Direct oral anticoagulants in embolic stroke of undetermined source: an updated meta-analysis.

The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84-1.09; p = 0.50; I2 = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I2 = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I2 = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I2 = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I2 = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87-2.83; p = 0.14; I2 = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67-1.42; p = 0.90; I2 = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I2 = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I2 = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin.

Importance of multiplanar reformation angiographic images for the detection of carotid web: A case series.

Carotid web (CW) is considered a variant of intimal fibromuscular dysplasia. CW represents between 9.4% and 37% of ischemic strokes that were initially misclassified as "cryptogenic." However, in Latin America, there is a lack of detection. We present 5 cases of ischemic stroke due to CW and discuss the usefulness of multiplanar reformatting (MPR) imaging in computed tomography angiography. The identification of CW with the use of tridimensional (3D) reconstructions and maximum intensity projection was 20%, the rest was misdiagnosed as atherosclerotic plaque. With the MPR, the identification of typical CW findings was improved, such as a thin septum, a shelf-like image, and a mountain shadow-like image. However, one must be alert to changes in the 3D disposition of the carotid bifurcation, as they may mask the typical CW findings. A good practice is to align the internal carotid artery exactly posterior to the external carotid artery in the sagittal plane.

Scanning of paroxysmal atrial fibrillation as an etiological risk factor in patients with acute ischemic stroke: prospective study

Abstract BACKGROUND: Prevention of recurrence of stroke depends on recognition of the underlying mechanism of ischemia. OBJECTIVE: To screen patients who were hospitalized with diagnosis of acute ischemic stroke in terms of atrial fibrillation (AF) with repeated Holter electrocardiography recordings. DESIGN AND SETTING: Prospective study conducted at Konya Education and Research Hospital, Turkey. METHODS: Patients with a diagnosis of acute ischemic stroke, without atrial fibrillation on electrocardiography (ECG), were evaluated. Their age, gender, histories of previous ischemic attack, occurrences of paroxysmal atrial fibrillation (PAF) and other risks were assessed during the first week after acute ischemic stroke and one month thereafter. ECG recordings were obtained from 130 patients through 24-hour ambulatory Holter. Patients without PAF attack during the first Holter were re-evaluated. RESULTS: PAF was detected through the first Holter in 33 (25.4%) out of 130 acute ischemic stroke patients. A second Holter was planned for 97 patients: 53 (54.6%) of them could not attend due to COVID-19 pandemic; while 44 (45.3%) patients had the second Holter and, among these, 4 (9.1%) had PAF. The only parameter associated with PAF was older age. Four (10.8%) of the 37 patients with PAF had also symptomatic carotid stenosis. CONCLUSIONS: Detecting the presence of PAF by screening patients with no AF in the ECG through Holter ECG examinations is valuable in terms of changing the course of the treatment. It should be kept in mind that the possibility of accompanying PAF cannot be ruled out in the presence of other factors that pose a risk of stroke.

Atrial fibrillation post central retinal artery occlusion: Role of implantable loop recorders.

OBJECTIVE: This study evaluated the risk of subclinical atrial fibrillation (AF) in patients with central retinal artery occlusion (CRAO) compared to those with cryptogenic stroke using implantable loop recorders (ILR). METHODS: We conducted a retrospective analysis of 273 consecutive patients who had ILRs inserted at our institution for either cryptogenic stroke (n = 227) or CRAO (n = 46). Our primary endpoint was a time to event analysis for the new diagnosis of AF by ILR. Univariable and multivariable Cox proportional hazard models were used to determine the predictors of time-to-AF. RESULTS: A total of 64 patients were found to have newly diagnosed AF by remote monitoring of the ILR. AF was detected in 57 of 227 (25%) cryptogenic stroke patients by the end of a maximum 5.1 years follow-up and in seven of 46 (15%) CRAO patients by the end of a maximum 3.6 years follow-up (P = .215, log-rank test). The Kaplan-Meier estimates for freedom from AF was 59.4% for CRAO and 66.6% for cryptogenic stroke (P = NS, log-rank test). Baseline variables predicting AF included older patients, higher CHADS2 VASC score, longer PR interval on initial EKG evaluation, and mitral annular calcification on transthoracic echocardiogram. CONCLUSIONS: Patients with CRAO are at risk for subclinical AF, similar to those with cryptogenic stroke. Long-term monitoring to detect AF may lead to changes in pharmacotherapy to reduce the risk for subsequent stroke.

Foramen oval permeable, un diagnóstico posible en manos del neurólogo. Descripción de caso / Patent Foramen Ovale, A Possible Diagnosis From The Neurologist. Case Report

Resumen Introducción: En pacientes con ictus isquémico criptogénico se ha descrito una alta prevalencia de alteraciones del septum auricular relacionadas con un riesgo aumentado de presentar recurrencia. Objetivo: Presentar la historia clínica de un paciente joven con antecedente de diabetes mellitus e ictus isquémico en el que no se demuestran alteraciones arteriales. A partir de la realización de un estudio de Doppler trasncraneal con test de burbujas se diagnostica un foramen oval permeable. Conclusión: En el paciente que describimos, la realización de un estudio de DTC como parte de la evaluación inicial ayudó a precisar la etiología. La demostración de un foramen ovale permeable tiene implicaciones en la prevención secundaria del ictus.

Abstract Introduction: A high prevalence of atrial septal defects is reported in patients with cryptogenic ischemic stroke, also related to an increase of the risk of recurrence. Objective: To report case of a young patient with a history of diabetes mellitus and ischemic stroke without arterial changes proven. A transcraneal Doppler study with a bubble test helped to diagnose a patent foramen ovale. Conclusion: As part of the initial evaluation of this patient, a TCD study has helped to clarify the stroke etiology. The demonstration of a patent foramen ovale has implications for the secondary prevention of stroke.

[May Thurner syndrome with ischemic cerebrovascular accident and permeable oval foramen]. / Síndrome de May Thurner con accidente cerebrovascular isquémico y foramen oval permeable.

The association of cerebral ischemic attack with patent foramen ovale has not been extensively studied, and frequently the site of origin of embolism is not detected despite routine studies. We present the case of a young patient with ischemic stroke and permeable oval foramen in the context of May Thurner syndrome. The May Thurner syndrome is an entity scarcely studied in the medical literature and it has also been infrequently related to ischemic vascular cerebral accident, but in patients with permeable oval foramen without evidence of the emboligen source, it is interesting to rule it out as a cause of paradoxical embolism.

Síndrome de May Thurner con accidente cerebrovascular isquémico y foramen oval permeable / May Thurner syndrome with ischemic cerebrovascular accident and permeable oval foramen

La asociación de accidente cerebral isquémico con foramen oval permeable, no ha sido extensamente estudiada, y frecuentemente el sitio de origen de la embolia no se detecta a pesar de los estudios de rutina. Se presenta el caso de un paciente joven con accidente cerebral vascular isquémico y foramen oval permeable en el contexto de síndrome de May Thurner. El síndrome de May Thurner es una entidad poco estudiada en la literatura médica y además se lo ha relacionado poco con accidente cerebral vascular isquémico, pero en pacientes con foramen oval permeable sin evidencia de la fuente embolígena, es interesante descartarlo como causa de embolia paradojal.

The association of cerebral ischemic attack with patent foramen ovale has not been extensively studied, and frequently the site of origin of embolism is not detected despite routine studies. We present the case of a young patient with ischemic stroke and permeable oval foramen in the context of May Thurner syndrome. The May Thurner syndrome is an entity scarcely studied in the medical literature and it has also been infrequently related to ischemic vascular cerebral accident, but in patients with permeable oval foramen without evidence of the emboligen source, it is interesting to rule it out as a cause of paradoxical embolism.

Mutaciones heterocigóticas en el gen de la α -galactosidasa A en dos pacientes con ACV criptogénico / α -galactosidase A Heterozygous mutations gene in two patients with cryptogenic stroke

RESUMEN La enfermedad de Fabry es una enfermedad genética con herencia ligada al cromosoma X recesiva, en la que se encuentra afectada la actividad de la enzima lisosomal a-galactosidasa A (GLA), con acumulación de diferentes metabolitos como la globotriaosilceramida (GL 3) y la globotriaosilceramida deacilada (liso GL 3), responsables de la disfunción multiorgánica y de las diversas manifestaciones fenotípicas, comprometiendo principalmente: sistema nervioso, piel tracto gastrointestinal, corazón y riñón. La manifestación neurológica más temprana es el dolor neuropático, sin embargo se pueden encontrar síntomas gastrointestinales, en piel y ojo, mientras que el daño renal y cardiaco se presentan como manifestaciones tardías al igual que el ataque cerebrovascular (ACV) que se presenta en la adultez. A continuación presentamos dos casos clínicos de pacientes con ACV criptogénico con mutaciones hetero-cigotas en el gen de la a-galactosidasa A

SUMMARY Fabry's disease is a recessive X linked genetic disorder in which lysosomal enzyme alpha-galactosidase A activity is affected, with accumulation of different kind of metabolites such as globotriaosylceramide and the deacylated globotriaosylceramide which are responsible for the multi-organ dysfunction that is seen in this disease, and also of the several phenotypic manifestations, mainly in nervous system, skin, gastrointestinal tract, heart and kidney. Earlier neurological manifestation is neuropathic pain could finding also gastrointestinal tract, skin and eye complaints while Cardiac and renal damage present later like as cerebrovascular disease which presents in adulthood. Two clinical cases of young patients with cryptogenic stroke with heterozygous mutations for Fabry's disease are presenting below.

Análisis de costo-efectividad de estrategias alternativas en el manejo de pacientes con accidente cerebrovascular criptogénico y foramen oval permeable / Cost-Effectiveness Analysis of Alternative Strategies for the Management of Patients with Cryptogenic Stroke and Patent Foramen Ovale / Cost-Effectiveness Analysis of Alternative Strategies for the Management of Patients with Cryptogenic Stroke and Patent Foramen Ovale

Antecedentes El foramen oval permeable (FOP) se ha asociado con el accidente cerebrovascular criptogénico (ACVC). El mejor tratamiento para evitar la recidiva en pacientes con ACVC y FOP es controversial. No existen datos de costo-utilidad en nuestra región para el manejo de estos pacientes. Objetivos Construir un modelo de decisión para el manejo de pacientes con ACVC y FOP y establecer la relación costo-utilidad de tres estrategias alternativas. Material y métodos Se realizó un análisis de costo-utilidad basado en un árbol de decisión con un horizonte temporal de 4 años considerando tres estrategias: aspirina (AAS), anticoagulación (ACO) o cierre percutáneo del FOP con dispositivo. Los beneficios se expresaron en QALYs. Se fijó un umbral de pago de $28.000 argentinos y se realizó un análisis de sensibilidad. Resultados En comparación con la AAS, la anticoagulación fue más costosa ($1.315 adicionales) y generó menos beneficios (QALY incremental -0,063). El cierre con dispositivo comparado con el tratamiento con AAS costaría $89.876 adicionales por QALY ganado. Dicho monto supera el umbral de pago predeterminado. Luego del análisis de sensibilidad, la AAS se mantuvo como la estrategia con mejor relación costo-utilidad, salvo cuando la probabilidad de recidiva con esta droga aumenta al 35%, en donde la anticoagulación presenta una tasa de costo-utilidad incremental de $1.356/QALY. Conclusión De acuerdo con este modelo, para pacientes con ACVC y FOP, la AAS sería la estrategia con mejor relación costo-utilidad en nuestro medio, salvo cuando la probabilidad de eventos se eleva sustancialmente, en cuyo caso sería apropiado el uso de anticoagulantes.

Background Patent foramen ovale (PFO) has been associated with cryp-togenic stroke (CS). There are still some controversies about the best treatment to prevent recurrences in patients with CS and PFO. Our region lacks cost-utility analysis of the management of these patients. Objectives To construct a decision model for the management of patients with CS and PFO and to establish the cost-utility ratio of three alternative strategies. Material and Methods We conducted a cost-utility analysis based on a decision tree with a time horizon of 4 years considering three strategies: aspirin (ASA), anticoagulants (AC) or percutaneous device closure of the PFO. The benefits were expressed in QALYs. A payment threshold of ARS $28,000 was established and a sensitivity analysis was performed. Results Anticoagulants were more expensive compared to ASA (additional cost of ARS $1,315) and produced less benefits (incremental (QALY -0.063). Percutaneous device closure had an additional cost of ARS $89,876 per QALY gained compared to ASA. This cost exceeds the predetermined payment threshold. After performing the sensitivity analysis, ASA remained as the strategy with the best cost-utility ratio; however, when the probability of recurrences with this drug increases to 35%, anticoagulants present an incremental cost-utility ratio of ARS $1.356/QALY. Conclusion According to this model, in patients with CS and PFO, ASA would be the strategy with the best cost-utility ratio in our environment unless recurrences develop; in this case the use of anticoagulants would be more appropriate.

Acidente vascular encefálico isquêmico em paciente portadora de forâmen oval patente: relato de caso / Ischemic stroke in patient carrier of patent foramen oval: case report

JUSTIFICATIVA E OBJETIVOS: O embolismo através do forâmen oval patente (FOP) é bem conhecido e parece ser o principal mecanismo envolvido em pacientes jovens com acidente vascular encefálico isquêmico (AVEi). Este estudo teve como objetivo demonstrar que o diagnóstico precoce e o tratamento adequado a cada caso são essenciais na redução de possíveis morbidades relacionadas à presença do FOP. RELATO DO CASO: Paciente do sexo feminino, 26 anos, branca, jornalista, natural de Colatina, ES. Sem antecedentes patológicos significativos, iniciou em maio de 2005 quadro de hiperestesia na face flexora do antebraço e da mão esquerda, associada à hemiparesia desproporcionada incompleta esquerda de predomínio braquial, de caráter progressivo. A investigação final firmou o diagnóstico de AVEi correlacionado com a presença de FOP. A paciente foi submetida ao fechamento percutâneo do FOP com prótese Amplatzer Cribifrom n35 e orientada a utilizar ácido acetilsalisílico (AAS) e clopidogrel de forma contínua. CONCLUSÃO: O diagnóstico pôde ser feito através de exames capazes de evidenciar a patência do forâmen oval, como o ecocardiograma transesofágico e o Doppler transcraniano, associados aos métodos diagnósticos de eventos isquêmicos cerebrais. O tratamento ainda é controverso sem evidência na literatura da melhor terapêutica clínica - se anticoagulante ou antiagregante - nem sobre o melhor tratamento invasivo, se cirúrgico ou fechamento percutâneo.

BACKGROUND AND OBJECTIVES: The embolism through the patent foramen oval (FOP) is well known and seems to be the main mechanism involved in young patients with AVEI. This paper aims to demonstrate that early diagnosis and more appropriate treatment in each case are essential in the morbidity reduction related to the possible presence of the FOP. CASE REPORT: Patient female, 26 years-old, white, journalist, a native of Colatina - ES. Without significant previously healthy, began in May 2005 featuring flexor hyperesthesia in the forearm and left hand, associated with left arm incomplete disproportionate dominance progressive hemiparesis. The research has the final diagnosis of ischemic stroke correlated with the presence of FOP. The patient was submitted to FOP percutaneous closure with Amplatzer Cribifrom n35 prosthetic and directed to use aspirin and clopidogrel continuously. CONCLUSION: The diagnosis can be done through examinations capable of demonstrating the foramen oval patency, as the transesophageal echocardiography and transcranial Doppler sonography, associated with ischemic stroke brain diagnostic methods. The treatment is still controversial, no evidence in the literature of better medical therapy - if anticoagulant or antiplatelet - not on the best invasive treatment, whether surgical or percutaneous closure.