Utilidad del estudio Doppler transcraneal en la detección de microembolias cerebrales

Introducción Las intervenciones terapéuticas, tanto en la fase aguda del ictus como en la prevención secundaria del infarto cerebral, requieren un diagnóstico etiológico preciso. La incorporación de técnicas diagnósticas más sofisticadas como la ultrasonografía dúplex-color, el Doppler transcraneal (DTC) y la ecocardiografía transesofágica (ETE), han demostrado la importancia clínica del mecanismo embólico que ha sido aceptado como la causa más frecuente de infarto cerebral en los bancos de datos de ictus más modernos. Sin embargo la fuente potencial de embolia cerebral es desconocida en un porcentaje importante de pacientes. En la actualidad el interés se centra en considerar al embolismo cerebral como un fenómeno ocasionado por la oclusión de la arteria receptora del émbolo, independientemente de que la fuente del émbolo sea conocida (corazón, aorta o arterias proximales) o no haya sido determinada. La reciente introducción de técnicas Doppler transcraneal capaces de detectar la existencia de microembolias cerebrales (MEs) resultan muy esperanzadores y, aunque el significado de las MEs continúa siendo parcialmente desconocido, cada vez existen más evidencias que sugieren que la detección de este fenómeno puede tener implicaciones tanto pronósticas como terapéuticas. Objetivos del estudio Objetivo principal Determinar la utilidad clínica de la detección de microembolias cerebrales mediante Doppler transcraneal en pacientes con ictus isquémico agudo. Para ello se plantearon los objetivos concretos que detallamos a continuación y que desglosamos para cada etapa de estudio. Etapa I. Investigación I. Utilidad del DTC con contraste (DTC-c) en el diagnóstico del shunt derecha-izquierda (ShDI) en el adulto joven. 1. Analizar la prevalencia de ShDI en el ictus isquémico en adultos jóvenes. 2. Comparar la eficacia del ecocardiograma-transtorácico con contraste (ETT-c) respecto al DTC-c. 3. Evaluar la importancia del ShDI como factor de riesgo potencial de ictus isquémico criptogénico. Etapa II. Investigación II. Utilidad del DTC-c en el diagnóstico del ShDI: la necesidad de cuantificar la magnitud del ShDI. 1. Determinar la prevalencia de ShDI en la población sana. 2. Determinar la prevalencia de ShDI en el ictus isquémico agudo, sin sesgos de edad ni subtipo de ictus. 3. Determinar la importancia de la presencia del ShDI como factor de riesgo vascular. 4. Determinar la sensibilidad y especificidad del DTC-c respecto al ecocardiograma-transesofágico con contraste (ETE-c) en pacientes con ictus criptogénico. 5. Determinar la capacidad del DTC-c en la cuantificación de la magnitud del ShDI cardiaco. Etapa II. Investigación III. Detección de microembolias sólidas mediante DTC en el ictus isquémico agudo. 1. Estudiar la prevalencia de MEs en una población no sesgada de pacientes con ictus isquémico en fase aguda. 2. Detectar y confirmar la actividad embolígena de fuentes sospechadas o conocidas de ictus embólico. 3. Determinar el valor pronóstico de la detección de MEs en el ictus isquémico agudo: gravedad del ictus, existencia de recurrencias precoces y grado de dependencia al alta. Material y método El trabajo que presentamos en esta tesis se desarrolla en 2 etapas, que se diferencian fundamentalmente en el planteamiento de un objetivo más inmediato, con disponibilidad de una tecnología más elemental en la primera de ellas. Los resultados del primer estudio no llevaron a diseñar y desarrollar una investigación más amplia y ambiciosa tanto en los objetivos propuestos como en los medios utilizados. El desarrollo del proyecto y las publicaciones resultado de cada fase se resumen en la siguiente tabla:Introduction Therapeutic intervention, both in the acute phase of stroke and in the secondary prevention of ischaemic stroke, requires a precise aetiological diagnosis. The introduction of more sophisticated diagnostic techniques such as duplex colour ultrasonography, transcranial Doppler (TCD) and transoesophageal echocardiography (TEE) has shown the clinical importance of the embolic mechanism, which most modern stroke data banks show to be the most frequent cause of ischaemic stroke. However, the potential source of cerebral emboli is unknown in a high percentage of patients. Currently cerebral embolism is considered to be a phenomenon caused by an occlusion of the artery in which the embolus occurs, independently to whether or not the source of the embolus is known (heart, aorta, or proximal arteries). New transcranial Doppler techniques which are capable of detecting the existence of cerebral microemboli (MES) are giving encouraging results and although the full significance of MES is still not fully understood, it is becoming ever more apparent that the detection of this phenomenon may have both prognostic and therapeutic implications. Objectives of the study Primary objective To determine the clinical utility of the detection of cerebral microemboli through transcranial Doppler in patients with acute ischaemic stroke. In order to achieve this the following specific objectives, outlined for each stage of the study, were set. Stage I. Investigation I. The usefulness of TCD with contrast (TCD-c) in the diagnosis of Right-to-Left shunt (RLSh) in young adults. 4. To analyse the prevalence of RLSh in ischaemic stroke in young adults. 5. To compare the efficacy of transthoracic echocardiogram with contrast (TEE-c) with TCD-c. 6. To evaluate the importance of RLSh as a potential risk factor in cryptogenic ischaemic stroke. Stage II. Investigation II. The usefulness of TCD-c in the diagnosis of RLSh: the need to quantify RLSh. 6. To determine the prevalence of RLSh in a healthy population. 7. To determine the prevalence of RLSh in acute ischaemic stroke in all age groups and stroke subtypes. 8. To determine the importance of RLSh as a vascular risk factor. 9. To determine the sensibility and specificity of TCD-c with respect to the transoesophageal echocardiogram with contrast (TEE-c) in patients with cryptogenic stroke. 10. To determine the capacity of TCD-c in the quantification of the magnitude of cardiac RLSh. Stage II. Investigation III. The detection of solid microemboli through TCD in acute ischaemic stroke. 4. To study the prevalence of MES in a non-selected patient group with acute ischaemic stroke. 5. To detect and confirm the embolic origin of suspected or known sources of embolic strokes. 6. To determine the prognostic value of the detection of MES in acute ischaemic stroke: severity of stroke, early recurrence and dependency. Material and method The study which we present in this thesis is undertaken in 2 stages, which differ from one another essentially in that the first has a more immediate objective and uses more elementary and widely available technology. The results of the first study led us to design and develop a wider and more ambitious study both with respect to the aims which were proposed and the resources which were used. The development of the project and the resulting publications are summarised in the following table

¿Som realment diferents els homes i les dones? Anàlisi de les diferències entre ambdós sexes en pacients amb malaltia vascular cerebral

Es recullen les dades dels pacients amb ictus agut (isquèmic i hemorràgic) que ingressen al nostre servei i es comparen les dades epidemiològiques, clíniques i de pronòstic de dones i homes. En l'anàlisi comparatiu s'objectiven diferències en quant als factors de risc entre ambdós sexes. I es troben factors independents de mal pronòstic en els pacients amb un ictus isquèmic: l'antecedent de cardiopatia isquèmica, l'escala de rankin previ i l'escala canadenca a l'ingrés. En l'anàlisi de regressió logística es troben factors independents de mal pronòstic en els pacients amb una hemorràgia cerebral l'edat i l'escala canadenca a l'ingrés

¿Som realment diferents els homes i les dones? Anàlisi de les diferències entre ambdós sexes en pacients amb malaltia vascular cerebral

Es recullen les dades dels pacients amb ictus agut (isquèmic i hemorràgic) que ingressen al nostre servei i es comparen les dades epidemiològiques, clíniques i de pronòstic de dones i homes. En l'anàlisi comparatiu s'objectiven diferències en quant als factors de risc entre ambdós sexes. I es troben factors independents de mal pronòstic en els pacients amb un ictus isquèmic: l'antecedent de cardiopatia isquèmica, l'escala de rankin previ i l'escala canadenca a l'ingrés. En l'anàlisi de regressió logística es troben factors independents de mal pronòstic en els pacients amb una hemorràgia cerebral l'edat i l'escala canadenca a l'ingrés

REVASCAT: a randomized trial of revascularization with SOLITAIRE FR® device vs. best medical therapy in the treatment of acute stroke due to anterior circulation large vessel occlusion presenting within eight-hours of symptom onset

REVASCAT is a prospective, multicenter, randomized trial seeking to establish whether subjects meeting following main inclusion criteria: age 18-80, baseline National Institutes of Health Stroke Scale = 6, evidence of intracranial internal carotid artery or proximal (M1 segment) middle cerebral artery occlu- sion, Alberta Stroke Program Early Computed Tomography score of > 7 on non-contrast CT or > 6 on diffusion-weighted magnetic resonance imaging , ineligible for or with persistent occlusion after intravenous alteplase and procedure start within 8 hours from symptom onset, have higher rates of favorable outcome when treated with the SolitaireTM FR embolectomy device compared to standard medical therapy alone The primary end-point, based on intention-to-treat cri- teria is the distribution of modified Rankin Scale scores at 90 days. Projected sample size is 690 patients. Estimated common odds ratio is 1•615. Randomization is performed under a mini- mization process using age, baseline NIHSS, therapeutic window, occlusion location and investigational center. The study follows a sequential analysis (triangular model) with the first approach to test efficacy at 174 patients and subsequent analyses (if necessary) at 346, 518, and 690 subjects. Secondary end-points are infarct volume evaluated on CT at 24 h, dra- matic early favorable response, defined as NIHSS of 0–2 or NIHSS improvement = 8 points at 24 h and successful recanali- zation in the Solitaire arm according to the thrombolysis in cerebral infarction (TICI) classification defined as TICI 2b or 3. Safety variables are mortality at 90 days, symptomatic intrac- ranial haemorrhage rates at 24 hours and procedure related complications.Peer Reviewe

REVASCAT: a randomized trial of revascularization with SOLITAIRE FR® device vs. best medical therapy in the treatment of acute stroke due to anterior circulation large vessel occlusion presenting within eight-hours of symptom onset

REVASCAT is a prospective, multicenter, randomized trial seeking to establish whether subjects meeting following main inclusion criteria: age 18-80, baseline National Institutes of Health Stroke Scale = 6, evidence of intracranial internal carotid artery or proximal (M1 segment) middle cerebral artery occlu- sion, Alberta Stroke Program Early Computed Tomography score of > 7 on non-contrast CT or > 6 on diffusion-weighted magnetic resonance imaging , ineligible for or with persistent occlusion after intravenous alteplase and procedure start within 8 hours from symptom onset, have higher rates of favorable outcome when treated with the SolitaireTM FR embolectomy device compared to standard medical therapy alone The primary end-point, based on intention-to-treat cri- teria is the distribution of modified Rankin Scale scores at 90 days. Projected sample size is 690 patients. Estimated common odds ratio is 1•615. Randomization is performed under a mini- mization process using age, baseline NIHSS, therapeutic window, occlusion location and investigational center. The study follows a sequential analysis (triangular model) with the first approach to test efficacy at 174 patients and subsequent analyses (if necessary) at 346, 518, and 690 subjects. Secondary end-points are infarct volume evaluated on CT at 24 h, dra- matic early favorable response, defined as NIHSS of 0–2 or NIHSS improvement = 8 points at 24 h and successful recanali- zation in the Solitaire arm according to the thrombolysis in cerebral infarction (TICI) classification defined as TICI 2b or 3. Safety variables are mortality at 90 days, symptomatic intrac- ranial haemorrhage rates at 24 hours and procedure related complications.Peer Reviewe

Ionic aspects of the physiology and biology of Macrobrachium rosenbergii (De Man) 1879

SIGLEAvailable from British Library Document Supply Centre- DSC:D171490 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Comparison between audio and video based modalities of central modified Rankin score (MRS) adjudication within a prospective, randomized trial on endovascular treatment for acute stroke

Peer Reviewe

Phone and video-based modalities of central blinded adjudication of modified rankin scores in an endovascular stroke trial

Background and Purpose-The standard outcome measure in stroke research is modified Rankin scale (mRS) evaluated by local blinded investigators. We aimed to assess feasibility and reliability of 2 central adjudication methods of mRS in the setting of a randomized endovascular stroke trial. Methods-This is a secondary analysis derived from the Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT) trial cohort. Primary outcome was distribution of mRS at 90 days. Local evaluation was done by certified investigators masked to treatment assignment using structured face-to-face interviews. In addition, central assessment was performed by 2 independent raters via structured phone interview (n=120) and via video recordings of the face-to-face interviews with local investigators (n=106). Interrater agreement was evaluated using kappa and discordance statistics. Sensitivity analyses for the primary end point using different adjudication approaches were performed. Correlation between mRS obtained with each modality and 24-hour follow-up infarct volumes was studied. Results-Using local evaluation as the reference, higher agreement rates were noted with central video than with central phone evaluations (k(w) 0.92 [0.88-0.96] versus 0.77 [0.72-0.83]). Discrepancies in mRS scoring between local and central raters (phone- and video-based) were similar in both treatment allocation arms. Sensitivity analyses showed benefit of endovascular treatment irrespective of adjudication method, but higher odds ratios were observed with local evaluations. Final infarct volume was similarly correlated with mRS across all 3 evaluation modalities. Conclusions-Central adjudication of mRS is feasible, reducing interrater variability and avoiding potential problems related to lack of blinding. Our findings may have implications in the planning of future randomized acute stroke trials, especially in those including nonpharmacological interventions.Peer Reviewe

Comparison between audio and video based modalities of central modified Rankin score (MRS) adjudication within a prospective, randomized trial on endovascular treatment for acute stroke

Peer Reviewe