Diffusion tensor images in children with early-treated, chronic, malignant phenylketonuric: correlation with intelligence assessment

Abstract

Background and purpose: Diffusion tensor (DT) images can provide information about the nature of white matter changes, including axonal loss and demyelination. We applied DT imaging to verify white matter changes in patients with malignant phenylketonuria (PKU) and to correlate the findings with clinical intelligence quotients (IQs).

Methods: We compared DT images with T2-weighted images in 12 patients with early-treated, chronic, stable malignant PKU and 12 age-matched control subjects. DT parameters included first, second, and third eigenvalues (EV1-3), apparent diffusion coefficients (ADCs), and fractional anisotropy (FA). Regions of interest were placed the frontoparietal, parieto-occipital, frontal and central white matter and in the anterior and posterior corpus callosum. Eight patients older than 3 years underwent IQ assessment including verbal, performance, and full-scale IQ tests.

Results: In the eight patients older than 3 years, no definite abnormal signal intensity changes were found on T2-weighted images. EV2, EV3, and FA of the parieto-occipital white matter were significantly different in patients and control subjects older than 3 years. EV3 and ADC of the parieto-occipital white matter were significantly and negatively correlated with verbal IQ (r = -0.79, P = .04) and performance IQ (r = -0.93, P = .03). FA of the parieto-occipital central white matter was positively correlated with verbal IQ (r = 0.75, P = .05).

Conclusion: Though treated early, patients with chronic, stable malignant PKU had abnormal DT findings in the parieto-occipital central white matter. EV2, EV3, and FA maps are potential tools for demonstrating brain changes due to malignant PKU.

Fig 1.

Control subject aged 27 months. Maps of the brain at the level of the lateral ventricular bodies show the right parietal-occipital central white matter with ROIs in the frontoparietal, parietal-occipital, frontal central white matter and in the anterior and posterior corpus callosum. A, EV1; B, EV2; C, EV3; D, trace ADC.; E, FA index. F, Color-coded fiber orientation. Left-right, anterior-posterior, and superior-inferior directions are associated with pure red, green, and blue, respectively. Combinations of these colors represent oblique fibers.

Fig 2.

PKU patient aged 25 months. Cerebral maps at the level of lateral ventricular bodies. A, EV1. B, EV2 increases in the bilateral frontal and parietal-occipital central parenchyma, more prominently in the right parietal-occipital central areas (arrows). High-EV2 area is more extensive in bilateral parietal-occipital central areas than in areas shown in Figure 1B. C, High EV3 is prominent in parietal-occipital central areas, more on the right (arrows) than the left. D, ADCs are diffusely increased, slightly in the bilateral frontal, right frontoparietal, and bilateral parietal-occipital central parenchyma (arrows); the difference is not significant. E, FA is reduced in parietal-occipital central white matter, more on the right (arrows) than the left.