Neonatal microstructural development of the internal capsule on diffusion tensor imaging correlates with severity of gait and motor deficits.
ABSTRACT Neonatal microstructural development in the posterior limbs of the internal capsule (PLIC) was assessed using diffusion tensor imaging (DTI) fractional anisotropy (FA) in 24 very-low-birthweight preterm infants at 37 weeks' gestational age and compared with the children's gait and motor deficits at 4 years of age. There were 14 participants with normal neonatal FA values (seven females, seven males; born at 27.6 weeks [SD 2.3] gestational age; birthweight 1027g [SD 229]) and 10 participants with low FA values in the PLIC (four females, six males; born at 28.4 weeks [SD 2.0] gestational age; birthweight 1041g [SD 322]). Seven of the 10 children with low FA and none of the children with normal FA had been diagnosed with CP by the time of gait testing. Among children with low neonatal FA, there was a strong negative correlation between FA of the combined left and right side PLIC and log NI (r=-0.89, p=0.001) and between FA and GMFCS (r=-0.65, p=0.04) at 4 years of age. There was no correlation between FA and gait NI or GMFCS at 4 years of age among children with normal neonatal FA. This preliminary study suggests neonatal DTI may be an important predictor of the severity of future gait and motor deficits.
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ABSTRACT: Brain injury in premature infants is characterized predominantly by perinatally acquired lesions in the cerebral white matter (WM). The impact of such injury on the subsequent development of cerebral WM is not clear. This study uses diffusion tensor magnetic resonance imaging (MRI) to evaluate the effects of cerebral WM injury on subsequent microstructural brain development in different WM areas of the brain. Twenty premature infants (gestational age: 29.1 +/- 1.9 weeks) were studied by conventional MRI within the first 3 weeks of life and again at term, with the addition at the latter time of diffusion tensor MRI. Ten of the preterm infants had cerebral WM injury identified by the early MRI and were matched with 10 premature infants of similar gestational age and neonatal course but with normal neonatal MRI scans. Diffusion tensor MRI at term was acquired in coronal and axial planes and used to determine the apparent diffusion coefficient, a measure of overall restriction to water diffusion, and the relative anisotropy (RA), a measure of preferred directionality of diffusion, in central WM, anterior frontal WM, occipital WM, temporal WM, and the posterior limb of the internal capsule. Diffusion vector maps were generated from the diffusion tensor analysis to define the microstructural architecture of the cerebral WM regions. At term, the diffusion tensor MRI revealed no difference in apparent diffusion coefficient among preterm infants with or without perinatal WM lesions. By contrast, RA, the measure of preferred directionality of diffusion and thereby dependent on development of axonal fibers and oligodendroglia, was 25% lower in central WM, the principal site of the original WM injury. However, RA was unaffected in relatively uninjured WM areas, such as temporal, anterior frontal, and occipital regions. Notably, RA values in the internal capsule, which contains fibers that descend from the injured cerebral WM, were 20% lower in the infants with WM injury versus those without. Diffusion vector maps showed striking alterations in the size, orientation, and organization of fiber tracts in central WM and in those descending to the internal capsule. Perinatal cerebral WM injury seems to have major deleterious effects on subsequent development of fiber tracts both in the cerebral WM and more distally. The ultimate impact of brain injury in the newborn should be considered as a function not only of tissue destruction, but also of impaired subsequent brain development.PEDIATRICS 04/2001; 107(3):455-60. · 4.47 Impact Factor
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ABSTRACT: Neuroimaging techniques have established new connections between etiological factors and disorders of early brain development. Neuroimaging has also strengthened the link between patterns of selective vulnerability in the developing brain and clinical syndromes, especially cerebral palsy. Both computed tomography (CT) and magnetic resonance imaging (MRI) identify early developmental malformations, including neural tube defects, callosal dysgenesis, neuronal migration disorders, posterior fossa malformations, and hydrocephalus. Periventricular white matter damage, most commonly seen in premature infants, is best visualized by cranial ultrasonography in the neonatal period and on MRI later in childhood. In term infants and children with genetic metabolic diseases, various applications of nuclear magnetic resonance, including MRI, have important diagnostic roles. The utility of diffusion-weighted imaging, MR spectroscopy, and functional MRI to further understanding of brain injury, biochemistry, and function is under active investigation. In summary, selecting the appropriate neuroimaging technique can improve diagnosis and management of childhood neurodevelopmental disorders.Journal of Developmental & Behavioral Pediatrics 09/2000; 21(4):291-302. · 1.75 Impact Factor
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ABSTRACT: To determine independent predictors of ambulation among children with cerebral palsy and to develop a simple tool that estimates the probability that a child will walk. In a retrospective study of all children with cerebral palsy who were not yet walking at 2 to 3(1/2) years of age, while receiving services from the California Department of Developmental Services during the years 1987-1999, we analyzed medical and functional data obtained annually by Department of Developmental Services physicians and social workers. Using logistic regression analyses, we determined independent predictors of a child's ability to walk well alone at least 20 feet, without assistive devices, by age 6. We then estimated the probabilities of walking at various levels of ability over time, using multistate survival analysis. Of 5366 study subjects, 2295 (43%) were evaluated at age 6; 12.8% could walk independently and 18.4% walked with support. Independent predictors of successful ambulation included early motor milestones such as sitting (odds ratio: 12.5; 95% confidence interval: 5.8-27.2) and pulling to a stand (odds ratio: 28.5; 95% confidence interval: 13.4-60.4) when compared with lack of rolling at age 2, cerebral palsy type other than spastic quadriparesis (odds ratio: 2.2; 95% confidence interval: 1.5-3.1), and preserved visual function (odds ratio: 2.4; 95% confidence interval: 1.1-5.4). Our ambulation charts depict the probability of remaining nonambulatory, transitioning to 1 of 3 possible ambulatory states, or expiring at all subsequent ages through age 14. The ambulation charts provide a simple straightforward way to estimate the probability that a child with cerebral palsy who is nonambulatory at 2 to 3 12 years of age will eventually walk with or without support.PEDIATRICS 12/2004; 114(5):1264-71. · 4.47 Impact Factor