RESUMO
Healthcare organizations have prioritized patient safety and quality improvement efforts to reduce central line-associated bloodstream infections (CLABSIs). Implementation of central venous catheter (CVC) insertion and maintenance bundles have significantly reduced infection rates. Nevertheless, CLABSIs continue to be a significant cause of mortality and morbidity in hospitals, and further efforts are necessary to improve CVC care practices. A hospital-wide committee at a tertiary care pediatric hospital identified gaps in our CVC maintenance practices resulting from CVC contamination events from a patient's body fluids. A lack of published literature on the topic resulted in the need to create an institutional clinical practice guideline (CPG) to develop guidance to mitigate potential CLASBIs from CVC contamination. Utilization of the CVC CPG in all inpatient units and other reduction strategies resulted in a steady decline in our CLABSI rates, particularly in those related to CVC contamination events. Case reports illustrate the effectiveness of the CPG.
Assuntos
Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Cateteres Venosos Centrais , Sepse , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Criança , Hospitais , Humanos , Melhoria de Qualidade , Sepse/prevenção & controleRESUMO
OBJECTIVES: The scope of transcranial Doppler ultrasound in the practice of pediatric neurocritical care is unknown. We have surveyed pediatric neurocritical care centers on their use of transcranial Doppler and analyzed clinical management practices. DESIGN: Electronic-mail recruitment with survey of expert centers using web-based questionnaire. SETTING: Survey of 43 hospitals (31 United States, 12 international) belonging to the Pediatric Neurocritical Care Research Group. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A 67% (29/43) hospital-response rate. Of these centers, 27 reported using transcranial Doppler in the PICU; two hospitals opted out due to lack of transcranial Doppler availability/use. The most common diagnoses for using transcranial Doppler in clinical care were intracranial/subarachnoid hemorrhage (20 hospitals), arterial ischemic stroke (14 hospitals), and traumatic brain injury (10 hospitals). Clinical studies were carried out and interpreted by credentialed individuals in 93% (25/27) and 78% (21/27) of the centers, respectively. A written protocol for performance of transcranial Doppler in the PICU was available in 30% (8/27 hospitals); of these, two of eight hospitals routinely performed correlation studies to validate results. In 74% of the centers (20/27), transcranial Doppler results were used to guide clinical care: that is, when to obtain a neuroimaging study (18 hospitals); how to manipulate cerebral perfusion pressure with fluids/vasopressors (13 hospitals); and whether to perform a surgical intervention (six hospitals). Research studies were also commonly performed for a range of diagnoses. CONCLUSIONS: At least 27 pediatric neurocritical care centers use transcranial Doppler during clinical care. In the majority of centers, studies are performed and interpreted by credentialed personnel, and findings are used to guide clinical management. Further studies are needed to standardize these practices.
Assuntos
Cuidados Críticos/métodos , Ultrassonografia Doppler Transcraniana/métodos , Lesões Encefálicas Traumáticas/diagnóstico , Circulação Cerebrovascular , Criança , Estado Terminal , Hospitais , Humanos , Unidades de Terapia Intensiva Pediátrica , Pediatria/normas , Guias de Prática Clínica como Assunto , Acidente Vascular Cerebral/diagnóstico , Hemorragia Subaracnóidea/diagnóstico , Inquéritos e QuestionáriosRESUMO
PURPOSE: Intracranial hypertension (ICH) is a common and treatable complication after severe traumatic brain injury (sTBI) in children. Describing the incidence and risk factors for developing ICH after sTBI could impact clinical practice. METHODS: Retrospective cohort study from 2006 to 2015 at two university-affiliated level I pediatric trauma centers of children admitted with accidental or abusive TBI, a post-resuscitation Glasgow Coma Score (GCS) of 8 or less, and an invasive intracranial pressure (ICP) monitor. Bivariate and multivariable logistic regression analysis were performed to identify demographic, injury, and imaging characteristics in patients who received ICP directed therapies for ICH (ICP > 20 mmHg). RESULTS: Eight to 5% (271/321) of monitored patients received ICP directed therapy for ICH during their PICU stay. Ninety-seven percent of patients had an abnormality on CT scan by either the Marshall or the Rotterdam score. Of the analyzed clinical and radiologic variables, only presence of hypoxia prior to PICU arrival, female sex, and a higher Injury Severity Score (ISS) were associated with increased risk of ICH (p < 0.05). CONCLUSIONS: In this retrospective study of clinical practice of ICP monitoring in children after sTBI, the vast majority of children had an abnormal CT scan and experienced ICH requiring clinical intervention. Commonly measured clinical variables and radiologic classification scores did not significantly add to the prediction for developing of ICH and further efforts are needed to define low-risk populations that would not develop ICH.
Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Hipertensão Intracraniana , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Criança , Feminino , Escala de Coma de Glasgow , Humanos , Hipertensão Intracraniana/diagnóstico por imagem , Hipertensão Intracraniana/etiologia , Pressão Intracraniana , Monitorização Fisiológica , Estudos RetrospectivosRESUMO
OBJECTIVES: We analyzed a prospective database of pediatric traumatic brain injury patients to identify predictors of outcome and describe the change in function over time. We hypothesized that neurologic status at hospital discharge would not reflect the long-term neurologic recovery state. DESIGN: This is a descriptive cohort analysis of a single-center prospective database of pediatric traumatic brain injury patients from 2001 to 2012. Functional outcome was assessed at hospital discharge, and the Glasgow Outcome Scale Extended Pediatrics or Glasgow Outcome Scale was assessed on average at 15.8 months after injury. SETTING: Children's Medical Center Dallas, a single-center PICU and Level 1 Trauma Center. PATIENTS: Patients, 0-17 years old, with complicated-mild/moderate or severe accidental traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Dichotomized long-term outcome was favorable in 217 of 258 patients (84%), 80 of 82 patients (98%) with complicated-mild/moderate injury and 133 of 172 severe patients (77%). In the bivariate analysis, younger age, motor vehicle collision as a mechanism of injury, intracranial pressure monitor placement, cardiopulmonary resuscitation at scene or emergency department, increased hospital length of stay, increased ventilator days (all with p < 0.01) and occurrence of seizures (p = 0.03) were significantly associated with an unfavorable outcome. In multiple regression analysis, younger age (p = 0.03), motor vehicle collision (p = 0.01), cardiopulmonary resuscitation (p < 0.01), and ventilator days (p < 0.01) remained significant. Remarkably, 28 of 60 children (47%) with an unfavorable Glasgow Outcome Scale at hospital discharge improved to a favorable outcome. In severe patients with an unfavorable outcome at hospital discharge, younger age was identified as a risk factor for remaining in an unfavorable condition (p = 0.1). CONCLUSIONS: Despite a poor neurologic status at hospital discharge, many children after traumatic brain injury will significantly improve at long-term assessment. The factors most associated with outcomes were age, cardiopulmonary resuscitation, motor vehicle collision, intracranial pressure placement, days on a ventilator, hospital length of stay, and seizures. The factor most associated with improvement from an unfavorable neurologic status at discharge was being older.
Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Avaliação da Deficiência , Feminino , Escala de Resultado de Glasgow , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica , Masculino , Avaliação de Resultados em Cuidados de Saúde , Alta do Paciente , Prognóstico , Estudos Prospectivos , Recuperação de Função Fisiológica , Centros de TraumatologiaRESUMO
BACKGROUND: There is a lack of data describing the risk factors for extubation failure (EF) or tracheostomy placement in pediatric neurocritical care (NCC) patients. METHODS: A retrospective chart review of children admitted to the pediatric intensive care unit who were intubated for >24 h with an acute neurocritical illness and had an extubation attempt. Bivariate and multivariate statistical analysis was performed to determine significant associations of demographic, neurologic, pulmonary, and clinical variables with EF and tracheostomy placement. Analysis of predictive factors for EF (within 48 h) and tracheostomy placement during the hospitalization was conducted on a first extubation attempt group (n = 193) and a second attempt group (n = 23) who experienced either EF or a "late re-intubation" (>48 h-7 days). RESULTS: Traumatic brain injury (37.3%) and seizures/status epilepticus (31.4%) were the most common diagnoses with neuromuscular weakness patients having the highest risk for EF and tracheostomy placement. EF occurred in 20/193 (10.4%) patients after their first attempt and 6/23 (26.1%) after a second attempt. Compared to those with a fair/strong cough, patients with a weak/absent cough had a relative risk (RR) of 9.4 for EF (95% CI, 4.9-17.9, p < 0.001) and 6.7 (95% CI, 2.3-18.9, p = 0.01) for tracheostomy placement on the first and second attempts, respectively. Glasgow Coma Score (GCS), endotracheal tube (ETT) secretion characteristics, and pulmonary variables were not associated with EF or tracheostomy placement. CONCLUSIONS: A weak/absent cough reflex is associated with an increased risk of failing extubation and placement of a tracheostomy in intubated pediatric NCC patients.
Assuntos
Extubação/estatística & dados numéricos , Unidades de Terapia Intensiva Pediátrica , Intubação Intratraqueal/estatística & dados numéricos , Doenças do Sistema Nervoso/terapia , Respiração Artificial/estatística & dados numéricos , Traqueostomia/estatística & dados numéricos , Lesões Encefálicas Traumáticas/terapia , Criança , Pré-Escolar , Estado Terminal , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , Estado Epiléptico/terapiaRESUMO
OBJECTIVES: Small series have suggested that outcomes after abusive head trauma are less favorable than after other injury mechanisms. We sought to determine the impact of abusive head trauma on mortality and identify factors that differentiate children with abusive head trauma from those with traumatic brain injury from other mechanisms. DESIGN: First 200 subjects from the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial-a comparative effectiveness study using an observational, cohort study design. SETTING: PICUs in tertiary children's hospitals in United States and abroad. PATIENTS: Consecutive children (age < 18 yr) with severe traumatic brain injury (Glasgow Coma Scale ≤ 8; intracranial pressure monitoring). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, injury-related scores, prehospital, and resuscitation events were analyzed. Children were dichotomized based on likelihood of abusive head trauma. A total of 190 children were included (n = 35 with abusive head trauma). Abusive head trauma subjects were younger (1.87 ± 0.32 vs 9.23 ± 0.39 yr; p < 0.001) and a greater proportion were female (54.3% vs 34.8%; p = 0.032). Abusive head trauma were more likely to 1) be transported from home (60.0% vs 33.5%; p < 0.001), 2) have apnea (34.3% vs 12.3%; p = 0.002), and 3) have seizures (28.6% vs 7.7%; p < 0.001) during prehospital care. Abusive head trauma had a higher prevalence of seizures during resuscitation (31.4 vs 9.7%; p = 0.002). After adjusting for covariates, there was no difference in mortality (abusive head trauma, 25.7% vs nonabusive head trauma, 18.7%; hazard ratio, 1.758; p = 0.60). A similar proportion died due to refractory intracranial hypertension in each group (abusive head trauma, 66.7% vs nonabusive head trauma, 69.0%). CONCLUSIONS: In this large, multicenter series, children with abusive head trauma had differences in prehospital and in-hospital secondary injuries which could have therapeutic implications. Unlike other traumatic brain injury populations in children, female predominance was seen in abusive head trauma in our cohort. Similar mortality rates and refractory intracranial pressure deaths suggest that children with severe abusive head trauma may benefit from therapies including invasive monitoring and adherence to evidence-based guidelines.
Assuntos
Lesões Encefálicas Traumáticas/epidemiologia , Maus-Tratos Infantis/estatística & dados numéricos , Adolescente , Lesões Encefálicas Traumáticas/classificação , Criança , Pré-Escolar , Feminino , Escala de Coma de Glasgow , Hospitais Pediátricos , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Fatores Socioeconômicos , Estados UnidosRESUMO
INTRODUCTION: We sought to determine if a family-centered care (FCC) handout intervention designed to encourage family engagement (FE) in the prevention of central line-associated bloodstream infections (CLABSIs) would alter parental perceptions of FCC and improve staff compliance with CLABSI bundle components. METHODS: A prospective quasiexperimental study of 121 legal guardians of children with a central venous catheter (CVC) admitted to the pediatric intensive care unit (PICU). Baseline (n = 59) and intervention (n = 62) groups of parents completed an 18-question online survey assessing basic CLABSI care practices and FCC principles. The intervention group received an FE handout before completing the survey with information about CLABSI prevention practices designed to encourage active participation in their child's CVC care. RESULTS: Independent sample t-tests found significant improvements in the intervention parents responses compared to the baseline group (no handout) on survey items assessing CLABSI knowledge (P < 0.001) and on parental perceptions of FCC in the domains of dignity and respect, information sharing, participation, and partnership (all with a P < 0.001). An improvement was observed in staff CLABSI maintenance bundle compliance in the postintervention period, increasing from 89% to 94%. CONCLUSIONS: Educating parents on CLABSI prevention strategies and encouraging family participation in CVC care was associated with improved parental perceptions of participation in their child's care, medical team's listening, attention, honesty, and explanation of treatment plans and was associated with an increase in staff compliance with CLABSI maintenance bundle practices.
RESUMO
BACKGROUND: Autoimmune encephalitis (AE) and acute disseminated encephalomyelitis (ADEM) are immune-mediated brain conditions that can cause substantial neurological sequalae. Data describing the clinical characteristics, treatments, and neurological outcomes for these conditions are needed. METHODS: This is a single-center retrospective review of children diagnosed with AE or ADEM over a nine-year period with discharge outcomes measured by the Modified Rankin Score. RESULTS: Seventy-five patients (23 with ADEM and 52 with AE) were identified. Patients with ADEM had a higher percentage of abnormal magnetic resonance imaging findings (100% vs 60.8%; P < 0.001) and a shorter time from symptom onset to diagnosis (6 vs 14 days; P = 0.024). Oligoclonal bands and serum and cerebrospinal fluid inflammatory indices were higher in patients with AE. Nearly all patients received corticosteroids followed by plasmapheresis or intravenous immunoglobulin, and treatment strategies did not differ significantly between groups. Second-line immune therapies were commonly used in patients with AE. Finally, patients with AE had trends toward longer hospital lengths of stay (21 vs 13 days) and a higher percentage of neurological disability at hospital discharge (59.6% vs 34.8%). CONCLUSIONS: Although patients with ADEM and AE may have similar presenting symptoms, we found significant differences in the frequency of imaging findings, symptom duration, and laboratory and cerebrospinal fluid profiles, which can assist in distinguishing between the diagnoses. Patients in both groups were treated with a combination of immunomodulating therapies, and neurological disability was common at hospital discharge.
Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalite , Adolescente , Doenças Autoimunes do Sistema Nervoso/diagnóstico por imagem , Doenças Autoimunes do Sistema Nervoso/metabolismo , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Doenças Autoimunes do Sistema Nervoso/terapia , Criança , Pré-Escolar , Encefalite/diagnóstico por imagem , Encefalite/metabolismo , Encefalite/fisiopatologia , Encefalite/terapia , Encefalomielite Aguda Disseminada/diagnóstico por imagem , Encefalomielite Aguda Disseminada/metabolismo , Encefalomielite Aguda Disseminada/fisiopatologia , Encefalomielite Aguda Disseminada/terapia , Feminino , Hospitalização , Humanos , Imageamento por Ressonância Magnética , Masculino , Avaliação de Resultados em Cuidados de Saúde , Troca Plasmática , Estudos RetrospectivosRESUMO
Transcranial Doppler ultrasonography (TCD) is being used in many pediatric intensive care units (PICUs) to aid in the diagnosis and monitoring of children with known or suspected pathophysiological changes to cerebral hemodynamics. Standardized approaches to scanning protocols, interpretation, and documentation of TCD examinations in this setting are lacking. A panel of multidisciplinary clinicians with expertise in the use of TCD in the PICU undertook a three-round modified Delphi process to reach unanimous agreement on 34 statements and then create practice recommendations for TCD use in the PICU. Use of these recommendations will help to ensure that high quality TCD images are captured, interpreted, and reported using standard nomenclature. Furthermore, use will aid in ensuring reproducible and meaningful study results between TCD practitioners and across PICUs.
RESUMO
The mechanisms underlying the formation of the glial scar after injury are poorly understood. In this report, we demonstrate that after cortical injury Olig2 is upregulated in reactive astrocytes coincident with proliferation of these cells. Short-term lineage tracing studies with glial subtype-restricted transgenic reporter lines indicate that Olig2-expressing cells in the astroglial but not the oligodendroglial lineage are the essential source of reactive astrocytes. In addition, cortical Olig2 ablation results in a decrease in proliferation of reactive astrocytes in response to injury. Cell-type-specific mutagenesis indicates that Olig2 ablation in GFAP+ astrocytes and their precursors rather than in neuronal or oligodendroglial cells is responsible for the reduction of reactive astrocyte proliferation. Thus, our studies suggest that Olig2 is critical for postinjury gliosis.
Assuntos
Astrócitos/fisiologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Lesões Encefálicas/patologia , Proliferação de Células , Córtex Cerebral/patologia , Regulação da Expressão Gênica/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Análise de Variância , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Linhagem da Célula , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Filamentos Intermediários/metabolismo , Camundongos , Camundongos Mutantes , Proteína Básica da Mielina/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Nestina , Fator de Transcrição 2 de Oligodendrócitos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismoRESUMO
OBJECTIVE: There is no consensus on the optimal timing and specific brain MRI sequences in the evaluation and management of severe pediatric traumatic brain injury (TBI), and information on current practices is lacking. The authors performed a survey of MRI practices among sites participating in a multicenter study of severe pediatric TBI to provide information for designing future clinical trials using MRI to assess brain injury after severe pediatric TBI. METHODS: Information on current imaging practices and resources was collected from 27 institutions participating in the Approaches and Decisions after Pediatric TBI Trial. Multiple-choice questions addressed the percentage of patients with TBI who have MRI studies, timing of MRI, MRI sequences used to investigate TBI, as well as the magnetic field strength of MR scanners used at the participating institutions and use of standardized MRI protocols for imaging after severe pediatric TBI. RESULTS: Overall, the reported use of MRI in pediatric patients with severe TBI at participating sites was high, with 40% of sites indicating that they obtain MRI studies in > 95% of this patient population. Differences were observed in the frequency of MRI use between US and international sites, with the US sites obtaining MRI in a higher proportion of their pediatric patients with severe TBI (94% of US vs 44% of international sites reported MRI in at least 70% of patients with severe TBI). The reported timing and composition of MRI studies was highly variable across sites. Sixty percent of sites reported typically obtaining an MRI study within the first 7 days postinjury, with the remainder of responses distributed throughout the first 30-day postinjury period. Responses indicated that MRI sequences sensitive for diffuse axonal injury and ischemia are frequently obtained in patients with TBI, whereas perfusion imaging and spectroscopy techniques are less common. CONCLUSIONS: Results from this survey suggest that despite the lack of consensus or guidelines, MRI is commonly obtained during the acute clinical setting after severe pediatric TBI. The variation in MRI practices highlights the need for additional studies to determine the utility, optimal timing, and composition of clinical MRI studies after TBI. The information in this survey describes current clinical MRI practices in children with severe TBI and identifies important challenges and objectives that should be considered when designing future studies.
Assuntos
Lesões Encefálicas Traumáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Lesões Encefálicas Traumáticas/epidemiologia , Criança , Pré-Escolar , Europa (Continente) , Feminino , Escala de Coma de Glasgow , Saúde Global , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Avaliação de Resultados em Cuidados de Saúde , Fatores de Tempo , Estados UnidosRESUMO
Although the phenomenon of ongoing neurogenesis in the hippocampus is well described, it remains unclear what relevance this has in terms of brain self-repair following injury. In a highly regulated developmental program, new neurons are added to the inner granular cell layer of the dentate gyrus (DG) where slowly dividing radial glial-like type 1 neural stem/progenitors (NSPs) give rise to rapidly proliferating type 2 neural progenitors which undergo selection and maturation into functional neurons. The induction of these early hippocampal progenitors after injury may represent an endogenous mechanism for brain recovery and remodeling. To determine what role early hippocampal progenitors play in remodeling following injury, we utilized a model of hypoxic-ischemic injury on young transgenic mice that express green fluorescent protein (GFP) specifically in neural progenitors. We demonstrate that this injury selectively activates programmed cell death in committed but immature neuroblasts, which is followed by proliferation of both early type 1 and later type 2 progenitors. This subsequently leads to newly generated neurons becoming stably incorporated into the DG.
Assuntos
Lesões Encefálicas/patologia , Hipocampo/patologia , Hipóxia-Isquemia Encefálica/patologia , Neurônios/patologia , Células-Tronco/patologia , Animais , Apoptose , Astrócitos/metabolismo , Astrócitos/patologia , Lesões Encefálicas/genética , Lesões Encefálicas/metabolismo , Diferenciação Celular , Proliferação de Células , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/lesões , Hipocampo/metabolismo , Hipóxia-Isquemia Encefálica/genética , Hipóxia-Isquemia Encefálica/metabolismo , Proteínas de Filamentos Intermediários/genética , Proteínas de Filamentos Intermediários/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Nestina , Neurônios/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Células-Tronco/classificação , Células-Tronco/metabolismoRESUMO
Extracorporeal membrane oxygenation (ECMO) is a form of advanced cardiorespiratory support provided to critically ill patients with severe respiratory or cardiovascular failure. While children undergoing ECMO therapy have significant risk for neurological morbidity, currently there is a lack of reliable bedside tool to detect the neurologic events for patients on ECMO. This study assessed the feasibility of frequency-domain near-infrared spectroscopy (NIRS) for detection of intracranial complications during ECMO therapy. The frequency-domain NIRS device measured the absorption coefficient (µa) and reduced scattering coefficient (µs') at six cranial positions from seven pediatric patients (0-16 years) during ECMO support and five healthy controls (2-14 years). Regional abnormalities in both absorption and scattering were identified among ECMO patients. A main finding in this study is that the abnormalities in scattering appear to be associated with lower-than-normal µs' values in regional areas of the brain. Because light scattering originates from the intracellular structures (such as nuclei and mitochondria), a reduction in scattering primarily reflects loss or decreased density of the brain matter. The results from this study indicate a potential to use the frequency-domain NIRS as a safe and complementary technology for detection of intracranial complications during ECMO therapy.
Assuntos
Encefalopatias/diagnóstico , Oxigenação por Membrana Extracorpórea/efeitos adversos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adolescente , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Luz , Masculino , Espalhamento de RadiaçãoRESUMO
Brain lesions after traumatic brain injury (TBI) are heterogeneous, rendering outcome prognostication difficult. The aim of this study is to investigate whether early magnetic resonance imaging (MRI) of lesion location and lesion volume within discrete brain anatomical zones can accurately predict long-term neurological outcome in children post-TBI. Fluid-attenuated inversion recovery (FLAIR) MRI hyperintense lesions in 63 children obtained 6.2±5.6 days postinjury were correlated with the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score at 13.5±8.6 months. FLAIR lesion volume was expressed as hyperintensity lesion volume index (HLVI)=(hyperintensity lesion volume / whole brain volume)×100 measured within three brain zones: zone A (cortical structures); zone B (basal ganglia, corpus callosum, internal capsule, and thalamus); and zone C (brainstem). HLVI-total and HLVI-zone C predicted good and poor outcome groups (p<0.05). GOS-E Peds correlated with HLVI-total (r=0.39; p=0.002) and HLVI in all three zones: zone A (r=0.31; p<0.02); zone B (r=0.35; p=0.004); and zone C (r=0.37; p=0.003). In adolescents ages 13-17 years, HLVI-total correlated best with outcome (r=0.5; p=0.007), whereas in younger children under the age of 13, HLVI-zone B correlated best (r=0.52; p=0.001). Compared to patients with lesions in zone A alone or in zones A and B, patients with lesions in all three zones had a significantly higher odds ratio (4.38; 95% confidence interval, 1.19-16.0) for developing an unfavorable outcome.
Assuntos
Lesões Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos , Avaliação de Resultados em Cuidados de Saúde , Adolescente , Fatores Etários , Gânglios da Base/patologia , Biomarcadores , Tronco Encefálico/patologia , Córtex Cerebral/patologia , Criança , Pré-Escolar , Corpo Caloso/patologia , Feminino , Escala de Resultado de Glasgow , Humanos , Lactente , Cápsula Interna/patologia , Masculino , Prognóstico , Tálamo/patologiaRESUMO
Patterns of hypoxic-ischemic brain injury in infants and children suggest vulnerability in regions of white matter development, and injured patients develop defects in myelination resulting in cerebral palsy and motor deficits. Reperfusion exacerbates the oxidative stress that occurs after such injuries and may impair recovery. Resuscitation after hypoxic-ischemic injury is routinely performed using 100% oxygen, and this practice may increase the oxidative stress that occurs during reperfusion and further damage an already compromised brain. We show that brief exposure (30 mins) to 100% oxygen during reperfusion worsens the histologic injury in young mice after unilateral brain hypoxia-ischemia, causes an accumulation of the oxidative metabolite nitrotyrosine, and depletes preoligodendrocyte glial progenitors present in the cortex. This damage can be reversed with administration of the antioxidant ebselen, a glutathione peroxidase mimetic. Moreover, mice recovered in 100% oxygen have a more disrupted pattern of myelination and develop a static motor deficit that mimics cerebral palsy and manifests itself by significantly worse performance on wire hang and rotorod motor testing. We conclude that exposure to 100% oxygen during reperfusion after hypoxic-ischemic brain injury increases secondary neural injury, depletes developing glial progenitors, interferes with myelination, and ultimately impairs functional recovery.
Assuntos
Hiperóxia/complicações , Hipóxia-Isquemia Encefálica , Neuroglia/patologia , Recuperação de Função Fisiológica , Células-Tronco/patologia , Animais , Córtex Cerebral/patologia , Doenças Desmielinizantes/etiologia , Camundongos , Oxigênio/administração & dosagem , Oxigênio/efeitos adversosRESUMO
Adult neural stem and progenitor cells may help remodel the brain in response to injury. The pro-apoptotic molecule Bax has recently been identified as a key player in adult neural stem cell survival. In Bax-deficient mice that have undergone traumatic brain injury, we find increased numbers of neural progenitor cells in the dentate gyrus and improved remodeling of the hippocampus. Exogenous potassium chloride mimics spreading depression (SD)-like events in vitro, and Bax-deficient neural stem cells proliferate in response to these events more robustly than wild-type neural stem cells. Selective potassium channel blockers interrupt SD-mediated stimulation of stem cells. In addition, the potassium channel Kv4.1 is expressed within neural stem and progenitor cells in the dentate gyrus and is increased in Bax-deficiency. These data suggest that the neuroprotection observed after injury in Bax-deficiency may be due to increased neurogenesis via activation of the Kv4 family of potassium channels.