Cerebrovascular alterations in mice lacking neuronal nitric oxide synthase gene expression.

Nitric oxide (NO) is known to mediate increases in regional cerebral blood flow elicited by CO2 inhalation. In mice with deletion of the gene for neuronal NO synthase (NOS), CO2 inhalation augments cerebral blood flow to the same extent as in wild-type mice. However, unlike wild-type mice, the increased flow in mutants is not blocked by the NOS inhibition, N omega-nitro-L-arginine, and CO2 exposure fails to increase brain levels of cGMP. Topical acetylcholine elicits vasodilation in the mutants which is blocked by N omega-nitro-L-arginine, indicating normal functioning of endothelial NOS. Moreover, immunohistochemical staining for endothelial NOS is normal in the mutants. Thus, following loss of neuronal NOS, the cerebral circulatory response is maintained by a compensatory system not involving NO.

Posterior circulation cerebrovascular syndromes: diagnosis and management.

One in five strokes affects the posterior circulation. Diagnosing posterior circulation stroke can be challenging, as the vascular anatomy can be variable, and because presenting symptoms are often non-specific and fluctuating. Nevertheless, making the correct diagnosis is important, as these strokes have a high chance of recurrence, can be life threatening, and can lead to equally life-threatening complications. Investigation and management largely follow those for stroke in general, although some specific differences exist. These include the preferred use of MRI for diagnosing posterior fossa lesions, the management of basilar artery thrombosis, which may have a longer time window for recanalisation therapy, and the use of endovascular therapies for secondary prevention, which, so far, have not shown any benefit in the treatment of vertebral or basilar artery stenosis. In this review, we summarise the anatomy, aetiology and presentation of posterior circulation stroke, and discuss current approaches to management.

Dysprosodic speech following basal ganglia insult: Toward a conceptual framework for the study of cerebral representation of prosody

Progress in understanding brain/behavior relationships in adult-acquired dysprosody has led to models of cortical hemispheric representation of prosodic processing based on functional (linguistic vs affective) or physical (timing vs pitch) parameters. These explanatory perspectives have not been reconciled, and also a number of neurobehavior syndromes that include dysprosody among their neurological signs have not yet been integrated. In addition to expanding the functional perspective on prosody, some of these syndromes have implicated a significant role of subcortical nuclei in prosodic competence. In this article, two patients with acquired dysprosodic speech following damage to basal ganglia nuclei were evaluated using behavioral, acoustic, cognitive, and radiographic approaches. Selective quantitative measures were performed on each individual’s performance to provide detailed verification and clarification of clinical observations, and to test hypotheses regarding prosodic function. These studies, combined with a review of related clinical research findings, exemplify the value of a broader perspective on the neurobehavioral dysfunction underlying acquired adult dysprosodic speech, and lead to a new, proposed conceptual framework for the cerebral representation of prosody.

Physiological consequences of early-life insult

The most commonly observed severe lung injuries in early life are the respiratory distress syndrome in premature infants and the acute respiratory distress syndrome in children. Both diseases are characterised by alveolar instability, fluid filled airspace and some degree of airway obstruction. In the acute phase, collapsed alveoli can be reopened with positive end-expiratory pressure and lung recruitment. New insight into the physiology of lung recruitment suggests that the shape of the pressure–volume curve is defined by the change in rate of alveolar opening and closing. Reduced lung volumes and severe ventilation maldistribution are found in the acute phase but may persist during childhood. Any severe lung injury in this early phase of life can cause significant structural and functional damage to the developing lung. Follow-up studies of children with chronic lung disease have shown that the functional abnormalities will improve but may still be present in later childhood.

COMPREENSÃO DO FUNCIONAMENTO MENTAL EM PACIENTES COM ACIDENTE CEREBROVASCULAR: UMA CONTRIBUIÇÃO DA PSICOLOGIA DA SAÚDE

O acidente cerebrovascular é uma doença de grande incidência no Brasil e no mundo. As pessoas que sofreram este tipo de acometimento podem apresentar seqüelas variadas, como motoras, cognitivas, sensoriais, sociais, afetivo-emocionais e transtornos psiquiátricos, levando a graus variados de dependência. Sendo assim, um estudo psicológico se faz importante, pois estas pessoas sofrerão mudanças em suas rotinas e no seu mundo interno.O presente trabalho trata-se de uma pesquisa clínico qualitativa, e teve como objetivos investigar as repercussões psicológicas de pacientes adultos que sofreram acidente cerebrovascular; compreender o funcionamento mental, a deterioração neuropsicológica e a adaptação humana desses pacientes, através da Escala de Avaliação Global do Funcionamento, do Desenho da Figura Humana, e da Escala do Diagnóstico Adaptativo Operacionalizado; compreender o sofrimento psicológico em narrativas da entrevista psicológica dessas pessoas e investigar como os indivíduos contam sua própria história numa compreensão psicossomática e psicanalítica. Para isso, utilizou-se o referencial teórico da Psicanálise e as concepções de Neuropsicanálise e Psicossomática. Foram analisados os relatos de cinco pacientes em tratamento num centro de reabilitação. Observou-se que por tratar-se de uma lesão cerebral, as repercussões psicológicas de quem sofreu acidente cerebrovascular devem ser observadas do ponto de vista neuropsicológico e a dinâmica afetivo-emocional. Os dados do Eixo V do DSM-IV, Escala de Avaliação Global do Funcionamento, e da Escala do Diagnóstico Adaptativo Operacionalizado de Ryad Simon apresentaram forte correlação estatística, embora a última seja mais compreensiva do ponto de vista psicanalítico; todos os pacientes apresentaram Adaptação Ineficaz. Quanto ao Desenho da Figura Humana, questionou-se a fidedignidade deste tipo de técnica nessa população, uma vez que os dados de organicidade interferem bastante. A história construída foi um instrumento importante para investigar como o indivíduo que sofreu acidente cerebrovascular contou sua própria história, seus mecanismos de defesa e as fantasias inconscientes, surgindo nesses relatos histórias importantes de depressão. Os mecanismos de defesa predominante no funcionamento mental desses pacientes foram a repressão e a desvalorização, no funcionamento neurótico, e a onipotência no funcionamento psicótico.(AU)

The presence of ascorbate induces expression of brain derived neurotrophic factor in SH-SY5Y neuroblastoma cells after peroxide insult, which is associated with increased survival

Oxidative stress and free radical production have been implicated in Alzheimer's disease, where low levels of the antioxidant vitamin C (ascorbate) have been shown to be associated with the disease. In this study, neuroblastoma SH-SY5Y cells were treated with hydrogen peroxide in the presence of ascorbate in order to elucidate the me0chanism(s) of protection against oxidative stress afforded by ascorbate. Protein oxidation, glutathione levels, cell viability and the effects on the proteome and its oxidized counterpart were monitored. SH-SY5Y cells treated with ascorbate prior to co-incubation with peroxide showed increased viability in comparison to cells treated with peroxide alone. This dual treatment also caused an increase in protein carbonyl content and a decrease in glutathione levels within the cells. Proteins, extracted from SH-SY5Y cells that were treated with either ascorbate or peroxide alone or with ascorbate prior to peroxide, were separated by two-dimensional gel electrophoresis and analyzed for oxidation. Co-incubation for 24 hours decreased the number of oxidised proteins (e.g. acyl CoA oxidase 3) and induced brain derived neurotrophic factor (BDNF) expression. Enhanced expression of BDNF may contribute to the protective effects of ascorbate against oxidative stress in neuronal cells.

Cerebrovascular dysfunction in the presence of chronic inflammation

Background: Patients with autoimmune disease have increased incidence of stroke. Hemorrhagic stroke (HS) is associated with loss of cerebrovascular function, leading to micro-vessel burst, and hemorrhage. We believe chronic inflammation is involved in loss of cerebrovascular function and HS. We established a hypertensive-arthritis model in spontaneously hypertensive rats (SHR) fed either standard rodent diet (0.59% NaCl) (RD) or high salt diet (4% NaCl) (HSD) and compared them to non-inflamed SHR. Methods: Complete Freund’s adjuvant (CFA) was injected into the left paw to induce mono-arthritis. Blood pressure and inflammation was monitored. At endpoint, animals were sacrificed and evaluated for HS while middle cerebral artery (MCA) was isolated for functional studies. Results: HS was observed in 90% of CFA-treated groups. The MCA of arthritic RD-SHR exhibited decreased ability to undergo pressure dependent constriction (PDC). All HSD-SHR showed a decreased response to PDC. However, arthritic HSD-SHR also demonstrated a diminished response to vasoactive peptides. Conclusion: HS occurring with CFA injection corresponds with loss of MCA function. Chronic HSD appears to further exacerbate vascular dysfunction in the MCA.

Influence of Outlet Boundary Conditions on Cerebrovascular Aneurysm Hemodynamics

Computational fluid dynamic (CFD) studies of blood flow in cerebrovascular aneurysms have potential to improve patient treatment planning by enabling clinicians and engineers to model patient-specific geometries and compute predictors and risks prior to neurovascular intervention. However, the use of patient-specific computational models in clinical settings is unfeasible due to their complexity, computationally intensive and time-consuming nature. An important factor contributing to this challenge is the choice of outlet boundary conditions, which often involves a trade-off between physiological accuracy, patient-specificity, simplicity and speed. In this study, we analyze how resistance and impedance outlet boundary conditions affect blood flow velocities, wall shear stresses and pressure distributions in a patient-specific model of a cerebrovascular aneurysm. We also use geometrical manipulation techniques to obtain a model of the patient’s vasculature prior to aneurysm development, and study how forces and stresses may have been involved in the initiation of aneurysm growth. Our CFD results show that the nature of the prescribed outlet boundary conditions is not as important as the relative distributions of blood flow through each outlet branch. As long as the appropriate parameters are chosen to keep these flow distributions consistent with physiology, resistance boundary conditions, which are simpler, easier to use and more practical than their impedance counterparts, are sufficient to study aneurysm pathophysiology, since they predict very similar wall shear stresses, time-averaged wall shear stresses, time-averaged pressures, and blood flow patterns and velocities. The only situations where the use of impedance boundary conditions should be prioritized is if pressure waveforms are being analyzed, or if local pressure distributions are being evaluated at specific time points, especially at peak systole, where the use of resistance boundary conditions leads to unnaturally large pressure pulses. In addition, we show that in this specific patient, the region of the blood vessel where the neck of the aneurysm developed was subject to abnormally high wall shear stresses, and that regions surrounding blebs on the aneurysmal surface were subject to low, oscillatory wall shear stresses. Computational models using resistance outlet boundary conditions may be suitable to study patient-specific aneurysm progression in a clinical setting, although several other challenges must be addressed before these tools can be applied clinically.

Aplicación de la escala National Institutes of Health Stroke Scale (NIHSS) en pacientes ingresados en el Hospital Vicente Corral Moscoso con diagnóstico de enfermedad cerebrovascular isquémica, enero-diciembre de 2004, Cuenca-Ecuador

Estudio descriptivo de pacientes con ictus isquémico ingresados en el Hospital Vicente Corral dentro de las 24 horas de inicio de síntomas, desde enero a diciembre de 2004. El daño neurológico inicial fue cuantificado usando la NIHSS. El desenlace neurológico fue valorado a los 7 días y 3 meses utilizando el Indice de Barthel. Resultados: De 75 pacientes ingresados en el período de estudio, 24 cumplieron los criterios de inclusión y 23 completaron el seguimiento. A los 3 meses 66.7de pacientes, con puntaje inicial NIHSS menor que 6 evolucionaron a un resultado excelente. Los pacientes con un puntaje NIHSS igual o mayor que 16 tuvieron un mal desenlace. El 50de pacientes con un puntaje de 16 a 20 y los pacientes con puntaje mayor que 20 fallecieron. En el análisis estadístico, un puntaje mayor a 13 tuvo un Odds Ratio de 49.5 (IC 954.5 - 480.5) para un desenlace fatal a los 3 meses. La asociación fue significativa lo que otorga al punto de corte de 13 puntos una gran validez para pronosticar un buen o mal desenlace. Conclusión. Aplicando el NIHSS a los pacientes con ictus isquémico observamos que un puntaje igual o mayor a 16 predice una alta probabilidad de muerte o severa incapacidad, mientras que un puntaje igual o menor a 6 pronostica una buena recuperación. Descriptores DeCS. Ictus isquémico, NIHSS, Índice de Barthel

Análisis del costo del manejo conservador del evento cerebrovascular isquémico en el Hospital Nacional Rosales, en pacientes ingresados durante el año 2014

El evento cerebrovascular (ECV) constituye una carga clínica y económica para cada sistema de salud, generando la búsqueda de estrategias terapéuticas efectivas con alta rentabilidad. Se clasifican en 2 grupos; hemorrágicos e isquémicos. El 80 % son de tipo isquémico. La incidencia mundial es de 1.5 a 4 casos por cada 1,000 habitantes. En El Salvador para el año 2005 el ECV se ubicaba en la tercera causa de muerte hospitalaria. Actualmente el tratamiento del ECV se basa en 2 apartados: el tratamiento agudo y la prevención de recurrencias. Materiales y métodos: se realizó un estudio de decisión-análisis, de datos retrospectivos tomados de fuentes documentales de pacientes con ECV isquémicos ingresados de enero a diciembre de 2015 en el Hospital Nacional Rosales (HNR). Resultados: se incluyeron 79 expedientes. Obteniendo un costo promedio de $569.77 por día de estancia. El costo de estudios diagnósticos por paciente fue de $379.06 USD, con un promedio de estancia de 7.46 días por paciente sin complicaciones y de $11.12 con complicaciones asociadas y con una mortalidad de 13.85 %. Conclusión: el ECV isquémico manejado conservadoramente, sin la administración de trombolisis con Alteplasa, considerada el manejo médico con mejor evidencia (I A), genera altos costos hospitalarios en el HNR.

La ateromatosis aórtica aumenta el riesgo de ataque cerebrovascular isquémico

Antecedentes: el ataque cerebrovascular isquémico (ACVi) es causa de mortalidad y discapacidad importante en adultos, siendo la cardioembolia, sobre todo por fibrilación auricular (FA), una etiología importante. Se conocen otras etiologías, cardíacas y no cardíacas, que no siempre pueden definirse, refiriéndose como probables o posibles de cardioaortoembolia. El rol de alguna de ellas, como la ateromatosis aórtica (AA), continúa siendo discutido. Objetivo: analizar fuentes posibles de cardioaortoembolia en pacientes con ACVi reciente. Material y método: estudio caso-control. Se analizaron 100 sujetos con ACVi de menos de 30 días de evolución estudiados prospectivamente con ecocardiograma transesofágico (ETE), entre febrero de 2012 y marzo de 2014. Se apareó cada caso según edad, sexo, presencia de flutter/FA y ausencia de prótesis valvular cardíaca, con un control que se buscó retrospectiva y aleatoriamente entre sujetos con ETE estudiados entre 2010 y 2015 sin ACVi. Se compararon variables binarias mediante test de McNemar y las cuantitativas por test de t pareado; se realizó regresión logística múltiple para ACVi con variables clínicas y hallazgos de ETE y p < 0,1 en el análisis univariado. Se consideró significativo p < 0,05. Variables cuantitativas se expresan en media y desvío estándar (DE) y nominales en valor absoluto y porcentaje, índice de probabilidad (OR) en su valor e intervalo de confianza (IC) 95%. Resultados: se formaron finalmente 76 pares caso-control. Edad casos: 64,3±1,4 y control 64,9±1,3 años (p=0,19); 39 mujeres (51,3%) y 15 sujetos (19,7%) con flutter/FA en cada grupo (p=1). No hubo diferencias significativas según factores de riesgo cardiovascular (FRCV) globales (p=0,06) ni alcoholismo (p=0,80); se encontraron diferencias significativas en la prevalencia de dislipemia (p=0,03) e hipertensión arterial (HTA) (p <0,05). Las indicaciones principales del ETE en los controles fueron: previo a cardioversión eléctrica de FA, sospecha de endocarditis, y valoración de valvulopatía mitral. La ateromatosis aórtica proximal y compleja (AAPC) (p=0,002, OR 5,5, IC95% 1,9-15,9) y la AA en forma global (p=0,001, OR 4,1, IC95% 1,8-9,3), además de la dislipemia (p=0,02, OR 2,8 IC95% 1,2-6,4), se asociaron significativamente con la presencia de ACVi en el análisis multivariado. Conclusión: la AA aumenta significativamente las chances de ACVi y las quintuplica cuando es proximal y compleja. La dislipemia se asoció a ACVi.