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1.
Stroke ; 55(10): 2573-2578, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39224979

RESUMO

Artificial intelligence (AI) large language models (LLMs) now produce human-like general text and images. LLMs' ability to generate persuasive scientific essays that undergo evaluation under traditional peer review has not been systematically studied. To measure perceptions of quality and the nature of authorship, we conducted a competitive essay contest in 2024 with both human and AI participants. Human authors and 4 distinct LLMs generated essays on controversial topics in stroke care and outcomes research. A panel of Stroke Editorial Board members (mostly vascular neurologists), blinded to author identity and with varying levels of AI expertise, rated the essays for quality, persuasiveness, best in topic, and author type. Among 34 submissions (22 human and 12 LLM) scored by 38 reviewers, human and AI essays received mostly similar ratings, though AI essays were rated higher for composition quality. Author type was accurately identified only 50% of the time, with prior LLM experience associated with improved accuracy. In multivariable analyses adjusted for author attributes and essay quality, only persuasiveness was independently associated with odds of a reviewer assigning AI as author type (adjusted odds ratio, 1.53 [95% CI, 1.09-2.16]; P=0.01). In conclusion, a group of experienced editorial board members struggled to distinguish human versus AI authorship, with a bias against best in topic for essays judged to be AI generated. Scientific journals may benefit from educating reviewers on the types and uses of AI in scientific writing and developing thoughtful policies on the appropriate use of AI in authoring manuscripts.


Assuntos
Inteligência Artificial , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico , Autoria , Publicações Periódicas como Assunto , Revisão da Pesquisa por Pares
2.
N Engl J Med ; 382(24): 2316-2326, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32521133

RESUMO

BACKGROUND: Randomized trials involving patients with stroke have established that outcomes are improved with the use of thrombectomy for large-vessel occlusion. These trials were performed in high-resource countries and have had limited effects on medical practice in low- and middle-income countries. METHODS: We studied the safety and efficacy of thrombectomy in the public health system of Brazil. In 12 public hospitals, patients with a proximal intracranial occlusion in the anterior circulation that could be treated within 8 hours after the onset of stroke symptoms were randomly assigned in a 1:1 ratio to receive standard care plus mechanical thrombectomy (thrombectomy group) or standard care alone (control group). The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. RESULTS: A total of 300 patients were enrolled, including 79 who had undergone thrombectomy during an open-label roll-in period. Approximately 70% in the two groups received intravenous alteplase. The trial was stopped early because of efficacy when 221 of a planned 690 patients had undergone randomization (111 to the thrombectomy group and 110 to the control group). The common odds ratio for a better distribution of scores on the modified Rankin scale at 90 days was 2.28 (95% confidence interval [CI], 1.41 to 3.69; P = 0.001), favoring thrombectomy. The percentage of patients with a score on the modified Rankin scale of 0 to 2, signifying an absence of or minor neurologic deficit, was 35.1% in the thrombectomy group and 20.0% in the control group (difference, 15.1 percentage points; 95% CI, 2.6 to 27.6). Asymptomatic intracranial hemorrhage occurred in 51.4% of the patients in the thrombectomy group and 24.5% of those in the control group; symptomatic intracranial hemorrhage occurred in 4.5% of the patients in each group. CONCLUSIONS: In this randomized trial conducted in the public health care system of Brazil, endovascular treatment within 8 hours after the onset of stroke symptoms in conjunction with standard care resulted in better functional outcomes at 90 days than standard care alone. (Funded by the Brazilian Ministry of Health; RESILIENT ClinicalTrials.gov number, NCT02216643.).


Assuntos
Acidente Vascular Cerebral/cirurgia , Trombectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Terapia Combinada , Procedimentos Endovasculares , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Hemorragias Intracranianas/etiologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Método Simples-Cego , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Trombectomia/efeitos adversos , Trombectomia/métodos , Tempo para o Tratamento , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento , Adulto Jovem
3.
Stroke ; 53(4): 1074-1084, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35291822

RESUMO

High blood pressure (BP) is common after ischemic stroke and associated with a poor functional outcome and increased mortality. The conundrum then arises on whether to lower BP to improve outcome or whether this will worsen cerebral perfusion due to aberrant cerebral autoregulation. A number of large trials of BP lowering have failed to change outcome whether treatment was started prehospital in the community or hospital. Hence, nuances on how to manage high BP are likely, including whether different interventions are needed for different causes, the type and timing of the drug, how quickly BP is lowered, and the collateral effects of the drug, including on cerebral perfusion and platelets. Specific scenarios are also important, including when to lower BP before, during, and after intravenous thrombolysis and endovascular therapy/thrombectomy, when it may be necessary to raise BP, and when antihypertensive drugs taken before stroke should be restarted. This narrative review addresses these and other questions. Although further large trials are ongoing, it is increasingly likely that there is no simple answer. Different subgroups of patients may need to have their BP lowered (eg, before or after thrombolysis), left alone, or elevated.


Assuntos
Isquemia Encefálica , Hipertensão , AVC Isquêmico , Acidente Vascular Cerebral , Anti-Hipertensivos , Pressão Sanguínea/fisiologia , Isquemia Encefálica/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Resultado do Tratamento
4.
Neurocrit Care ; 34(2): 547-556, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32770342

RESUMO

BACKGROUND: Small and remote acute ischemic lesions may occur in up to one-third of patients with spontaneous intracerebral hemorrhage (ICH). Possible mechanisms include cerebral embolism, small vessel disease, blood pressure variability and others. The embolic mechanism has not been adequately studied. Using transcranial Doppler (TCD), we assessed the incidence of spontaneous microembolic signals (MESs) in patients with acute ICH. METHODS: Twenty acute ICH patients were prospectively evaluated within 48 h of hospital admission. Clinical and imaging data were collected. Continuous TCD monitoring was performed in both middle cerebral arteries for a one-hour period on days 1, 3 and 7 of hospital admission. Monitoring was performed in the emergency room, ICU or ward, according to patient location. We compared the frequency and risk factors for MES in patients with ICH and in 20 age- and gender-matched controls without history of ischemic or hemorrhagic stroke. RESULTS: The mean age was 57.5 ± 14.1 years, and 60% were male. MESs were detected in 7 patients with ICH and in one control patient without ICH (35% vs 5%, p = 0.048). The frequency of MES on day 1 was 15% (3 of 20 patients), on day 3, 26% (5 of 19 patients) and on day 7, 37.5% (3 of 8 patients). Among patients with ICH, those with MES had a tendency to higher frequencies of dyslipidemia (83% vs 33%, p = 0.13) and lobar location of hemorrhages (71% vs 30%, p = 0.15). Two out of 6 patients with ICH who also underwent MRI had remote DWI lesions, of whom one showed MES on TCD. CONCLUSION: Micro-embolic signals occur in over one-third of patients with ICH. Further research is needed to identify the sources of cerebral microembolism and their relationship with small acute infarcts in ICH.


Assuntos
Hemorragia Cerebral , Embolia Intracraniana , Estudos de Casos e Controles , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/epidemiologia , Embolia Intracraniana/etiologia , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana
5.
Neural Plast ; 2021: 8858394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34426738

RESUMO

Transcranial direct current stimulation (tDCS) has the potential to improve upper limb motor outcomes after stroke. According to the assumption of interhemispheric inhibition, excessive inhibition from the motor cortex of the unaffected hemisphere to the motor cortex of the affected hemisphere may worsen upper limb motor recovery after stroke. We evaluated the effects of active cathodal tDCS of the primary motor cortex of the unaffected hemisphere (ctDCSM1UH) compared to sham, in subjects within 72 hours to 6 weeks post ischemic stroke. Cathodal tDCS was intended to inhibit the motor cortex of the unaffected hemisphere and hence decrease the inhibition from the unaffected to the affected hemisphere and enhance motor recovery. We hypothesized that motor recovery would be greater in the active than in the sham group. In addition, greater motor recovery in the active group might be associated with bigger improvements in measures in activity and participation in the active than in the sham group. We also explored, for the first time, changes in cognition and sleep after ctDCSM1UH. Thirty subjects were randomized to six sessions of either active or sham ctDCSM1UH as add-on interventions to rehabilitation. The NIH Stroke Scale (NIHSS), Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA), Barthel Index (BI), Stroke Impact Scale (SIS), and Montreal Cognitive Assessment (MoCA) were assessed before, after treatment, and three months later. In the intent-to-treat (ITT) analysis, there were significant GROUP∗TIME interactions reflecting stronger gains in the sham group for scores in NIHSS, FMA, BI, MoCA, and four SIS domains. At three months post intervention, the sham group improved significantly compared to posttreatment in FMA, NIHSS, BI, and three SIS domains while no significant changes occurred in the active group. Also at three months, NIHSS improved significantly in the sham group and worsened significantly in the active group. FMA scores at baseline were higher in the active than in the sham group. After adjustment of analysis according to baseline scores, the between-group differences in FMA changes were no longer statistically significant. Finally, none of the between-group differences in changes in outcomes after treatment were considered clinically relevant. In conclusion, active CtDCSM1UH did not have beneficial effects, compared to sham. These results were consistent with other studies that applied comparable tDCS intensities/current densities or treated subjects with severe upper limb motor impairments during the first weeks post stroke. Dose-finding studies early after stroke are necessary before planning larger clinical trials.


Assuntos
Córtex Motor/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/fisiopatologia , Estimulação Transcraniana por Corrente Contínua , Extremidade Superior/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento
6.
Lancet ; 392(10154): 1269-1278, 2018 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-30319114

RESUMO

Along with the rising global burden of disability attributed to stroke, costs of stroke care are rising, providing the impetus to direct our research focus towards effective measures of stroke prevention. In this Series paper, we discuss strategies for reducing the risk of the emergence of disease (primordial prevention), preventing the onset of disease (primary prevention), and preventing the recurrence of disease (secondary prevention). Our focus includes global strategies and campaigns, and measurements of the effectiveness of worldwide preventive interventions, with an emphasis on low-income and middle-income countries. Our findings reveal that effective tobacco control, adequate nutrition, and development of healthy cities are important strategies for primordial prevention, whereas polypill strategies, use of mobile technology (mHealth), along with salt reduction and other dietary interventions, are effective in the primary prevention of stroke. An effective collaboration between various health-care sectors, government policies, and campaigns can successfully implement secondary prevention strategies, through surveillance and registries, such as the WHO's non-communicable diseases programmes, across high-income and low-income countries.


Assuntos
Carga Global da Doença , Acidente Vascular Cerebral/prevenção & controle , Países em Desenvolvimento , Promoção da Saúde , Humanos , Prevenção Primária , Medição de Risco , Fatores de Risco , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologia , Organização Mundial da Saúde
7.
J Stroke Cerebrovasc Dis ; 28(6): 1500-1508, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30935810

RESUMO

OBJECTIVE: The role of heparin in acute ischemic stroke is controversial. We investigated the effect of heparin on ischemic lesion growth. METHODS: Data were analyzed on nonthrombolyzed ischemic stroke patients in whom diffusion-weighted imaging (DWI)/perfusion-weighted imaging (PWI) MRI was performed less than 12 hours of last known well and showed a PWI-DWI lesion mismatch, and who underwent follow-up neuroimaging at least 4 days after admission. Lesion growth was assessed by (1) absolute lesion growth and (2) percentage mismatch lost (PML). Univariate and multivariate regression analysis, and propensity score matching, were used to determine the effects of heparin on ischemic lesion growth. RESULTS: Of the 113 patients meeting study criteria, 59 received heparin within 24 hours. Heparin use was associated with ∼5-fold reductions in PML (3.5% versus 19.2%, P = .002) and absolute lesion growth (4.7 versus 20.5 mL, P = .009). In multivariate regression models, heparin independently predicted reduced PML (P = .04) and absolute lesion growth (P = .04) in the entire cohort, and in multiple subgroups (patients with and without proximal artery occlusion; DWI volume greater than 5 mL; cardio-embolic mechanism; DEFUSE-3 target mismatch). In propensity score matching analysis where patients were matched by admission NIHSS, DWI volume and proximal artery occlusion, heparin remained an independent predictor of PML (P = .048) and tended to predict absolute lesion growth (P = .06). Heparin treatment did not predict functional outcome at discharge or 90 days. CONCLUSION: Early heparin treatment in acute ischemic stroke patients with PWI-DWI mismatch attenuates ischemic lesion growth. Clinical trials with careful patient selection are warranted to investigate the potential ischemic protective effects of heparin.


Assuntos
Anticoagulantes/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Heparina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
J Neurosci ; 37(28): 6797-6809, 2017 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-28607171

RESUMO

Alzheimer's disease (AD) is characterized by progressive cognitive decline, increasingly attributed to neuronal dysfunction induced by amyloid-ß oligomers (AßOs). Although the impact of AßOs on neurons has been extensively studied, only recently have the possible effects of AßOs on astrocytes begun to be investigated. Given the key roles of astrocytes in synapse formation, plasticity, and function, we sought to investigate the impact of AßOs on astrocytes, and to determine whether this impact is related to the deleterious actions of AßOs on synapses. We found that AßOs interact with astrocytes, cause astrocyte activation and trigger abnormal generation of reactive oxygen species, which is accompanied by impairment of astrocyte neuroprotective potential in vitro We further show that both murine and human astrocyte conditioned media (CM) increase synapse density, reduce AßOs binding, and prevent AßO-induced synapse loss in cultured hippocampal neurons. Both a neutralizing anti-transforming growth factor-ß1 (TGF-ß1) antibody and siRNA-mediated knockdown of TGF-ß1, previously identified as an important synaptogenic factor secreted by astrocytes, abrogated the protective action of astrocyte CM against AßO-induced synapse loss. Notably, TGF-ß1 prevented hippocampal dendritic spine loss and memory impairment in mice that received an intracerebroventricular infusion of AßOs. Results suggest that astrocyte-derived TGF-ß1 is part of an endogenous mechanism that protects synapses against AßOs. By demonstrating that AßOs decrease astrocyte ability to protect synapses, our results unravel a new mechanism underlying the synaptotoxic action of AßOs in AD.SIGNIFICANCE STATEMENT Alzheimer's disease is characterized by progressive cognitive decline, mainly attributed to synaptotoxicity of the amyloid-ß oligomers (AßOs). Here, we investigated the impact of AßOs in astrocytes, a less known subject. We show that astrocytes prevent synapse loss induced by AßOs, via production of transforming growth factor-ß1 (TGF-ß1). We found that AßOs trigger morphological and functional alterations in astrocytes, and impair their neuroprotective potential. Notably, TGF-ß1 reduced hippocampal dendritic spine loss and memory impairment in mice that received intracerebroventricular infusions of AßOs. Our results describe a new mechanism underlying the toxicity of AßOs and indicate novel therapeutic targets for Alzheimer's disease, mainly focused on TGF-ß1 and astrocytes.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Astrócitos/metabolismo , Sinapses/metabolismo , Sinapses/patologia , Fator de Crescimento Transformador beta1/metabolismo , Peptídeos beta-Amiloides , Animais , Células Cultivadas , Humanos , Masculino , Camundongos , Espécies Reativas de Oxigênio/metabolismo
9.
J Biol Chem ; 292(18): 7395-7406, 2017 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-28302722

RESUMO

AMP-activated kinase (AMPK) is a key player in energy sensing and metabolic reprogramming under cellular energy restriction. Several studies have linked impaired AMPK function to peripheral metabolic diseases such as diabetes. However, the impact of neurological disorders, such as Alzheimer disease (AD), on AMPK function and downstream effects of altered AMPK activity on neuronal metabolism have been investigated only recently. Here, we report the impact of Aß oligomers (AßOs), synaptotoxins that accumulate in AD brains, on neuronal AMPK activity. Short-term exposure of cultured rat hippocampal neurons or ex vivo human cortical slices to AßOs transiently decreased intracellular ATP levels and AMPK activity, as evaluated by its phosphorylation at threonine residue 172 (AMPK-Thr(P)172). The AßO-dependent reduction in AMPK-Thr(P)172 levels was mediated by glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype and resulted in removal of glucose transporters (GLUTs) from the surfaces of dendritic processes in hippocampal neurons. Importantly, insulin prevented the AßO-induced inhibition of AMPK. Our results establish a novel toxic impact of AßOs on neuronal metabolism and suggest that AßO-induced, NMDA receptor-mediated AMPK inhibition may play a key role in early brain metabolic defects in AD.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Fragmentos de Peptídeos/metabolismo , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/genética , Trifosfato de Adenosina/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Proteínas Facilitadoras de Transporte de Glucose/genética , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Hipocampo/patologia , Humanos , Insulina/farmacologia , Neurônios/patologia , Fragmentos de Peptídeos/genética , Ratos , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo
10.
J Stroke Cerebrovasc Dis ; 27(10): 2712-2719, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30033098

RESUMO

OBJECTIVE: To characterize isolated upper extremity (UE) weakness from stroke. METHODS: In our Get with the Guidelines-Stroke dataset (n = 7643), 87 patients (1.14%) had isolated UE weakness and underwent thorough stroke evaluation with diffusion-weighted magnetic resonance imaging and good-quality arterial imaging. We analyzed clinical-imaging features, etiology, management, and outcome. Since isolated UE weakness is typically associated with contralateral hand-knob area infarcts, patients were classified into Group-A (motor strip infarct) or Group-B (non-motor strip infarct). RESULTS: The mean age was 68 years; 66% were male, 72% had hypertension, 22% diabetes, 53% hyperlipidemia, and 16% were smokers. In Group-A (n = 71), 18 patients had single and 53 had multiple infarcts involving the contralateral motor strip. In Group-B (n = 16), 6 patients had contralateral subcortical white matter infarcts, 9 had bihemispheric infarcts and 1 had a brainstem infarct. Compared to Group-B, patients in Group-A more often had carotid artery stenosis or irregular plaque (84.5% versus 50%, P = .006) and large-artery atherosclerosis mechanism (46% versus 19%, P = .05), and less often cardioembolic mechanism (13% versus 44%, P = .008). Among 36 patients with large-artery mechanism, 27 had less than 70% stenosis including 19 with plaque ulceration/thrombus. Recurrent strokes occurred in 10 patients (11.5%), including 5 with mild-moderate carotid stenosis and plaque ulceration/thrombosis, over 1515 days follow-up. CONCLUSION: Stroke mechanism in acute isolated UE weakness is variable. Contralateral motor-strip infarcts are associated with carotid stenosis, often with plaque ulceration ("vulnerable carotid plaque"), and infarcts in other locations with cardioembolism. Recurrent stroke risk is high especially with mild-moderate carotid artery stenosis and plaque ulceration/thrombus.


Assuntos
Isquemia Encefálica/etiologia , Córtex Motor/fisiopatologia , Força Muscular , Debilidade Muscular/etiologia , Músculo Esquelético/inervação , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/terapia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada , Imagem de Difusão por Ressonância Magnética , Avaliação da Deficiência , Embolia/complicações , Embolia/diagnóstico por imagem , Feminino , Cardiopatias/complicações , Cardiopatias/diagnóstico por imagem , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atividade Motora , Córtex Motor/diagnóstico por imagem , Debilidade Muscular/diagnóstico , Debilidade Muscular/fisiopatologia , Placa Aterosclerótica , Prognóstico , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Ruptura Espontânea , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Extremidade Superior
11.
Stroke ; 48(5): 1278-1284, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28411260

RESUMO

BACKGROUND AND PURPOSE: The Emergency Medical Services field triage to stroke centers has gained considerable complexity with the recent demonstration of clinical benefit of endovascular treatment for acute ischemic stroke. We sought to describe a new smartphone freeware application designed to assist Emergency Medical Services professionals with the field assessment and destination triage of patients with acute ischemic stroke. METHODS: Review of the application's platform and its development as well as the different variables, assessments, algorithms, and assumptions involved. RESULTS: The FAST-ED (Field Assessment Stroke Triage for Emergency Destination) application is based on a built-in automated decision-making algorithm that relies on (1) a brief series of questions assessing patient's age, anticoagulant usage, time last known normal, motor weakness, gaze deviation, aphasia, and hemineglect; (2) a database of all regional stroke centers according to their capability to provide endovascular treatment; and (3) Global Positioning System technology with real-time traffic information to compute the patient's eligibility for intravenous tissue-type plasminogen activator or endovascular treatment as well as the distances/transportation times to the different neighboring stroke centers in order to assist Emergency Medical Services professionals with the decision about the most suitable destination for any given patient with acute ischemic stroke. CONCLUSIONS: The FAST-ED smartphone application has great potential to improve the triage of patients with acute ischemic stroke, as it seems capable to optimize resources, reduce hospital arrivals times, and maximize the use of both intravenous tissue-type plasminogen activator and endovascular treatment ultimately leading to better clinical outcomes. Future field studies are needed to properly evaluate the impact of this tool in stroke outcomes and resource utilization.


Assuntos
Isquemia Encefálica/diagnóstico , Tomada de Decisão Clínica/métodos , Sistemas de Apoio a Decisões Clínicas/instrumentação , Acidente Vascular Cerebral/diagnóstico , Triagem/métodos , Algoritmos , Sistemas de Informação Geográfica/instrumentação , Humanos , Smartphone , Transporte de Pacientes/métodos
12.
Stroke ; 47(8): 1997-2002, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27364531

RESUMO

BACKGROUND AND PURPOSE: Patients with large vessel occlusion strokes (LVOS) may be better served by direct transfer to endovascular capable centers avoiding hazardous delays between primary and comprehensive stroke centers. However, accurate stroke field triage remains challenging. We aimed to develop a simple field scale to identify LVOS. METHODS: The Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale was based on items of the National Institutes of Health Stroke Scale (NIHSS) with higher predictive value for LVOS and tested in the Screening Technology and Outcomes Project in Stroke (STOPStroke) cohort, in which patients underwent computed tomographic angiography within the first 24 hours of stroke onset. LVOS were defined by total occlusions involving the intracranial internal carotid artery, middle cerebral artery-M1, middle cerebral artery-2, or basilar arteries. Patients with partial, bihemispheric, and anterior+posterior circulation occlusions were excluded. Receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value of FAST-ED were compared with the NIHSS, Rapid Arterial Occlusion Evaluation (RACE) scale, and Cincinnati Prehospital Stroke Severity (CPSS) scale. RESULTS: LVO was detected in 240 of the 727 qualifying patients (33%). FAST-ED had comparable accuracy to predict LVO to the NIHSS and higher accuracy than RACE and CPSS (area under the receiver operating characteristic curve: FAST-ED=0.81 as reference; NIHSS=0.80, P=0.28; RACE=0.77, P=0.02; and CPSS=0.75, P=0.002). A FAST-ED ≥4 had sensitivity of 0.60, specificity of 0.89, positive predictive value of 0.72, and negative predictive value of 0.82 versus RACE ≥5 of 0.55, 0.87, 0.68, and 0.79, and CPSS ≥2 of 0.56, 0.85, 0.65, and 0.78, respectively. CONCLUSIONS: FAST-ED is a simple scale that if successfully validated in the field, it may be used by medical emergency professionals to identify LVOS in the prehospital setting enabling rapid triage of patients.


Assuntos
Arteriopatias Oclusivas/diagnóstico , Isquemia Encefálica/diagnóstico , Encéfalo/diagnóstico por imagem , Serviços Médicos de Emergência , Acidente Vascular Cerebral/diagnóstico , Triagem/métodos , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/diagnóstico por imagem , Isquemia Encefálica/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico por imagem
13.
J Enzyme Inhib Med Chem ; 31(6): 1464-70, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26928712

RESUMO

Acetylcholinesterase inhibitors and compounds that trigger Aß amyloid oligomerization and fibrillization represent an opportunity to discover new drug candidates to treat Alzheimer's disease. In this work, we synthesized nine new acylhydrazones and a known one, both employing 3-carboethoxy-4-quinolone derivatives as starting materials with chemical yields ranging from 63% to 90%. We evaluated the effect of these compounds on the acetylcholinesterase (AChE) activity and the fibrillization of Aß42 peptide. Except for one acylhydrazone, the compounds exhibited good inhibitory effect on AChE (1.2 µM < IC50 values < 17 µM). They also showed a significant decrease in the thioflavin-T fluorescence emission, suggesting an inhibitory effect on the Aß42 fibril formation.


Assuntos
4-Quinolonas/química , Acetilcolinesterase/efeitos dos fármacos , Peptídeos beta-Amiloides/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Hidrazonas/farmacologia , Fragmentos de Peptídeos/efeitos dos fármacos , Peptídeos beta-Amiloides/química , Hidrazonas/química , Fragmentos de Peptídeos/química , Análise Espectral/métodos
15.
J Stroke Cerebrovasc Dis ; 24(9): e271-3, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26198371

RESUMO

BACKGROUND: Vasospasm has been rarely described as a complication associated with craniopharyngioma surgery. Herein we describe a patient who developed symptomatic vasospasm and delayed cerebral ischemia after transsphenoidal surgery for a craniopharyngioma. CASE REPORT: A 67-year-old woman became drowsy 2 weeks after a transsphenoidal resection of a craniopharyngioma. A head computed tomography (CT) was unremarkable except for postoperative findings. Electroencephalogram and laboratory studies were within the normal limits. A repeated CT scan 48 hours after the initial symptoms showed bilateral infarcts in the territory of the anterior cerebral arteries (ACA). Transcranial Doppler (TCD) showed increased blood flow velocities in both anterior cerebral arteries (169 cm/second in the left ACA and 145 cm/second in the right ACA) and right middle cerebral artery (164 cm/second) compatible with vasospasm. A CT angiography confirmed the findings. She was treated with induced hypertension and her level of consciousness improved. TCD velocities normalized after 2 weeks. CONCLUSION: Cerebral vasospasm should be considered in the differential diagnosis of patients with altered neurologic status in the postoperative period following a craniopharyngioma resection.


Assuntos
Isquemia Encefálica/etiologia , Craniofaringioma/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/fisiopatologia , Vasoespasmo Intracraniano/etiologia , Idoso , Angiografia Cerebral , Feminino , Humanos , Tomografia Computadorizada por Raios X
16.
J Stroke Cerebrovasc Dis ; 24(9): e275-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26198372

RESUMO

BACKGROUND: Subarachnoid hemorrhage (SAH) associated with anticoagulation is a rare event. About 30% of in-hospital patients with aneurysmal SAH develop delayed cerebral ischemia (DCI); however, the occurrence of vasospasm and DCI in patients with nonaneurysmal SAH is still controversial. METHODS: This study is a case report of a patient experiencing an anticoagulation-induced SAH complicated by vasospasm and DCI. RESULTS: A 38-year-old woman presented to our hospital with a sudden onset of severe headache. Head computed tomography (CT) showed bleeding in the posterior fossa subarachnoid space. There was no aneurysm in the CT angiography. The International Normalized Ratio at hospital admission was 9. Anticoagulation was held, and she was treated with fresh frozen plasma (15 mg/kg) and parenteral vitamin K. The patient remained in the intensive care unit and had daily transcranial Doppler (TCD) monitorization. TCD examination detected increased blood flow velocities in the basilar and vertebral arteries, meeting criteria for definitive vasospasm. CT angiography confirmed the presence of posterior circulation vasospasm. Magnetic resonance (MR) imaging 2 weeks after the bleeding showed a small area of restricted diffusion in the left superior cerebellar artery territory. MR angiography showed resolution of the vasospasm at this time point and TCD velocities normalized. CONCLUSIONS: In conclusion, this case report suggests that vasospasm and consequent DCI is a possible mechanism of secondary lesion after anticoagulation-induced SAH. To our knowledge, this is the first report of vasospasm and DCI due to warfarin-associated SAH.


Assuntos
Isquemia Encefálica/etiologia , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/etiologia , Adulto , Anticoagulantes/efeitos adversos , Feminino , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Hemorragia Subaracnóidea/induzido quimicamente , Ultrassonografia Doppler Transcraniana , Varfarina/efeitos adversos
17.
Glia ; 62(12): 1917-31, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25042347

RESUMO

The balance between excitatory and inhibitory synaptic inputs is critical for the control of brain function. Astrocytes play important role in the development and maintenance of neuronal circuitry. Whereas astrocytes-derived molecules involved in excitatory synapses are recognized, molecules and molecular mechanisms underlying astrocyte-induced inhibitory synapses remain unknown. Here, we identified transforming growth factor beta 1 (TGF-ß1), derived from human and murine astrocytes, as regulator of inhibitory synapse in vitro and in vivo. Conditioned media derived from human and murine astrocytes induce inhibitory synapse formation in cerebral cortex neurons, an event inhibited by pharmacologic and genetic manipulation of the TGF-ß pathway. TGF-ß1-induction of inhibitory synapse depends on glutamatergic activity and activation of CaM kinase II, which thus induces localization and cluster formation of the synaptic adhesion protein, Neuroligin 2, in inhibitory postsynaptic terminals. Additionally, intraventricular injection of TGF-ß1 enhanced inhibitory synapse number in the cerebral cortex. Our results identify TGF-ß1/CaMKII pathway as a novel molecular mechanism underlying astrocyte control of inhibitory synapse formation. We propose here that the balance between excitatory and inhibitory inputs might be provided by astrocyte signals, at least partly achieved via TGF-ß1 downstream pathways. Our work contributes to the understanding of the GABAergic synapse formation and may be of relevance to further the current knowledge on the mechanisms underlying the development of various neurological disorders, which commonly involve impairment of inhibitory synapse transmission.


Assuntos
Astrócitos/química , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Neurônios/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Animais , Animais Recém-Nascidos , Astrócitos/metabolismo , Células Cultivadas , Córtex Cerebral/citologia , Meios de Cultivo Condicionados/farmacologia , Embrião de Mamíferos , Inibidores Enzimáticos/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/metabolismo , Humanos , Injeções Intraventriculares , Masculino , Camundongos , N-Metilaspartato/farmacologia , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Neurônios/ultraestrutura , Receptores de GABA-A/metabolismo , Sinapses/metabolismo , Sinapses/ultraestrutura , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo
18.
J Stroke Cerebrovasc Dis ; 22(8): e658-60, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23830958

RESUMO

Alteplase (recombinant tissue plasminogen activator [rt-PA]) label approval by the Food and Drug Administration remarks the contraindication of its use with known intracranial neoplasm because of potential bleeding complications. Despite this concern, the real risk of intracerebral bleeding in patients with intracranial neoplasms treated with rt-PA is unknown, and there are few reports of thrombolysis in patients with brain tumors. We report a case of a 78-year-old man who was seen in our emergency department within 2 hours from sudden onset of aphasia, right-sided hemiplegia, hypoesthesia, and homonymous hemianopsia. The National Institutes of Health Stroke Scale (NIHSS) score at admission was 20. Intra-arterial thrombolysis was performed with administration of .3 mg/kg of alteplase combined with mechanical thrombectomy. At discharge, his NIHSS score was 1, and after 90 days, his modified Rankin score was 1. To our knowledge, this is the first report of intra-arterial thrombolysis in a patient with acute ischemic stroke with an intracranial tumor.


Assuntos
Fibrinolíticos/administração & dosagem , Infarto da Artéria Cerebral Média/tratamento farmacológico , Neoplasias Meníngeas/complicações , Meningioma/complicações , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Angiografia Cerebral/métodos , Avaliação da Deficiência , Humanos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/diagnóstico , Masculino , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Índice de Gravidade de Doença , Trombectomia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Stroke ; 43(8): 2078-85, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22700532

RESUMO

BACKGROUND AND PURPOSE: Little is known about adoption or success of telestroke networks outside of published or federally funded programs. Under contract to the Health Resource Services Administration, we conducted an environmental scan of telestroke programs in the United States. METHODS: An analyst contacted all potential programs identified in comprehensive online searches, interviewed respondents, and collected response data about structural and functional components of currently operating telestroke programs. RESULTS: Among 97 potential programs contacted, 56 programs had confirmed telestroke activity, and 38 programs (68%) from 27 states participated. Hospital and community characteristics of nonparticipating programs were similar to those of participating ones. The top 3 clinical needs met by the telestroke were emergency department consultation (100%), patient triage (83.8%), and inpatient teleconsultation (46.0%). Telestroke programs were in operation a median of 2.44 years (interquartile range, 1.36-3.44 years); 94.6% used 2-way, real-time interactive video plus imaging, but only 44% used dedicated telemedicine consultation software. The mean number of spokes per hub increased significantly from 2007 to 2008 to 2009 (3.78 versus 7.60; P<0.05), and >80% of spoke sites were rural or small hospitals. Reimbursement was absent for >40% of sites. Sites rated inability to obtain physician licensure (27.77%), lack of program funds (27.77%), and lack of reimbursement (19.44%) as the most important barriers to program growth. CONCLUSIONS: Telestroke is a widespread and growing practice model. Important barriers to expansion amenable to change relate to organizational, technical, and educational domains and external economic and regulatory forces.


Assuntos
Acidente Vascular Cerebral/terapia , Telemedicina/tendências , Sistemas Computacionais , Credenciamento , Documentação , Hospitais , Humanos , Seguro Saúde/economia , Seguro Saúde/tendências , Licenciamento , Sistemas On-Line , Encaminhamento e Consulta , Mecanismo de Reembolso , Consulta Remota , Acidente Vascular Cerebral/diagnóstico , Telemedicina/economia , Telemedicina/estatística & dados numéricos , Telefone , Estados Unidos , Comunicação por Videoconferência
20.
J Emerg Med ; 42(5): 559-65, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22305149

RESUMO

BACKGROUND: Posterior fossa strokes, particularly those related to basilar occlusion, pose a high risk for progression and poor neurological outcomes. The clinical history and examination are often not adequately sensitive or specific for detection. STUDY OBJECTIVES: Because this population stands to benefit from acute interventions such as intravenous and intra-arterial tissue plasminogen activator, mechanical thrombectomy, and intensive monitoring for neurologic deterioration, this study examined the sensitivity of non-contrast head computed tomography (NCCT) for diagnosing posterior fossa strokes in the emergency department. METHODS: This study analyzed a prospectively collected database of acute ischemic stroke patients who underwent head NCCT within 30 h of symptom onset and who were subsequently found to have a posterior fossa infarct on brain magnetic resonance imaging (MRI) performed within 6 h of the NCCT. RESULTS: There were 67 patients identified who had restricted diffusion on MRI in the posterior fossa. The National Institutes of Health Stroke Scale (NIHSS) scores ranged from 0 to 36, median 3. Only 28 patients had evidence of infarction on the initial NCCT scan. The timing of NCCT scans ranged from 1.2 to 28.9 h after symptom onset. The sensitivity of NCCT was 41.8% (95% confidence interval 30.1-54.4). The longest period of time between symptom onset and a negative NCCT with a subsequent positive diffusion-weighted imaging MRI was 26.7 h. CONCLUSIONS: Head NCCT imaging is frequently insensitive for detecting posterior fossa infarction. Temporal evolution of strokes in this distribution, coupled with beam-hardening artifact, may contribute to this limitation. When a posterior fossa stroke is suspected and the NCCT is non-diagnostic, MRI is the preferred imaging modality to exclude posterior fossa infarction.


Assuntos
Infarto Cerebral/diagnóstico , Fossa Craniana Posterior/irrigação sanguínea , Imageamento por Ressonância Magnética/normas , Tomografia Computadorizada por Raios X/normas , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade
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