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2.
J Stroke Cerebrovasc Dis ; 29(10): 105134, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32912530

RESUMO

BACKGROUND: Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke (AIS) caused by large vessel occlusion of the anterior circulation within 6 hours of symptoms onset and can be performed with an extended window up to 24 hours in selected patients. Nevertheless, the outcomes of MT with extended window are unknown in developing countries. OBJECTIVE: Explore the safety and efficacy of MT for AIS performed beyond 6 hours from symptoms onset in Brazil. METHODS: We reviewed data from AIS patients treated with MT beyond 6 hours of stroke onset, from 2015 to 2018 in a Brazilian public hospital. Patients had an occlusion of the intracranial internal carotid artery and/or proximal segment of the middle cerebral artery. CT Perfusion mismatch was evaluated using the RAPID® software. We evaluated the modified Rankin scale (mRS) and mortality at 90 days, and rate of symptomatic intracranial hemorrhage (sICH). RESULTS: Fifty-four patients were included, with a mean age of 65.6 ± 16.1 years, 55.6% were male, and the median NIHSS score at presentation was 17. Successful recanalization (TICI 2b to 3) was obtained in 92.6% of patients and sICH rate was 11.1%. Overall, 34% of the patients had a good outcome (mRS ≤2) at 90 days and the mortality rate was 20.3%. CONCLUSION: Our study, the first series of MT for AIS treated with extended window reported in Latin America, shows that MT can be performed with safety and lead to adequate functional outcomes in this context. Further studies should explore the barriers to broad implementation of MT for AIS in Latin America.


Assuntos
Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/terapia , Circulação Cerebrovascular , Infarto da Artéria Cerebral Média/terapia , Artéria Cerebral Média/fisiopatologia , Trombectomia , Tempo para o Tratamento , Idoso , Idoso de 80 Anos ou mais , Brasil , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/fisiopatologia , Avaliação da Deficiência , Feminino , Hospitais Públicos , Humanos , Infarto da Artéria Cerebral Média/diagnóstico , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Imagem de Perfusão , Recuperação de Função Fisiológica , Estudos Retrospectivos , Centros de Atenção Terciária , Trombectomia/efeitos adversos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
3.
PLoS One ; 15(9): e0238946, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956397

RESUMO

BACKGROUND: The origin of low frequency cerebral hemodynamic fluctuations (CHF) in the resting state remains unknown. Breath-by breath O2-CO2 exchange ratio (bER) has been reported to correlate with the cerebrovascular response to brief breath hold challenge at the frequency range of 0.008-0.03Hz in healthy adults. bER is defined as the ratio of the change in the partial pressure of oxygen (ΔPO2) to that of carbon dioxide (ΔPCO2) between end inspiration and end expiration. In this study, we aimed to investigate the contribution of respiratory gas exchange (RGE) metrics (bER, ΔPO2 and ΔPCO2) to low frequency CHF during spontaneous breathing. METHODS: Twenty-two healthy adults were included. We used transcranial Doppler sonography to evaluate CHF by measuring the changes in cerebral blood flow velocity (ΔCBFv) in bilateral middle cerebral arteries. The regional CHF were mapped with blood oxygenation level dependent (ΔBOLD) signal changes using functional magnetic resonance imaging. Temporal features and frequency characteristics of RGE metrics during spontaneous breathing were examined, and the simultaneous measurements of RGE metrics and CHF (ΔCBFv and ΔBOLD) were studied for their correlation. RESULTS: We found that the time courses of ΔPO2 and ΔPCO2 were interdependent but not redundant. The oscillations of RGE metrics were coherent with resting state CHF at the frequency range of 0.008-0.03Hz. Both bER and ΔPO2 were superior to ΔPCO2 in association with CHF while CHF could correlate more strongly with bER than with ΔPO2 in some brain regions. Brain regions with the strongest coupling between bER and ΔBOLD overlapped with many areas of default mode network including precuneus and posterior cingulate. CONCLUSION: Although the physiological mechanisms underlying the strong correlation between bER and CHF are unclear, our findings suggest the contribution of bER to low frequency resting state CHF, providing a novel insight of brain-body interaction via CHF and oscillations of RGE metrics.


Assuntos
Circulação Cerebrovascular/fisiologia , Taxa Respiratória/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Encéfalo/fisiologia , Dióxido de Carbono/sangue , Feminino , Voluntários Saudáveis , Hemodinâmica/fisiologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Artéria Cerebral Média/fisiologia , Oxigênio/sangue , Pressão Parcial , Respiração , Descanso/fisiologia , Ultrassonografia Doppler Transcraniana/métodos , Vasodilatação/fisiologia
4.
Medicine (Baltimore) ; 99(36): e22116, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899095

RESUMO

INTRODUCTION: Hemichorea-hemiballismus, which spans a spectrum of involuntary, continuous, nonpatterned movement involving one side of the body, can emerge as the initial manifestation of acute ischemic stroke. However, because of its rarity in the community, the diagnosis and treatment are often delayed. PATIENT CONCERNS: We report a unique case of a 47-year-old female who presented with acute onset hemichorea-hemiballismus. No obvious focal sign apart from involuntary, continuous, nonpatterned movement of her left arm and leg was presented. DIAGNOSIS: Initial diffusion-weighted magnetic resonance imaging (MRI) was negative but significant increase of blood flow velocity in the right middle cerebral artery (MCA) stem was revealed by transcranial doppler sonography. Repeated MRI showed acute infarction in the contralateral globus pallidus. Isolated dissection of the right MCA typified by intimal flap with double lumen was identified by digital subtraction angiography and high-resolution magnetic resonance imaging (HR-MRI). INTERVENTIONS: The patient was initially treated with dual antiplatelet agents but the uncontrollable movement deteriorated during hospitalization. Antithrombotic therapy was then intensified with combination of tirofiban and low-molecular-weight heparin. Other symptomatic treatment included volume expansion with colloidal fluid to improve cerebral perfusion. Her involuntary movement gradually diminished and the patient was discharged with rivaroxaban 15 mg/daily. OUTCOMES: The patient had recovered with significant reduction in her hemichorea-hemiballismus. Three-month follow-up HR-MRI showed complete resolution of the MCA dissection lesions. CONCLUSION: Prompt recognition of acute onset hemichorea-hemiballismus as the manifestation of acute ischemic stroke in appropriate clinical setting may reduce diagnostic delay. Multiple imaging techniques including cerebral digital subtraction angiography and HR-MRI can be applied to diagnosis and further clarify the mechanism of stroke, which facilitate in selection of secondary prevention therapies.


Assuntos
Aneurisma Dissecante/complicações , Aneurisma Dissecante/patologia , Coreia/etiologia , Discinesias/etiologia , Artéria Cerebral Média/patologia , Doença Aguda , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/tratamento farmacológico , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Inibidores da Agregação de Plaquetas/uso terapêutico
5.
Stroke ; 51(10): 3133-3137, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32842922

RESUMO

BACKGROUND AND PURPOSE: Reliable recognition of large vessel occlusion (LVO) on noncontrast computed tomography (NCCT) may accelerate identification of endovascular treatment candidates. We aim to validate a machine learning algorithm (MethinksLVO) to identify LVO on NCCT. METHODS: Patients with suspected acute stroke who underwent NCCT and computed tomography angiography (CTA) were included. Software detection of LVO (MethinksLVO) on NCCT was tested against the CTA readings of 2 experienced radiologists (NR-CTA). We used a deep learning algorithm to identify clot signs on NCCT. The software image output trained a binary classifier to determine LVO on NCCT. We studied software accuracy when adding National Institutes of Health Stroke Scale and time from onset to the model (MethinksLVO+). RESULTS: From 1453 patients, 823 (57%) had LVO by NR-CTA. The area under the curve for the identification of LVO with MethinksLVO was 0.87 (sensitivity: 83%, specificity: 71%, positive predictive value: 79%, negative predictive value: 76%) and improved to 0.91 with MethinksLVO+ (sensitivity: 83%, specificity: 85%, positive predictive value: 88%, negative predictive value: 79%). CONCLUSIONS: In patients with suspected acute stroke, MethinksLVO software can rapidly and reliably predict LVO. MethinksLVO could reduce the need to perform CTA, generate alarms, and increase the efficiency of patient transfers in stroke networks.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Aprendizado Profundo , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Bases de Dados Factuais , Humanos , Artéria Cerebral Média/diagnóstico por imagem , Sensibilidade e Especificidade , Software , Tomografia Computadorizada por Raios X
6.
J Stroke Cerebrovasc Dis ; 29(9): 104830, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807407

RESUMO

BACKGROUND AND PURPOSE: Nitric oxide (NO) plays a key role in ischemia and shows potential as a biomarker for ischemia. We measured mixed venous nitrite (NO2-) as a proxy for NO, during controlled cerebral ischemia in patients with moyamoya disease (MMD) during direct extracranial/intracranial (EC/IC) bypass surgery with temporary occlusion of the M4 branch of the middle cerebral artery (MCA) to permit anastomosis with the superficial temporal artery (STA). This small, focal ischemic event is not reliably detected using cerebral oximetry, somatosensory evoked potentials (SSEPs) or electroencephalography (EEG). METHODS: We enrolled nine adult MMD patients (n=8 female, n=1 male) undergoing direct EC/IC bypass surgery. Nitrite was measured at least one hour prior to MCA occlusion, and before, during and after anastomosis. Cortical function was monitored using either multi-lead EEG and SSEPs, or frontal EEG activity. RESULTS: Mixed venous NO2- was significantly elevated (p<0.05) within 12 min following arterial occlusion vs. baseline. An M4 branch of the MCA was cross clamped for a median duration of 18 (IQR = 5) minutes during anastomosis. One patient with elevated NO2- showed a transient neurologic deficit that resolved 3 days post-operatively. CONCLUSIONS: Mixed venous NO2- was significantly elevated shortly following cerebral artery occlusion vs. baseline in a majority of the study subjects, suggesting that NO2- is a potential biomarker for ischemia. Since all patients received identical burst suppression anesthesia and vasopressors, the fact that NO2- was not elevated during cross-clamp in all patients supports the conclusion that the NO2- elevation is likely due to ischemia.


Assuntos
Isquemia Encefálica/diagnóstico , Revascularização Cerebral , Artéria Cerebral Média/cirurgia , Doença de Moyamoya/cirurgia , Nitritos/sangue , Artérias Temporais/cirurgia , Oclusão Terapêutica , Adulto , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Revascularização Cerebral/efeitos adversos , Circulação Cerebrovascular , Circulação Colateral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Doença de Moyamoya/sangue , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/fisiopatologia , Valor Preditivo dos Testes , Fatores de Risco , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/fisiopatologia , Oclusão Terapêutica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Vasodilatação
7.
J Stroke Cerebrovasc Dis ; 29(9): 105000, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807419

RESUMO

PURPOSE: To date, digital subtraction angiography (DSA) has been considered as the gold imaging modality for assessing graft patency after extracranial-intracranial bypass. The utility of a noninvasive and quantitative method of assessing graft flow postoperatively was evaluated by using quantitative ultrasonography. METHOD: All STA-MCA bypass surgery performed over a 5-year period at a single institution were reviewed. Measured by duplex ultrasonography, pre-operative (day1) and post-operative (day1, day7, 3month and 6 month) graft blood flow rates were recorded and analyzed. Results were correlated to Matsushima grade determined by DSA performed within 24 h when ultrasonography was conducted to confirm the graft function. RESULTS: 100 patients with 131 operated hemispheres were included in this study. The mean flow rates in the STA graft on pre-operative day1, post-operative day 1 and 7, at 3- and 6-month postoperatively were 24.1, 106.7, 112.6, 97.4 and 79.7 ml/min respectively. The mean post-operative flow in the STA graft graded as A/B/C were significantly different (168.0 ± 34.8 ml/min, 91.0 ± 15.5, 42.1 ± 17.2 ml/min, respectively, p = 0.000). 124.5 ml/min and 65.5 ml/min are good cut-off value for predicting post-operative graft Matsushima grade. The analysis also showed excellent agreement between ultrasonography and DSA for assessing bypass function (κ = 0.78). CONCLUSIONS: The patency of the STA grafts can be assessed noninvasively by quantitative ultrasonography, which results are comparable to those of conventional DSA. This, therefore, suggest that quantitative ultrasonography may be an alternative method to standard DSA for serial follow up of STA grafts.


Assuntos
Angiografia Digital , Angiografia Cerebral , Revascularização Cerebral , Transtornos Cerebrovasculares/cirurgia , Artéria Cerebral Média/cirurgia , Artérias Temporais/cirurgia , Ultrassonografia Doppler em Cores , Velocidade do Fluxo Sanguíneo , Revascularização Cerebral/efeitos adversos , Circulação Cerebrovascular , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Feminino , Humanos , Masculino , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
8.
J Neurol Sci ; 417: 117078, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32768718

RESUMO

BACKGROUND AND AIM: COVID-19 pandemic has resulted in an unprecedented increased usage of Personal protective equipment (PPE) by healthcare-workers. PPE usage causes headache in majority of users. We evaluated changes in cerebral hemodynamics among healthcare-workers using PPE. METHODS: Frontline healthcare-workers donning PPE at our tertiary center were included. Demographics, co-morbidities and blood-pressure were recorded. Transcranial Doppler (TCD) monitoring of middle cerebral artery was performed with 2-MHz probe. Mean flow velocity (MFV) and pulsatility index (PI) were recorded at baseline, after donning N95 respirator-mask, and after donning powered air-purifying respirator (PAPR), when indicated. End-tidal carbon-dioxide (ET-CO2) pressure was recorded for participants donning PAPR in addition to the N95 respirator-mask. RESULTS: A total of 154 healthcare-workers (mean age 29 ± 12 years, 67% women) were included. Migraine was the commonest co-morbidity in 38 (25%) individuals while 123 (80%) developed de-novo headache due to N95 mask. Donning of N95 respirator-mask resulted in significant increase in MFV (4.4 ± 10.4 cm/s, p < 0.001) and decrease in PI (0.13 ± 0.12; p < 0.001) while ET-CO2 increased by 3.1 ± 1.2 mmHg (p < 0.001). TCD monitoring in 24 (16%) participants donning PAPR and N95 respirator mask together showed normalization of PI, accompanied by normalization of ET-CO2 values within 5-min. Combined use of N95 respirator-mask and PAPR was more comfortable as compared to N95 respirator-mask alone. CONCLUSION: Use of N95 respirator-mask results in significant alterations in cerebral hemodynamics. However, these effects are mitigated by the use of additional PAPR. We recommend the use of PAPR together with the N95 mask for healthcare-workers doing longer duties in the hospital wards.


Assuntos
Betacoronavirus , Pessoal de Saúde , Máscaras/efeitos adversos , Doenças Profissionais/prevenção & controle , Pandemias , Dispositivos de Proteção Respiratória , Adulto , Velocidade do Fluxo Sanguíneo , Dióxido de Carbono/análise , Circulação Cerebrovascular , Infecções por Coronavirus/prevenção & controle , Estudos Transversais , Feminino , Cefaleia/etiologia , Hemodinâmica , Humanos , Masculino , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Doenças Profissionais/etiologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Fluxo Pulsátil , Ultrassonografia Doppler Transcraniana , Adulto Jovem
9.
Medicine (Baltimore) ; 99(31): e21434, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756153

RESUMO

RATIONALE: Intracranial aneurysm with the first manifestation of acute subdural hematoma (aSDH) is rare in the field of neurosurgery. Usually subarachnoid hemorrhage or intracranial hematoma happens after the rupture of an intracranial aneurysm, whereas trauma is the primary cause of aSDH. PATIENT CONCERNS: Here, we present the case of a 71-year-old woman who presented with spontaneous aSDH with progressive headache and vomiting. DIAGNOSIS: Urgent head computed tomography (CT) identified an aSHD, but the patient had no history of trauma. CT angiography (CTA) identified the cause of the aSDH as rupture of an intracranial aneurysm in the left middle cerebral artery. INTERVENTIONS: Emergent craniotomy with hematoma evacuation was performed. OUTCOMES: Due to prompt diagnosis and appropriate intervention, the patient recovered fully with no disability. LESSONS: This unique case demonstrates that aSDH caused by intracranial aneurysm rupture requires timely identification and appropriate action to prevent adverse outcomes. We performed a comprehensive systematic literature review to examine the etiology and pathogenesis of non-traumatic aSDH. Furthermore, digital subtraction angiography should be considered in patients diagnosed with an aSDH with no known cause.


Assuntos
Angiografia Digital/métodos , Hematoma Subdural Agudo/etiologia , Aneurisma Intracraniano/patologia , Artéria Cerebral Média/diagnóstico por imagem , Ruptura/complicações , Adulto , Idoso , Angiografia Digital/normas , Angiografia por Tomografia Computadorizada/métodos , Craniotomia/métodos , Feminino , Cefaleia/etiologia , Hematoma Subdural Agudo/diagnóstico por imagem , Hematoma Subdural Agudo/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/patologia , Resultado do Tratamento , Vômito/etiologia
10.
J Stroke Cerebrovasc Dis ; 29(9): 105081, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807478

RESUMO

BACKGROUND: Cerebrovascular reactivity (CVR) to acetazolamide (ACZ) on single-photon emission computed tomography (SPECT) can be used to assess the severity of chronic cerebral ischemia; however, this is an invasive method. We examined whether whole-brain magnetic resonance angiography (MRA) at 7T could non-invasively detect impaired CVR in patients with chronic cerebral ischemia by demonstrating the leptomeningeal collaterals (LMCs). METHODS: Fifty-seven patients with symptomatic unilateral cervical stenosis underwent whole-brain time-of-flight MRA at 7T and cerebral perfusion SPECT before/after the ACZ challenge. MRA images were visually assessed based on 6-point grading systems to evaluate the development of LMCs toward the middle cerebral artery (MCA) and antegrade flow of MCA. CVR of the affected side was calculated from the SPECT data. Subsequently, we compared the LMC grades on MRA with CVR on SPECT. RESULTS: CVR was significantly lower in grades ≥ 2 of LMCs than in grades 0-1 (P < 0.05) when applying LMCs from the anterior cerebral artery (ACA) and/or posterior cerebral artery (PCA). These differences were more evident than those in the grading of the antegrade MCA flow. The LMC grades from ACA/PCA readily detected reduced CVR (< 18.4%) with a sensitivity/specificity of 0.79/0.82. CONCLUSION: The development of LMCs on whole-brain MRA at 7T can non-invasively detect reduced CVR with a high sensitivity/specificity in patients with unilateral cervical stenosis.


Assuntos
Angiografia Cerebral/métodos , Circulação Cerebrovascular , Circulação Colateral , Angiografia por Ressonância Magnética , Meninges/irrigação sanguínea , Artéria Cerebral Média/diagnóstico por imagem , Insuficiência Vertebrobasilar/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/fisiopatologia , Imagem de Perfusão , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Tomografia Computadorizada de Emissão de Fóton Único , Insuficiência Vertebrobasilar/fisiopatologia
11.
Acta Neurochir (Wien) ; 162(11): 2725-2729, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32720013

RESUMO

The clinical manifestations of coronavirus disease 2019 (COVID-19) are non-specific and multi-inflammatory. They vary from mild to severe manifestations that can be life-threatening. The association of SARS-CoV-2 infection and pseudoaneurysm formation or rupture of an already existing aneurysm is still unexplored. Several mechanisms may be involved, including the direct destruction to the artery by the viral infection or through the release of the inflammatory cytokines. We are presenting a case of a 13-year-old girl with a ruptured cerebral pseudoaneurysm of the left middle cerebral artery (M2 segment) with severe intracerebral hemorrhage as the earliest manifestation of COVID-19 infection.


Assuntos
Falso Aneurisma/etiologia , Aneurisma Roto/etiologia , Hemorragia Cerebral/etiologia , Infecções por Coronavirus/complicações , Artéria Cerebral Média , Pneumonia Viral/complicações , Adolescente , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/etiologia , Aneurisma Dissecante/cirurgia , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/cirurgia , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Angiografia Digital , Ascite/etiologia , Betacoronavirus , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Angiografia Cerebral , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Angiografia por Tomografia Computadorizada , Coronavirus , Infecções por Coronavirus/diagnóstico , Craniotomia , Progressão da Doença , Feminino , Hepatomegalia/etiologia , Humanos , Nefropatias/etiologia , Pandemias , Pneumonia Viral/diagnóstico , Síndrome do Desconforto Respiratório do Adulto/etiologia , Infarto do Baço/etiologia , Tomografia Computadorizada por Raios X
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(4): 515-520, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32691560

RESUMO

Objective: To assess the value of contrast-enhanced ultrasound (CEUS) and color Doppler ultrasound (DUS) on hemodynamic changes and cerebral perfusion quantitative analyses in Sprague-Dawley (SD) rats with focal permanent ischemic stroke. Methods: Sixteen SD rats with thin skulls were subjected to establish middle cerebral artery occlusion (MCAO) model. CEUS images were performed before modeling (T 0), immediately after modeling (5-15 min after modeling, T 1), 3 h after modeling (T 2), followed by the measurement of bilateral middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA) using DUS. The peak systolic velocity (PSV), end-diastolic velocity (EDV) and mean velocity (MV) of these arteries were obtained. The brain time-intensity curve was taken as interest region of the whole right brain, and the quantitative parameters of CEUS were obtained, including peak intensity (PI), area under the curve ( AUC), wash in slope (WIS), time to peak (TTP), rise time (RT) and time from peak to one half (TPH). The modified neurological deficit score (mNSS) of the rats was performed 3 h after the modeling, and the data of the rats with a score of 9-11 were statistically analyzed. Results: A total of 12 rats were successfully modeled and completed with mNSS score 9-11. No blood flow signals were observed on the right MCA and ACA in the 12 rats at T 1 and T 2. From T 0 to T 1, PI, AUC and WIS of the right hemisphere decreased sharply with TTP and RT significantly prolonged, and the differences were statistically significant. However, there was no significant difference in hemodynamic parameters at that period of time. From T 1 to T 2, there were no significant changes in CEUS quantitative parameters (except AUCand TPH), while PSV, EDV, MV of LMCA and bilateral PCA showed significant acceleration, and the differences were statistically significant. Conclusion: CEUS and DUS can reveal the intracranial hemodynamics and brain tissue perfusion trends of MCAO rats, which could be new methods in assessment of ischemic stroke model at multiple time points.


Assuntos
Infarto da Artéria Cerebral Média , Artéria Cerebral Média , Ultrassonografia Doppler em Cores , Ultrassonografia , Animais , Velocidade do Fluxo Sanguíneo , Meios de Contraste , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/diagnóstico por imagem , Ratos , Ratos Sprague-Dawley
16.
JAMA Netw Open ; 3(6): e205323, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32585017

RESUMO

Importance: Severe early onset fetal growth restriction caused by placental dysfunction leads to high rates of perinatal mortality and neonatal morbidity. The phosphodiesterase 5 inhibitor, sildenafil, inhibits cyclic guanosine monophosphate hydrolysis, thereby activating the effects of nitric oxide, and might improve uteroplacental function and subsequent perinatal outcomes. Objective: To determine whether sildenafil reduces perinatal mortality or major morbidity. Design, Setting, and Participants: This placebo-controlled randomized clinical trial was conducted at 10 tertiary referral centers and 1 general hospital in the Netherlands from January 20, 2015, to July 16, 2018. Participants included pregnant women between 20 and 30 weeks of gestation with severe fetal growth restriction, defined as fetal abdominal circumference below the third percentile or estimated fetal weight below the fifth percentile combined with Dopplers measurements outside reference ranges or a maternal hypertensive disorder. The trial was stopped early owing to safety concerns on July 19, 2018, whereas benefit on the primary outcome was unlikely. Data were analyzed from January 20, 2015, to January 18, 2019. The prespecified primary analysis was an intention-to-treat analysis including all randomized participants. Interventions: Participants were randomized to sildenafil, 25 mg, 3 times a day vs placebo. Main Outcomes and Measures: The primary outcome was a composite of perinatal mortality or major neonatal morbidity until hospital discharge. Results: Out of 360 planned participants, a total of 216 pregnant women were included, with 108 women randomized to sildenafil (median gestational age at randomization, 24 weeks 5 days [interquartile range, 23 weeks 3 days to 25 weeks 5 days]; mean [SD] estimated fetal weight, 458 [160] g) and 108 women randomized to placebo (median gestational age, 25 weeks 0 days [interquartile range, 22 weeks 5 days to 26 weeks 3 days]; mean [SD] estimated fetal weight, 464 [186] g). In July 2018, the trial was halted owing to concerns that sildenafil may cause neonatal pulmonary hypertension, whereas benefit on the primary outcome was unlikely. The primary outcome, perinatal mortality or major neonatal morbidity, occurred in the offspring of 65 participants (60.2%) allocated to sildenafil vs 58 participants (54.2%) allocated to placebo (relative risk, 1.11; 95% CI, 0.88-1.40; P = .38). Pulmonary hypertension, a predefined outcome important for monitoring safety, occurred in 16 neonates (18.8%) in the sildenafil group vs 4 neonates (5.1%) in the placebo group (relative risk, 3.67; 95% CI, 1.28-10.51; P = .008). Conclusions and Relevance: These findings suggest that antenatal maternal sildenafil administration for severe early onset fetal growth restriction did not reduce the risk of perinatal mortality or major neonatal morbidity. The results suggest that sildenafil may increase the risk of neonatal pulmonary hypertension. Trial Registration: ClinicalTrials.gov Identifier: NCT02277132.


Assuntos
Peso ao Nascer , Término Precoce de Ensaios Clínicos , Retardo do Crescimento Fetal/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Doenças Placentárias/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Retardo do Crescimento Fetal/etiologia , Idade Gestacional , Humanos , Hipertensão Pulmonar/induzido quimicamente , Recém-Nascido , Doenças do Recém-Nascido/induzido quimicamente , Doenças do Recém-Nascido/prevenção & controle , Análise de Intenção de Tratamento , Masculino , Artéria Cerebral Média/fisiologia , Mortalidade Perinatal , Inibidores da Fosfodiesterase 5/efeitos adversos , Doenças Placentárias/fisiopatologia , Pré-Eclâmpsia/etiologia , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Fluxo Pulsátil , Citrato de Sildenafila/efeitos adversos , Artérias Umbilicais/fisiologia
17.
Am J Physiol Cell Physiol ; 319(2): C381-C391, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32491927

RESUMO

Several microRNAs (miRNAs or miRs) regulate cerebral ischemic injury outcomes; however, little is known about the role of miR-539-5p during cerebral ischemic injury or the postischemic state. Cerebral ischemic injury was modeled in vitro by exposing human cortical neurons to oxygen-glucose deprivation (OGD) and in vivo by occluding the middle cerebral artery (MCAO) in a rat model. The effects of miR-539-5p, histone deacetylase 1 (HDAC1), and early growth response 2 (EGR2) on cerebral ischemia were investigated using gain- and loss-of-function experiments. We identified changes in miR-539-5p, HDAC1, EGR2, and phosphorylated c-Jun NH2-terminal kinase (JNK). The interaction among miR-539-5p, HDAC1, and EGR2 was determined by dual luciferase reporter gene assay, chromatin immunoprecipitation, and coimmunoprecipitation. We also investigated the effects on cell viability and apoptosis and changes in inflammatory cytokine expression and spatial memory on MCAO rats. miR-539-5p and EGR2 were poorly expressed, while HDAC1 was highly expressed in OGD-treated HCN-2 cells. miR-539-5p targeted HDAC1, while HDAC1 prevented acetylation of EGR2 resulting in its downregulation and subsequent activation of the JNK pathway. Overexpression of miR-539-5p or EGR2 or silencing HDAC1 improved viability and reduced apoptosis of OGD-treated HCN-2 cells in vitro. Furthermore, overexpression of miR-539-5p improved spatial memory, while decreasing cell apoptosis and inflammation in MCAO rats. Collectively, these data suggest that miR-539-5p targets HDAC1 to upregulate EGR2, thus blocking the JNK signaling pathway, by which cerebral ischemic injury is alleviated.


Assuntos
Isquemia Encefálica/genética , Histona Desacetilase 1/genética , MicroRNAs/genética , Animais , Apoptose/genética , Isquemia Encefálica/patologia , Citocinas/metabolismo , Progressão da Doença , Proteína 2 de Resposta de Crescimento Precoce/genética , Regulação da Expressão Gênica/genética , Glucose/metabolismo , Humanos , Inflamação/genética , Artéria Cerebral Média/lesões , Artéria Cerebral Média/patologia , Neurônios/metabolismo , Neurônios/patologia , Ratos
18.
No Shinkei Geka ; 48(6): 515-520, 2020 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-32572003

RESUMO

We experienced a case of an unruptured cerebral aneurysm arising from a duplicate origin of the middle cerebral artery(MCA). Initially, we diagnosed the condition as an unruptured aneurysm arising from the internal carotid artery on three-dimensional computed tomography;neck clipping was attempted. However, an unidentified vessel was found around the aneurysmal neck, which could not be easily separated from the aneurysm, making neck clipping difficult. Thus, we only completed coating of the aneurysm without neck clipping. Postoperatively, cerebral angiography showed that the unidentified vessel originated from the internal carotid artery and fused with the MCA horizontal segment. We recognized that the identified vessel was a duplicate origin of the MCA. Few reports on the treatment of an aneurysm arising from a duplicate origin of the MCA are available;there has been no discussion on whether this vessel can be occluded. We assumed that occlusion of the proximal end of the duplicate origin of the MCA together with the aneurysm was unlikely to cause ischemia as the duplicate origin of the MCA fuse with MCA. Coil embolization was performed for the aneurysm, and the duplicate origin was unexpectedly preserved immediately after coil embolization. However, it was not enhanced on cerebral angiography performed after several months, and no cerebral infarction was noted on magnetic resonance imaging. If preservation of the duplicate origin of the MCA is difficult, occlusion of the aneurysm together with the proximal end of the duplicate origin of the MCA can be considered as a surgical strategy.


Assuntos
Aneurisma Intracraniano , Artéria Carótida Interna , Angiografia Cerebral , Humanos , Artéria Cerebral Média , Tomografia Computadorizada por Raios X
19.
No Shinkei Geka ; 48(6): 533-540, 2020 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-32572006

RESUMO

Aplastic or twig-like middle cerebral artery(Ap/T-MCA)is a rare congenital anomaly, and several cases of ruptured cerebral aneurysm associated with Ap/T-MCA have been reported. Recently, the association of ring finger protein 213(RNF213)mutations with moyamoya disease has been identified, and the involvement of such mutations in intracranial arterial stenosis lesions other than those of moyamoya disease has been suggested. A 53-year-old woman with headache and nausea was admitted to our hospital. Computed tomography showed a diffuse subarachnoid hemorrhage. Cerebral angiography revealed left-sided Ap/T-MCA and two aneurysms in several fine arterioles. We performed trapping of these aneurysms. In the clinical course after surgery, she developed aphasia and mild motor paralysis. The patient was transferred to a rehabilitation hospital. The genetic screening revealed that she carried a heterozygous mutation of RNF213(c. 14429G>A p. R4810K). This is the first report of an association between Ap/T-MCA and RNF213 mutations. In patients with the RNF213 mutation, there is also the possibility of a progression of the intracranial arterial stenosis to other sites. Such patients should be carefully observed after the completion of their treatment.


Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Doença de Moyamoya , Adenosina Trifosfatases/genética , Angiografia Cerebral , Feminino , Humanos , Pessoa de Meia-Idade , Artéria Cerebral Média , Mutação , Ubiquitina-Proteína Ligases/genética
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