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1.
J Neurovirol ; 26(5): 631-641, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32876900

RESUMO

A subset of patients with coronavirus 2 disease (COVID-19) experience neurological complications. These complications include loss of sense of taste and smell, stroke, delirium, and neuromuscular signs and symptoms. The etiological agent of COVID-19 is SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), an RNA virus with a glycoprotein-studded viral envelope that uses ACE2 (angiotensin-converting enzyme 2) as a functional receptor for infecting the host cells. Thus, the interaction of the envelope spike proteins with ACE2 on host cells determines the tropism and virulence of SARS-CoV-2. Loss of sense of taste and smell is an initial symptom of COVID-19 because the virus enters the nasal and oral cavities first and the epithelial cells are the receptors for these senses. Stroke in COVID-19 patients is likely a consequence of coagulopathy and injury to cerebral vascular endothelial cells that cause thrombo-embolism and stroke. Delirium and encephalopathy in acute and post COVID-19 patients are likely multifactorial and secondary to hypoxia, metabolic abnormalities, and immunological abnormalities. Thus far, there is no clear evidence that coronaviruses cause inflammatory neuromuscular diseases via direct invasion of peripheral nerves or muscles or via molecular mimicry. It appears that most of neurologic complications in COVID-19 patients are indirect and as a result of a bystander injury to neurons.


Assuntos
Betacoronavirus/patogenicidade , Encefalopatias/complicações , Infecções por Coronavirus/complicações , Transtornos do Olfato/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/complicações , Acidente Vascular Cerebral/complicações , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/virologia , Encefalopatias/imunologia , Encefalopatias/patologia , Encefalopatias/virologia , Efeito Espectador , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Pulmão/virologia , Neurônios/patologia , Neurônios/virologia , Transtornos do Olfato/imunologia , Transtornos do Olfato/patologia , Transtornos do Olfato/virologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Embolia Pulmonar/imunologia , Embolia Pulmonar/patologia , Embolia Pulmonar/virologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/virologia
2.
Nat Commun ; 11(1): 4078, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843630

RESUMO

Acute stroke causes complex, pathological, and systemic responses that have not been treatable by any single medication. In this study, using a murine transient middle cerebral artery occlusion stroke model, a novel therapeutic strategy is proposed, where blood replacement (BR) robustly reduces infarctions and improves neurological deficits in mice. Our analyses of immune cell subsets suggest that BR therapy substantially decreases neutrophils in blood following a stroke. Electrochemiluminescence detection demonstrates that BR therapy reduces cytokine storm in plasma and ELISA demonstrates reduced levels of matrix metalloproteinase-9 (MMP-9) in the plasma and brains at different time points post-stroke. Further, we have demonstrated that the addition of MMP-9 to the blood diminishes the protective effect of the BR therapy. Our study is the first to show that BR therapy leads to profoundly improved stroke outcomes in mice and that the improved outcomes are mediated via MMP-9. These results offer new insights into the mechanisms of stroke damage.


Assuntos
Substitutos Sanguíneos/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Encéfalo/metabolismo , Animais , Encéfalo/patologia , Infarto Encefálico/tratamento farmacológico , Isquemia Encefálica/patologia , Morte Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/complicações , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia
3.
Rinsho Shinkeigaku ; 60(9): 597-602, 2020 Sep 29.
Artigo em Japonês | MEDLINE | ID: mdl-32779594

RESUMO

An 82-year-old man with advanced lung cancer who had declined aggressive therapy was transferred to our hospital due to sudden-onset consciousness disturbance, global aphasia, and right hemiplegia. An electrocardiogram showed atrial fibrillation, and brain MRI and MRA revealed acute ischemic lesions of the left hemisphere and occlusion of the left internal carotid artery (ICA), respectively. We diagnosed acute ischemic stroke due to left ICA occlusion and performed endovascular thrombectomy, which resulted in complete recanalization of the left ICA after retrieval of the culprit embolus. Pathological examination of the retrieved thrombus revealed the presence of tumor tissue, as well as fibrin or red blood cells. Treatment was continued after admission, but the patient died of respiratory failure on day 40 of hospitalization. Autopsy revealed invasion of the tumor in the pulmonary vein, but not in the wall of the left atrium where thrombi were present. However, pathological examination of these thrombi in the left atrium revealed tumor tissue, along with fibrin or red blood cells. These findings suggest that the wall of the left atrium, in which lung cancer had not invaded, may be an incubator of a mixed embolus containing tumor tissue and thrombi in a case of cerebral embolism associated with both lung cancer and atrial fibrillation.


Assuntos
Fibrilação Atrial/complicações , Embolia Intracraniana/etiologia , Embolia Intracraniana/patologia , Neoplasias Pulmonares/complicações , Células Neoplásicas Circulantes , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/complicações , Autopsia , Artéria Carótida Interna , Evolução Fatal , Átrios do Coração , Humanos , Embolia Intracraniana/diagnóstico por imagem , Angiografia por Ressonância Magnética , Masculino , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X
4.
J Neurovirol ; 26(5): 619-630, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32839951

RESUMO

The recent pandemic outbreak of coronavirus is pathogenic and a highly transmittable viral infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2). In this time of ongoing pandemic, many emerging reports suggested that the SARS-CoV-2 has inimical effects on neurological functions, and even causes serious neurological damage. The neurological symptoms associated with COVID-19 include headache, dizziness, depression, anosmia, encephalitis, stroke, epileptic seizures, and Guillain-Barre syndrome along with many others. The involvement of the CNS may be related with poor prognosis and disease worsening. Here, we review the evidence of nervous system involvement and currently known neurological manifestations in COVID-19 infections caused by SARS-CoV-2. We prioritize the 332 human targets of SARS-CoV-2 according to their association with brain-related disease and identified 73 candidate genes. We prioritize these 73 genes according to their spatio-temporal expression in the different regions of brain and also through evolutionary intolerance analysis. The prioritized genes could be considered potential indicators of COVID-19-associated neurological symptoms and thus act as a possible therapeutic target for the prevention and treatment of CNS manifestations associated with COVID-19 patients.


Assuntos
Betacoronavirus/patogenicidade , Encéfalo/metabolismo , Infecções por Coronavirus/genética , Interações Hospedeiro-Patógeno/genética , Proteínas do Tecido Nervoso/genética , Pneumonia Viral/genética , Proteínas Virais/genética , Encéfalo/patologia , Encéfalo/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Depressão , Tontura/complicações , Tontura/genética , Tontura/patologia , Tontura/virologia , Encefalite/complicações , Encefalite/genética , Encefalite/patologia , Encefalite/virologia , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/genética , Síndrome de Guillain-Barré/patologia , Síndrome de Guillain-Barré/virologia , Cefaleia/complicações , Cefaleia/genética , Cefaleia/patologia , Cefaleia/virologia , Humanos , Proteínas do Tecido Nervoso/classificação , Proteínas do Tecido Nervoso/metabolismo , Transtornos do Olfato/complicações , Transtornos do Olfato/genética , Transtornos do Olfato/patologia , Transtornos do Olfato/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Mapeamento de Interação de Proteínas , Convulsões/complicações , Convulsões/genética , Convulsões/patologia , Convulsões/virologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/virologia , Proteínas Virais/metabolismo
5.
PLoS One ; 15(8): e0237928, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817637

RESUMO

We recently reported a family-based genome wide association study (GWAS) for pediatric stroke pointing our attention to two significantly associated genes of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family ADAMTS2 (rs469568, p = 8x10-6) and ADAMTS12 (rs1364044, p = 2.9x10-6). To further investigate these candidate genes, we applied a targeted resequencing approach on 48 discordant sib-pairs for pediatric stroke followed by genotyping of the detected non-synonymous variants in the full cohort of 270 offspring trios and subsequent fine mapping analysis. We identified eight non-synonymous SNPs in ADAMTS2 and six in ADAMTS12 potentially influencing the respective protein function. These variants were genotyped within a cohort of 270 affected offspring trios, association analysis revealed the ADAMTS12 variant rs77581578 to be significantly under-transmitted (p = 6.26x10-3) to pediatric stroke patients. The finding was validated in a pediatric venous thromboembolism (VTE) cohort of 189 affected trios. Subsequent haplotype analysis of ADAMTS12 detected a significantly associated haplotype comprising the originally identified GWAS variant. Several ADAMTS genes such as ADAMTS13 are involved in thromboembolic disease process. Here, we provide further evidence for ADAMTS12 to likely play a role in pediatric stroke. Further functional studies are warranted to assess the functional role of ADAMTS12 in the pathogenesis of stroke.


Assuntos
Proteínas ADAMTS/genética , Predisposição Genética para Doença , Acidente Vascular Cerebral/genética , Criança , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos/genética , Humanos , Masculino , Pediatria , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/patologia
6.
PLoS One ; 15(8): e0236831, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857781

RESUMO

AIM: The aim of this study was to explore the current and potential use of information and communication technology (ICT) to enhance coherent person-centred rehabilitation after stroke, from the perspectives of physiotherapists and occupational therapists. METHOD: Five occupational therapists and four physiotherapists from different phases of the Danish stroke rehabilitation process were included and two focus group interviews were carried out. A grounded theory approach was used throughout the study and a constant comparative method was used in the analysis. RESULTS: Three subcategories were identified from the analysis of interviews with participants: 1) ICT and apps as meaningful and supportive in the rehabilitation process, 2) ICT as a tool in communication and documentation and 3) Barriers to the integration of ICT and apps in the rehabilitation process. From these categories one core category emerged: The potential of a personalized app solution to facilitate coherent person-centred rehabilitation. CONCLUSION: ICT was perceived as important to integrate in stroke rehabilitation both for assessment, training and to compensate for remaining deficits. The development of a personalized app solution could accommodate stroke survivors' and significant others' need for insight into and overview over the rehabilitation process as well as access to relevant information, which would thereby empower them. Furthermore, a personalized app solution could also facilitate follow-up after discharge and was perceived to ease the communication and documentation within and between sectors, as well as communication with both stroke survivors and significant others.


Assuntos
Terapeutas Ocupacionais/psicologia , Fisioterapeutas/psicologia , Reabilitação do Acidente Vascular Cerebral , Adulto , Comunicação , Grupos Focais , Teoria Fundamentada , Humanos , Entrevistas como Assunto , Assistência Centrada no Paciente , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/psicologia
7.
Stroke ; 51(9): e223-e226, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32684144

RESUMO

BACKGROUND AND PURPOSE: Ischemic infarction of the corpus callosum is rare and infarction isolated to the corpus callosum alone rarer still, accounting for much <1% of ischemic stroke in most stroke registries. About half of callosal infarctions affect the splenium. METHODS: During a 2-week period, at the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City, 4 patients at Montefiore Medical Center in the Bronx were found to have ischemic lesions of the splenium of the corpus callosum, 2 with infarction isolated to the corpus callosum. RESULTS: All patients tested positive for COVID-19 and 3 had prolonged periods of intubation. All had cardiovascular risk factors. Clinically, all presented with encephalopathy and had evidence of coagulopathy and raised inflammatory markers. CONCLUSIONS: Infarction of the splenium of the corpus callosum is exceedingly rare and a cluster of such cases suggests COVID-19 as an inciting agent, with the mechanisms to be elucidated.


Assuntos
Infarto Cerebral/complicações , Infarto Cerebral/patologia , Infecções por Coronavirus/complicações , Corpo Caloso/patologia , Pneumonia Viral/complicações , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Complicações do Diabetes/complicações , Evolução Fatal , Feminino , Humanos , Hipertensão/complicações , Hipotireoidismo/complicações , Inflamação/sangue , Intubação Intratraqueal , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Reabilitação do Acidente Vascular Cerebral
8.
J Rehabil Med ; 52(6): jrm00071, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32488283

RESUMO

OBJECTIVE: To compare to what extent the presence of contralateral spatial neglect affects functional recovery and outcome among patients with right or left stroke after subacute inpatient rehabilitation. METHODS: Observational cohort study comparing functional improvement and outcome. The same admission data-set was used as in part 1 of this study. RESULTS: Right and left stroke rehabilitants with equally mild neglect and those without neglect (a total of 4 subgroups) all improved proportionally as much, but those with neglect, irrespective of stroke side needed a longer stay in inpatient rehabilitation. At discharge, total disability did not differ significantly between the 2 neglect subgroups, but those with left stroke had significantly lower Functional Independence Measure cognitive sub-score and score in communication. Rehabilitants with neglect, irrespective of stroke side had higher motor, cognitive and total disability and were more often institutionalized than those without neglect. CONCLUSION: Mild neglect did not impair recovery after right or left stroke, but rehabilitants with neglect were more disabled and needed a longer rehabilitation inpatient stay than those without neglect.


Assuntos
Recuperação de Função Fisiológica/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/complicações , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Pacientes Internados , Masculino , Alta do Paciente , Transtornos da Percepção/reabilitação , Acidente Vascular Cerebral/patologia
9.
J Clin Neurosci ; 78: 418-419, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32522486

RESUMO

A6-year-oldgirl presented with acute-onset headache andfluctuating right-sided weakness.HerPedNIHSSwas13. Brain MRI/MRA showed acute pontine arterial ischemic stroke(AIS)and remote right cerebellar and thalamic infarcts.No antecedent trauma or other stroke risk factors were identified. Clinical suspicion of bow hunter syndromewas raised. CTshowed congenital C2-C3 fusion and dynamic angiogramconfirmed the diagnosis. The management challenges of this rare condition are discussed below.


Assuntos
Mucopolissacaridose II/complicações , Acidente Vascular Cerebral/etiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Criança , Gerenciamento Clínico , Feminino , Humanos , Angiografia por Ressonância Magnética , Imagem por Ressonância Magnética/efeitos adversos , Acidente Vascular Cerebral/patologia , Artéria Vertebral/patologia , Insuficiência Vertebrobasilar/complicações
10.
Nature ; 582(7812): 395-398, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32494010

RESUMO

Neuroprotectant strategies that have worked in rodent models of stroke have failed to provide protection in clinical trials. Here we show that the opposite circadian cycles in nocturnal rodents versus diurnal humans1,2 may contribute to this failure in translation. We tested three independent neuroprotective approaches-normobaric hyperoxia, the free radical scavenger α-phenyl-butyl-tert-nitrone (αPBN), and the N-methyl-D-aspartic acid (NMDA) antagonist MK801-in mouse and rat models of focal cerebral ischaemia. All three treatments reduced infarction in day-time (inactive phase) rodent models of stroke, but not in night-time (active phase) rodent models of stroke, which match the phase (active, day-time) during which most strokes occur in clinical trials. Laser-speckle imaging showed that the penumbra of cerebral ischaemia was narrower in the active-phase mouse model than in the inactive-phase model. The smaller penumbra was associated with a lower density of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive dying cells and reduced infarct growth from 12 to 72 h. When we induced circadian-like cycles in primary mouse neurons, deprivation of oxygen and glucose triggered a smaller release of glutamate and reactive oxygen species, as well as lower activation of apoptotic and necroptotic mediators, in 'active-phase' than in 'inactive-phase' rodent neurons. αPBN and MK801 reduced neuronal death only in 'inactive-phase' neurons. These findings suggest that the influence of circadian rhythm on neuroprotection must be considered for translational studies in stroke and central nervous system diseases.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Modelos Animais de Doenças , Neurônios/patologia , Neuroproteção , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/prevenção & controle , Animais , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/prevenção & controle , Glucose/deficiência , Humanos , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/fisiopatologia , Pesquisa Médica Translacional , Falha de Tratamento
11.
BMC Neurol ; 20(1): 252, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576150

RESUMO

BACKGROUND: High adherence to a Mediterranean Diet is associated with reduced incidence and mortality of acute ischemic stroke (AIS) but may also be associated with severity. Our purpose was to investigate the association of adherence to a Mediterranean diet and severity in a prospective hospital register of AIS patients. METHODS: We included AIS patients admitted from February 2017 to July 2019. All were assessed by a neurologist with a standard stroke protocol, including NIHSS. Adherence to Mediterranean diet was prospectively measured by the 14-point Mediterranean Diet Adherence Screener (MEDAS) and defined as low (0-6 points) or high (7-14 points). Demographic and clinical characteristics were compared by group with univariate analysis. A Generalized Linear Model (GLM) was used to investigate the association of admission NIHSS as a continuous ordinal variable and an ordinal logistic regression (OLR) analysis to determine the independent association of the NIHSS quartiles with adherence to Mediterranean diet. RESULTS: Three hundred sixty-eight patients were included, mean age 68.3 (17.7), 158 (42.9%) females. The median NIHSS score was 3 (IQR 1-9) and the median MEDAS score was 6 (IQR 4.5-8). Patients with high MEDAS scores had significantly lower; admission NIHSS scores, sedentary lifestyle, body mass index, total and LDL cholesterol levels, but higher alcohol consumption. After adjustments, high adherence to Mediterranean diet remained independently associated with lower stroke severity both in the GLM (ß coefficient = - 0.19, p = 0.01) and in the OLR model (OR for lower NIHSS quartiles 0.6 (95% CI 0.37-0.98, p = 0.04). CONCLUSIONS: Higher pre-stroke adherence to a Mediterranean diet is independently associated with lower AIS severity.


Assuntos
Dieta Mediterrânea , Acidente Vascular Cerebral , Idoso , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia
12.
Medicine (Baltimore) ; 99(21): e20206, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481290

RESUMO

In last decades, many scholars have studied the relationship between aldehyde dehydrogenase 2 (ALDH2) rs671 and ischemic stroke (IS), however, the results obtained from these studies were inconclusive. The purpose of this study was to investigate the association between rs671 and the risk of IS by systematically review.Two researchers independently screened relevant published literatures, derived data and estimated the risk of bias of the research in Pubmed, Embase, Ovid, China National Knowledge Infrastructure (CNKI), Cochrane Library and China Biomedical Literature Database throughout March 29, 2020. All statistical analyses were performed with the Stata 12.0 software. The data of the study was analyzed using fixed and random effects models. The results were expressed by odds ratio (OR) and 95% confidence interval (95%CI).A total of 10 articles were included this study. The total number of samples for all studies was 5265, including 2762 cases and 2503 controls. Statistical results indicated statistical differences between ALDH2 rs671 polymorphism and IS under dominant model (AA vs. AG + GG) and allelic model (A vs G), ORs (95% CI) were 1.66 (1.27-2.17) (P = .00) and 1.34 (1.05-1.71) (P = .02), respectively. But there was no statistical difference under recessive model (AA + AG vs GG), OR (95% CI) was 1.40 (0.99-1.97), P = .06.ALDH2 rs671 polymorphism was related to IS risk for Chinese population and the A allele of rs671 may be a risk factor of IS.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Isquemia Encefálica/diagnóstico , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/genética , Revisões Sistemáticas como Assunto , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Fatores de Risco , Sensibilidade e Especificidade , Acidente Vascular Cerebral/patologia
13.
Neurology ; 95(1): e79-e88, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32493718

RESUMO

OBJECTIVE: To examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS). METHODS: For the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool-based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes. RESULTS: Patients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p < 0.001). Median WMHv in all patients with AIS was 5.86 cm3 (interquartile range 2.18-14.61 cm3) and differed significantly across CCS subtypes (p < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p < 0.001), and diabetes mellitus (p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes (p < 0.001). CONCLUSION: In this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke.


Assuntos
Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Aprendizado Profundo , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
14.
Mol Immunol ; 123: 74-87, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32438202

RESUMO

BACKGROUND: Idebenone is a well-appreciated mitochondrial protectant while the mechanisms underlying the neuroprotection in cerebral ischemia and reperfusion (I/R) remain elusive. It has been manifested NLRP3 inflammasom activation contributed to I/R induced damage. It raises questions how exactly NLRP3 inflammasom was activated in microglia and neuron and whether idebenone reverses the process in I/R. METHODS: I/R rat model was utilized and BV2, primary microglia and PC12 cells were subjected to oxygen-glucose deprivation (OGD). Then, western-blotting, q-PCR, immunofluorescence staining, ELISA, flow cytometry and immunoprecipitation analysis were performed. RESULTS: We found ROS-NLRP3 singaling was activated in BV2 cells at OGD/R 24 h. Importantly, microglial NLRP3 activation was essential for NLRP3 activation in PC12 cells under microglial-neuronal co-culture circumstance, which has been confirmed to induced neuronal apoptosis. Further, we found mitochondrial dysfunction in OGD/R led to mt-DNA translocation as well as generation of mt-ROS, resulting cytosolic accumulation of oxidized mt-DNA. Ultimately, oxidized mt-DNA binding to NLRP3 contributed to further activation of NLRP3 and dramatically augmented inflammation in BV2 and PC12 cells. Furthermore, idebenone treatment inhibited the process, thus suppressing the NLRP3-mediated inflammatory injury after OGD/R. In vivo, NLRP3 was activated in microglia of I/R rats and inhibition of NLRP3 was observed in idebenone treatment group, which had less neurological deficit and less infarct volume. INTERPRETATION: Our data revealed the anti-inflammatory effects of idebenone via suppressing activation of NLRP3 and ameliorating NLRP3-mediating damage in I/R, which may provide new insight in therapeutic strategy for ischemic stroke.


Assuntos
Isquemia Encefálica , Encefalite/prevenção & controle , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuroproteção/efeitos dos fármacos , Traumatismo por Reperfusão , Ubiquinona/análogos & derivados , Animais , Animais Recém-Nascidos , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/imunologia , Isquemia Encefálica/metabolismo , Células Cultivadas , Encefalite/etiologia , Inflamassomos/metabolismo , Inflamassomos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células PC12 , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico
15.
Stroke ; 51(6): 1835-1843, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32397936

RESUMO

Background and Purpose- oxLDL (oxidized low-density lipoprotein) has been known for its potential to induce endothelial dysfunction and used as a major serological marker of oxidative stress. Recently, LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1), a lectin-like receptor for oxLDL, has attracted attention in studies of neuronal apoptosis and stroke. We aim to investigate the impact of LOX-1-deficiency on spontaneous hypertension-related brain damage in the present study. Methods- We generated a LOX-1 deficient strain on the genetic background of stroke-prone spontaneously hypertensive rat (SHRSP), an animal model of severe hypertension and spontaneous stroke. In this new disease model with stroke-proneness, we monitored the occurrence of brain abnormalities with and without salt loading by multiple procedures including T2 weighted magnetic resonance imaging and also explored circulatory miRNAs as diagnostic biomarkers for cerebral ischemic injury by microarray analysis. Results- Both T2 weighted magnetic resonance imaging abnormalities and physiological parameter changes could be detected at significantly delayed timing in LOX-1 knockout rats compared with wild-type SHRSP, in either case of normal rat chow and salt loading (P<0.005 in all instances; n=11-20 for SHRSP and n=13-23 for LOX-1 knockout rats). There were no significant differences in the form of magnetic resonance imaging findings between the strains. A number of miRNAs expressed in the normal rat plasma, including rno-miR-150-5p and rno-miR-320-3p, showed significant changes after spontaneous brain damage in SHRSP, whereas the corresponding changes were modest or almost unnoticeable in LOX-1 knockout rats. There appeared to be the lessening of correlation of postischemic miRNA alterations between the injured brain tissue and plasma in LOX-1 knockout rats. Conclusions- Our data show that deficiency of LOX-1 has a protective effect on spontaneous brain damage in a newly generated LOX-1-deficient strain of SHRSP. Further, our analysis of miRNAs as biomarkers for ischemic brain damage supports a potential involvement of LOX-1 in blood brain barrier disruption after cerebral ischemia. Visual Overview- An online visual overview is available for this article.


Assuntos
Barreira Hematoencefálica , Isquemia Encefálica , Deleção de Genes , Hipertensão , Receptores Depuradores Classe E/deficiência , Acidente Vascular Cerebral , Animais , Barreira Hematoencefálica/lesões , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Isquemia Encefálica/sangue , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , MicroRNA Circulante , Hipertensão/sangue , Hipertensão/genética , Hipertensão/patologia , MicroRNAs/sangue , MicroRNAs/genética , Ratos , Ratos Endogâmicos SHR , Ratos Transgênicos , Receptores Depuradores Classe E/metabolismo , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia
16.
Medicine (Baltimore) ; 99(18): e19742, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358348

RESUMO

Hemodynamic changes occurring at the segments of arterial bifurcations, up and down stream of stenotic vessels appear to play a critical role in the development of atherosclerosis. Therefore, we hypothesized that basilar artery (BA) geometry may be related to the distribution of atherosclerotic plaque.In this retrospective cross-sectional study, all patients hospitalized with ischemic stroke and intracranial atherosclerotic disease were sifted from March 2017 to October 2017. Sixty-seven patients with intracranial atherosclerotic disease (39 with and 28 without BA atherosclerosis) were analyzed. Magnetic resonance imaging, magnetic resonance angiography, and high-resolution black-blood MRI were performed within 7 days after symptoms onset. BA tortuosity, plaque location, and plaque enhancement were assessed. Plaque burden and vascular remodeling were measured.Of the 39 patients with BA atherosclerosis, plaques preferred to be formed at the inner arc than the outer arc (27/39, 69% vs 12/39, 31%) in the tortuous BA. In addition, patients with BA plaque had a greater vascular tortuosity compared with those without plaque (113.1 ±â€Š10.2 vs 107 ±â€Š4.6; P = .034). Finally, patients with apparent BA plaque had greater plaque enhancement (14/21, 67% vs 5/18, 28%; P = .017) and plaque burden (0.76 ±â€Š0.15 vs 0.70 ±â€Š0.09; P = .036) compared with those with minimal plaque.Plaque may be more likely to form at the inner arc of tortuous BA with atherosclerotic disease, and increased BA tortuosity is associated with its likelihood to form plaque.


Assuntos
Aterosclerose/patologia , Artéria Basilar/patologia , Placa Aterosclerótica/patologia , Acidente Vascular Cerebral/patologia , Idoso , Aterosclerose/diagnóstico por imagem , Artéria Basilar/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Remodelação Vascular
17.
Medicine (Baltimore) ; 99(20): e20151, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443330

RESUMO

BACKGROUND: This study will specifically investigate the effect of butylphthalide on hemodynamics in patients with watershed stroke (WS). METHODS: We will search the following databases from their inceptions to the March 1, 2020: Cochrane Library, MEDLINE, EMBASE, PsycINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and China National Knowledge Infrastructure. All relevant randomized controlled trials on exploring the effect of butylphthalide on hemodynamics in patients with WS will be considered for inclusion. No language limitation will be imposed to this study. All study quality will be checked using Cochrane risk of bias tool. RevMan 5.3 software will be utilized for data analysis. RESULTS: This study will summarize the latest evidence to investigate the effect of butylphthalide on hemodynamics in patients with WS. CONCLUSION: Findings from this study will provide theoretical basis of butylphthalide on hemodynamics in patients with WS for clinician and future research. DISSEMINATION AND ETHICS: This study is carried out based on the published data, thus, no ethical approval is required. We will submit this study to a peer-reviewed journal for publication. SYSTEMATIC REVIEW REGISTRATION: INPLASY 202030006.


Assuntos
Benzofuranos/farmacologia , Hemodinâmica/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Benzofuranos/administração & dosagem , Benzofuranos/efeitos adversos , China/epidemiologia , Humanos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/efeitos adversos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
18.
PLoS One ; 15(5): e0232017, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379765

RESUMO

BACKGROUND: Methods used to categorize functional status to predict health outcomes across post-acute care settings vary significantly. OBJECTIVES: We compared three methods that categorize functional status to predict 30-day and 90-day hospital readmission across inpatient rehabilitation facilities (IRF), skilled nursing facilities (SNF) and home health agencies (HHA). RESEARCH DESIGN: Retrospective analysis of 2013-2014 Medicare claims data (N = 740,530). Data were randomly split into two subsets using a 1:1 ratio. We used half of the cohort (development subset) to develop functional status categories for three methods, and then used the rest (testing subset) to compare outcome prediction. Three methods to generate functional categories were labeled as: Method I, percentile based on proportional distribution; Method II, percentile based on change score distribution; and Method III, functional staging categories based on Rasch person strata. We used six differentiation and classification statistics to determine the optimal method of generating functional categories. SETTING: IRF, SNF and HHA. SUBJECTS: We included 130,670 (17.7%) Medicare beneficiaries with stroke, 498,576 (67.3%) with lower extremity joint replacement and 111,284 (15.0%) with hip and femur fracture. MEASURES: Unplanned 30-day and 90-day hospital readmission. RESULTS: For all impairment conditions, Method III best predicted 30-day and 90-day hospital readmission. However, we observed overlapping confidence intervals among some comparisons of three methods. The bootstrapping of 30-day and 90-day hospital readmission predictive models showed the area under curve for Method III was statistically significantly higher than both Method I and Method II (all paired-comparisons, p<.001), using the testing sample. CONCLUSIONS: Overall, functional staging was the optimal method to generate functional status categories to predict 30-day and 90-day hospital readmission. To facilitate clinical and scientific use, we suggest the most appropriate method to categorize functional status should be based on the strengths and weaknesses of each method.


Assuntos
Modelos Teóricos , Readmissão do Paciente/estatística & dados numéricos , Cuidados Semi-Intensivos , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Artroplastia de Substituição , Feminino , Fraturas Ósseas/patologia , Humanos , Revisão da Utilização de Seguros , Masculino , Medicare , Alta do Paciente , Curva ROC , Estudos Retrospectivos , Acidente Vascular Cerebral/patologia , Fatores de Tempo , Estados Unidos
19.
PLoS One ; 15(4): e0231860, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315353

RESUMO

Many poststroke hemiplegic patients have an asymmetrical wheelchair-sitting posture. This study aimed to investigate the impact of different back support shapes on asymmetrical sitting posture and pressure points among poststroke hemiplegic patients during an activities of daily living-related reaching task. This study included 23 poststroke hemiplegic patients who performed tasks that involved the movement of objects using the unaffected upper limb to the affected side while sitting in a conventional wheelchair (C-WC) with a flat back support or a wheelchair providing pelvic and thoracic support (P-WC). Body alignment angles from video images and pressure distribution on supporting surfaces were measured using a two-dimensional motion analysis software (Dartfish) and a pressure mapping system (FSA). Regarding movement performance, although postural asymmetry increased in both wheelchair types, the degree of postural variation was smaller with P-WC use than C-WC use (p < 0.05), with partly reduced postural asymmetry. With P-WC, one-sided ischial asymmetrical pressure was significantly less after the movement (p < 0.05). In conclusion, P-WC's back support shape contributed to a decrease in postural asymmetry for pelvic girdle support both at rest and during movement. This highlights the importance of a wheelchair back support shape and may help to increase the quality of activities of daily living movement in poststroke hemiplegic patients in wheelchairs.


Assuntos
Pelve/fisiologia , Acidente Vascular Cerebral/patologia , Cadeiras de Rodas , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Feminino , Hemiplegia/etiologia , Hemiplegia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Postura , Pressão , Postura Sentada , Acidente Vascular Cerebral/complicações
20.
Neurology ; 94(18): e1885-e1891, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32253350

RESUMO

OBJECTIVES: Homonymous hemianopia (HH) is the most frequent visual-field defect after a stroke. Some of these patients also have visual hallucinations, the origin and frequency of which remain largely unknown. The aims of this work were to determine the occurrence of visual hallucinations among poststroke hemianopic patients in function of the location (Brodmann areas) of the brain lesion, as determined by MRI, and to study the neuroanatomic correlates of these hallucinations by nature, frequency, and type. METHODS: One hundred sixteen patients with HH who had had a stroke in the posterior region, including the occipital lobe, participated in the study. We evaluated the frequency and nature of visual hallucinations with the Questionnaire for Hallucinations in Homonymous Hemianopia. The volume of each patient's brain lesion was modeled in 3 dimensions. RESULTS: Of 116 patients with an HH from a cortical infarction, 85 were excluded due to confounding factors associated with hallucinations. In the final cohort of 31 patients matched for lesion location and etiology, 58% had experienced hallucinations. A significant inverse correlation between lesion size and the frequency of visual hallucinations emerged. The presence of visual hallucinations in poststroke hemianopic patients requires a relatively small lesion that includes, at the very least, loss of the striate cortex but that spares Brodmann area 19, 20, and 37. CONCLUSION: Our results suggest that visual hallucinations might be due to complex interactions between damaged areas and intact areas of the visual cortex. We discuss these findings regarding models of perception and of visual recognition. Our results also have implications for the clinical care of patients with HH who have had a stroke.


Assuntos
Encéfalo/patologia , Alucinações/etiologia , Hemianopsia/etiologia , Acidente Vascular Cerebral/complicações , Idoso , Feminino , Alucinações/patologia , Hemianopsia/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/patologia
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