Dataset Information

Age-related decline in the microstructural integrity of white matter in children with early- and continuously-treated PKU: a DTI study of the corpus callosum.

ABSTRACT: Structural, volumetric, and microstructural abnormalities have been reported in the white matter of the brain in individuals with phenylketonuria (PKU). Very little research, however, has been conducted to investigate the development of white matter in children with PKU, and the developmental trajectory of their white matter microstructure is unknown. In the current study, diffusion tensor imaging (DTI) was used to examine the development of the microstructural integrity of white matter across six regions of the corpus callosum in 34 children (7-18 years of age) with early- and continuously-treated PKU. Comparison was made with 61 demographically-matched healthy control children. Two DTI variables were examined: mean diffusivity (MD) and relative anisotropy (RA). RA was comparable to that of controls across all six regions of the corpus callosum. In contrast, MD was restricted for children with PKU in anterior (i.e., genu, rostral body, anterior midbody) but not posterior (posterior midbody, isthmus, splenium) regions of the corpus callosum. In addition, MD restriction became more pronounced with increasing age in children with PKU in the two most anterior regions of the corpus callosum (i.e., genu, rostral body). These findings point to an age-related decrement in the microstructural integrity of the anterior white matter of the corpus callosum in children with PKU.

SUBMITTER: White DA

PROVIDER: S-EPMC3640282 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Publications

Age-related decline in the microstructural integrity of white matter in children with early- and continuously-treated PKU: a DTI study of the corpus callosum.

White Desiree A DA Connor Lisa Tabor LT Nardos Binyam B Shimony Joshua S JS Archer Rebecca R Snyder Abraham Z AZ Moinuddin Asif A Grange Dorothy K DK Steiner Robert D RD McKinstry Robert C RC

Molecular genetics and metabolism 20100101

Structural, volumetric, and microstructural abnormalities have been reported in the white matter of the brain in individuals with phenylketonuria (PKU). Very little research, however, has been conducted to investigate the development of white matter in children with PKU, and the developmental trajectory of their white matter microstructure is unknown. In the current study, diffusion tensor imaging (DTI) was used to examine the development of the microstructural integrity of white matter across s ...[more]

PMID: 20123469

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Project description:Alcohol dependence exacts a toll on brain white matter microstructure, which has the potential of repair with prolonged sobriety. Diffusion tensor imaging (DTI) enables in-vivo quantification of tissue constituents and localisation of tracts potentially affected in alcohol dependence and its recovery. We did an extended longitudinal study of alcoholism's trajectory of effect on selective fibre bundles with sustained sobriety or decline with relapse.Participants were drawn from a longitudinal, 1·5T DTI database of 841 scans of individuals with various medical or neuropsychiatric conditions and normal ageing. Participants diagnosed with alcohol dependence had to meet the criteria from DSM-IV for alcohol dependence. Controls were screened and free of any DSM-IV axis I diagnosis, including being without history of alcohol or drug abuse or dependence. Tract-based spatial statistics (TBSS) quantified white matter integrity throughout the brain in 47 alcohol-dependent individuals and 56 controls examined 2-5 times over 1-8 year intervals. We identified regions showing group differences with a white matter atlas. For macrostructural comparison, we measured corpus callosum and centrum semiovale volumes on MRI.This study took place in the USA, between June 23, 2000, and Sept 6, 2011. TBSS identified a large cluster (threshold p<0·001), where controls showed significant fractional anisotropy (FA) decrease with ageing and alcohol-dependent individuals had significantly lower FA than controls regardless of age. Over the examination interval, 27 (57%) alcohol-dependent individuals abstained, ten (21%) relapsed into light drinking, and ten (21%) relapsed into heavy drinking (>5 kg of alcohol/year). Despite abnormally low FA, age trajectories of the abstainers were positive and progressing toward normality, whereas those of the relapsers and controls were negative. Axial diffusivity (lower values indexing myelin integrity) was abnormally high in the total alcohol-dependent group; however, the abstainers' slopes paralleled those of controls, whereas the heavy-drinking relapsers' slopes showed accelerated ageing. Callosal genu and body microstructure but not macrostructure showed untoward alcohol-related effects. Affected projection and association tracts had an anterior and superior neuroanatomical distribution.Return to heavy drinking resulted in accelerating microstructural white matter damage. Despite evidence for damage, alcohol-dependent individuals maintaining sobriety over extended periods showed improvement in brain fibre tract integrity reflective of fibre reorganisation and myelin restoration, indicative of a neural mechanism explaining recovery.US National Institute on Alcohol Abuse and Alcoholism (AA012388, AA017168, AA005965, AA013521-INIA).

Dataset Information

Age-related decline in the microstructural integrity of white matter in children with early- and continuously-treated PKU: a DTI study of the corpus callosum.

Publications

Age-related decline in the microstructural integrity of white matter in children with early- and continuously-treated PKU: a DTI study of the corpus callosum.

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