Brain MRI findings in aspartylglucosaminuria.

BACKGROUND AND PURPOSE: The aim of this study was to identify characteristic 3.0 T brain MRI findings in patients with aspartylglucosaminuria (AGU), a rare lysosomal storage disorder. Previous AGU patient material imaged at 1.0 and 1.5 T was also re-evaluated. MATERIALS AND METHODS: Twenty-five brain MRI examinations from 20 AGU patients were included in the study. Thirteen patients underwent a prospective 3.0 T MRI (5 male, 8 female, aged 9-45 years). Twelve examinations from nine patients (4 male, 5 female, aged 8-33 years) previously imaged at 1.0 or 1.5 T were re-evaluated. Two patients were included in both the prospective and the retrospective groups. Visual analysis of the T1- and T2-weighted images was performed by two radiologists. RESULTS: The previously reported signal intensity changes in T2-weighted images were visible at all field strengths, but they were more distinct at 3.0 T than at 1.0 or 1.5 T. These included signal intensity decrease in the thalami and especially in the pulvinar nuclei, periventricular signal intensity increase and juxtacortical high signal foci. Poor differentiation between gray and white matter was found in all patients. Some degree of cerebral and/or cerebellar atrophy and mild ventricular dilatation were found in nearly all patients. This study also disclosed various unspecific findings, including a higher than normal incidence of dilated perivascular spaces, arachnoid cysts, pineal cysts and mildly dilated cavum veli interpositi. CONCLUSION: This study revealed particular brain MRI findings in AGU, which can raise the suspicion of this rare disease in clinical practice.

Detection of Aspartylglucosaminuria Patients from Magnetic Resonance Images by a Machine-Learning-Based Approach.

Magnetic resonance (MR) imaging data can be used to develop computer-assisted diagnostic tools for neurodegenerative diseases such as aspartylglucosaminuria (AGU) and other lysosomal storage disorders. MR images contain features that are suitable for the classification and differentiation of affected individuals from healthy persons. Here, comparisons were made between MRI features extracted from different types of magnetic resonance images. Random forest classifiers were trained to classify AGU patients (n = 22) and healthy controls (n = 24) using volumetric features extracted from T1-weighted MR images, the zone variance of gray level size zone matrix (GLSZM) calculated from magnitude susceptibility-weighted MR images, and the caudate-thalamus intensity ratio computed from T2-weighted MR images. The leave-one-out cross-validation and area under the receiver operating characteristic curve were used to compare different models. The left-right-averaged, normalized volumes of the 25 nuclei of the thalamus and the zone variance of the thalamus demonstrated equal and excellent performance as classifier features for binary organization between AGU patients and healthy controls. Our findings show that texture-based features of susceptibility-weighted images and thalamic volumes can differentiate AGU patients from healthy controls with a very low error rate.

Statistical Permutation Test Reveals Progressive and Region-Specific Iron Accumulation in the Thalami of Children with Aspartylglucosaminuria.

Aspartylglucosaminuria (AGU) is a rare lysosomal storage disorder causing developmental delay, intellectual disability, and eventual death. A distinct feature in AGU is iron accumulation within the thalamus. Our aim is to demonstrate that susceptibility-weighted images (SWI) could be used as an MRI biomarker to evaluate the response within the AGU population to newly evolving treatments. SWI from 16 patients with AGU and 16 age-matched controls were used in the analysis. Thalamic volume with an iron accumulation was identified using a permutation test. Group differences were investigated for both the complete thalamus and the iron accumulation regions. Group-wise age correlation within these volumes were assessed with analysis of variance and multivariate regression. We found a statistically significant and large difference (p-value = 0.01, Cohen's D = 0.97) for the whole thalamus comparison and an even greater difference in the iron accumulation regions (p-value < 0.01, Cohen's D = 3.52). Furthermore, we found strong evidence for iron accumulation as a linear function of age with R2 = 0.65 only for AGU. The statistical analysis of SWI provides tools for assessing the degree of iron accumulation. This method could be used to study the response to treatments, in that a successful treatment would be expected to result in a decline in iron accumulation.

Hippocampal volumes in juvenile neuronal ceroid lipofuscinosis: a longitudinal magnetic resonance imaging study.

BACKGROUND: Juvenile neuronal ceroid lipofuscinosis is an inherited, autosomal recessive, progressive, neurodegenerative disorder of childhood. It belongs to the lysosomal storage diseases, which manifest with loss of vision, seizures, and loss of cognitive and motor functions, and lead to premature death. Imaging studies have shown cerebral and cerebellar atrophy, yet no previous studies evaluating particularly hippocampal atrophy have been published. This study evaluates the hippocampal volumes in adolescent juvenile neuronal ceroid lipofuscinosis patients in a controlled 5-year follow-up magnetic resonance imaging study. METHODS: Hippocampal volumes of eight patients (three female, five male) and 10 healthy age- and sex-matched control subjects were measured from two repeated magnetic resonance imaging examinations. Three male patients did not have controls and were excluded from the statistics. In the patient group, the first examination was performed at the mean age of 12.2 years and the second examination at the mean age of 17.3 years. In the control group, the mean ages at the time of examinations were 12.5 years and 19.3 years. RESULTS: Progressive hippocampal atrophy was found in the patient group. The mean total hippocampal volume decreased by 0.85 cm³ during the 5-year follow-up in the patient group, which corresponds to a 3.3% annual rate of volume loss. The whole brain volume decreased by 2.9% per year. The observed annual rate of hippocampal atrophy also exceeded the previously reported 2.4% annual loss of total gray matter volume in juvenile neuronal ceroid lipofuscinosis patients. CONCLUSIONS: These data suggest that progressive hippocampal atrophy is one of the characteristic features of brain atrophy in juvenile neuronal ceroid lipofuscinosis in adolescence.