Placental Transfusion for Asphyxiated Infants.

The current recommendation for umbilical cord management of non-vigorous infants (limp, pale, and not breathing) who need resuscitation at birth is to immediately clamp the umbilical cord. This recommendation is due in part to insufficient evidence for delayed cord clamping (DCC) or umbilical cord milking (UCM). These methods may provide a neuroprotective mechanism that also facilitates cardiovascular transition for non-vigorous infants at birth

Adolescent Brain Development and the Risk for Alcohol and Other Drug Problems

Dynamic changes in neurochemistry, fiber architecture, and tissue composition occur in the adolescent brain. The course of these maturational processes is being charted with greater specificity, owing to advances in neuroimaging and indicate grey matter volume reductions and protracted development of white matter in regions known to support complex cognition and behavior. Though fronto-subcortical circuitry development is notable during adolescence, asynchronous maturation of prefrontal and limbic systems may render youth more vulnerable to risky behaviors such as substance use. Indeed, binge-pattern alcohol consumption and comorbid marijuana use are common among adolescents, and are associated with neural consequences. This review summarizes the unique characteristics of adolescent brain development, particularly aspects that predispose individuals to reward seeking and risky choices during this phase of life, and discusses the influence of substance use on neuromaturation. Together, findings in this arena underscore the importance of refined research and programming efforts in adolescent health and interventional needs

Reduced microstructural white matter integrity in a genetic metabolic disorder : a diffusion tensor MRI study

Infantile nephropathic cystinosis is a genetic metabolic disorder in which cystine accumulates continuously in lysosomes, forming intracellular crystals throughout various organs in the body, including the kidneys, liver, thyroid, and brain. Cognitive deficits are particularly evident in the visuospatial domain and are accompanied by impairments in arithmetic and tactile recognition. Though the genetic causes and behavioral expression of this disorder are well characterized, the underlying neuropathological features are only grossly defined. The available literature suggests that cerebral white matter may be preferentially affected in this group, as cystine crystals have been identified in oligodendrocytes and perivascular macrophages. Within this context, the current study used diffusion tensor MRI to investigate whether early processes in this disorder contribute to selective neuropathological changes. Accordingly, white matter integrity in the dorsal visual pathway (the "where" system) was examined in a young group (ages 3-7 years) of children with cystinosis (n = 24) and compared to an age- matched group of typically developing children (n = 24). A secondary aim of this study was to characterize the relationship between diffusion fractional anisotropy (FA), visuospatial functioning and white blood cell cystine level (an indicator of disease load). Voxel-based analysis identified reduced FA primarily in bilateral inferior parietal white matter in children with cystinosis. Other areas bearing similar attenuations in anisotropy were found in the right mid-temporal and subgyral frontal regions. To expand this approach on a single-subject level, a region-of-interest (ROI) analysis was conducted focusing on parietal and temporal subregions, corresponding to the neuroanatomical visual pathways. In addition to changes in the inferior parietal lobule (IPL) as identified by voxel- level analysis, results of ROI analysis indicated bilaterally decreased FA in the superior parietal lobule (SPL). These findings occurred in the context of nonsignificant differences in FA in inferior temporal regions. A concomitant increase in the apparent diffusion coefficient (MD) in bilateral SPL and IPL was evident in the cystinosis group, with comparable MD values in inferior temporal white matter. Together, this pattern of findings is consistent with the hypothesized dissociation between the dorsal and ventral pathways in children with cystinosis. Results of multiple regression analysis revealed an interaction between age and FA, which when decomposed into simple effects, indicated a stronger relationship between FA and visuospatial functioning for older cystinosis children. Specifically, decremented performance on a task of visual-motor integration was associated with reduced FA in the right IPL in school-aged children with cystinosis (age > 5 years, n = 13, r = .74). Spearman correlations between white blood cell cystine level and MD in the right IPL (r = .46) and SPL (r = .50) were evident across the entire cystinosis group. In addition, correlations between cystine level and bilateral parietal MD became apparent in school-aged children, suggesting a progressive effect of cystine accumulation in addition to early white matter changes. Taken together, significant attenuations in FA suggest that the genetic deletion underlying cystinosis results in early and regionally selective neuropathological changes which may involve myelin-forming oligodendroglia or their precursors. Contrary to expectations, relationships between anisotropy, cognitive performance, and cystine level, were only present in the older children of our group. These findings suggest that the accumulation of cystine over time may constitute a secondary progressive effect that interferes with white matter maturation. Moreover, the extent of cognitive deficit observed in children with cystinosis may result from an interaction of both the static and progressive processes in this conditio

Reduced microstructural white matter integrity in a genetic metabolic disorder: A diffusion tensor MRI study

ABSTRACT OF THE DISSERATIONReduced microstructural white matter integrity in a genetic metabolic disorder: A diffusion tensor MRI studybySunita BavaDoctor of Philosophy in Clinical PsychologyUniversity of California, San Diego,San Diego State University, 2007Professor Doris Trauner, ChairInfantile nephropathic cystinosis is a genetic metabolic disorder in which cystine accumulates continuously in lysosomes, forming intracellular crystals throughout various organs in the body, including the kidneys, liver, thyroid, and brain. Cognitive deficits are particularly evident in the visuospatial domain and are accompanied by impairments in arithmetic and tactile recognition. Though the genetic causes and behavioral expression of this disorder are well characterized, the underlying neuropathological features are only grossly defined. The available literature suggests that cerebral white matter may be preferentially affected in this group, as cystine crystals have been identified in oligodendrocytes and perivascular macrophages. Within this context, the current study used diffusion tensor MRI to investigate whether early processes in this disorder contribute to selective neuropathological changes. Accordingly, white matter integrity in the dorsal visual pathway (the "where" system) was examined in a young group (ages 3-7 years) of children with cystinosis (n = 24) and compared to an age-matched group of typically developing children (n = 24). A secondary aim of this study was to characterize the relationship between diffusion fractional anisotropy (FA), visuospatial functioning and white blood cell cystine level (an indicator of disease load). Voxel-based analysis identified reduced FA primarily in bilateral inferior parietal white matter in children with cystinosis. Other areas bearing similar attenuations in anisotropy were found in the right mid-temporal and subgyral frontal regions. To expand this approach on a single-subject level, a region-of-interest (ROI) analysis was conducted focusing on parietal and temporal subregions, corresponding to the neuroanatomical visual pathways. In addition to changes in the inferior parietal lobule (IPL) as identified by voxel-level analysis, results of ROI analysis indicated bilaterally decreased FA in the superior parietal lobule (SPL). These findings occurred in the context of nonsignificant differences in FA in inferior temporal regions. A concomitant increase in the apparent diffusion coefficient (MD) in bilateral SPL and IPL was evident in the cystinosis group, with comparable MD values in inferior temporal white matter. Together, this pattern of findings is consistent with the hypothesized dissociation between the dorsal and ventral pathways in children with cystinosis. Results of multiple regression analysis revealed an interaction between age and FA, which when decomposed into simple effects, indicated a stronger relationship between FA and visuospatial functioning for older cystinosis children. Specifically, decremented performance on a task of visual-motor integration was associated with reduced FA in the right IPL in school-aged children with cystinosis (age > 5 years, n = 13, r = .74). Spearman correlations between white blood cell cystine level and MD in the right IPL (r = .46) and SPL (r = .50) were evident across the entire cystinosis group. In addition, correlations between cystine level and bilateral parietal MD became apparent in school-aged children, suggesting a progressive effect of cystine accumulation in addition to early white matter changes.Taken together, significant attenuations in FA suggest that the genetic deletion underlying cystinosis results in early and regionally selective neuropathological changes which may involve myelin-forming oligodendroglia or their precursors. Contrary to expectations, relationships between anisotropy, cognitive performance, and cystine level, were only present in the older children of our group. These findings suggest that the accumulation of cystine over time may constitute a secondary progressive effect that interferes with white matter maturation. Moreover, the extent of cognitive deficit observed in children with cystinosis may result from an interaction of both the static and progressive processes in this condition

White matter characterization of adolescent binge drinking with and without co-occurring marijuana use: a 3-year investigation.

The aims of this study were to investigate the consequences of prolonged patterns of alcohol and marijuana use on white matter integrity and neurocognitive functioning in late adolescence, and examine neurodevelopmental trajectories over three years of regular follow-up visits. Three groups of demographically similar teens received assessments every 1.5 years (controls with consistently minimal substance use, n=16; teens who gradually increase their heavy episodic drinking n=17, and continuous binge drinkers with heavy marijuana use, n=21), including comprehensive neuropsychological evaluations, diffusion tensor imaging, and detailed substance use interviews. One-way ANOVA identified fifteen white matter clusters that significantly differed between groups at 3-year follow-up, ages 19-22; controls consistently demonstrated higher values of tissue integrity across fiber tracts. Repeated measures ANOVA revealed significant declines in white matter integrity from baseline to 3-year follow-up in the subsample of substance users, along with poorer global neurocognitive performance in alcohol users with heavy marijuana use by the 18-month follow-up. Findings suggest healthier brain white matter microstructure and better neurocognitive performance for teens free from heavy alcohol and marijuana use. Long-term engagement in these substances may adversely influence white matter and increase vulnerability for development of neuropathology purported to underlie future risk-taking and addictive behaviors

Placental Transfusion for Asphyxiated Infants.

The current recommendation for umbilical cord management of non-vigorous infants (limp, pale, and not breathing) who need resuscitation at birth is to immediately clamp the umbilical cord. This recommendation is due in part to insufficient evidence for delayed cord clamping (DCC) or umbilical cord milking (UCM). These methods may provide a neuroprotective mechanism that also facilitates cardiovascular transition for non-vigorous infants at birth