Doble terapia antiagregante en pacientes con accidente cerebrovascular isquémico agudo: Recomendación del grupo CIERTO / Dual antiplatelet therapy for secondary stroke prevention in patients with acute ischemic stroke. CIERTO group recommendation

El inicio precoz del tratamiento con antiagregantes plaquetarios es considerado el estándar de cuidado para pacientes con accidente cerebrovascular isquémico agudo. Distintos esquemas de antiagregación se han comparado con resultados que sugieren que la combinación de múltiples antiagregantes se asocian a menor riesgo de recurrencia de accidente cerebrovascular (ACV) pero a expensas de un aumento en el riesgo de sangrado, lo que a largo plazo termina opacando dichos beneficos. Sin embargo, considerando que el riesgo de recurrencia de ACV es mayor en el periodo inmediato al evento, la indicación de doble tratamiento antiagregante por tiempos limitados podría asociarse a beneficios relevantes. Con este concepto, se realizó una revisión sistemática rápida con el objetivo de evaluar el efecto del tratamiento con doble antiagregación por un periodo corto intentando maximizar el beneficio y reducir al mínimo el riesgo de sangrado. Se incluyeron todos los estudios primarios identificados en los que se comparó un esquema de doble antiagregación, iniciado en el periodo agudo del evento índice (ACV o accidente isquémico transitorio - AIT), contra un esquema de simple antiagregación. El cuerpo de la evidencia mostró que la intervención (doble antiagregación) reduce el riesgo de recurrencia de ACV y probablemente se asocie a un aumento marginal en el riesgo de sangrado mayor. Sugerimos indicar doble esquema antiplaquetario para el tratamiento inicial de pacientes con ACV isquémico menor (Score NIH < o igual a 3 o AIT).

One of the main pillars of acute ischemic stroke management is antiplatelet therapy. Different treatment schemes have been compared, suggesting that the combination of multiple antiplatelet drugs is associated with a reduced risk of stroke recurrence. However, it has also been associated with an increased risk of bleeding complications which, in the long term, surpass the mentioned benefits. However, considering that most stroke recurrences occur i n the short term, a time limited double antiplatelet scheme could result in significant benefits to patients with acute ischemic stroke. On this basis, we conducted a rapid systematic review of the literature in order to evaluate the effects of a short-term double antiplatelet therapy both on stroke recurrence and complications. All trials comparing double versus single antiplatelet therapy in patients with acute ischemic stroke were included. Results showed that double therapy reduces recurrence risk but probably marginally increases major bleeding complications. We suggest double antiplatelet therapy for the initial management of patients with minor (Score NIH < or equal to 3 or transient isquemic attack -TIA) acute ischemic stroke.

Comparison of Outcomes after Device Closure and Medication Alone in Patients with Patent Foramen Ovale and Cryptogenic Stroke in Korean Population

PURPOSE: To compare the effectiveness of device closure and medical therapy in prevention of recurrent embolic event in the Korean population with cryptogenic stroke and patent foramen ovale (PFO). MATERIALS AND METHODS: Consecutive 164 patients (men: 126 patients, mean age: 48.1 years, closure group: 72 patients, medical group: 92 patients) were enrolled. The primary end point was a composite of death, stroke, transient ischemic attack (TIA), or peripheral embolism. RESULTS: Baseline characteristics were similar in the two groups, except age, which was higher in the medical group (45.3±9.8 vs. 50.2±6.1, p<0.0001), and risk of paradoxical embolism score, which was higher in the closure group (6.2±1.6 vs. 5.7±1.3, p=0.026). On echocardiography, large right-to-left shunt (81.9% vs. 63.0%, p=0.009) and shunt at rest/septal hypermobility (61.1% vs. 23.9%, p<0.0001) were more common in the closure group. The device was successfully implanted in 71 (98.6%) patients. The primary end point occurred in 2 patients (2 TIA, 2.8%) in the closure group and in 2 (1 death, 1 stroke, 2.2%) in the medical group. Event-free survival rate did not differ between the two groups. CONCLUSION: Compared to medical therapy, device closure of PFO in patients with cryptogenic stroke did not show difference in reduction of recurrent embolic events in the real world's setting. However, considering high risk of echocardiographic findings in the closure group, further investigation of the role of PFO closure in the Asian population is needed.

Accidente isquémico transitorio de causa hemodinámica / Transient ischemic attack of hemodynamic cause

El síncope es una perdida súbita y transitoria del estado de conciencia y el tono postural con restitución completa. Según su etiología se clasifica como reflejo (neuromediado), cardíaco, neurológico (isquemia vertebrobasilar) o indeterminado. Los síncopes neurológicos se observan en contexto de accidente cerebrovascular isquémico o accidente isquémico transitorio; frecuentemente se asocian a signos deficitarios focales. Presentamos el caso de un síncope no neurológico con signos deficitarios focales en una paciente con marcada enfermedad ateromatosa. (AU)

Syncope is the abrupt and transient loss of consciousness associated with absence of postural tone, followed by complete and usually rapid spontaneous recovery. In terms of etiology, syncope is classified as reflex (neurally mediated), cardiac, neurologic (vertebrobasilar ischemia) or indeterminate. The neurologic syncope occurs in the setting of stroke or transient ischemic attack, being most frequently associated with focal neurologic symptoms. We report a case of non-neurologic syncope followed with focal neurologic symptoms in a patient with atherosclerosis disease. (AU)

Atorvastatin protects GABAergic and dopaminergic neurons in the nigrostriatal system in an experimental rat model of transient focal cerebral ischemia / La atorvastatina protege las neuronas gabérgicas y dopaminérgicas del sistema nigroestriatal en un modelo experimental de isquemia cerebral focal transitoria en ratas

Introduction: Cerebral ischemia is the third leading cause of death and the primary cause of permanent disability worldwide. Atorvastatin is a promising drug with neuroprotective effects that may be useful for the treatment of stroke. However, the effects of atorvastatin on specific neuronal populations within the nigrostriatal system following cerebral ischemia are unknown. Objective: To evaluate the effects of atorvastatin on dopaminergic and GABAergic neuronal populations in exofocal brain regions in a model of transient occlusion of the middle cerebral artery. Materials and methods: Twenty-eight male eight-week-old Wistar rats were used in this study. Both sham and ischemic rats were treated with atorvastatin (10 mg/kg) or carboxymethylcellulose (placebo) by gavage at 6, 24, 48 and 72 hours post-reperfusion. We analyzed the immunoreactivity of glutamic acid decarboxylase and tyrosine hydroxylase in the globus pallidus, caudate putamen and substantia nigra. Results: We observed neurological damage and cell loss in the caudate putamen following ischemia. We also found an increase in tyrosine hydroxylase immunoreactivity in the medial globus pallidus and substantia nigra reticulata, as well as a decrease in glutamic acid decarboxylase immunoreactivity in the lateral globus pallidus in ischemic animals treated with a placebo. However, atorvastatin treatment was able to reverse these effects, significantly decreasing tyrosine hydroxylase levels in the medial globus pallidus and substantia nigra reticulata and significantly increasing glutamic acid decarboxylase levels in the lateral globus pallidus. Conclusion: Our data suggest that post-ischemia treatment with atorvastatin can have neuro-protective effects in exofocal regions far from the ischemic core by modulating the GABAergic and dopaminergic neuronal populations in the nigrostriatal system, which could be useful for preventing neurological disorders.

Introducción. La isquemia cerebral es la tercera causa de muerte y la primera de discapacidad permanente en el mundo. La atorvastatina es un fármaco neuroprotector prometedor para el tratamiento de la apoplejía; sin embargo, su acción sobre las poblaciones neuronales del sistema nigroestriatal después de la isquemia aún se desconoce. Objetivo. Evaluar el efecto de la atorvastatina sobre poblaciones gabérgicas y dopaminérgicas en regiones exofocales en un modelo de oclusión transitoria de la arteria cerebral media. Materiales y métodos. Se utilizaron 28 ratas Wistar macho de ocho semanas de edad. Los ejemplares con isquemia simulada y los ejemplares sometidos a isquemia fueron tratados con atorvastatina (10 mg/kg) y carboximetilcelulosa (placebo) administrados por medio de sonda a las 6, 24, 48 y 72 horas después de la reperfusión. Se analizó la inmunorreacción de la descarboxilasa del ácido glutámico y de la tirosina hidroxilasa en el globo pálido, el putamen caudado y la sustancia negra. Resultados. Los datos confirmaron el daño neurológico y la pérdida celular en el putamen caudado. Se incrementó la inmunorreacción de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata , disminuyendo la inmunorreacción de la descarboxilasa del ácido glutámico en el globo pálido lateral de los animales isquémicos tratados con placebo; sin embargo, el tratamiento con atorvastatina pudo revertirla, lo que logró una disminución significativa de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata y aumentando los niveles de descarboxilasa del ácido glutámico en el globo pálido lateral. Conclusión. Nuestros datos sugieren que la atorvastatina en el tratamiento posterior a la isquemia ejerce neuroprotección en las zonas exofocales, modulando las poblaciones neuronales gabérgicas y dopaminérgicas del sistema nigroestriatal, lo que podría prevenir trastornos neurológicos.

Stroke management in a university hospital in the largest South American city / Manejo do acidente vascular cerebral em um hospital universitário na maior cidade da América do Sul

OBJECTIVE: To describe characteristics and provision of care for patients admitted with cerebrovascular disorders (CVD), focusing on ischemic stroke (IS), in a large, public, academic hospital in São Paulo, Brazil. METHOD: We retrieved information about 357 patients with CVD admitted to the Neurology Emergency Department (NED) and Neurology Ward (NW) of our institution. We described patient characteristics and management of IS in NED and in NW. RESULTS: IS was diagnosed in 79.6 percent of CVD patients admitted to NED; 2.7 percent were submitted to thrombolysis. Extent of IS investigation and management were significantly different in NED and NW. CONCLUSION: IS patients in our center were younger than in developed countries. IS management was significantly influenced by patient characteristics. This information can aid in planning strategies to decrease stroke burden.

OBJETIVO: Descrever características e manejo de pacientes internados com diagnóstico de doença cerebrovascular (DCV), enfocando principalmente o acidente vascular cerebral isquêmico (AVCI), em um hospital público universitário em São Paulo. MÉTODO: Coletamos informações de 357 pacientes com DCV internados no Pronto-Socorro de Neurologia (PSN) e na Enfermaria de Neurologia (EN) de nossa instituição. Descrevemos características dos pacientes e manejo do AVCI no PSN e na EN. RESULTADOS: O AVCI foi diagnosticado em 79,6 por cento dos pacientes com DCV admitidos no PSN; 2,7 por cento foram submetidos a trombólise. A extensão da investigação e o manejo da doença foram significativamente diferentes no PSN e na EN. CONCLUSÃO: os pacientes com AVCI em nosso centro foram mais jovens que em países desenvolvidos. O manejo do AVCI foi influenciado significativamente pelas características dos pacientes. Estas informações podem auxiliar no planejamento de estratégias para diminuir as conseqüências das DCV em nosso meio.

Aspirin non-responders in Thai ischemic stroke/TIA patients.

BACKGROUND: Aspirin resistance has been defined as inability of aspirin to protect individuals from thrombotic complications or to produce an anticipated effect from laboratory tests of platelet function. Most reported information comes from Western patients with coronary artery disease and aspirin resistance is defined by laboratory criteria. The purpose of the present study was to look for aspirin non-responders in Thai patients who presented with acute/subacute ischemic stroke and transient ischemic attack (TIA). MATERIAL AND METHOD: The authors prospectively included acute ischemic stroke/TIA patients who were treated at Thammasat Hospital from August, 2006 to July, 2007 and had already been on aspirin. Information about compliance of medication, reasons for taking aspirin, doses of aspirin, baseline characteristics, and stroke subtypes of the patients were collected. RESULTS: There were 194 acute/subacute ischemic stroke/TIA patients during the study period Forty-six patients (23.7%), who had already been on aspirin (aspirin non-responder), while having new stroke/TIA, were studied Eighteen patients were on aspirin 300-325 mg and 28 patients were on 81 mg per day. Most patients had taken aspirin 300-325mg/day as secondary prevention, while half of the patients taking aspirin 81 mg/d had diabetes mellitus and took aspirin as primary prevention. CONCLUSION: Aspirin non-responders in ischemic stroke patients are common. Future study is required to clarify mechanisms of aspirin non-responders in Thai patients.

Isquemia cerebral transitoria y riesgo de infarto cerebral isquémico / Transitory cerebral isquemia and risk of cerebral ischemic stroke

La enfermedad vascular cerebral es la principal causa de hospitalización neurológica en el mundo. Costa Rica no es la excepción; en nuestros hospitales cada día es más frecuente el número de pacientes que ingresan con infartos cerebrales isquémicos. Esta común enfermedad obedece a la prevalencia de enfermedades crónicas con la hipertensión arterial, diabetes mellitus, dislipidemias, tabaquismo y la alta expectativa de vida de los costarricenses, todos considera dos factores de riesgo. Aproximadamente un 80 por ciento de los infartos cerebrales son isquémicos secundarios a la oclusión arterial aguda de un territorio vascular específico, el restante 20 por ciento corresponde a la variante hemorrágica. Las secuelas neurológicas secudarias a esta entidad son la principal causa de discapacidad crónica en los pacientes y conlleva una alta morbilidad y mortalidad. Aunque muchos sufren el infarto cerebral isquémico en forma aguda, otro grupo de pacientes experimenta uno o varios episodios previos de isquemia cerebral transitoria, lo cual los pone en riesgo de sufrir un infarto cerebral isquémico durante un periodo corto, es decir son pacientes vulnerables. Esta revisión pretende actualizar los conocimientos médicos, especialmente para aquellos que trabajan en la atención primaria y en los servicios de urgencias hospitalarias, que reconozcan a este grupo de pacientes y les brinden la atención médica necesaria para de prevenir un infarto cerebral isquémico. La isquemia cerebral transitoria debe ser considerada como una emergencia neurológica. Descriptores: Isquemia cerebral transitoria, emergencia neurológica, infarto cerebral isquémico.

Gastro-duodenal mucosal changes associated with low-dose aspirin therapy: a prospective, endoscopic study.

OBJECTIVES: The association of low-dose aspirin use and gastro-intestinal bleeding is well described. However, the gastroduodenal mucosal changes associated with low-dose aspirin therapy have not been properly evaluated. We undertook a prospective, endoscopic study to evaluate gastro-duodenal mucosal lesions produced by low-dose aspirin. METHODS: Forty-seven patients with non-hemorrhagic cerebral infarct or transient ischemic attacks and normal upper gastrointestinal endoscopy were randomized to receive either enteric-coated (n=25) or plain (n=22) aspirin (150 mg/day). Follow-up endoscopy was done at 2, 4 and 8 weeks; gastro-duodenal mucosal lesions, if present, were scored. Forty-seven patients with hemorrhagic infarct who were not treated with aspirin served as controls. RESULTS: Twenty eight (60%) of 47 patients receiving aspirin had mucosal lesions; stomach alone was the most frequent site (32%), followed by both stomach and duodenum (23%). Frequency of mucosal changes in the stomach at 8 weeks (19%) was significantly lower (p<0.05) than those at 2 weeks (53%) and 4 weeks (55%). Coated (56%) and plain (63.6%) aspirin induced mucosal lesions with similar frequency. CONCLUSION: Administration of low-dose aspirin, either plain or enteric-coated, induces endoscopic gastro-duodenal mucosal lesions in a large majority of patients. The frequency of damage decreased after 8 weeks of therapy.

Magnesium chloride alone or in combination with diazepam fails to prevent hippocampal damage following transient forebrain ischemia

In the central nervous system, magnesium ion (Mg2+) acts as an endogenous modulator of N-methyl-D-aspartate (NMDA)-coupled calcium channels, and may play a major role in the pathomechanisms of ischemic brain damage. In the present study, we investigated the effects of magnesium chloride (MgCl2, 2.5, 5.0 or 7.5 mmol/kg), either alone or in combination with diazepam (DZ), on ischemia-induced hippocampal cell death. Male Wistar rats (250-300 g) were subjected to transient forebrain ischemia for 15 min using the 4-vessel occlusion model. MgCl2 was applied systemically (sc) in single (1x, 2 h post-ischemia) or multiple doses (4x, 1, 2, 24 and 48 h post-ischemia). DZ was always given twice, at 1 and 2 h post-ischemia. Thus, ischemia-subjected rats were assigned to one of the following treatments: vehicle (0.1 ml/kg, N = 34), DZ (10 mg/kg, N = 24), MgCl2 (2.5 mmol/kg, N = 10), MgCl2 (5.0 mmol/kg, N = 17), MgCl2 (7.5 mmol/kg, N = 9) or MgCl2 (5 mmol/kg) + DZ (10 mg/kg, N = 14). Seven days after ischemia the brains were analyzed histologically. Fifteen minutes of ischemia caused massive pyramidal cell loss in the subiculum (90.3 percent) and CA1 (88.4 percent) sectors of the hippocampus, vehicle vs sham). Compared to the vehicle-treated group, all pharmacological treatments failed to attenuate the ischemia-induced death of both subiculum (lesion: 86.7-93.4 percent) and CA1 (lesion: 85.5-91.2 percent) pyramidal cells. Both DZ alone and DZ + MgCl2 reduced rectal temperature significantly. No animaldeath was observed after drug treatment. These data indicate that exogenous magnesium, when administered systemically post-ischemia even in different multiple dose schedules, alone or with diazepam, is not useful against the histopathological effects of transient global cerebral ischemia in rats

Estudo controlado do mimodipina no acidente vascular cerebral isquêmico / A controled trial of nimodipine in acute ischemic stroke

Recentes investigaçöes sugerem que as concentraçöes celulares de cálcio, aumentadas, estäo implicadas na morte neuronal após a isquemia. Para determinar se o tratamento com um bloqueador de canal de cálcio melhoraria a sobrevivência e o quadro neurológico após o AVCi, selecionamos 186 pacientes em um estudo prospectivo, duplo-cego, randomizado, controlado por placebo, utilizando nimodipina (30mg a cada seis horas) administrada dentro de 24 horas do início dos sintomas de um acidente vascular cerebral isquêmico. Durante o período de tratamento de quatro semanas, a mortalidade por todas as causas foi significativamente reduzida com nimodipina quando comparada com placebo (oito mortes 8,5 por cento, versus 19 mortes - 20,4 por cento). Durante um seguimento de seis meses, um número adicional de oito pacientes morreu em cada grupo. No grupo com nimodipina, foi observado, também, melhores resultados neurológicos, pela avaliaçäo da escala neurológica de Mathew. A melhora na avaliaçäo neurológica foi mais acentuada nos pacientes com déficit de moderado a severo, ao início do tratamento. Näo ocorreram efeitos colaterais importantes à exceçäo de um episódio reversível de azotemia, que pode ter sido relacionado ao tratamento com nimodipina. Nossos dados sugerem que pacientes com acidente vascular cerebral isquêmico podem ser bveneficiados pelo tratamento precoce com nimodipina

Acción de la furnidipina tópica sobre arterias cerebrales humanas / Action of topic furnidipine over human brain arteries

Se evaluó la acción de un nuevo calcio antagonista, la furnidipina por vía tópica sobre arterias cerebrales de distinto diámetro de 15 pacientes neuroquirúrgicos. Se demostró un efecto mas notorio del fármaco, vasodilatando arterias de menos de 200 u de diámetro y preferentemente de arterias de menos de 100 u de diámetro. Se postula que este fármaco mejora las vías de circulación colateral a nivel de la microcirculación cerebral

Cerebral vasospasm

Vasoespasmo cerebral ocorre em patologias como enxaqueca, hemorragia subaracnóidea, trauma de crânio, após isquemia e/ou hipoxia. A fisiopatologia do vasoespasmo cerebral nestas patologias näo está completamente desvendada. Neste artigo säo analisados os fatores neuroquímicos e morfológicos responsáveis pelo controle circulatório cerebral. As alteraçöes circulatórios que seguem a hemorragia subaracnóidea säo utilizadas como exemplo. Conclui-se que fatores bioquímicos, fisiológicos e morfológicos säo responsáveis pelas manifestaçöes vasculares que ocorrem após a hemorragia subaracnóidea. Alternativas de tratamento do vasoespasmo cerebral säo discutidas

Vasoespasmo cerebral: fisiopatología y tratamiento / Cerebral vasoespasm: physiopathology and treatment

El vasoespasmo cerebral es un fenómeno que complica frecuentemente la hemorragia subaracnoídea secubdaria a un aneurisma cerebral roto, presentándose en el 40-50% durante su curso clínico. Existen algunos hechos comunes a los casos que se complican con un vasoespasmo: a) Hay un "intervalo libre" de 2 a 3 días entre la ruptura del aneurisma y la aparición del déficit isquémico neurológico retardado. b) Este déficit isquémico retardado siempre se correlaciona con la presencia de coágulos sanguíneos en el espacio subaracnoídeo, alrededor de las arterias de la base del cerebro. c) Mientras mayor sea la cuantía del sangramiento y por ende, de los coágulos en el espacio subaracnoídeo, mayor es la posibilidad de desarrollo de un vasoespasmo. En esta revisión se detallan las posibilidades etiopatogénicas y fisiopatológicas más aceprtadas, como explicación a este debatido e importante fenómeno y se reseñan las tentativas terapéuticas más en boga