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1.
Artigo em Inglês | MEDLINE | ID: mdl-38485613

RESUMO

Surgical intervention for epilepsy emerged in the second half of the 20th century as an important option for pediatric patients with medically refractory epilepsy. Both the number of patients undergoing epilepsy surgery and the available surgical procedures for epilepsy have expanded in the last 3 decades, and now range from surgical resection to neuromodulatory device placement1,2 Studies showing that many patients who would be excellent candidates for surgery are still not being offered appropriate interventions have prompted an interest in ensuring that all providers who see patients with epilepsy are aware of the options for epilepsy surgery to facilitate earlier referrals when medications have not been effective3 In this article, we will introduce the pediatrician to the process involved in determining epilepsy surgery candidacy and to surgical outcomes, with the goal of empowering pediatric providers to refer their medically refractory epilepsy patients to a pediatric epilepsy center.

2.
Pediatr Emerg Care ; 39(10): 780-785, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37163683

RESUMO

OBJECTIVES: We sought to investigate the association between adherence to the American Epilepsy Society (AES) 2016 guidelines for management of convulsive status epilepticus (SE) and clinical outcomes among children requiring interhospital transport for SE. We hypothesized that pretransport guideline nonadherence would be associated with needing higher level of care posttransfer. METHODS: This was a retrospective cohort study of children aged 30 days to 18 years transferred to our pediatric tertiary center from 2017 to 2019 for management of SE. Their care episodes were classified as 2016 American Epilepsy Society guideline adherent or nonadherent. There were 40 referring hospitals represented in this cohort. RESULTS: Of 260 care episodes, 55 (21%) were guideline adherent, 184 (71%) were guideline nonadherent, and 21 (8%) had insufficient data to determine guideline adherence. Compared with the adherent group, patients in the nonadherent care group had longer hospitalizations (32 hours [17-68] vs 21 hours [7-48], P = 0.006), were more likely to require intensive care unit admission (47% vs 31%), and less likely to be discharged home from the emergency department (16% vs 35%; χ 2 test, P = 0.01). Intubation rates did not differ significantly between groups (25% vs 18%, P = 0.37). When we fit a multivariable model to adjust for confounding variables, guideline nonadherence was associated with need for higher level of care (odds ratio, 2.04; 95% confidence interval, 1.04-3.99). Treatment guideline adherence did not improve over the 3-year study period (2017: 22%, 2018: 19%, 2019: 29% [χ 2 test for differences between any 2 years, P = 0.295]). CONCLUSIONS: Guideline nonadherence pretransport was associated with longer hospitalizations and need for higher level of care among children transferred for SE at our institution. These findings suggest a need to improve SE guideline adherence through multifaceted quality improvement efforts targeting both the prehospital and community hospital settings.


Assuntos
Serviço Hospitalar de Emergência , Estado Epiléptico , Humanos , Criança , Estudos Retrospectivos , Centros de Atenção Terciária , Fidelidade a Diretrizes , Estado Epiléptico/terapia
3.
Pediatr Neurol ; 120: 52-58, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34020112

RESUMO

BACKGROUND: Subpial hemorrhages are underrecognized, underreported, and poorly understood. The spectrum of their clinical manifestations and consequences in neonates has not been fully described. Here, we describe the demographic, clinical, and radiographic characteristics of neonates with subpial hemorrhages. METHODS: We reviewed the medical records and neuroimaging studies of neonates with subpial hemorrhage who were admitted to our neonatal intensive care unit between September 2009 and December 2020. RESULTS: Of 114 neonates with intracranial hemorrhage, 31 (27%) had subpial hemorrhage. The majority of neonates in our cohort were male (68%) and born at term (55%). The most common imaging indication was apneas and/or seizures in 58%. Common comorbid conditions included cardiorespiratory failure (42%), hypoxic-ischemic encephalopathy (26%), and coagulopathy (23%). Subpial hemorrhages were multifocal in 45% of neonates, located in the temporal lobe in 45% of neonates, and tended to be larger in neonates with coagulopathy, birth trauma, or hydrocephalus requiring neurosurgical intervention. Subpial hemorrhage was associated with another type of intracranial bleed in 77% of cases and with arterial ischemic stroke in 16% of cases. Of 17 patients with more than one year of follow-up data, 14 (82%) have developmental delay and four (24%) have epilepsy. Of 14 patients with follow-up imaging, 10 (71%) had encephalomalacia subjacent to the subpial hemorrhage. CONCLUSIONS: This is the largest cohort of neonates with subpial hemorrhages to date. Outcome data are limited by duration of follow-up and may be confounded by comorbid conditions and other concurrent hemorrhages. Further study is needed to define the spectrum of risk factors and expected neurological outcomes.


Assuntos
Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Deficiências do Desenvolvimento/etiologia , Epilepsia/etiologia , Doenças do Recém-Nascido , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/terapia , Feminino , Seguimentos , Hospitais Pediátricos , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico por imagem , Doenças do Recém-Nascido/etiologia , Doenças do Recém-Nascido/terapia , Unidades de Terapia Intensiva Neonatal , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pia-Máter/diagnóstico por imagem , Pia-Máter/patologia , Estudos Retrospectivos , Centros de Atenção Terciária
4.
AJR Am J Roentgenol ; 216(4): 1056-1065, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33566637

RESUMO

OBJECTIVE. Subpial hemorrhages, typically seen in neonates, are rare but can harm the adjacent brain parenchyma. The purpose of this review is to summarize the anatomy and pathophysiology of subpial hemorrhage and highlight its characteristic neuro-imaging pattern. CONCLUSION. The distinctive neuroimaging pattern of subpial hemorrhage is best appreciated on brain MRI, which shows the morphology over the cortex and injury to adjacent cortex and subcortical white matter. These findings do not occur in subarachnoid and subdural hemorrhages. Recognizing the pattern of subpial hemorrhages should guide prognostic precision, prognostication, and counseling.


Assuntos
Doenças do Recém-Nascido/diagnóstico por imagem , Hemorragia Subaracnóidea/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/fisiopatologia , Imageamento por Ressonância Magnética , Neuroimagem , Pia-Máter/diagnóstico por imagem , Fatores de Risco , Hemorragia Subaracnóidea/fisiopatologia , Tomografia Computadorizada por Raios X
5.
Epilepsy Behav ; 115: 107404, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33323339

RESUMO

The diagnosis of childhood absence epilepsy (CAE) is typically based on history and description of spells, supported by an office-based positive hyperventilation test and confirmed by routine electroencephalography (EEG). In the current coronavirus disease 2019 (COVID-19) pandemic, many pediatric neurologists have switched to telemedicine visits for nonemergent outpatient evaluations. We present a series of children diagnosed as having CAE on the basis of a positive hyperventilation test performed during remote televisits. Several of these children were begun on treatment for CAE prior to obtaining an EEG, with significant seizure reduction. Our series documents the feasibility of CAE diagnosis and management by telemedicine.


Assuntos
Anticonvulsivantes/uso terapêutico , COVID-19/prevenção & controle , Gerenciamento Clínico , Epilepsia Tipo Ausência/diagnóstico , Epilepsia Tipo Ausência/tratamento farmacológico , Telemedicina/métodos , COVID-19/epidemiologia , Criança , Pré-Escolar , Eletroencefalografia/métodos , Eletroencefalografia/tendências , Epilepsia Tipo Ausência/epidemiologia , Feminino , Humanos , Hiperventilação/diagnóstico , Hiperventilação/epidemiologia , Masculino , Neurologistas/tendências , Pediatras/tendências , SARS-CoV-2 , Telemedicina/tendências , Ácido Valproico/uso terapêutico
7.
Curr Neurol Neurosci Rep ; 19(1): 5, 2019 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-30712068

RESUMO

PURPOSE OF REVIEW: After decades of hype, cell-based therapies are emerging into the clinical arena for the purposes of promoting recovery after stroke. In this review, we discuss the most recent science behind the role of cell-based therapies in ischemic stroke and the efforts to translate these therapies into human clinical trials. RECENT FINDINGS: Preclinical data support numerous beneficial effects of cell-based therapies in both small and large animal models of ischemic stroke. These benefits are driven by multifaceted mechanisms promoting brain repair through immunomodulation, trophic support, circuit reorganization, and cell replacement. Cell-based therapies offer tremendous potential for improving outcomes after stroke through multimodal support of brain repair. Based on recent clinical trials, cell-based therapies appear both feasible and safe in all phases of stroke. Ongoing translational research and clinical trials will further refine these therapies and have the potential to transform the approach to stroke recovery and rehabilitation.


Assuntos
Isquemia Encefálica/terapia , Encéfalo/fisiologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Regeneração Nervosa/fisiologia , Acidente Vascular Cerebral/terapia , Animais , Encéfalo/patologia , Isquemia Encefálica/patologia , Terapia Baseada em Transplante de Células e Tecidos/tendências , Humanos , Transplante de Células-Tronco/métodos , Transplante de Células-Tronco/tendências , Acidente Vascular Cerebral/patologia , Pesquisa Translacional Biomédica/métodos , Pesquisa Translacional Biomédica/tendências
8.
Neurogenesis (Austin) ; 3(1): e1168504, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27605441

RESUMO

Brain development involves multiple levels of molecular coordination in forming a functional nervous system. The hippocampus is a brain area that is important for memory formation and spatial reasoning. During early postnatal development of the hippocampal circuit, Fibroblast growth factor 22 (FGF22) and FGF7 act to establish a balance of excitatory and inhibitory tone. Both FGFs are secreted from CA3 dendrites, acting on excitatory or inhibitory axon terminals formed onto CA3 dendrites, respectively. Mechanistically, FGF22 utilizes FGFR2b and FGFR1b to induce synaptic vesicle recruitment within axons of dentate granule cells (DGCs), and FGF7 utilizes FGFR2b to induce synaptic vesicle recruitment within interneuron axons. FGF signaling eventually induces gene expression in the presynaptic neurons; however, the effects of FGF22-induced gene expression within DGCs and FGF7-induced gene expression within interneurons in the context of a developing hippocampal circuit have yet to be explored. Here, we propose one hypothetical mechanism of FGF22-induced gene expression in controlling adult neurogenesis.

9.
Development ; 142(10): 1818-30, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25926357

RESUMO

Neurons in the brain must establish a balanced network of excitatory and inhibitory synapses during development for the brain to function properly. An imbalance between these synapses underlies various neurological and psychiatric disorders. The formation of excitatory and inhibitory synapses requires precise molecular control. In the hippocampus, the structure crucial for learning and memory, fibroblast growth factor 22 (FGF22) and FGF7 specifically promote excitatory or inhibitory synapse formation, respectively. Knockout of either Fgf gene leads to excitatory-inhibitory imbalance in the mouse hippocampus and manifests in an altered susceptibility to epileptic seizures, underscoring the importance of FGF-dependent synapse formation. However, the receptors and signaling mechanisms by which FGF22 and FGF7 induce excitatory and inhibitory synapse differentiation are unknown. Here, we show that distinct sets of overlapping FGF receptors (FGFRs), FGFR2b and FGFR1b, mediate excitatory or inhibitory presynaptic differentiation in response to FGF22 and FGF7. Excitatory presynaptic differentiation is impaired in Fgfr2b and Fgfr1b mutant mice; however, inhibitory presynaptic defects are only found in Fgfr2b mutants. FGFR2b and FGFR1b are required for an excitatory presynaptic response to FGF22, whereas only FGFR2b is required for an inhibitory presynaptic response to FGF7. We further find that FGFRs are required in the presynaptic neuron to respond to FGF22, and that FRS2 and PI3K, but not PLCγ, mediate FGF22-dependent presynaptic differentiation. Our results reveal the specific receptors and signaling pathways that mediate FGF-dependent presynaptic differentiation, and thereby provide a mechanistic understanding of precise excitatory and inhibitory synapse formation in the mammalian brain.


Assuntos
Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Sinapses/metabolismo , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Células Cultivadas , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Camundongos , Camundongos Knockout , Neurogênese/genética , Neurogênese/fisiologia , Neurônios/citologia , Neurônios/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética
10.
Clin Cancer Res ; 17(13): 4309-19, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21565982

RESUMO

PURPOSE: The type I Melanoma Antigen GEnes (MAGEs) are commonly expressed in cancers, fueling speculation that they may be therapeutic targets with oncogenic potential. They form complexes with RING domain proteins that have E3 ubiquitin ligase activity and promote p53 degradation. MAGE-A3 was detected in tumor specimens from patients with multiple myeloma and its expression correlated with higher frequencies of Ki-67(+) malignant cells. In this report, we examine the mechanistic role of MAGE-A in promoting survival of proliferating multiple myeloma cells. EXPERIMENTAL DESIGN: The impact of MAGE-A3 expression on survival and proliferation in vivo was examined by immunohistochemical analysis in an independent set of tumor specimens segregated into two groups: newly diagnosed, untreated patients and patients who had relapsed after chemotherapy. The mechanisms of MAGE-A3 activity were investigated in vitro by silencing its expression by short hairpin RNA interference in myeloma cell lines and primary cells and assessing the resultant effects on proliferation and apoptosis. RESULTS: MAGE-A3 was detected in a significantly higher percentage of relapsed patients compared with newly diagnosed, establishing a novel correlation with progression of disease. Silencing of MAGE-A showed that it was dispensable for cell cycling, but was required for survival of proliferating myeloma cells. Loss of MAGE-A led to apoptosis mediated by p53-dependent activation of proapoptotic Bax expression and by reduction of survivin expression through both p53-dependent and -independent mechanisms. CONCLUSIONS: These data support a role for MAGE-A in the pathogenesis and progression of multiple myeloma by inhibiting apoptosis in proliferating myeloma cells through two novel mechanisms.


Assuntos
Antígenos de Neoplasias/metabolismo , Apoptose , Regulação Neoplásica da Expressão Gênica , Proteínas Inibidoras de Apoptose/metabolismo , Mieloma Múltiplo/metabolismo , Proteínas de Neoplasias/metabolismo , Proteína X Associada a bcl-2/metabolismo , Antígenos de Neoplasias/genética , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Feminino , Inativação Gênica , Humanos , Proteínas Inibidoras de Apoptose/genética , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Proteínas de Neoplasias/genética , Transdução de Sinais/genética , Survivina , Proteína Supressora de Tumor p53/metabolismo
11.
J Biochem ; 149(6): 641-53, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21508038

RESUMO

The establishment of a functional brain requires coordinated and stereotyped formation of synapses between neurons. For this, trans-synaptic molecular cues (synaptic organizers) are exchanged between a neuron and its target to organize appropriate synapses. The understanding of signalling mechanisms by which such synaptic organizers lead to synapse formation is just being elucidated. However, recent studies revealed that some of these cues act through receptor protein tyrosine kinases (RPTKs) or phosphatases (RPTPs). Synaptogenic RPTKs and RPTPs pattern synaptic network through affecting local protein-protein binding dynamics, changing the phosphorylation state of signalling cascades, or promoting gene expression. Each RPTK or RPTP has distinct roles in synapse formation, serving at different synapses or showing differential synaptogenic effects. Thus, tyrosine phosphorylation signalling plays critical roles in building the orchestrated synaptic circuitry in the brain.


Assuntos
Transdução de Sinais , Sinapses/metabolismo , Tirosina/metabolismo , Animais , Humanos , Modelos Biológicos , Neurônios/metabolismo , Fosforilação , Proteínas Tirosina Fosfatases/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo
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