Child neurology: a separate and necessary discipline.
Explore the source record for details and available documents.
Child↗
Biomedical subjects
Stephen Ashwal
Publications and source records attributed to Stephen Ashwal.
Comparison of two neonatal ischemic injury models using magnetic resonance imaging.
Using an 11.7-Tesla magnetic resonance imaging (MRI) scanner in 10-d-old rat pups we report on the evolution of injury over 28 d in a model of neonatal stroke (transient filament middle cerebral artery occlusion, tfMCAO) and a model of hypoxic-ischemic injury (Rice-Vannucci model, RVM). In both models, diffusion-weighted imaging (DWI) was more sensitive in the early detection of ischemia than T2-weighted imaging (T2WI). Injury volumes in both models were greater on d 1 for DWI and d 3 for T2WI, decreased over time and by d 28 T2WI injury volumes (tfMCAO 10.3% of ipsilateral hemisphere; RVM 23.9%) were definable. The distribution of injury with tfMCAO was confined to the vascular territory of the middle cerebral artery and a definable core and penumbra evolved over time. Ischemic injury in the RVM was more generalized and greater in cortical regions. Contralateral hemispheric involvement was only observed in the RVM. Our findings demonstrate that high-field MRI over extended periods of time is possible in a small animal model of neonatal brain injury and that the tfMCAO model should be used for studies of neonatal stroke and that the RVM does not reflect the vascular distribution of injury seen with focal ischemia.
Animals↗
Prospective longitudinal proton magnetic resonance spectroscopic imaging in adult traumatic brain injury.
PURPOSE: To investigate whether longitudinal magnetic resonance proton spectroscopic imaging (MRSI) demonstrates regional metabolite abnormalities after traumatic brain injury (TBI) that predict long-term neurologic outcome. MATERIALS AND METHODS: Two-dimensional-MRSI (point resolved spectroscopy sequence [PRESS]; TR/TE = 3000/144 msec; 10 mm) was acquired prospectively in 42 adults with severe TBI through the level of the corpus callosum 7 +/- 4 days after injury. Measurements were repeated in 31 patients six to 12 months after injury. Regional and pooled (all regions combined) mean ratios were compared with control values and then used to predict long-term (six- to -12-month) neurologic outcome (good vs. poor) using a logistic regression model. RESULTS: Initial pooled mean N-acetylaspartate (NAA) ratios were lower (P < 0.01) and choline (Cho)/creatine (Cr) ratios higher (P < 0.01) in all TBI patients compared to controls. Ratios from the corpus callosum region were affected most and predicted long-term dichotomized outcome with 83% accuracy. When repeated at six to 12 months after injury, pooled mean NAA/Cr remained lower (P = 0.03) and Cho/Cr remained higher (P = 0.01) in patients with poor outcomes. CONCLUSION: The NAA/Cr ratio from the corpus callosum was most useful for outcome prediction. Chronic alterations of metabolite ratios are likely due to neuronal loss and glial proliferation long after injury.
Adolescent↗
MR spectroscopy: predicting long-term neuropsychological outcome following pediatric TBI.
PURPOSE: To identify useful acute indicators of long-term neurocognitive outcome beyond clinical variables for children and adolescents treated for a traumatic brain injury (TBI). MATERIALS AND METHODS: The efficacy of magnetic resonance spectroscopy (MRS) acquired 6+/-4 days after TBI in 20 children/adolescents in predicting intellectual and neuropsychological functioning one to four years post injury was assessed. Short echo-time single voxel MRS (SVS) from normal-appearing brain was compared to intermediate echo-time multivoxel MR spectroscopic imaging (MRSI) from normal-appearing and visibly-injured brain acquired through the level of the corpus callosum (CC). RESULTS: N-acetyl aspartate (NAA) was moderate to strongly correlated with cognitive scores. Mean NAA/creatine (Cre) from MRSI alone explained over 40% of the variance in cognitive scores and 18% of the variance above and beyond demographic and clinical variables alone. Mild to moderate associations were noted between SVS metabolites (glutamate/glutamine [Glx] and myoinositol [mI]) and cognitive scores, with no such associations apparent for choline (Cho) or Cre. Exploratory analyses revealed trends for regional neuroimaging data and specific cognitive abilities. CONCLUSION: Acute MR spectroscopy of the pediatric brain injury patient improves prognostic ability and may provide valuable information for early treatment and intervention planning.
Adolescent↗
Susceptibility-weighted imaging and proton magnetic resonance spectroscopy in assessment of outcome after pediatric traumatic brain injury.
OBJECTIVE: To assess the role of magnetic resonance imaging, specifically magnetic resonance spectroscopy (MRS) and susceptibility-weighted imaging (SWI), in the evaluation of children with traumatic brain injury (TBI). DATA SOURCES: Literature review and data from our recently published clinical studies. STUDY SELECTION: Children with pediatric TBI who underwent SWI. SWI is a 3-dimensional high-resolution magnetic resonance imaging technique that is more sensitive in detecting hemorrhagic lesions seen with diffuse axonal injury (DAI) than conventional imaging. MRS acquires metabolite information that reflects neuronal integrity and function from multiple brain regions and offers early prognostic information regarding outcome. DATA EXTRACTION: Literature review. DATA SYNTHESIS: Literature review and review of recently published data from our institution. CONCLUSIONS: The data suggest that more sensitive imaging techniques that provide early evidence of injury and that are better predictors of outcome are needed to identify children at risk for such deficits. Specifically, the number and volume of hemorrhagic DAI lesions as well as changes in spectral metabolites such as reduced N-acetylaspartate or elevations in choline-related compounds correlate with neurologic disability and impairments of global intelligence, memory, and attention.
Aspartic Acid↗
Translational stroke research in the developing brain.
Preclinical animal models can help guide the development of clinical pediatric and newborn stroke trials. Data obtained using currently available models of hypoxia-ischemia and focal stroke have demonstrated the need for age-appropriate models. There are age-related differences in susceptibility of the immature brain to oxidative stress and inflammation, as well as in the rate and degree of apoptotic neuronal death. These issues need to be carefully addressed in designing future clinical trials.
Adult↗
Postmortem intracranial neuropathology in children following cardiac transplantation.
At Loma Linda University Children's Hospital, the medical information of 405 pediatric patients who received orthotopic cardiac transplantation were reviewed. Of those who died (n=136), 86% (n=117) underwent postmortem examinations, and the brain was examined in 61% (n=82, male=39). The number and type of intracranial lesions present were compiled, and these were matched to underlying functional cardiac disease categories. Intracranial abnormalities were present in 87%. Infarct was the most common primary central nervous system pathology in hypoplastic left heart syndrome (41%) but was also observed frequently in children with obstructive lesions (37%), cyanotic disease (31%), or cardiac shunting (29%). Secondary findings included extraparenchymal hemorrhage in obstructive lesions (31%); hypoxic changes occurred in 15% of patients with cyanotic disease and in 14% of those with cardiac shunting. Thirty-three percent of children with restrictive lesions had no neuropathology reported. Postmortem examination brain weights were matched against age and sex norms, with 29% of females and 36% of males below two standard deviations. These findings revealed that intracranial pathology was present in the majority of transplanted children who underwent postmortem examination, and that infarctive changes constituted the most common neuropathologic abnormality. Additionally, a number of children had significantly reduced brain weight.
Adolescent↗
Use of advanced neuroimaging techniques in the evaluation of pediatric traumatic brain injury.
Advanced neuroimaging techniques are now used to expand our knowledge of traumatic brain injury, and increasingly, they are being applied to children. This review will examine four of these methods as they apply to children who present acutely after injury. (1) Susceptibility weighted imaging is a 3-dimensional high-resolution magnetic resonance imaging technique that is more sensitive than conventional imaging in detecting hemorrhagic lesions that are often associated with diffuse axonal injury. (2) Magnetic resonance spectroscopy acquires metabolite information reflecting neuronal integrity and function from multiple brain regions and provides sensitive, noninvasive assessment of neurochemical alterations that offers early prognostic information regarding the outcome. (3) Diffusion weighted imaging is based on differences in diffusion of water molecules within the brain and has been shown to be very sensitive in the early detection of ischemic injury. It is now being used to study the direct effects of traumatic injury as well as those due to secondary ischemia. (4) Diffusion tensor imaging is a form of diffusion weighted imaging and allows better evaluation of white matter fiber tracts by taking advantage of the intrinsic directionality (anisotropy) of water diffusion in human brain. It has been shown to be useful in identifying white matter abnormalities after diffuse axonal injury when conventional imaging appears normal. An important aspect of these advanced methods is that they demonstrate that 'normal-appearing' brain in many instances is not normal, i.e. there is evidence of significant undetected injury that may underlie a child's clinical status. Availability and integration of these advanced imaging methods will lead to better treatment and change the standard of care for use of neuroimaging to evaluate children with traumatic brain injury.
Body Water↗
Brain death in infants and children.
Explore the source record for details and available documents.
Angiography, Digital Subtraction↗
Use of opioids in asphyxiated term neonates: effects on neuroimaging and clinical outcome.
Perinatal asphyxia is a common cause of neurologic morbidity in neonates who are born at term. Asphyxiated neonates are frequently treated with analgesic medications, including opioids, for pain and discomfort associated with their care. On the basis of previous laboratory studies suggesting that opioids may have neuroprotective effects, we conducted a retrospective review of medical records of 52 neonates who were admitted to our neonatal intensive care unit between 1995 and 2002 and had undergone magnetic resonance imaging (MRI) of the brain. Our review revealed that 33% of neonates received morphine or fentanyl. The neonates who received opioids also had experienced hypoxic/ischemic insults of greater magnitude as suggested by higher plasma lactate levels and lower 5-min Apgar scores. It is interesting that the MRI studies of neonates who were treated with opioids during the first week of life demonstrated significantly less brain injury in all regions studied. More important, follow-up studies of a subgroup of opioid-treated neonates whose MRI scans were obtained in the second postnatal week had better long-term neurologic outcomes. Our results suggest that the use of opioids in the first week of life after perinatal asphyxia have no significant long-term detrimental effects and may increase the brain's resistance to hypoxic-ischemic insults.
Analgesics, Opioid↗
Patterns of brain injury in term neonatal encephalopathy.
OBJECTIVES: To determine whether the pattern of brain injury in term neonatal encephalopathy is associated with distinct prenatal and perinatal factors and to determine whether the pattern of injury is associated with 30-month neurodevelopmental outcome. STUDY DESIGN: A total of 173 term newborns with neonatal encephalopathy from 2 centers underwent magnetic resonance imaging (MRI) at a median of 6 days of age (range, 1-24 days). Patterns of injury on MRI were defined on the basis of the predominant site of injury: watershed predominant, basal ganglia/thalamus predominant, and normal. RESULTS: The watershed pattern of injury was seen in 78 newborns (45%), the basal ganglia/thalamus pattern was seen in 44 newborns (25%), and normal MRI studies were seen in 51 newborns (30%). Antenatal conditions such as maternal substance use, gestational diabetes, premature rupture of membranes, pre-eclampsia, and intra-uterine growth restriction did not differ across patterns. The basal ganglia/thalamus pattern was associated with more severe neonatal signs, including more intensive resuscitation at birth ( P = .001), more severe encephalopathy ( P = .0001), and more severe seizures ( P = .0001). The basal ganglia/thalamus pattern was associated with the most impaired motor and cognitive outcome at 30 months. CONCLUSION: The patterns of brain injury in term neonatal encephalopathy are associated with different clinical presentations and neurodevelopmental outcomes. Measured prenatal risk factors did not predict the pattern of brain injury.
Brain Diseases↗
Susceptibility weighted imaging: neuropsychologic outcome and pediatric head injury.
Traumatic brain injury is among the most frequent pediatric neurologic disorders in the United States, affecting multiple aspects of neuropsychologic functioning. This study assessed the efficacy of susceptibility weighted imaging as a predictor of long-term neuropsychologic functioning after pediatric brain injury compared with magnetic resonance spectroscopic imaging. Susceptibility weighted imaging is a relatively new method that is considered superior to traditional magnetic resonance imaging sequences for detecting hemorrhagic diffuse axonal injury. In this study, imaging and spectroscopy were acquired 6 +/- 4 days after injury. Measures of neuropsychologic functioning were administered to 18 children and adolescents 1-4 years post injury. Negative correlations between lesion number and volume with neuropsychologic functioning were demonstrated. Lesion volume explained over 32% of the variance in cognitive performance, explaining at least an additional 20% beyond injury severity and age at injury alone and 19% beyond magnetic resonance spectroscopic metabolite variables. Exploratory analyses resulted in notable trends, with lesions in deeper brain regions more strongly associated with poorer neuropsychologic performance. Improved detection of the extent of diffuse axonal injury following a brain injury will allow for a better understanding of its association with long-term outcome, which in turn can improve prognostic efficacy for effective treatment planning.
Adolescent↗
Proton MR spectroscopic imaging depicts diffuse axonal injury in children with traumatic brain injury.
BACKGROUND AND PURPOSE: Diffuse axonal injury (DAI) after traumatic brain injury (TBI) is important in patient assessment and prognosis, yet they are underestimated with conventional imaging techniques. We used MR spectroscopic imaging (MRSI) to detect DAI and determine whether metabolite ratios are accurate in predicting long-term outcomes and to examine regional differences in injury between children with TBI and control subjects. METHODS: Forty children with TBI underwent transverse proton MRSI through the level of the corpus callosum within 1-16 days after injury. T2-weighted, fluid-attenuated inversion recovery, and susceptibility-weighted MR imaging was used to identify voxels as normal-appearing or as nonhemorrhagic or hemorrhagic injury. Neurologic outcome was evaluated at 6-12 months after injury. Metabolite ratios for total (all voxels), normal-appearing, and hemorrhagic brain were compared and used in a logistic regression model to predict long-term outcome. Total and regional metabolite ratios were compared with control data. RESULTS: A significant decrease in N-acetylaspartate (NAA)/creatine (Cr) and increase in choline (Cho)/Cr (evidence of DAI) was observed in normal-appearing (P < .05) and visibly injured (hemorrhagic) brain (P < .001) compared with controls. In normal-appearing brain NAA/Cr decreased more in patients with poor outcomes (1.32 +/- 0.54) than in those with good outcomes (1.61 +/- 0.50, P = .01) or control subjects (1.86 +/- 0.1, P = .00). In visibly injured brains, ratios were similarly altered in all patients. In predicting outcomes, ratios from normal-appearing and visibly-injured brain were 85% and 67% accurate, respectively. CONCLUSION: MRSI can depict injury in brain that appears normal on imaging and is useful for predicting long-term outcomes.
Adolescent↗
Pediatric neurology's midlife crisis.
Explore the source record for details and available documents.
Neurology↗
Proton spectroscopy detected myoinositol in children with traumatic brain injury.
Previous studies have shown that proton magnetic resonance spectroscopy (MRS) is useful in predicting neurologic prognosis in children with traumatic brain injury (TBI). Reductions in N-acetyl derived metabolites and presence of lactate have been predictive of poor outcomes. We examined another spectroscopy metabolite, myoinositol (mI), to determine whether it is altered after TBI. Found primarily in astrocytes, mI functions as an osmolyte and is involved in hormone response pathways and protein-kinase C activation. Myoinositol is elevated in the newborn brain and is increased in a variety of diseases. We studied 38 children (mean age 11 y; range 1.6-17 y) with TBI using quantitative short echo time occipital gray and parietal white matter proton MRS at a mean of 7 d (range 1-17 d) after injury. We found that occipital gray matter mI levels were increased in children with TBI (4.30 +/- 0.73) compared with controls (3.53 +/- 0.48; p = 0.003). We also found that patients with poor outcomes 6-12 mo after injury had higher mI levels (4.78 +/- 0.68) than patients with good outcomes (4.15 +/- 0.69; p < 0.05). Myoinositol is elevated after pediatric TBI and is associated with a poor neurologic outcome. The reasons for its elevation remain unclear but may be due to astrogliosis or to a disturbance in osmotic function.
Adolescent↗
Diffuse axonal injury in children: clinical correlation with hemorrhagic lesions.
An inception cohort of 40 children and adolescents with traumatic brain injury and suspected diffuse axonal injury were studied using a new high-resolution magnetic resonance imaging susceptibility-weighted technique that is very sensitive for hemorrhage. A blinded comparison was performed between the extent of parenchymal hemorrhage and initial clinical variables as well as outcomes measured at 6 to 12 months after injury. Children with lower Glasgow Coma Scale scores (< or =8, n = 30) or prolonged coma (>4 days, n = 20) had a greater average number (p = 0.007) and volume (p = 0.008) of hemorrhagic lesions. Children with normal outcomes or mild disability (n = 30) at 6 to 12 months had, on average, fewer hemorrhagic lesions (p = 0.003) and lower volume (p = 0.003) of lesions than those who were moderately or severely disabled or in a vegetative state. Significant differences also were observed when comparing regional injury to clinical variables. Because susceptibility-weighted imaging is much more sensitive than conventional T2*-weighted gradient-echo sequences in detecting hemorrhagic diffuse axonal injury, more accurate and objective assessment of injury can be obtained early after insult, and may provide better prognostic information regarding duration of coma as well as long-term outcome.
Adolescent↗
Neuropsychological outcome of infant heart transplant recipients.
OBJECTIVE: To assess long-term neuropsychological outcomes of infant heart transplant recipients. STUDY DESIGN: Fifty-five children (mean age, 6.4 years) with a primary diagnosis of hypoplastic left heart syndrome or other cardiac disorders participated in the study. Six areas of risk were assessed (birth; preoperative, intraoperative, and postoperative status; long-term medical complications; and socioeconomic factors). Neuropsychological evaluations included the following: Wechsler Scales of Intelligence, Wechsler Individual Achievement Test, Berry Visual Motor Integration Scale, Comprehensive Evaluation of Language Function, and Achenbach Child Behavioral Checklist. RESULTS: Intellectual functioning scores revealed a mean full-scale IQ of 81 +/- 19. Intraoperative and postoperative variables (bypass time, hospital course, and lowest posttransplant pH), long-term medical complications (serious infections and posttransplant surgical procedures), and socioeconomic factors were associated with cognitive functioning. Visual-motor functioning was also related to bypass and total support time. CONCLUSIONS: Long-term outcomes reveal low-average neuropsychological functioning and are related to intrasurgical-postsurgical, long-term medical, and socioeconomic factors. The neuropsychological and psychosocial functioning of infant heart transplant recipients will be important to address as they mature during adolescence and adulthood.
Child↗