Magnetic resonance spectroscopy outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders

Abstract

Magnetic resonance (MR) technology offers noninvasive methods for in vivo assessment of neuroabnormalities. A comprehensive neuropsychological/behavioral, MR imaging (MRI), MR spectroscopy (MRS) and functional MRI (fMRI) assessment was administered to children with fetal alcohol spectrum disorders (FASD) to determine whether global and/or focal abnormalities could be identified and to distinguish diagnostic subclassifications across the spectrum. The four study groups included (1) FAS/partial FAS; (2) static encephalopathy/alcohol exposed (SE/AE); (3) neurobehavioral disorder/alcohol exposed (ND/AE) as diagnosed with the FASD 4-Digit Code; and (4) healthy peers with no prenatal alcohol exposure. Results are presented in four separate reports: MRS (reported here) and neuropsychological/behavioral, MRI and fMRI outcomes (reported separately). MRS was used to compare neurometabolite concentrations [choline (Cho), n-acetyl-aspartate (NAA) and creatine (Cre)] in a white matter region and a hippocampal region between the four study groups. Choline concentration in the frontal/parietal white matter region, lateral to the midsection of the corpus callosum, was significantly lower in FAS/PFAS relative to all other study groups. Choline decreased significantly with decreasing frontal white matter volume and corpus callosum length. These outcomes suggest low choline concentrations may reflect white matter deficits among FAS/PFAS. Choline also decreased significantly with increasing severity of the 4-Digit FAS facial phenotype, increasing impairment in psychological performance and increasing alcohol exposure. NAA and Cre concentrations did not vary significantly. This study provides further evidence of the vulnerability of the cholinergic system in FASD.

Higher functioning children with prenatal alcohol exposure: Is there a specific neurocognitive profile?

“…Given that we were interested in examining these relations in individuals with PAE without intellectual disabilities (IQ ≥ 70), the result is that covarying IQ yielded little change in the outcome of the data analyses without such control. While we understand differing points of view and the statistical assumptions related to the appropriateness of controlling for IQ when it represents a characteristic intrinsic to individuals with developmental disabilities, we believe it an important issue to consider when addressing characteristics of children with PAE as previous studies have examined groups with highly differing mean IQ scores (Astley et al, 2009) that could result in spurious conclusions as to the nature and the uniqueness of the deficits shown by individuals with PAE.…”

Fetal alcohol-induced hyperactivity is reversed by treatment with the PPARα agonist fenofibrate in a rat model

“…These clinical data can be correlated with laboratory data showing that in utero alcohol exposure in rats leads to hyperactivity and/or attention deficits in the offspring, but a relevant model has yet to be validated (Hausknecht et al 2005;Mothes et al 1996; Thomas et al 1998;Torres and Zimmerberg 1992). A specific group of brain regions that appear to be involved in ADHD (the cortex, striatum, and cerebellum) are sensitive to the toxic effects of alcohol administered during the fetoembryonic period (Astley et al 2009;Riikonen et al 1999Riikonen et al , 2005. Damage to these neuronal circuits may lead to functional impairments in neurotransmission systems and thus trigger the emergence of characteristic symptoms.…”

Atypical Hemispheric Asymmetry in Fetal Alcohol Spectrum Disorders: A Review of the Effects of Prenatal Alcohol Exposure on Language Lateralization.

“…Consequently FAS represents the leading preventable cause of intellectual disability (Abel & Sokol, 1987). That said, it is important to note that not every child exposed to alcohol prenatally exhibits CNS dysfunction or brain abnormalities; equally, not every child who exhibits CNS dysfunction or brain abnormalities has FAS (Astley et al, 2009).…”

“…Though not a medical diagnosis, FASD describes the range of outcomes resulting from alcohol consumption during pregnancy (Muk -herjee et al, 2005). The damage resulting from prenatal alcohol exposure is highly variable, covering a spectrum of aberrations from a microcellular and neurochemical level (e.g., reduced choline; Astley et al, 2009) to broad structural abnormalities (e.g., cerebral dysgenesis; Roebuck et al, 1998, for review). Cognitive and behavioural sequelae are similarly variable, encompassing the full continuum from mild developmental delay to global developmental disability affecting both motor and cognitive domains.…”

“…In addition, many previous investigations have failed to compare the consequences of prenatal alcohol consumption on the left and right hemispheres. For example, Astley et al (2009) conducted a comprehensive investigation of an impressively large sample of children with an FAS diagnosis and children prenatally exposed to alcohol, combining structural and functional imaging techniques with a comprehensive neuropsychological and psychiatric battery. However the authors did not make comparisons between the left and right hemispheres.…”