RESUMO
Stroke is a leading cause of death and disability in the United States. Most strokes are ischemic, resulting in both cognitive and motor impairments. Animal models of ischemic stroke such as the distal middle cerebral artery occlusion (dMCAO) and photothrombotic stroke (PTS) procedures have become invaluable tools, with their own advantages and disadvantages. The dMCAO model is clinically relevant as it occludes the artery most affected in humans, but yields variability in the infarct location as well as the behavioral and cognitive phenotypes disrupted. The PTS model has the advantage of allowing for targeted location of infarct, but is less clinically relevant. The present study evaluates phenotype disruption over time in mice subjected to either dMCAO, PTS, or a sham surgery. Post-surgery, animals were tested over 28 days on standard motor tasks (grid walk, cylinder, tapered beam, and rotating beam), as well as a novel odor-based operant task; the 5:1 Odor Discrimination Task (ODT). Results demonstrate a significantly greater disturbance of motor control with PTS as compared with Sham and dMCAO. Disruption of the PTS group was detected up to 28 days post-stroke on the grid walk, and up to 7 days on the rotating and tapered beam tasks. PTS also led to significant short-term disruption of ODT performance (1-day post-surgery), exclusively in males, which appeared to be driven by motoric disruption of the lick response. Together, this data provides critical insights into the selection and optimization of animal models for ischemic stroke research. Notably, the PTS procedure was best suited for producing disruptions of motor behavior that can be detected with common behavioral assays and are relatively enduring, as is observed in human stroke.
Assuntos
Modelos Animais de Doenças , Infarto da Artéria Cerebral Média , Camundongos Endogâmicos C57BL , Animais , Masculino , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/complicações , Camundongos , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/complicações , Atividade Motora/fisiologia , AVC Trombótico , Feminino , Odorantes , Discriminação Psicológica/fisiologia , Comportamento Animal/fisiologia , AVC Isquêmico/fisiopatologiaRESUMO
Despite substantial progress in mapping the trajectory of network plasticity resulting from focal ischemic stroke, the extent and nature of changes in neuronal excitability and activity within the peri-infarct cortex of mice remains poorly defined. Most of the available data have been acquired from anesthetized animals, acute tissue slices, or infer changes in excitability from immunoassays on extracted tissue, and thus may not reflect cortical activity dynamics in the intact cortex of an awake animal. Here, in vivo two-photon calcium imaging in awake, behaving mice was used to longitudinally track cortical activity, network functional connectivity, and neural assembly architecture for 2 months following photothrombotic stroke targeting the forelimb somatosensory cortex. Sensorimotor recovery was tracked over the weeks following stroke, allowing us to relate network changes to behavior. Our data revealed spatially restricted but long-lasting alterations in somatosensory neural network function and connectivity. Specifically, we demonstrate significant and long-lasting disruptions in neural assembly architecture concurrent with a deficit in functional connectivity between individual neurons. Reductions in neuronal spiking in peri-infarct cortex were transient but predictive of impairment in skilled locomotion measured in the tapered beam task. Notably, altered neural networks were highly localized, with assembly architecture and neural connectivity relatively unaltered a short distance from the peri-infarct cortex, even in regions within 'remapped' forelimb functional representations identified using mesoscale imaging with anaesthetized preparations 8 weeks after stroke. Thus, using longitudinal two-photon microscopy in awake animals, these data show a complex spatiotemporal relationship between peri-infarct neuronal network function and behavioral recovery. Moreover, the data highlight an apparent disconnect between dramatic functional remapping identified using strong sensory stimulation in anaesthetized mice compared to more subtle and spatially restricted changes in individual neuron and local network function in awake mice during stroke recovery.
Assuntos
Córtex Somatossensorial , Animais , Camundongos , Córtex Somatossensorial/fisiopatologia , AVC Trombótico/fisiopatologia , Masculino , Neurônios/fisiologia , Rede Nervosa/fisiopatologia , Modelos Animais de Doenças , Acidente Vascular Cerebral/fisiopatologia , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/fisiologiaRESUMO
BACKGROUND: Intravenous injection of alteplase, a recombinant tPA (tissue-type plasminogen activator) as a thrombolytic agent has revolutionized ischemic stroke management. However, tPA is a more complex enzyme than expected, being for instance able to promote thrombolysis, but at the same time, also able to influence neuronal survival and to affect the integrity of the blood-brain barrier. Accordingly, the respective impact of endogenous tPA expressed/present in the brain parenchyma versus in the circulation during stroke remains debated. METHODS: To address this issue, we used mice with constitutive deletion of tPA (tPANull [tPA-deficient mice]) or conditional deletion of endothelial tPA (VECad [vascular endothelial-Cadherin-Cre-recombinase]-Cre∆tPA). We also developed parabioses between tPANull and wild-type mice (tPAWT), anticipating that a tPAWT donor would restore levels of tPA to normal ones, in the circulation but not in the brain parenchyma of a tPANull recipient. Stroke outcomes were investigated by magnetic resonance imaging in a thrombo-embolic or a thrombotic stroke model, induced by local thrombin injection or FeCl3 application on the endothelium, respectively. RESULTS: First, our data show that endothelial tPA, released into the circulation after stroke onset, plays an overall beneficial role following thrombo-embolic stroke. Accordingly, after 24 hours, tPANull/tPANull parabionts displayed less spontaneous recanalization and reperfusion and larger infarcts compared with tPAWT/tPAWT littermates. However, when associated to tPAWT littermates, tPANull mice had similar perfusion deficits, but less severe brain infarcts. In the thrombotic stroke model, homo- and hetero-typic parabionts did not differ in the extent of brain damages and did not differentially recanalize and reperfuse. CONCLUSIONS: Together, our data reveal that during thromboembolic stroke, endogenous circulating tPA from endothelial cells sustains a spontaneous recanalization and reperfusion of the tissue, thus, limiting the extension of ischemic lesions. In this context, the impact of endogenous parenchymal tPA is limited.
Assuntos
Acidente Vascular Cerebral , AVC Trombótico , Animais , Camundongos , Modelos Animais de Doenças , Células Endoteliais , Endotélio , Camundongos Knockout , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Ativador de Plasminogênio Tecidual/genética , Ativador de Plasminogênio Tecidual/metabolismoRESUMO
BACKGROUND: Cardiocerebral infarction (CCI) is a rare and life-threatening presentation of simultaneous acute myocardial infarction and acute ischemic stroke that requires prompt recognition and proper treatment. CCI is time sensitive and carries a high mortality rate. There is no standardized treatment algorithm that addresses both conditions simultaneously. CASE REPORT: We present a 29-year-old man with simultaneous myocardial infarction and thrombotic stroke after coital activity. He presented to the Emergency Department with left-sided extremity weakness and numbness and radicular left-sided chest pain. He suffered a cardiac arrest during his evaluation and required emergent percutaneous coronary intervention with stent placement. He was resuscitated successfully and had an uncomplicated clinical course, with improved neurologic recovery prior to discharge. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: CCI is a rare condition that typically occurs in elderly patients with risk factors for cardiovascular disease. Management is challenging due to the time-sensitive nature of diagnosis and treatment of each condition. Treatment is not standardized, unlike individual evidence-based algorithms for thrombotic stroke and acute myocardial infarction. Risks and benefits for each treatment plan should be weighed and therapy should be directed toward the most immediate life-threatening process. This case would add to the literature surrounding this condition and help guide emergency physicians toward the most optimal treatment strategies for this patient population. This case also raises awareness of the existence of this condition and its potential presence in young, otherwise healthy patients.
Assuntos
AVC Isquêmico , Infarto do Miocárdio , AVC Trombótico , Masculino , Humanos , Idoso , Adulto , AVC Isquêmico/complicações , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Infarto , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND AND OBJECTIVES: Disability after stroke occurs across ischemic stroke subtypes, with a suggestion that embolic strokes are more devastating. Whether this difference is as a result of differences in comorbidities or differences in severity at the time of the stroke event is not known. The primary hypothesis was that participants with embolic stroke would have more severe stroke at the time of admission and a higher risk of mortality, compared with thrombotic stroke participants even with consideration of confounders over time, with a secondary hypothesis that this association would differ by race and sex. METHODS: Atherosclerosis Risk in Communities (ARIC) study participants with incident adjudicated ischemic stroke, stroke severity and mortality data, and complete covariates were included. Multinomial logistic regression models determined the association between stroke subtype (embolic vs thrombotic) and admission NIH Stroke Scale (NIHSS) category (minor [≤5], mild [6-10], moderate [11-15], severe [16-20], and very severe [>20]) adjusted for covariates from visits most proximal to the stroke. Separate ordinal logistic models evaluated for interaction by race and sex. Adjusted Cox proportional hazard models estimated the association between stroke subtype and all-cause mortality (through December 31, 2019). RESULTS: Participants (N = 940) were mean age 71 years (SD = 9) at incident stroke, 51% female, and 38% Black. Using adjusted multinomial logistic regression, the risk of having a more severe stroke (reference NIHSS ≤5) was higher among embolic stroke vs thrombotic stroke patients, with a step-wise increase for embolic stroke patients when moving from mild (odds ratio [OR] 1.95, 95% CI 1.14-3.35) to very severe strokes (OR 4.95, 95% CI 2.34-10.48). After adjusting for atrial fibrillation, there was still a higher risk of having a worse NIHSS among embolic vs thrombotic strokes but with attenuation of effect (very severe stroke OR 3.91, 95% CI 1.76-8.67). Sex modified the association between stroke subtype and severity (embolic vs thrombotic stroke, p interaction = 0.03, per severity category, females OR 2.38, 95% CI 1.55-3.66; males OR 1.75, 95% CI 1.09-2.82). The risk of death (median follow-up 5 years, interquartile range 1-12) was also increased for embolic vs thrombotic stroke patients (hazard ratio 1.66, 95% CI 1.41-1.97). DISCUSSION: Embolic stroke was associated with greater stroke severity at the time of the event and a higher risk of death vs thrombotic stroke, even after careful adjustment for patient-level differences.
Assuntos
Aterosclerose , AVC Embólico , AVC Isquêmico , AVC Trombótico , Idoso , Feminino , Humanos , Masculino , Aterosclerose/complicações , Aterosclerose/epidemiologia , AVC Embólico/complicações , Embolia/complicações , AVC Isquêmico/complicações , Fatores de RiscoRESUMO
INTRODUCTION: Patients with stroke are at a high risk of recurrence, and although they receive antiplatelet therapies such as clopidogrel for secondary prevention of non-cardioembolic stroke, the recurrence rate remains high. Three phase 3 trials (PRASTRO-I/II/III) were conducted to determine the efficacy of prasugrel in preventing recurrent stroke. Here, we performed an integrated analysis of these studies to confirm the generalizability of the PRASTRO-III findings and to supplement the small sample size of the study. METHODS: Patients from PRASTRO-I, PRASTRO-II, and PRASTRO-III with ischemic stroke (large-artery atherosclerosis or small-artery occlusion) and at least one of the following were included: hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease, or ischemic stroke history. The primary efficacy endpoint was the composite incidence of ischemic stroke, myocardial infarction (MI), and death from other vascular causes in the intention-to-treat population. Bleeding events (life-threatening bleeding, major bleeding, and clinically relevant bleeding) were evaluated as the primary safety endpoint. Cumulative incidences and 95% confidence intervals (CIs) were calculated for the study outcomes using the Kaplan-Meier method. Hazard ratios (HRs) and 95% CIs were calculated using the Cox regression model. RESULTS: The data of 2,184, 274, and 230 patients from PRASTRO-I, PRASTRO-II, and PRASTRO-III, respectively, were analyzed (N = 2,688; prasugrel, N = 1,337; clopidogrel, N = 1,351). Stroke at enrollment was classified as large-artery atherosclerosis in 49.3% of patients and small-artery occlusion in 50.7% of patients. The primary efficacy endpoint composite incidence (prasugrel vs. clopidogrel) was 3.4% versus 4.3% (HR: 0.771, 95% CI: 0.522-1.138). The incidence of each component of the primary efficacy endpoint for prasugrel versus clopidogrel was 3.1% (n = 41) versus 4.1% (n = 55) for ischemic stroke, 0.3% (n = 4) versus 0.2% (n = 3) for MI, and no events of death from other vascular causes. For the primary safety endpoint, bleeding events were reported in 6.0% of patients in the prasugrel group versus 5.5% of patients in the clopidogrel group (HR: 1.074, 95% CI: 0.783-1.473). CONCLUSIONS: This integrated analysis supports the findings of PRASTRO-III. Prasugrel is a promising treatment that results in a numerical reduction in the composite incidence of ischemic stroke, MI, and death from other vascular causes in patients with ischemic stroke who are at a high risk of stroke recurrence. No major safety issues were observed for prasugrel.
Assuntos
Síndrome Coronariana Aguda , Aterosclerose , AVC Isquêmico , Infarto do Miocárdio , Acidente Vascular Cerebral , AVC Trombótico , Humanos , Síndrome Coronariana Aguda/induzido quimicamente , Síndrome Coronariana Aguda/complicações , Aterosclerose/induzido quimicamente , Aterosclerose/complicações , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/complicações , AVC Isquêmico/complicações , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , AVC Trombótico/induzido quimicamente , Resultado do TratamentoAssuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , AVC Trombótico , Humanos , Cloridrato de Prasugrel , Prevenção Secundária , Inibidores da Agregação Plaquetária , Clopidogrel , Síndrome Coronariana Aguda/complicações , Acidente Vascular Cerebral/prevenção & controle , Resultado do TratamentoRESUMO
AIM: To examine the efficacy and safety of prasugrel vs clopidogrel in thrombotic stroke patients at risk of ischemic stroke. METHODS: This multicenter, active-controlled, randomized, double-blind, double-dummy, parallel group study enrolled thrombotic stroke patients aged ≥ 50 years at risk of ischemic stroke. Patients received prasugrel (3.75 mg/day) or clopidogrel (75 or 50 mg/day) for 24-48 weeks; other antiplatelet drugs were prohibited. The primary efficacy endpoint was the composite incidence of ischemic stroke, myocardial infarction (MI), and death from other vascular causes from the start to 1 day after treatment completion or discontinuation. Secondary efficacy endpoints included the incidences of ischemic stroke, MI, death from other vascular causes, ischemic stroke and transient ischemic attack, and stroke. Safety endpoints included bleeding events and adverse events (AEs). RESULTS: In the prasugrel (N=118) and clopidogrel (N=112; all received 75 mg) groups, the primary efficacy endpoint composite incidence (95% confidence interval) was 6.8% (3.0%-12.9%) and 7.1% (3.1%-13.6%), respectively. The risk ratio (prasugrel/clopidogrel) was 0.949 (0.369-2.443). Secondary efficacy endpoints followed a similar trend. The combined incidences of life-threatening, major, and clinically relevant bleeding were 5.0% and 3.5% in the prasugrel and clopidogrel groups, respectively. The incidences of all bleeding events and AEs were 19.2% and 24.6% and 76.7% and 82.5% in the prasugrel and clopidogrel groups, respectively. No serious AEs were causally related to prasugrel. CONCLUSIONS: We observed a risk reduction of 5% with prasugrel vs clopidogrel, indicating comparable efficacy. There were no major safety issues for prasugrel.
Assuntos
Síndrome Coronariana Aguda , AVC Isquêmico , Infarto do Miocárdio , Acidente Vascular Cerebral , AVC Trombótico , Humanos , Cloridrato de Prasugrel/efeitos adversos , Clopidogrel/efeitos adversos , AVC Isquêmico/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Infarto do Miocárdio/epidemiologia , Hemorragia/induzido quimicamente , Fatores de Risco , AVC Trombótico/induzido quimicamente , AVC Trombótico/tratamento farmacológico , Resultado do Tratamento , Síndrome Coronariana Aguda/tratamento farmacológicoRESUMO
Pyroptosis, a type of programmed cell death illuminated by inflammasomes and active caspases, is implicated in post-stroke inflammation. Our previous study showed that lncRNA taurine upregulated gene 1 (Tug1) sponging miR-145a-5p modulated microglial activation after oxygen-glucose deprivation (OGD). However, the role and mechanism of Tug1 on post-stroke pyroptosis is not fully clear. Photo-thrombosis stroke mice and OGD-treated BV-2 microglia were established respectively. Tug1 knockdown or overexpression was achieved by intraventricular infusion of AAV-shTug1 in vivo, or transfection of siTug1 and pcDNA3.1-Tug1 in vitro. Neurological function and infarction volume were evaluated. Meanwhile, pyroptosis-associated proteins (IL-1ß, IL-18, NLRP3, ASC, cleaved-caspase-1, and GSDMD-N), TLR4, and p-p65/p65 as well as Tug1 and miR-145a-5p were detected 24 h after photo-thrombosis or 4 h after OGD by qRT-PCR, western blot, and ELISA. The correlation between Tug1/miR-145a-5p/Tlr4 axis and pyroptosis was explored by dual-luciferase reporter assay and functional gain-and-loss experiments. Photo-thrombosis or OGD caused neural injury and upregulated pyroptosis-associated proteins, Tug1, TLR4, and p-p65 as well as downregulated miR-145a-5p, which was prevented by Tug1 knockdown in vivo and in vitro. Tlr4 gene, putatively binding with miR-145a-5p by bioinformatics analysis, was found to be a direct target of miR-145a-5p with negative interactions. Furthermore, miR-145a-5p inhibitor abolished the inhibitive effects of siTug1 on TLR4 and p-p65 as well as pyroptosis-associated proteins, whereas miR-145a-5p mimics abrogated the enhanced effects of pcDNA3.1-Tug1 on that, suggesting an involvement of Tug1/miR-145a-5p/Tlr4 axis on pyroptosis. Tug1 contributes NLRP3 inflammasome-dependent pyroptosis through miR-145a-5p/Tlr4 axis post-stroke, providing a promising therapeutic strategy against inflammatory injury.
Assuntos
MicroRNAs , RNA Longo não Codificante , AVC Trombótico , Animais , Caspase 1/metabolismo , Linhagem Celular , Glucose/farmacologia , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Camundongos , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Oxigênio/farmacologia , Piroptose , RNA Longo não Codificante/genética , Taurina/farmacologia , Receptor 4 Toll-Like/metabolismoRESUMO
Vaccine-induced thrombosis with thrombocytopenia (VITT) is a recently-described condition associated with arterial and venous thrombosis following vaccination with the ChAdOx1 nCoV-19 (AstraZeneca) vaccine. This report describes two cases of stroke caused by arterial and venous thromboses presenting within 28 days of receiving the AstraZeneca vaccine. The patients were otherwise young and healthy with minimal risk factors for thrombosis yet developed a rapid, ultimately fatal neurological deterioration.The patients were significantly thrombocytopenic with disproportionately raised D-dimers, both of which are widely reported in this condition. Both cases had measurable immunoglobulin G platelet factor-4 antibodies detected via enzyme-linked immunosorbent assay, similar to those described in heparin-induced thrombocytopenia.These cases illustrate that physicians should be especially mindful of VITT in the context of evolving evidence on treatment and in view of the potentially rapid and catastrophic neurological deterioration, leading to fatality despite best supportive care.
Assuntos
Acidente Vascular Cerebral , Trombose , AVC Trombótico , ChAdOx1 nCoV-19 , Heparina , Humanos , Acidente Vascular Cerebral/complicações , Trombose/etiologiaRESUMO
Approximately 50% of stroke survivors experience gastrointestinal complications. The innate immune response plays a role in changes to the gut-brain axis after stroke. The purpose of this study is to examine the importance of inflammasome-mediated pyroptosis in disruption of the gut-brain axis after experimental stroke. B6129 mice were subjected to a closed-head photothrombotic stroke. We examined the time course of inflammasome protein expression in brain and intestinal lysate using western blot analysis at 1-, 3-, and 7-days post-injury for caspase-1, interleukin-1ß, nod-like receptor protein 3 (NLRP3), and apoptosis speck-like protein containing a caspase-recruiting domain (ASC) and gasdermin-D (GSDMD) cleavage. In a separate group of mice, we processed brain tissue 24 and 72 h after thrombotic stroke for immunohistochemical analysis of neuronal and endothelial cell pyroptosis. We examined intestinal tissue for morphological changes and pyroptosis of macrophages. We performed behavioral tests and assessed gut permeability changes to confirm functional changes after stroke. Our data show that thrombotic stroke induces inflammasome activation in the brain and intestinal tissue up to 7-day post-injury as well as pyroptosis of neurons, cerebral endothelial cells, and intestinal macrophages. We found that thrombotic stroke leads to neurocognitive and motor function deficits as well as increased gut permeability. Finally, the adoptive transfer of serum-derived EVs from stroke mice into naive induced inflammasome activation in intestinal tissues. Taken together, these results provide novel information regarding possible mechanisms underlying gut complications after stroke and the identification of new therapeutic targets for reducing the widespread consequences of ischemic brain injury.
Assuntos
Acidente Vascular Cerebral , AVC Trombótico , Animais , Camundongos , Piroptose , Inflamassomos/metabolismo , Células Endoteliais/metabolismo , Eixo Encéfalo-Intestino , Caspases/metabolismoRESUMO
Stroke is one of the most prevalent diseases worldwide caused primarily by a thrombotic vascular occlusion that leads to cell death. To date, t-PA (tissue-type plasminogen activator) is the only thrombolytic therapy approved which targets fibrin as the main component of ischemic stroke thrombi. However, due to its highly restrictive criteria, t-PA is only administrated to less than 10% of all stroke patients. Furthermore, the research in neuroprotective agents has been extensive with no translational results from medical research to clinical practice up to now. Since we first described the key role of NETs (Neutrophil Extracellular Traps) in platelet-rich thrombosis, we asked, first, whether NETs participate in fibrin-rich thrombosis and, second, if NETs modulation could prevent neurological damage after stroke. To this goal, we have used the thromboembolic in situ stroke model which produces fibrin-rich thrombotic occlusion, and the permanent occlusion of the middle cerebral artery by ligature. Our results demonstrate that NETs do not have a predominant role in fibrin-rich thrombosis and, therefore, DNase-I lacks lytic effects on fibrin-rich thrombosis. Importantly, we have also found that NETs exert a deleterious effect in the acute phase of stroke in a platelet-TLR4 dependent manner and, subsequently, that its pharmacological modulation has a neuroprotective effect. Therefore, our data strongly support that the pharmacological modulation of NETs in the acute phase of stroke, could be a promising strategy to repair the brain damage in ischemic disease, independently of the type of thrombosis involved.
Assuntos
Armadilhas Extracelulares , Acidente Vascular Cerebral , Trombose , AVC Trombótico , Armadilhas Extracelulares/metabolismo , Fibrina/metabolismo , Humanos , Isquemia/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Trombose/tratamento farmacológico , Trombose/etiologia , Trombose/prevenção & controleRESUMO
BACKGROUND: Malaria is still major problem in developing countries, such as Pakistan. Besides fever, body ache and vomiting it can present with acute kidney injury, proteinuria, hematuria and cerebral manifestations which are more common with falciparum malaria. Neurological manifestations are rare presentation of malaria and should be consider in patients who are admitting with features of neuropathy and stroke. CASE PRESENTATION: We describe an unusual case of falciparum malaria, complicated by acute kidney injury who developed Polyneuropathy and intra-arterial thrombosis in middle cerebral artery territory. Our patient recovered his renal functions during admission and recovered his power and sensation in his limbs as well after 1 month. CONCLUSION: Malaria cause neurological manifestations including axonal and sensory neuropathy, cerebral venous and arterial thrombosis, PMNS, cerebellar signs and symptoms, psychosis, etc. With prompt diagnosis and early treatment they can be cure and regain their motor and sensory functions to normal level.
Assuntos
Injúria Renal Aguda/etiologia , Malária Falciparum/complicações , Artéria Cerebral Média , Polineuropatias/etiologia , AVC Trombótico/etiologia , Adolescente , Humanos , Angiografia por Ressonância Magnética , Masculino , AVC Trombótico/diagnósticoRESUMO
BACKGROUND: Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis. METHODS: We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days. FINDINGS: Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087). INTERPRETATION: These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window. FUNDING: Stryker Neurovascular.
Assuntos
Hemorragia Cerebral/epidemiologia , Procedimentos Endovasculares/efeitos adversos , Hemorragia Pós-Operatória/epidemiologia , Trombectomia/efeitos adversos , AVC Trombótico/cirurgia , Hemorragia Cerebral/etiologia , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/estatística & dados numéricos , Humanos , Hemorragia Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombectomia/métodos , Trombectomia/estatística & dados numéricos , AVC Trombótico/mortalidade , Tempo para o Tratamento , Resultado do TratamentoRESUMO
This concise review of the epidemiology, pathophysiology, evaluation, acute management, and prevention of ischemic stroke targets internists, family practitioners, and emergency physicians who manage patient with stroke.
Assuntos
Anticoagulantes/uso terapêutico , AVC Isquêmico , Inibidores da Agregação Plaquetária/uso terapêutico , Trombectomia , Terapia Trombolítica , AVC Embólico/epidemiologia , AVC Embólico/fisiopatologia , AVC Embólico/prevenção & controle , AVC Embólico/terapia , Procedimentos Endovasculares , Humanos , AVC Isquêmico/epidemiologia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/prevenção & controle , AVC Isquêmico/terapia , AVC Trombótico/epidemiologia , AVC Trombótico/fisiopatologia , AVC Trombótico/prevenção & controle , AVC Trombótico/terapiaAssuntos
Ácido Fólico/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , AVC Trombótico/prevenção & controle , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/uso terapêutico , Humanos , Resistência à Insulina , Pioglitazona/uso terapêuticoRESUMO
OBJECTIVES: This study assessed the temporal trends in the incidence of ischemic stroke among patients hospitalized with takotsubo cardiomyopathy (TCM) stratified by the subtypes of ischemic stroke (cardioembolic versus thrombotic). Predictors of each stroke subtype, the association with atrial fibrillation (AF), the occurrence of ventricular fibrillation/ventricular tachycardia (VF/VT), cardiogenic shock (CS), in-hospital mortality, length of stay (LOS), and total healthcare cost were also assessed. BACKGROUND: Ischemic stroke in TCM is thought to be primarily cardioembolic from left ventricular mural thromboembolism. Limited data are available on the incidence of thrombotic ischemic stroke in TCM. MATERIALS AND METHODS: We identified 27,970 patients hospitalized with the primary diagnosis of TCM from the 2008 to 2017 National Inpatient Sample, of which 751 (3%) developed ischemic stroke. Of those with ischemic stroke, 571 (76%) had thrombotic stroke while 180 (24%) had cardioembolic stroke. Cochrane armitage test was used to assess the incidence of thrombotic and cardioembolic strokes and multivariate regression was used to identify risk factors associated with each stroke subtype. We compared the incidence of AF, VF/VT, CS, LOS, in-hospital mortality and total cost between hospitalized patients with TCM alone to those with cardioembolic and thrombotic strokes. RESULTS: From 2008 - 2017, the incidence of thrombotic stroke (4.7%-9.5% (p< 0.0001) increased while it was unchanged for cardioembolic stroke (0.5%-0.7% P=0.5). In the multivariate regression, peripheral artery disease, prior history of stroke, and hyperlipidemia were significantly associated with thrombotic stroke, while CS, AF, and Asian race (compared to White race) were associated with cardioembolic stroke. Both cardioembolic and thrombotic strokes were associated with higher odds of IHM, AF, CS, longer LOS and increased cost. Trends in in-hospital mortality and the utilization of thrombolysis, cerebral angiography, and mechanical thrombectomy among patients with TCM and ischemic stroke were unchanged from 2008 to 2017. CONCLUSION: Among patients with TCM and ischemic stroke, thrombotic stroke was more common compared to cardioembolic stroke. Ischemic stroke was associated with poorer outcomes, including higher in-hospital mortality and increased healthcare resource utilization in TCM.
Assuntos
AVC Embólico/epidemiologia , Hospitalização/tendências , Cardiomiopatia de Takotsubo/epidemiologia , AVC Trombótico/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Angiografia Cerebral/tendências , Bases de Dados Factuais , AVC Embólico/diagnóstico , AVC Embólico/mortalidade , AVC Embólico/terapia , Feminino , Custos de Cuidados de Saúde/tendências , Mortalidade Hospitalar/tendências , Humanos , Incidência , Pacientes Internados , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/mortalidade , Cardiomiopatia de Takotsubo/terapia , Trombectomia/economia , Trombectomia/mortalidade , Trombectomia/tendências , AVC Trombótico/diagnóstico , AVC Trombótico/mortalidade , AVC Trombótico/terapia , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Recent observations raised concern that the intravenous recombinant tissue plasminogen activator (rt-PA) may result in damage to stroke patients caused by small artery occlusion (SAO). Thus, we perform a protocol for meta-analysis to investigate the efficacy and safety of intravenous thrombolysis with rt-PA in SAO-patients. METHODS: The search-style electronic libraries, including Pubmed, Embase, the Cochrane Library, Web of Science, Wanfang Data, VIP Chinese Journals, and China Biomedical Literature Service System are used for document retrieval in June 2021 with no restrictions on language. The risk of bias in include articles will be assessed using the Cochrane Risk of Bias Tool. We perform the meta-analysis by Stata version 10.0 software and calculated the statistics using the inverse variance statistical method. Binary outcomes are presented as Mantel-Haenszel-style risk ratios with 95% confidence interval. Continuous outcomes are reported as mean differences. RESULTS: The results of the article will be shown in a peer-reviewed journal. CONCLUSION: Intravenous rt-PA may be effective and safe in SAO-patients.
Assuntos
Arteriopatias Oclusivas/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Hemorragias Intracranianas/epidemiologia , Terapia Trombolítica/métodos , AVC Trombótico/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Arteriopatias Oclusivas/complicações , Fibrinolíticos/efeitos adversos , Humanos , Injeções Intravenosas , Hemorragias Intracranianas/induzido quimicamente , Metanálise como Assunto , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Revisões Sistemáticas como Assunto , AVC Trombótico/etiologia , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: The aim of this study was to assess the effects of experimentally induced photothrombotic stroke on structural and mechanical properties of rat m. flexor carpi ulnaris. METHODS: Two groups of Young-adult male Sprague-Dawley rats were measured: stroke (n = 9) and control (n = 7). Photothrombotic stroke was induced in the forelimb region of the primary sensorimotor cortex. Four weeks later, muscle-tendon unit and muscle belly length-force characteristics of the m. flexor carpi ulnaris, mechanical interaction with the neighbouring m. palmaris longus, the number of sarcomeres in series within muscle fibres, and the physiological cross-sectional area were measured. RESULTS: Stroke resulted in higher force and stiffness of the m. flexor carpi ulnaris at optimum muscle-tendon unit length, but only for the passive conditions. Stroke did not alter the length-force characteristics of m. flexor carpi ulnaris muscle belly, morphological characteristics, and the extent of mechanical interaction with m. palmaris longus muscle. CONCLUSION: The higher passive force and passive stiffness at the muscle-tendon unit level in the absence of changes in structural and mechanical characteristics of the muscle belly indicates that the experimentally induced stroke resulted in an increased stiffness of the tendon.
Assuntos
Músculo Esquelético/anatomia & histologia , Músculo Esquelético/fisiologia , Tendões/fisiologia , AVC Trombótico/patologia , Animais , Fenômenos Biomecânicos , Isquemia Encefálica , Membro Anterior/patologia , Contração Isométrica , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
RATIONALE: Systemic lupus erythematosus (SLE) is an important cause of stroke, more than a half the cases present as acute ischemic stroke. Thrombolysis is an effective choice in most cases, but for large vessel occlusion, mechanical thrombectomy is more effective. Here we reported a case of SLE-related stroke with left middle cerebral artery (MCA) occlusion, who was successfully treated by MT and tirofiban. PATIENT CONCERN: A 38-year-old female suffered from right hemiplegia and aphasia for 8âhours. She was diagnosed with SLE 20âyears ago, and neuropsychiatric SLE was considered 8âmonths before this onset. One month ago, glucocorticoids were discontinued by herself because of deterioration of bilateral femoral head osteonecrosis. DIAGNOSIS: Left MCA occlusion was confirmed by computed tomography perfusion. INTERVENTION: Immediate mechanical thrombectomy was performed and tirofiban was given to prevent re-occlusion of left MCA. Twenty fourhours later oral antiplatelet was given after intracranial hemorrhage was ruled out. OUTCOMES: Her neurological symptom improved several days later, and she was transferred to further rehabilitation. At 4 months follow-up she can live independently with mild hypophrasia. There was no further events of ischemic stroke in 1-year follow-up. LESSONS: Mechanical thrombectomy is a highly effective and indispensable treatment for SLE related large vessel occlusion. In addition, tirofiban may reduce vessel reocclusion in special cases such as SLE and artery stenosis.