RESUMEN
The knowledge of brain syndromes is essential for stroke physicians and neurologists, particularly those that can be extremely difficult and challenging to diagnose due to the great variability of symptom presentation and yet of clinical significance in terms of potential devastating effect with poor outcome. The diagnosis and understanding of stroke syndromes has improved dramatically over the years with the advent of modern imaging, while the management is similar to general care as recommended by various guidelines in addition to care of such patients on specialized units with facilities for continuous monitoring of vital signs and dedicated stroke therapy. Such critical care can be provided either in the acute stroke unit, the medical intensive care unit or the neurological intensive care unit. There may be no definitive treatment at reversing stroke syndromes, but it is important to identify the signs and symptoms for an early diagnosis to prompt quick treatment, which can prevent further devastating complications following stroke. The aim of this article is to discuss some of the important clinical stroke syndromes encountered in clinical practice and discuss their management.
Asunto(s)
Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Fenómeno de la Extremidad Ajena/complicaciones , Fenómeno de la Extremidad Ajena/diagnóstico , Fenómeno de la Extremidad Ajena/terapia , Infartos del Tronco Encefálico/complicaciones , Infartos del Tronco Encefálico/diagnóstico , Infartos del Tronco Encefálico/terapia , Síndrome de Horner/complicaciones , Síndrome de Horner/diagnóstico , Síndrome de Horner/terapia , Humanos , Síndrome Medular Lateral/complicaciones , Síndrome Medular Lateral/diagnóstico , Síndrome Medular Lateral/terapia , Cuadriplejía/complicaciones , Cuadriplejía/diagnóstico , Cuadriplejía/terapia , Accidente Cerebrovascular/diagnóstico , Enfermedades Talámicas/complicaciones , Enfermedades Talámicas/diagnóstico , Enfermedades Talámicas/terapiaRESUMEN
BACKGROUND: Hypothermia is one of the most robust experimental neuroprotective interventions against cerebral ischemia. Identification of molecular pathways and gene networks together with single genes or gene families that are significantly associated with neuroprotection might help unravel the mechanisms of therapeutic hypothermia. MATERIAL AND METHODS: We performed a microarray analysis of ischemic rat brains that underwent 90 min of middle cerebral artery occlusion (MCAO) and 48 h of reperfusion. Hypothermia was induced for 4 h, starting 1 h after MCAO in male Wistar rats. At 48 h, magnetic resonance imaging (MRI) was performed for infarct volumetry, and functional outcome was determined by a neuroscore. The brain gene expression profile of sham (S), ischemia (I), and ischemia plus hypothermia (HI) treatment were compared by analyzing changes of individual genes, pathways, and networks. Real-time reverse-transcribed polymerase chain reaction (RT-PCR) was performed on selected genes to validate the data. RESULTS: Rats treated with HI had significantly reduced infarct volumes and improved neuroscores at 48 h compared with I. Of 4067 genes present on the array chip, HI compared with I upregulated 50 (1.23%) genes and downregulated 103 (3.20%) genes equal or greater than twofold. New genes potentially mediating neuroprotection by hypothermia were HNRNPAB, HIG-1, and JAK3. On the pathway level, HI globally suppressed the ischemia-driven gene response. Twelve gene networks were identified to be significantly altered by HI compared with I. The most significantly altered network contained genes participating in apoptosis suppression. CONCLUSIONS: Our data suggest that although hypothermia at the pathway level restored gene expression to sham levels, it selectively regulated the expression of several genes implicated in protein synthesis and folding, calcium homeostasis, cellular and synaptic integrity, inflammation, cell death, and apoptosis.
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Hipotermia Inducida , Ataque Isquémico Transitorio/metabolismo , Ataque Isquémico Transitorio/terapia , Animales , Apoptosis/genética , Apoptosis/fisiología , Temperatura Corporal/fisiología , Bases de Datos Genéticas , Regulación hacia Abajo/genética , Regulación hacia Abajo/fisiología , Perfilación de la Expresión Génica , Hemodinámica/fisiología , Infarto de la Arteria Cerebral Media/mortalidad , Infarto de la Arteria Cerebral Media/patología , Ataque Isquémico Transitorio/genética , Imagen por Resonancia Magnética , Masculino , Análisis por Micromatrices , Vías Nerviosas/fisiología , ARN/biosíntesis , ARN/aislamiento & purificación , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Reperfusión , Reproducibilidad de los Resultados , Programas Informáticos , Regulación hacia Arriba/genética , Regulación hacia Arriba/fisiologíaRESUMEN
BACKGROUND: Aspirin plus clopidogrel (A+C) may be more effective than aspirin only (AO) acutely after TIA and minor stroke, but the risk of bleeding in the acute phase is uncertain. We determined this risk, focusing particularly on aspirin-naïve patients. METHODS: We studied consecutive referrals to the EXPRESS study clinic from 1/4/02 to 31/3/08. A 30- to 90-day course of A+C was given to patients presenting acutely. Bleeding events were identified by face-to-face follow-up, diagnostic coding, and blood transfusion data. Unpublished data from the FASTER pilot trial were also studied. RESULTS: Among 633 EXPRESS patients treated with aspirin (+/- clopidogrel), there were 12 spontaneous bleeds (6 minor, 6 major/life-threatening) within 90 days after assessment, with a higher risk for A+C vs. AO (8/247 vs. 4/386, p = 0.047 overall; 5/247 vs. 1/386, p = 0.03 for major/life-threatening bleeds). The excess of major/life-threatening bleeds on A+C vs. AO was seen in aspirin-naïve patients, (4/137 vs. 0/273, p = 0.01), but not in prior-aspirin patients (1/110 vs. 1/113, p = 0.98). All symptomatic bleeds in the FASTER pilot also occurred in aspirin-naïve patients randomized to A+C (6/104 vs. 0/94, p = 0.03). In a pooled analysis, major/life-threatening bleeding on A+C occurred in 9/241 aspirin-naïve patients (90-day risk = 4.8%, 1.6-8.0) versus 1/204 prior-aspirin patients (p = 0.009). CONCLUSION: Although based on relatively few outcomes, the high risk of major bleeding on A+C acutely after TIA or minor stroke in aspirin-naïve patients is a cause for concern. The potential risk to patients is sufficient to mandate detailed monitoring of bleeding risk in ongoing trials and stratify results by whether patients were aspirin-naïve.
Asunto(s)
Aspirina/efectos adversos , Hemorragia/inducido químicamente , Ataque Isquémico Transitorio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/efectos adversos , Accidente Cerebrovascular/tratamiento farmacológico , Ticlopidina/análogos & derivados , Anciano , Aspirina/uso terapéutico , Clopidogrel , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Hemorragia/epidemiología , Humanos , Incidencia , Ataque Isquémico Transitorio/prevención & control , Estudios Longitudinales , Masculino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/prevención & control , Ticlopidina/efectos adversos , Ticlopidina/uso terapéuticoRESUMEN
Attaching and effacing bacterial pathogens attach to the apical surface of epithelial cells and disrupt epithelial barrier function, increasing permeability and allowing luminal contents access to the underlying milieu. Previous in vitro studies demonstrated that the neuropeptide vasoactive intestinal peptide (VIP) regulates epithelial paracellular permeability, and the high concentrations and close proximity of VIP-containing nerve fibers to intestinal epithelial cells would support such a function in vivo. The aim of this study was to examine whether VIP treatment modulated Citrobacter rodentium-induced disruption of intestinal barrier integrity and to identify potential mechanisms of action. Administration of VIP had no effect on bacterial attachment although histopathological scoring demonstrated a VIP-induced amelioration of colitis-induced epithelial damage compared with controls. VIP treatment prevented the infection-induced increase in mannitol flux a measure of paracellular permeability, resulting in levels similar to control mice, and immunohistochemical studies demonstrated that VIP prevented the translocation of tight junction proteins: zonula occludens-1, occludin, and claudin-3. Enteropathogenic Escherichia coli (EPEC) infection of Caco-2 monolayers confirmed a protective role for VIP on epithelial barrier function. VIP prevented EPEC-induced increase in long myosin light chain kinase (MLCK) expression and myosin light chain phosphorylation (p-MLC). Furthermore, MLCK inhibition significantly attenuated bacterial-induced epithelial damage both in vivo and in vitro. In conclusion, our results indicate that VIP protects the colonic epithelial barrier by minimizing bacterial-induced redistribution of tight junction proteins in part through actions on MLCK and MLC phosphorylation.
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Antiinflamatorios/administración & dosificación , Traslocación Bacteriana/efectos de los fármacos , Citrobacter rodentium/patogenicidad , Colitis/prevención & control , Colon/efectos de los fármacos , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Mucosa Intestinal/efectos de los fármacos , Péptido Intestinal Vasoactivo/administración & dosificación , Animales , Azepinas/farmacología , Adhesión Bacteriana , Células CACO-2 , Claudina-3 , Colitis/metabolismo , Colitis/microbiología , Colitis/patología , Colon/metabolismo , Colon/microbiología , Colon/patología , Modelos Animales de Enfermedad , Infecciones por Enterobacteriaceae/complicaciones , Infecciones por Enterobacteriaceae/metabolismo , Infecciones por Enterobacteriaceae/microbiología , Humanos , Inyecciones Intraperitoneales , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Manitol/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Cadenas Ligeras de Miosina/metabolismo , Quinasa de Cadena Ligera de Miosina/antagonistas & inhibidores , Quinasa de Cadena Ligera de Miosina/metabolismo , Naftalenos/farmacología , Ocludina , Permeabilidad , Fosfoproteínas/metabolismo , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo , Uniones Estrechas/microbiología , Factores de Tiempo , Proteína de la Zonula Occludens-1RESUMEN
Saccharomyces boulardii has received increasing attention as a probiotic effective in the prevention and treatment of infectious and inflammatory bowel diseases. The aim of this study was to examine the ameliorating effects of S. boulardii on Citrobacter rodentium colitis in vivo and identify potential mechanisms of action. C57BL/6 mice received 2.5 x 10(8) C. rodentium by gavage on day 0, followed by S. boulardii (25 mg; 5 x 10(8) live cells) gavaged twice daily from day 2 to day 9. Animal weights were monitored until death on day 10. Colons were removed and assessed for epithelial barrier function, histology, and myeloperoxidase activity. Bacterial epithelial attachment and type III secreted proteins translocated intimin receptor Tir (the receptor for bacterial intimin) and EspB (a translocation apparatus protein) required for bacterial virulence were assayed. In infected mice, S. boulardii treatment significantly attenuated weight loss, ameliorated crypt hyperplasia (234.7 +/- 7.2 vs. 297.8 +/- 17.6 microm) and histological damage score (0.67 +/- 0.67 vs. 4.75 +/- 0.75), reduced myeloperoxidase activity (2.1 +/- 0.4 vs. 4.7 +/- 0.9 U/mg), and attenuated increased mannitol flux (17.2 +/- 5.0 vs. 31.2 +/- 8.2 nm.cm(-2).h(-1)). The ameliorating effects of S. boulardii were associated with significantly reduced numbers of mucosal adherent C. rodentium, a marked reduction in Tir protein secretion and translocation into mouse colonocytes, and a striking reduction in EspB expression and secretion. We conclude that S. boulardii maintained colonic epithelial barrier integrity and ameliorated inflammatory sequelae associated with C. rodentium infection by attenuating C. rodentium adherence to host epithelial cells through putative actions on the type III secretion system.
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Proteínas Bacterianas/metabolismo , Citrobacter rodentium/patogenicidad , Colitis/prevención & control , Colon/microbiología , Infecciones por Enterobacteriaceae/prevención & control , Probióticos/uso terapéutico , Saccharomyces/crecimiento & desarrollo , Factores de Virulencia/metabolismo , Adhesinas Bacterianas/metabolismo , Animales , Adhesión Bacteriana , Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas Bacterianas/genética , Traslocación Bacteriana , Citrobacter rodentium/genética , Citrobacter rodentium/crecimiento & desarrollo , Citrobacter rodentium/metabolismo , Colitis/metabolismo , Colitis/microbiología , Colitis/patología , Colon/ultraestructura , Infecciones por Enterobacteriaceae/complicaciones , Infecciones por Enterobacteriaceae/metabolismo , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Mucosa Intestinal/microbiología , Mucosa Intestinal/ultraestructura , Manitol/metabolismo , Potenciales de la Membrana , Ratones , Ratones Endogámicos C57BL , Permeabilidad , Peroxidasa/metabolismo , Receptores de Superficie Celular/metabolismo , Factores de Tiempo , Transcripción Genética , Virulencia , Factores de Virulencia/genéticaRESUMEN
OBJECTIVES: To evaluate whether the presence of leukoaraiosis or multiple lacunes is associated with symptomatic intracerebral hemorrhage (ICH) and 90-day outcome after thrombolytic treatment with tissue plasminogen activator (tPA). METHODS: Data were from a Canadian national registry of thrombolyzed patients with ischemic stroke. A total of 820 scans were assessed, blind to clinical features, for the presence of severe vs no/moderate leukoaraiosis, and of multiple (>2) vs no/single lacunar infarcts. Logistic regression was used to determine if an independent interaction existed between the presence and degree of leukoaraiosis/lacunes and risk of symptomatic ICH, and to evaluate the predictive role of leukoaraiosis and lacunes in relation to 90-day outcome. RESULTS: An overall symptomatic ICH rate of 3.5% was observed. The rate of symptomatic ICH increased up to 10% in patients with severe leukoaraiosis and multiple lacunes. A significant association was observed between ICH risk and either severe leukoaraiosis (RR = 2.7 [95% CI 1.1 to 6.5]) or multiple lacunes (RR = 3.4 [95% CI 1.5 to 7.6]). Patients with multiple lacunes, but not leukoaraiosis, had higher mortality at 90 days compared to those with one or no lacunes (OR = 2.9, 95% CI 1.3 to 6.2, p = 0.008). No difference was observed in the good outcome rate among patients with and without leukoaraiosis or lacunes or both. CONCLUSION: The presence of small vessel disease on CT scan does not affect overall clinical outcome at 3 months in routine community use of tPA for ischemic stroke. A significant increase in the risk of symptomatic ICH is observed.
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Isquemia Encefálica/tratamiento farmacológico , Hemorragia Cerebral/inducido químicamente , Leucoaraiosis/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Activador de Tejido Plasminógeno/efectos adversos , Enfermedad Aguda/terapia , Anciano , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Infarto Encefálico/complicaciones , Infarto Encefálico/patología , Infarto Encefálico/fisiopatología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/fisiopatología , Canadá , Arterias Cerebrales/efectos de los fármacos , Arterias Cerebrales/patología , Arterias Cerebrales/fisiopatología , Hemorragia Cerebral/patología , Hemorragia Cerebral/fisiopatología , Estudios de Cohortes , Femenino , Fibrinolíticos/efectos adversos , Humanos , Leucoaraiosis/patología , Leucoaraiosis/fisiopatología , Masculino , Fibras Nerviosas Mielínicas/patología , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatologíaRESUMEN
ATP-sensitive potassium (K(ATP)) channels are weak inward rectifiers that appear to play an important role in protecting neurons against ischemic damage. Cerebral stroke is a major health issue, and vulnerability to stroke damage is regional within the brain. Thus, we set out to determine whether K(ATP) channels protect cortical neurons against ischemic insults. Experiments were performed using Kir6.2(-/-) K(ATP) channel knockout and Kir6.2(+/+) wildtype mice. We compared results obtained in Kir6.2(-/-) and wildtype mice to evaluate the protective role of K(ATP) channels against focal ischemia in vivo, and, using cortical slices, against anoxic stress in vitro. Immunohistochemistry confirmed the presence of K(ATP) channels in the cortex of wildtype, but not Kir6.2(-/-), mice. Results from in vivo and in vitro experimental models indicate that Kir6.2-containing K(ATP) channels in the cortex provide protection from neuronal death. Briefly, in vivo focal ischemia (15 min) induced severe neurological deficits and large cortical infarcts in Kir6.2(-/-) mice, but not in wildtype mice. Imaging analyses of cortical slices exposed briefly to oxygen and glucose deprivation (OGD) revealed a substantial number of damaged cells (propidium iodide-labeled) in the Kir6.2(-/-) OGD group, but few degenerating neurons in the wildtype OGD group, or in the wildtype and Kir6.2(-/-) control groups. Slices from the three control groups had far more surviving cells (anti-NeuN antibody-labeled) than slices from the Kir6.2(-/-) OGD group. These findings suggest that stimulation of endogenous cortical K(ATP) channels may provide a useful strategy for limiting the damage that results from cerebral ischemic stroke.
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Corteza Cerebral/metabolismo , Citoprotección/genética , Hipoxia-Isquemia Encefálica/metabolismo , Neuronas/metabolismo , Canales de Potasio de Rectificación Interna/metabolismo , Animales , Infarto Encefálico/genética , Infarto Encefálico/metabolismo , Infarto Encefálico/fisiopatología , Muerte Celular/genética , Supervivencia Celular/genética , Corteza Cerebral/fisiopatología , Predisposición Genética a la Enfermedad/genética , Hipoxia-Isquemia Encefálica/genética , Hipoxia-Isquemia Encefálica/fisiopatología , Masculino , Ratones , Ratones Noqueados , Degeneración Nerviosa/genética , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/fisiopatología , Técnicas de Cultivo de Órganos , Canales de Potasio de Rectificación Interna/genéticaRESUMEN
This review will analyse particular criteria in the analysis of stroke diagnosis and treatment, which are pivotal for the successful translation of experimental data from the laboratory to humans.
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Hemorragia Cerebral/terapia , Accidente Cerebrovascular/terapia , Animales , Bencenosulfonatos/uso terapéutico , Modelos Animales de Enfermedad , Humanos , Fármacos Neuroprotectores/uso terapéutico , Biosíntesis de Proteínas , Accidente Cerebrovascular/tratamiento farmacológico , Terapia TrombolíticaRESUMEN
OBJECTIVES: To test the hypothesis that insular cortical ischaemia is associated with acute hypertension and hyperglycaemia. METHODS: From the Canadian Activase for Stroke Effectiveness Study, which included only patients treated with thrombolysis hyperacutely (ie, within 3 h of onset of stroke), 966 patients were identified with ischaemia affecting (n = 685), or sparing (n = 281), the insular cortex. Demographic and clinical data, pretreatment indices of blood pressure, blood glucose, atrial fibrillation, and clinical imaging and outcome measures were compared between the two groups. Multivariable linear regression was used to assess predictors of systolic blood pressure and glucose levels before thrombolysis. RESULTS: Pretreatment hypertension (p = 0.009), but not hyperglycaemia (p = 0.32), was predicted by insular ischaemia in univariable linear regression analyses. After adjusting for other factors, however, insular cortical ischaemia was not found to be an independent predictor for acute hypertension or hyperglycaemia. CONCLUSIONS: Raised blood pressure or serum glucose levels in hyperacute (<3 h) cerebral ischaemia is not independently predicted by insular involvement. Several hours are required for sympathetic manifestations of insular ischaemia to evolve.
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Isquemia Encefálica/complicaciones , Hiperglucemia/etiología , Hipertensión/etiología , Enfermedad Aguda , Factores de Edad , Anciano , Glucemia , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Severe transient forebrain ischemia causes selective neuronal death in the hippocampal cornus ammonis 1 region. We tested the hypothesis that fimbria-fornix deafferentation can provide long-term protection to cornus ammonis 1 neurons and modulate neurogenesis following ischemia. Fimbria-fornix lesion or sham-fimbria-fornix lesion was performed on Wistar rats 13 days prior to 10 min forebrain ischemia or sham ischemia. Temperature was regulated and rats survived for 7, 14 or 28 days. Immunofluorescent bromodeoxyuridine and neuron specific nuclear protein staining and immunochemistry terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining were performed. At 7 days after ischemia, 73%+/-14% of cornus ammonis 1 neurons were damaged, while deafferentation reduced the injury to 36%+/-17% of cornus ammonis 1 neurons. This protection persisted for at least 28 days. Ischemia significantly increased the number of bromodeoxyuridine-positive cells (85-90 cells/section in stroke group vs. 6 to 11 cells/section in normal or sham stroke group), with very few terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-stained cells adjacent to the hippocampal cornus ammonis 1. Fimbria-fornix lesioning followed by ischemia increased the percentage of new neurons 13-fold over ischemia alone and 6.5-fold over sham lesion plus ischemia. The results indicate that fimbria-fornix deafferentation provides long-term neuroprotection in cornus ammonis 1 following forebrain ischemia and promotes neurogenesis after ischemic insults.
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Proliferación Celular , Fórnix/fisiología , Hipocampo/patología , Ataque Isquémico Transitorio/patología , Neuronas/patología , Análisis de Varianza , Animales , Bromodesoxiuridina/metabolismo , Recuento de Células/métodos , Supervivencia Celular/fisiología , Modelos Animales de Enfermedad , Fórnix/lesiones , Inmunohistoquímica/métodos , Ataque Isquémico Transitorio/fisiopatología , Masculino , Microscopía Confocal/métodos , Organogénesis/fisiología , Fosfopiruvato Hidratasa/metabolismo , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVES: Controversy exists about the optimal imaging technique in acute stroke. It was hypothesised that CT is comparable with DWI, when both are read systematically using quantitative scoring. METHODS: Ischaemic stroke patients who had CT within six hours and DWI within seven hours of onset were included. Five readers used a quantitative scoring system (ASPECTS) to read the baseline (b) and follow up CT and DWI. Use of MRI in acute stroke was also assessed in patients treated with tissue plasminogen activator (tPA) by prospectively recording reasons for exclusion. Patients were followed clinically at three months. RESULTS: bDWI and bCT were available for 100 consecutive patients (admission median NIHSS = 9). The mean bDWI and bCT ASPECTS were positively related (p<0.001). The level of interrater agreement ranged from good to excellent across all modalities and time periods. Bland-Altman plots showed more variability between bCT and bDWI than at 24 hours. The difference between bCT and bDWI was < or =2 ASPECTS points. Of bCT scans with ASPECTS 8-10, 81% had DWI ASPECTS 8-10. Patients with bCT ASPECTS of 8-10 were 1.9 times more likely to have a favourable outcome at 90 days than those with a score of 0-7 (95% CI 1.1 to 3.1, p = 0.002). The relative likelihood of favourable outcome with a bDWI ASPECTS 8-10 was 1.4 (95% CI 1.0 to 1.9, p = 0.10). Of patients receiving tPA 45% had contraindications to urgent MRI. CONCLUSION: The differences between CT and DWI in visualising early infarction are small when using ASPECTS. CT is faster and more accessible than MRI, and therefore is the better neuroimaging modality for the treatment of acute stroke.
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Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiología , Encéfalo , Imagen de Difusión por Resonancia Magnética , Tomografía Computarizada por Rayos X , Anciano , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Circulación Cerebrovascular/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios Prospectivos , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To study the workload of and use of acute intervention within an established acute stroke service, the Calgary Stroke Programme (CSP). METHODS: Prospective record of all acute referrals, diagnoses, and management decisions over a 4 month period. RESULTS: The CSP received 572 referrals (median: 32 per week), 88% of which were made between 7 am and midnight. Of the 427 patients seen in person, 29% had not had an acute stroke or transient ischaemic attack (TIA). Fifty percent of patients with suspected acute stroke were referred within 3 h of symptom onset and 11% with acute ischaemic stroke (equating to 35% of those referred within 3 h of onset and seen in person) were treated with thrombolysis. CONCLUSION: Centralisation of services facilitates the rapid referral of, and use of acute interventions in, patients with acute stroke and TIA. Centralised services are likely to be busy (although less so at night), to attract large numbers of patients with disorders that mimic stroke and TIA, and yet still likely to treat only the minority of acute strokes using thrombolysis. These observations may help those planning similar services and underline the need to develop more widely applicable treatments for acute stroke.
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Atención Integral de Salud/métodos , Ataque Isquémico Transitorio/terapia , Accidente Cerebrovascular/terapia , Carga de Trabajo , Enfermedad Aguda , Adulto , Femenino , Fibrinolíticos/uso terapéutico , Hospitalización , Humanos , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/rehabilitación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Derivación y Consulta/estadística & datos numéricos , Sistema de Registros , Accidente Cerebrovascular/epidemiología , Rehabilitación de Accidente CerebrovascularRESUMEN
INTRODUCTION: Retinal artery occlusion represents a medical emergency with poor prognosis for visual recovery. Spontaneous improvement is estimated to occur in less than 15% of central retinal artery occlusion (CRAO) cases and conventional treatments have provided only limited benefit. Intra-arterial thrombolysis has been reported as a potentially efficacious and safe treatment. METHODS: We performed a retrospective chart review of all retinal artery occlusion cases treated with intra-arterial recombinant tissue-type plasminogen activator (rtPA) from January 1998 to May 2004. Patients received Goldmann perimetry visual field testing at a variable interval following the procedure (2 days-2.5 years). Visual acuity (VA) was re-assessed in May 2004. RESULTS: Eight cases (59-77 years) were treated for CRAO, 6-18 hours post-onset with intra-arterial rtPA (10-20 mg over 15-60 minutes); one case of branch occlusion (BRAO) was treated with 30 mg rtPA over 75 minutes, 12 hours post-onset. Among the six patients with CRAO assessed in clinic, three experienced improvement in VA by two or more gradations (Snellen lines); three improved by one gradation. However, none achieved a final VA better than 20/300. The case of branch occlusion improved to a VA of 20/20. All patients had residual monocular field defects. CONCLUSIONS: Our findings reveal a limited benefit for intra-arterial tPA compared to the rate of spontaneous improvement and conventional forms of therapy for retinal artery occlusion.
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Oclusión de la Arteria Retiniana/tratamiento farmacológico , Terapia Trombolítica , Activador de Tejido Plasminógeno/uso terapéutico , Adulto , Anciano , Canadá , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Oclusión de la Arteria Retiniana/diagnóstico , Estudios Retrospectivos , Factores de Tiempo , Agudeza Visual/fisiología , Pruebas del Campo Visual , Campos VisualesRESUMEN
OBJECTIVES: In this study we define the probability of vascular abnormality in the middle cerebral artery (MCA) territory according to the extent of ischaemic change seen using computed tomography (CT). We assessed the sensitivity and specificity of the hyperdense middle cerebral artery (HMCA) and the "dot" sign using magnetic resonance angiography (MRA). METHODS: Patients presenting with ischaemic stroke had a CT scan (<6 h) prior to MRI (<7 h). A quantitative CT scoring system (ASPECTS) was applied to CT and diffusion weighted images (DWI) at baseline and follow up (24 h) by five independent observers. The presence of HMCA and the MCA "dot" sign was also evaluated. An expert reader assessed the 3D time of flight (TOF) MRA in the anterior circulation for areas of decreased vascular signal in the MCA territory, with an absent signal taken to represent severely reduced or absent flow. RESULTS: A total of 100 consecutive patients had baseline CT and MR scans. The median NIHSS was 9. The median CT ASPECTS was 8 and equalled the median DWI ASPECTS. There were a total of 10 HMCA and 19 MCA "dot" signs, with four patients having both HMCA and "dot" signs. A total of 47 MRA flow signal abnormalities were observed in the anterior circulation. CONCLUSIONS: In the absence of accessible neurovascular imaging, the extent of CT ischaemia (ASPECTS) is a strong predictor of vascular occlusion. The CT hyperdense artery signs have a high positive predictive value but low negative predictive value.
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Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/patología , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/patología , Angiografía por Resonancia Magnética , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/etiología , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
Caffeinol has been proposed as a neuroprotectant for human trials. This review covers a variety of animal models used and various attempts to take animal protocols to human trials. The accompanying paper discusses the rabbit model that was used to identify the efficacy of tissue plasminogen activator (tPA) treatment. To date, this is the only model that was able to achieve laboratory to clinical translational success. Use of caffeinol as a cytoprotective agent in rat models yielded exciting results, which led to clinical trials. However, caffeinol given with tPA in rabbits leads to increased hemorrhage. Caffeinol alone does not prove to be neuroprotective, as vasodilation by itself is not efficacious. However, vasodilation combined with thrombolysis (caffeinol with tPA) poses an increased risk of hemorrhage. For a more translational approach to study neuroprotection and neuroprotective agents in human trials, it is necessary to demonstrate the efficacy of the procedure and purported agents in several animal models.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Cafeína/uso terapéutico , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/prevención & control , Modelos Animales de Enfermedad , Quimioterapia Combinada , Etanol/uso terapéutico , Fibrinolíticos/efectos adversos , Humanos , Activador de Tejido Plasminógeno/uso terapéuticoRESUMEN
It has long been accepted that high concentrations of glutamate can destroy neurons, and this is the basis of the theory of excitotoxicity during brain injury such as stroke. Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists such as Selfotel, Aptiganel, Gavestinel and others failed to show neuroprotective efficacy in human clinical trials or produced intolerable central nervous system adverse effects. The failure of these agents has been attributed to poor studies in animal models and to poorly designed clinical trials. We also speculate that NMDA receptor antagonism may have hindered endogenous mechanisms for neuronal survival and neuroregeneration. It remains to be proven in human stroke whether NMDA receptor antagonism can be neuroprotective.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Antagonistas de Aminoácidos Excitadores/farmacología , Isquemia/patología , N-Metilaspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Supervivencia Celular , Modelos Animales de Enfermedad , Guanidinas/farmacología , Humanos , Indoles/farmacología , Neuronas/patología , Ácidos Pipecólicos/farmacologíaAsunto(s)
Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/tratamiento farmacológico , Enfermedad Aguda , Biomarcadores/análisis , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiología , Isquemia Encefálica/prevención & control , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/prevención & control , Trastornos Cerebrovasculares/complicaciones , Imagen de Difusión por Resonancia Magnética , Progresión de la Enfermedad , Servicios Médicos de Urgencia/organización & administración , Servicios Médicos de Urgencia/tendencias , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Humanos , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/tratamiento farmacológico , Valor Predictivo de las Pruebas , Medición de Riesgo , Síndrome , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/uso terapéuticoRESUMEN
One hundred seventy-six consecutive patients treated with IV tissue plasminogen activator (tPA) for acute ischemic stroke were examined prospectively, and orolingual angioedema was found in nine (5.1%; 95% CI 2.3 to 9.5). The reaction was typically mild, transient, and contralateral to the ischemic hemisphere. Risk of angioedema was associated with angiotensin-converting enzyme inhibitors (relative risk [RR] 13.6; 95% CI 3.0 to 62.7) and signs on initial CT of ischemia in the insular and frontal cortex (RR 9.1; 95% CI 1.4 to 30.0).