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

BACKGROUND: Magnetic resonance (MR) technology offers noninvasive methods for in vivo assessment of neuroabnormalities. METHODS: A comprehensive neuropsychological/psychiatric battery, coupled with MR imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) assessments, were administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified, and distinguish diagnostic subclassifications across the spectrum. The 4 study groups included: (i) fetal alcohol syndrome (FAS)/partial FAS (PFAS); (ii) static encephalopathy/alcohol exposed (SE/AE); (iii) neurobehavioral disorder/alcohol exposed (ND/AE) as diagnosed with the FASD 4-Digit Code; and (iv) healthy peers with no prenatal alcohol exposure. Presented here are the MRI assessments that were used to compare the sizes of brain regions between the 4 groups. The neuropsychological/behavioral, MRS, and fMRI outcomes are reported separately. RESULTS: Progressing across the 4 study groups from Controls to ND/AE to SE/AE to FAS/PFAS, the mean absolute size of the total brain, frontal lobe, caudate, putamen, hippocampus, cerebellar vermis, and corpus callosum length decreased incrementally and significantly. The FAS/PFAS group (the only group with the 4-Digit FAS facial phenotype) had disproportionately smaller frontal lobes relative to all other groups. The FAS/PFAS and SE/AE groups [the 2 groups with the most severe central nervous system (CNS) dysfunction] had disproportionately smaller caudate regions relative to the ND/AE and Control groups. The prevalence of subjects in the FAS/PFAS, SE/AE, and ND/AE groups that had 1 or more brain regions, 2 or more SDs below the mean size observed in the Control group was 78, 58, and 43%, respectively. Significant correlations were observed between size of brain regions and level of prenatal alcohol exposure, magnitude of FAS facial phenotype, and level of CNS dysfunction. CONCLUSIONS: Magnetic resonance imaging provided further validation that ND/AE, SE/AE, and FAS/PFAS as defined by the FASD 4-Digit Code are 3 clinically distinct and increasingly more affected diagnostic subclassifications under the umbrella of FASD. Neurostructural abnormalities are present across the spectrum. MRI could importantly augment diagnosis of conditions under the umbrella of FASD, once population-based norms for structural development of the human brain are established.

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

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.

Neuropyschological and behavioral outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders.

BACKGROUND: Clinical and research advancements in the field of fetal alcohol spectrum disorders (FASD) require accurate and valid identification of FASD clinical subgroups. OBJECTIVES: A comprehensive neuropsychological battery, coupled with magnetic resonance imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) were administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified across the spectrum, and distinguish diagnostic subclassifications within the spectrum. The neuropsychological outcomes of the comprehensive neuroimaging study are presented here. METHODS: The study groups included: 1) FAS/Partial FAS; 2) Static Encephalopathy/Alcohol Exposed (SE/AE); 3) Neurobehavioral Disorder/Alcohol Exposed (ND/AE) as diagnosed by an interdisciplinary team using the FASD 4-Digit Code; and 4) healthy peers with no prenatal alcohol. A standardized neuropsychological battery was administered to each child and their primary caregiver by a psychologist. RESULTS: Use of the 4-Digit Code produced three clinically and statistically distinct FASD clinical subgroups. The three subgroups (ND/AE, SE/AE and FAS/PFAS) reflected a linear continuum of increasing neuropsychological impairment and physical abnormality, representing the full continuum of FASD. Behavioral and psychiatric disorders were comparably prevalent across the three FASD groups, and significantly more prevalent than among the Controls. All three FASD subgroups had comparably high levels of prenatal alcohol exposure. CONCLUSIONS: Although ND/AE, SE/AE, and FAS/PFAS are distinct FASD subgroups, these groups are not distinguishable solely by their neuropsychological profiles. While all children within a group shared the same magnitude of neuropsychological impairment, the patterns of impairment showed considerable individual variability. MRI, MRS and fMRI further distinguished these FASD subgroups.

Functional magnetic resonance imaging outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders.

A comprehensive neuropsychological/psychiatric, MR imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) assessment was administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified, and 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); and 4. healthy peers with no prenatal alcohol exposure. fMRI outcomes are reported here. The neuropsychological/psychiatric, MRI, and MRS outcomes are reported separately. fMRI was used to assess activation in seven brain regions during performance of N-back working memory tasks. Children across the full spectrum of FASD exhibited significant working memory deficits and altered activation patterns in brain regions that are known to be involved in working memory. These results demonstrate the potential research and diagnostic value of this non-invasive MR tool in the field of FASD.

Comparison of Three Approaches to Supplementary Reading Instruction for Low-Achieving Second-Grade Readers.

PURPOSE: This research evaluated the relative effectiveness of three instructional approaches to supplementing the regular reading program for second graders with low word reading and/or pseudoword reading skills. METHOD: In the instructional experiment, 96 second graders with low reading achievement were randomly assigned to one of four conditions: (a) explicit and reflective word recognition, (b) explicit and reflective reading comprehension, (c) combined explicit word recognition and explicit reading comprehension, or (d) treated control that only practiced reading skills without any instruction. In the extension study, these conditions were compared to an untreated control group of 29 second graders. RESULTS: In the instructional experiment, combined word recognition and reading comprehension treatment increased phonological decoding (pronouncing pseudowords) significantly more than the treated control or word recognition only treatment and had the highest effect size. The comprehension only treatment was not significantly different from the treated control. In the extension study, (a) the treated children receiving supplemental instruction improved significantly more in phonological decoding and reading real words than did those in the regular program, and (b) the combined word recognition and reading comprehension treatment, which was explicit, had the highest effect sizes for both pseudoword and real-word reading. CLINICAL IMPLICATIONS: The most effective supplemental instruction for increasing phonological decoding was combining explicit word recognition and explicit reading comprehension training.