Preoperative brain injury in newborns with transposition of the great arteries

BACKGROUND: The objective was to determine the timing and mechanism of brain injury using preoperative and postoperative magnetic resonance imaging (MRI) and three-dimensional MR spectroscopic imaging (MRSI) in newborns with transposition of the great arteries (TGA) repaired with full-flow cardiopulmonary bypass. METHODS: Ten term newborns with TGA undergoing an arterial switch operation were studied with MRI, MRSI, and neurologic examination preoperatively and postoperatively at a median of 5 days (2 to 9 days) and 19 days (14 to 26 days) of age, respectively. Five term historical controls were studied at a median of 4 days (3 to 9 days). Lactate/choline (marker of cerebral oxidative metabolism) and N-acetylaspartate (NAA)/choline (marker of cerebral metabolism and density) were measured bilaterally from the basal ganglia, thalamus, and corticospinal tracts. RESULTS: Four TGA newborns had brain injury on the preoperative MRI. The only new lesion detected on the postoperative study was a focal white matter lesion in one newborn with a normal preoperative MRI. The MRSI of age-adjusted lactate/choline was quantitatively higher in newborns with TGA compared with those without heart disease (p < 0.0001), even in newborns without MRI evidence of preoperative brain injury. Lactate/choline decreased after surgery but remained elevated compared with controls. In newborns with TGA, those with preoperative brain injury on MRI had lower NAA/choline globally (p = 0.04) than those with normal preoperative MRI. Five newborns had a decline in NAA/choline from the preoperative to postoperative studies. CONCLUSIONS: Abnormal brain metabolism and injury was observed preoperatively in newborns with TGA. Brain injury is not solely related to the operative course.     

Hemodynamic changes during complete umbilical cord occlusion in fetal sheep related to hippocampal neuronal damage

Objectives: The purpose of our study was to examine the physiologic changes caused by 10 minutes of umbilical cord occlusion in fetal sheep and to determine the correlation between fetal acidemia or cerebral ischemia and hippocampal neuronal damage. Study design: Thirteen fetal sheep were instrumented and catheterized. Carotid artery blood flow (CaF), fetal mean arterial blood pressure (FMABP), pH, PCO₂, base excess, oxygen saturation (SatO₂), and PO₂ were monitored throughout the occlusion study. Brain sections were examined for the hippocampal neuronal damage. Results: Our data showed severe ischemia (CaF: 10 ± 7 mL/min; FMABP: 29 ± 8 mm Hg) and acidemia (pH: 7.0 ± 0.05; base excess: −9.9 ± 2.4 mEq/L) at the end of occlusion. The neuronal damage score had significant correlations with ischemia and also with reperfusion, but not with the acidemic or hypoxic parameters. Conclusion: We demonstrated that the degree of hippocampal damage was correlated with the degree of ischemia and reperfusion. (Am J Obstet Gynecol 2003;188:413-8.)     

Predictors of 30-month outcome after perinatal depression: role of proton MRS and socioeconomic factors

The objective was to determine in infants with perinatal depression whether the relative concentrations of N-acetylaspartate and lactate in the neonatal period are associated with (1) neurodevelopmental outcome at 30 mo of age or (2) deterioration in outcome from age 12 to 30 mo; and to determine whether socioeconomic factors are associated with deterioration in outcome. Thirty-seven term neonates were prospectively studied with single-voxel proton magnetic resonance spectroscopy of the basal nuclei and intervascular boundary zones. Thirty-month outcomes were classified as normal [if Mental Development Index of the Bayley Scales of Infant Development (MDI) >85 and neuromotor scores (NMS) <3; n = 15], abnormal [if MDI or=3 at 12 and 30 mo; n = 11], or deteriorated [if normal at 12 mo and abnormal at 30 mo (MDI or=3); n = 11]. Thirty percent (11/37) of our cohort deteriorated between 12 and 30 mo. N-acetylaspartate/choline decreased across the groups ordered as normal, deteriorated, and abnormal [in basal nuclei (p 相似文献   

Age-dependent differences in glutathione peroxidase activity after traumatic brain injury

Children younger than 4 years old have worse outcome after traumatic brain injury (TBI) compared to older children and adults. This increased susceptibility may in part be due to differences in the response to oxidative stress. We hypothesized that the immature brain does not have an adequate compensatory response to injury from oxidative stress. To begin to address this hypothesis, we first compared the general dimensions and water content in postnatal day 21 (P21) and adult murine brain in the naive state as well as after injury (edema). We examined glutathione peroxidase (GPx ) activity in cortical and subcortical regions in P21 and adult murine brain following a controlled cortical impact. Brain dimensions including areas of the mantle and hemispheres were similar in each of these groups. The thickness of the cortical mantle was significantly greater in the immature brain as compared to the mature brain (p = 0.01, respectively). Brain edema was assessed through changes in water content, and the response to oxidative challenge was identified by changes in GPx activity. The P21 brain was similar in vulnerability to posttraumatic brain edema when compared to adult. GPx activity in the adult brain was increased within 24 h post-injury in the cortex, thalamus and hippocampus (ANOVA, p < 0.05), whereas there was no compensatory increase in GPx activity in P21 brain, although baseline levels had reached adult levels developmentally. These findings support our hypothesis and illuminate the important role of oxidative stress after TBI in the immature brain that warrants further study.     

Psychometric properties of the Unified Parkinson’s Disease Rating Scale and of the Short Parkinson’s Evaluation Scale

Abstract. The internal consistency (Cronbachs alpha and item-total correlation) and construct validity (factor analysis, intercorrelations, and relationship with Hoehn and Yahr staging and Schwab and Englands ADL scale) of the sections motor examination and activities of daily living of the Unified Parkinsons Disease Rating Scale (UPDRS) and of the Short Parkinsons Evaluation Scale (SPES) were analyzed in 59 subjects with Parkinsons disease (PD) with various degrees of disability. Our results indicate that the SPES is easier and quicker than UPDRS and that it maintains many psychometric properties similar to those of the UPDRS, but with the reduction of a number of items and ordinal levels of each item studied here (producing more homogenous sections than the original versions). The tremor items would be better represented as a separate section in both scales.     

Nucleated red blood cell counts: not associated with brain injury or outcome

The objective was to determine whether an elevated nucleated red blood cell count at birth after perinatal depression is associated with brain injury as measured by (1) proton magnetic resonance spectroscopy and (2) abnormal neurodevelopmental outcome at 30 months of age. The nucleated red blood cell counts from the first 24 hours of life were statistically analyzed in 33 term infants enrolled in a prospective study of the value of magnetic resonance imaging for the determination of neurodevelopmental outcome after perinatal depression. Nucleated red blood cell counts were elevated in 13/33 (39%). Abnormal outcome (19/33, 54%) was associated with Score for Neonatal Acute Physiology-Perinatal Extension (P = 0.04), decreased N-acetylaspartate to choline ratio in the basal ganglia (P = 0.009), and increased lactate to choline ratio in the basal ganglia (P = 0.02), but not with cord pH, Apgar score, or nucleated red blood cell value. In a logistic regression model, increasing nucleated red blood cell counts did not increase the odds of an abnormal outcome at 30 months of age (OR 1.02, P = 0.17). In a population of neonates with perinatal depression, the nucleated red blood cell count at birth does not correlate with magnetic resonance spectroscopy or 30-month neurodevelopmental outcome. The nucleated red blood cell count should not be used as a surrogate marker for subsequent brain injury.     

Oxidant mechanisms in neonatal hypoxia-ischemia

The neonatal brain appears to be selectively vulnerable to oxidative stress. Several potential mechanisms associated with altered reactive oxygen species metabolism would explain the increased susceptibility. They include increased accumulation of hydrogen peroxide with subsequent neurotoxicity. This enhanced neurotoxicity from H2O2 accumulation may be related to inadequate scavenging abilities of the immature nervous system, such as lower glutathione peroxidase activity. Contributing to the immaturity of the scavenging enzymes is the inability of the developing nervous system to maintain glutathione stores. The immature nervous system is rich in iron, and has more free iron than the mature nervous system. As H2O2 accumulates because of these improper defense mechanisms, it is exposed to this free iron. This exposure results in the generation of OH radical (Fenton reaction), a more potent free radical that can cause severe damage. The rapid conversion of H2O2 to OH in the setting of free iron sets up the immature nervous system for increased cytotoxicity. Understanding the molecular mechanisms of oxidative stress will lead to better therapies for neonatal hypoxia-ischemia.     

Hypoxia-ischemia induces heat shock protein-like (HSP72) immunoreactivity in neonatal rat brain

The expression of heat shock protein immunoreactivity in rat brain was evaluated in a model of neonatal hypoxia-ischemia. One-week-old rats were subjected to left carotid artery coagulation and exposure to 8% O2/92% N2 for 2 h (moderate injury) or 3.5 h (severe injury). Animals were sacrificed 1, 12 and 24 h after the hypoxic insult. Cells immunoreactive for the 72 kDa heat shock protein (HSP72) were observed in ipsilateral cortex as early as 1 h after the termination of the hypoxia. After 12 h, neurons in the ipsilateral hippocampus and cortex stained intensely for HSP72 immunoreactivity in the moderately injured group. In the severely injured brains, bilateral staining was observed in neurons and vessels of the hippocampus and cortex. Therefore, cells containing HSP72 immunoreactivity may serve as an early marker for neuronal injury from hypoxia-ischemia in the neonatal rat brain and more importantly may illustrate previously unrecognized areas of central nervous system vulnerability.     

Quantitative diffusion tensor MRI fiber tractography of sensorimotor white matter development in premature infants

Diffusion tensor MRI (DTI) fiber tracking is the first non-invasive and in vivo technique for the delineation and quantitation of specific white matter pathways. In this study, quantitative fiber tracking was used to assess the structural development of the motor tract and somatosensory radiation in premature human newborns. These pathways are unmyelinated in the youngest premature infants and begin to myelinate during late preterm maturation. Previous studies have only been able to delineate parts of these pathways that could be manually outlined in 2D based on anatomical landmarks. Furthermore, these previous studies could not separate motor and sensory regions. A high-sensitivity neonatal head coil was employed in conjunction with an MR-compatible incubator to perform high-resolution imaging of the premature infant brain. The motor and somatosensory tracts were successfully delineated with 3D DTI fiber tracking in 37 exams of preterm newborns between 28 and 43 weeks gestational age. Both streamline deterministic and probabilistic methods were employed to perform quantitative fiber tractography. Tract-specific measurements of diffusion parameters including fractional anisotropy, directionally averaged diffusivity, and eigenvalues were obtained from the motor and sensory pathways. Using both deterministic and probabilistic fiber tracking, all tract-specific diffusion parameters were found to be significantly correlated with age and the motor tracts were found to have higher anisotropy and lower diffusivity than the sensory pathway. By segmenting the 3D fiber tracks by slice, measurements from different axial levels of the brain were found to vary with region and age. In summary, deterministic and probabilistic DTI fiber tracking methods were used to quantify the developmental changes of motor and somatosensory pathways in premature infants.