic stroke from the stroke unit during the years 2009-2011. We study the diagnostic and etiological contribution to the etiological study. Apply a selection criteria: 'high risk patient with need of test performance during admission' (age < 60 years, abnormal baseline electrocardiogram, cardiomegaly on chest radiograph or baseline history of heart disease, suspected endocarditis and/or active neoplasia) and analyzed their validity. RESULTS: From 930 inpatients, 201 (21.6%), underwent echocardiogram. Cardioembolic source was detected in 9.95%. After application of selection criteria, only 97 patients (10.4%) should have undergone it. The proposed criteria have a sensitivity 95%, specificity 56.9%, positive predictive value 19.6% and negative predictive value of 99%. CONCLUSIONS: The application of our criteria in undetermined stroke patients help us to identify with high efficiency cardioembolic sources postponing the test to an ambulatory scenario in the rest of the patients.

TITLE: Es necesaria la realizacion de un ecocardiograma transtoracico a todos los pacientes con ictus isquemico indeterminado durante el ingreso?Introduccion. El 15-30% de los ictus isquemicos son de origen cardioembolico. El ecocardiograma transtoracico desempena un papel fundamental en la evaluacion, diagnostico y manejo de la fuente embolica. La ausencia de recomendaciones oficiales para el empleo del ecocardiograma en pacientes con ictus isquemico lleva a una solicitud universal de la prueba, presentando una baja rentabilidad diagnostica. Objetivo. Analizar la rentabilidad diagnostica del ecocardiograma transtoracico en pacientes con ictus isquemico indeterminado tras la aplicacion de criterios clinicos predefinidos de riesgo. Pacientes y metodos. Se analizan los ecocardiogramas realizados a pacientes con ictus isquemico agudo solicitados durante 2009-2011 desde el servicio de neurologia. Se estudia la rentabilidad diagnostica y su aportacion al estudio etiologico. Se aplican unos 'criterios de seleccion de paciente de alto riego con necesidad de realizacion de la prueba durante el ingreso' (edad < 60 anos, alteraciones en el ecocardiograma basal, cardiomegalia en la radiografia de torax basal, antecedentes de cardiopatia, sospecha clinica de endocarditis o neoplasia activa) y se analiza su validez. Resultados. De 930 pacientes, se realizo ecocardiograma a 201 (21,6%) y se detecto una fuente cardioembolica en el 9,95%. Tras la aplicacion de criterios de seleccion, el numero de ecocardiogramas paso a 97 (10,4%). Los criterios propuestos presentan: sensibilidad, 95%; especificidad, 56,9%; valor predictivo positivo, 19,6%, y valor predictivo negativo, 99%. Conclusiones. La aplicacion de nuestros criterios a pacientes con ictus indeterminado identifica con alta eficiencia la fuente cardioembolica, lo que permite la realizacion del ecocardiograma transtoracico ambulatorio en el resto de los pacientes.

Cost-effectiveness analysis of the neuroprotective agent edaravone for noncardioembolic cerebral infarction.

BACKGROUND: The free radical scavenger edaravone has been reported useful for improvement in activities of daily living and for prevention of recurrent stroke in the edaravone versus sodium ozagrel in acute noncardioembolic ischemic stroke (EDO) trial. The aim of this report was to evaluate the cost-effectiveness of edaravone compared to the intravenous antiplatelet drug ozagrel sodium (ozagrel) for noncardioembolic stroke (non-CES) based on the EDO trial data. METHODS: A cost-effectiveness analysis was performed using the Markov model, which also incorporated the long-term course after the acute stage of non-CES. From the perspective of a health care payer, direct medical costs and nursing care costs were taken into account in the cost analysis. The quality-adjusted life year (QALY) served as an indicator of effectiveness. Simulation at 5 and 10 years after the onset of non-CES was carried out. The study involved 68-year-old patients with non-CES, selected against the EDO trial subject selection criteria. A 14-day treatment with edaravone 60 mg/day or ozagrel 160 mg/day was assumed as acute treatment for non-CES. RESULTS: The use of edaravone was associated with a reduction in total costs (0.51 million yen [$6,374] at 5 years and 0.64 million yen [$8,039]) at 10 years after the onset of non-CES) and improvement in QALYs (0.23 at 5 years and 0.38 at 10 years). Compared to ozagrel therapy, edaravone therapy was a cost-saving strategy for treating non-CES. CONCLUSIONS: Compared to ozagrel therapy, edaravone therapy for non-CES is not only useful from a clinical viewpoint, but also valuable from a socioeconomic perspective.

Perfil clínico epidemiológico de pacientes con accidente cerebrovascular en el Instituto Hondureño de Seguridad Social / Clinical and epidemiological profile of patients with stroke at The Honduran Social Security Institute

Introducción: En Honduras los accidentes cerebro vasculares (ACV) son la octava causa de muerte a nivel nacional y cuarta causa de muerte en hospitales estatales. Es la primera causa neurológica de ingresos en el Hospital Escuela. El objetivo del estudio fue determinar el perfil clínico epidemiológico de los pacientes con ACV atendidos en el Instituto Hondureño de Seguridad Social (IHSS) en Tegucigalpa. Pacientes y métodos: Se realizó un estudio transversal descriptivo incluyendo a 56 pacientes con diagnóstico de ACV durante el período enero a diciembre del año 2006. Resultados. Predominó el ACV isquémico (68%). Los hombres sufrieron ACV de tipo hemorrágico más que las mujeres (34% vs. 25% respectivamente). La hipertensión arterial fue el antecedente de riesgo predominante (66%, 37/56), seguido de la diabetes mellitus (26.7%, 15/56). El 55% de las mujeres y el 36% de los hombres habían presentado un ACV previo. Discusión. Los resultados muestran que el principal factor de riesgo para ACV en pacientes del IHSS continúa siendo la hipertensión arterial, predominando el ECV Isquémico. Los pacientes requirieron ser atendidos en diversas unidades de tratamiento hospitalario...

Should routine echocardiography be performed in all patients with stroke?

BACKGROUND: Cardiogenic embolism accounts for 15% to 30% of ischemic strokes. Echocardiography is frequently being used as a screening test for sources of cardiac embolism in patients with stroke. However, the value of routine use of echocardiography for this task remains controversial. We evaluated the diagnostic yield of echocardiography in unselected patients with acute ischemic stroke. METHODS: Consecutive patients with ischemic stroke or a transient ischemic attack were included in the study. Transthoracic echocardiography was performed in all patients, complemented by transesophageal echocardiography in selected patients. RESULTS: In all, 807 echocardiographic examinations (743 transthoracic and 64 transesophageal) were performed in 775 consecutive patients. A potential cardiac source of embolism (CSE) was found in 144 (18%) of the patients. The most frequent potential causes of cardiac embolism included atrial fibrillation (7%) and patent foramen ovale (6%). Results were more likely to have impact on therapeutic decisions in younger patients. Numbers needed to test for detection of CSE increased 10-fold from 6 in patients younger than 50 years to 62 in patients aged 70 years and older. CONCLUSION: Echocardiography may provide important information on the cause of ischemic stroke. However, echocardiographic screening for a CSE is not warranted in all patients. In patients with younger than 50 years with stroke, echocardiography has a higher diagnostic yield and should routinely be performed. In older patients routine echocardiography results in a high rate of unspecific findings, and should be applied selectively, targeted at specific clinical questions.

Serum S-100b protein as a biomarker for the assessment of neuroprotectants.

The study of biomarkers associated with stroke has proved to be of considerable utility. The astroglial protein S-100b is a candidate marker for cerebral tissue damage. We used a rat embolic model produced by injection of microspheres to demonstrate that serum S-100b is a useful biochemical marker for ischemic brain injury. Serum S-100b levels were significantly increased following microsphere injection, which was closely correlated with the development of brain edema. We found that structurally and mechanistically independent neuroprotective agents, such as 3-[2-[4-(3-chloro-2-methylphenylmethyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e), a novel calmodulin antagonist, and the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801, are capable of attenuating increased serum S-100b levels and brain edema. In contrast, the hyperosmolar agent glycerol, which has no direct neuroprotective action, had little effect on serum S-100b levels, despite a significant decrease in brain water content. These results suggest that lowering of serum S-100b is mediated by neuroprotection against ischemic brain injury. Thus, serum S-100b reflects the extent of brain damage following cerebral ischemia and serves as a useful biomarker for the assessment of neuroprotectants.

[Comparative assessment of persistent and paroxysmal atrial fibrillation as causes of cardiocerebral embolism]. / Sravnitel'naia otsenka postoiannoi i paroksizmal'noi fibrilliatsii predserdii v patogeneze kardiotserebral'noi émbolii.

In 66 patients with embolic stroke of cardiac origin (33 with persistent and 33 with paroxysmal atrial fibrillation) transthoracic and transesophageal (21 patients, 31.2%) echocardiography was used for detection of atrial thrombosis. Lone atrial fibrillation was significantly more frequent among patients with paroxysmal atrial fibrillation. Frequency of thrombosis of left atrial appendage was similar in patients with nonrheumatic persistent and paroxysmal atrial fibrillation.

An assessment of perfusion deficits in decompression illness using 99Tcm HMPAO SPET and statistical parametric mapping.

AIM: The aim of this study was to use statistical parametric mapping (SPM) to investigate differences in the regional cerebral blood flow (rCBF) of decompression illness (DCI) and non-diving control subjects. METHODS: Twenty DCI subjects were imaged using 99Tcm hexamethylproplylene amine oxime (HMPAO) single photon emission tomography (SPET) within days of their incident of DCI, and on a second occasion between 2 and 27 months after their DCI event. SPM was used to make a comparison between decompression illness studies and a second group of non-diving control studies for both early and late imaging of DCI. A paired comparison of early and late imaging was also performed testing for correlation between time of imaging and changes in the rCBF pattern. RESULTS: The comparison between control subjects and early imaging of decompression illness showed a large, significant (P = 0.002), irregularly shaped, multi-focal area of reduced uptake in the left occipito-parieto-temporal region of the brain. Comparisons between control and repeat decompression illness imaging studies showed two areas of reduced uptake. The first was similar to that found in the initial comparison although it was less significant (P = 0.035). The second region was similar but contra-lateral to the first region with significance P < 0.001. An attempt to correlate any changes in rCBF with the time that elapsed between each set of imaging found no areas of significant correlation. CONCLUSION: 99Tcm HMPAO SPET images of decompression illness display areas of reduced perfusion, which persist in the majority of cases.