The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.

Tratamiento endovascular de una estenosis crítica basilar con dispositivo stent Solitaire ®: primera experiencia en nuestro centro / Endovascular treatment of critical basilar stenosis with a Solitaire ® stent device: a first experience in our centre

Introducción. Aunque la arterioesclerosis intracraneal es una causa importante de ictus, la actitud terapéutica no está claramente establecida. En este sentido, el estudio SAMMPRIS comparó el tratamiento médico intensivo con la angioplastia y colocación de stent, con resultados favorables al tratamiento farmacológico. Estos resultados podrían, en parte, deberse al dispositivo utilizado (stent Wingspan ®). Caso clínico. Varón de 71 años con una estenosis grave de la arteria basilar, en quien se repetían episodios de focalidad neurológica transitoria a pesar del tratamiento con doble antiagregación y estatinas. En estas circunstancias se decidió realizar una arteriografía terapéutica con angioplastia y colocación de un stent Solitaire ® para optimizar resultados y se logró una estenosis residual del 40%. La evolución fue favorable y los controles posteriores muestran una mínima progresión. Conclusión. Según nuestro conocimiento, éste es el primer caso publicado de tratamiento de una estenosis crítica de la arteria basilar mediante la colocación de un stent Solitaire ® (AU)

Introduction. Although intracranial arteriosclerosis is an important cause of stroke, the therapeutic attitude has still not been clearly established. Hence, the SAMMPRIS study compared intensive medical treatment with angioplasty and stent placement, with outcomes favouring the pharmacological treatment. These results could be partly due to the device used (Wingspan ® stent). Case report. A 71-year-old male with a severe stenosis of the basilar artery, who suffered repeated episodes of transient neurological focus despite being treated with antiplatelet therapy and statins. Given the circumstances, the decision was made to perform a therapeutic arteriography with angioplasty and placement of a Solitaire ® stent in order to optimise results, a residual stenosis of 40% being achieved. Subsequent progress was favourable and the control tests carried out showed a minimum progression. Conclusions. As far as we know, this is the first case of critical stenosis of the basilar artery being treated by placement of a Solitaire® stent to be reported in the literature (AU)

[Endovascular treatment of critical basilar stenosis with a Solitaire® stent device: a first experience in our centre]. / Tratamiento endovascular de una estenosis crítica basilar con dispositivo stent Solitaire®: primera experiencia en nuestro centro.

INTRODUCTION: Although intracranial arteriosclerosis is an important cause of stroke, the therapeutic attitude has still not been clearly established. Hence, the SAMMPRIS study compared intensive medical treatment with angioplasty and stent placement, with outcomes favouring the pharmacological treatment. These results could be partly due to the device used (Wingspan® stent). CASE REPORT: A 71-year-old male with a severe stenosis of the basilar artery, who suffered repeated episodes of transient neurological focus despite being treated with antiplatelet therapy and statins. Given the circumstances, the decision was made to perform a therapeutic arteriography with angioplasty and placement of a Solitaire® stent in order to optimise results, a residual stenosis of 40% being achieved. Subsequent progress was favourable and the control tests carried out showed a minimum progression. CONCLUSIONS: As far as we know, this is the first case of critical stenosis of the basilar artery being treated by placement of a Solitaire® stent to be reported in the literature.

TITLE: Tratamiento endovascular de una estenosis critica basilar con dispositivo stent Solitaire ®: primera experiencia en nuestro centro.Introduccion. Aunque la arterioesclerosis intracraneal es una causa importante de ictus, la actitud terapeutica no esta claramente establecida. En este sentido, el estudio SAMMPRIS comparo el tratamiento medico intensivo con la angioplastia y colocacion de stent, con resultados favorables al tratamiento farmacologico. Estos resultados podrian, en parte, deberse al dispositivo utilizado (stent Wingspan ®). Caso clinico. Varon de 71 años con una estenosis grave de la arteria basilar, en quien se repetian episodios de focalidad neurologica transitoria a pesar del tratamiento con doble antiagregacion y estatinas. En estas circunstancias se decidio realizar una arteriografia terapeutica con angioplastia y colocacion de un stent Solitaire ® para optimizar resultados y se logro una estenosis residual del 40%. La evolucion fue favorable y los controles posteriores muestran una minima progresion. Conclusion. Segun nuestro conocimiento, este es el primer caso publicado de tratamiento de una estenosis critica de la arteria basilar mediante la colocacion de un stent Solitaire ®.

[High performance of an implantable Holter monitor in the detection of concealed paroxysmal atrial fibrillation in patients with cryptogenic stroke and a suspected embolic mechanism]. / Altorendimiento del holter implantable en la detecciónde fibrilación auricular paroxística oculta en pacientescon ictus criptogénico y sospecha de mecanismo embólico.

INTRODUCTION: Implantable loop recorders (ILR) may allow detection of occult paroxysmal atrial fibrillation (PAF) in patients with cryptogenic ischemic stroke. However, optimal selection algorithm and ideal duration of monitoring remain unclear. AIM. To determine the incidence and time-profile of PAF in patients with cryptogenic ischemic stroke studied with Reveal XT ILR, who were selected based on a high suspicion of cerebral embolism. SELECTION CRITERIA: absence of stroke etiology after complete study including vascular imaging, transesophageal echocardiography and at least 24 hours of cardiac rhythm monitoring, and confirmation of acute embolic occlusion of intracranial artery by transcranial duplex or characteristics of acute ischemic lesion on neuroimaging suggesting embolic mechanism of ischemia. After implanting Reveal XT ILR, patients were trained to perform transmissions monthly or when symptoms occurred. We reviewed the information online each month and patients underwent clinical visits at 3rd and 6th month and then every six months. RESULTS: We included 101 patients with cryptogenic ischemic stroke and at least one month of follow-up after ILR implant. Mean age was 67 years, 54 women (53.5%). Mean follow-up after implantation was 281 ± 212 days. Occult PAF was detected in 34 patients (33.7%). Frequency of false positives: 22.8%. Median time from implant to arrhythmia detection was 102 days (range: 26-240 days). 24 (70%) patients with PAF had several arrhythmic episodes detected with ILR. The majority of events (75%) were detected during the first six months of monitoring. CONCLUSIONS: In our patients with probably embolic cryptogenic ischemic stroke, PAF was detected by Reveal XT ILR in 33.7%. One in four events occurred after the first six months of monitoring.

TITLE: Alto rendimiento del holter implantable en la deteccion de fibrilacion auricular paroxistica oculta en pacientes con ictus criptogenico y sospecha de mecanismo embolico.Introduccion. El holter implantable permite detectar fibrilacion auricular paroxistica (FAP) oculta en pacientes con ictus criptogenico, pero se desconoce que algoritmo de seleccion tiene un mayor rendimiento y la duracion optima de monitorizacion. Objetivo. Conocer la frecuencia y el tiempo hasta detectar la FAP mediante un holter implantable Reveal XT ® en pacientes con ictus criptogenico seleccionados por sospecha elevada de embolismo cerebral. Pacientes y metodos. Criterios de seleccion: ausencia de etiologia del ictus tras el estudio completo incluyendo un ecocardiograma transesofagico, monitorizacion ECG y holter de 24 horas, asi como confirmacion de oclusion aguda embolica de la arteria intracraneal por duplex transcraneal o bien alta sospecha de embolismo por caracteristicas de neuroimagen. Tras implantar el holter Reveal XT se formo a los pacientes para que emprendieran transmisiones todos los meses o ante sintomas. Se reviso la informacion online mensualmente y se realizaron visitas clinicas en las unidades de Neurologia y Cardiologia. Resultados. Se incluyeron 101 pacientes con ictus criptogenico y al menos un mes de seguimiento: edad media de 67 años, 54 mujeres (53,5%). Tiempo medio de seguimiento: 281 ± 212 dias. Se detecto FAP oculta en 34 pacientes (33,7%) y falsos positivos en 23 (22,8%). Mediana desde el implante hasta la deteccion de la arritmia: 102 dias (rango: 26-240 dias). En un 70% de los pacientes se registraron multiples episodios de FAP. El 75% de los eventos se detectaron durante los primeros seis meses de monitorizacion. Conclusiones. El algoritmo de seleccion de pacientes con ictus criptogenico segun sospecha de embolismo cerebral se asocio a una elevada frecuencia (33,7%) de FAP oculta con holter implantable. Uno de cada cuatro eventos sucedio tras los primeros seis meses de monitorizacion.

Alto rendimiento del holter implantable en la detección de fibrilación auricular paroxística oculta en pacientes con ictus criptogénico y sospecha de mecanismo embólico / High performance of an implantable Holter monitor in the detection of concealed paroxysmal atrial fibrillation in patients with cryptogenic stroke and a suspected embolic mechanism

Introducción. El holter implantable permite detectar fibrilación auricular paroxística (FAP) oculta en pacientes con ictus criptogénico, pero se desconoce qué algoritmo de selección tiene un mayor rendimiento y la duración óptima de monitorización. Objetivo. Conocer la frecuencia y el tiempo hasta detectar la FAP mediante un holter implantable Reveal XT ® en pacientes con ictus criptogénico seleccionados por sospecha elevada de embolismo cerebral. Pacientes y métodos. Criterios de selección: ausencia de etiología del ictus tras el estudio completo incluyendo un ecocardiograma transesofágico, monitorización ECG y holter de 24 horas, así como confirmación de oclusión aguda embólica de la arteria intracraneal por dúplex transcraneal o bien alta sospecha de embolismo por características de neuroimagen. Tras implantar el holter Reveal XT se formó a los pacientes para que emprendieran transmisiones todos los meses o ante síntomas. Se revisó la información online mensualmente y se realizaron visitas clínicas en las unidades de Neurología y Cardiología. Resultados. Se incluyeron 101 pacientes con ictus criptogénico y al menos un mes de seguimiento: edad media de 67 años, 54 mujeres (53,5%). Tiempo medio de seguimiento: 281 ± 212 días. Se detectó FAP oculta en 34 pacientes (33,7%) y falsos positivos en 23 (22,8%). Mediana desde el implante hasta la detección de la arritmia: 102 días (rango: 26-240 días). En un 70% de los pacientes se registraron múltiples episodios de FAP. El 75% de los eventos se detectaron durante los primeros seis meses de monitorización (AU)

Introduction. Implantable loop recorders (ILR) may allow detection of occult paroxysmal atrial fibrillation (PAF) in patients with cryptogenic ischemic stroke. However, optimal selection algorithm and ideal duration of monitoring remain unclear. Aim. To determine the incidence and time-profile of PAF in patients with cryptogenic ischemic stroke studied with Reveal XT ® ILR, who were selected based on a high suspicion of cerebral embolism. Patients and methods. Selection criteria: absence of stroke etiology after complete study including vascular imaging, transesophageal echocardiography and at least 24 hours of cardiac rhythm monitoring, and confirmation of acute embolic occlusion of intracranial artery by transcranial duplex or characteristics of acute ischemic lesion on neuroimaging suggesting embolic mechanism of ischemia. After implanting Reveal XT ILR, patients were trained to perform transmissions monthly or when symptoms occurred. We reviewed the information online each month and patients underwent clinical visits at 3rd and 6th month and then every six months. Results. We included 101 patients with cryptogenic ischemic stroke and at least one month of follow-up after ILR implant. Mean age was 67 years, 54 women (53.5%). Mean follow-up after implantation was 281 ± 212 days. Occult PAF was detected in 34 patients (33.7%). Frequency of false positives: 22.8%. Median time from implant to arrhythmia detection was 102 days (range: 26-240 days). 24 (70%) patients with PAF had several arrhythmic episodes detected with ILR. The majority of events (75%) were detected during the first six months of monitoring. Conclusions. In our patients with probably embolic cryptogenic ischemic stroke, PAF was detected by Reveal XT ILR in 33.7%. One in four events occurred after the first six months of monitoring (AU)