Topological Alterations of the Structural Brain Connectivity Network in Children with Juvenile Neuronal Ceroid Lipofuscinosis.

BACKGROUND AND PURPOSE: We used diffusion MR imaging to investigate the structural brain connectivity networks in juvenile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disease of childhood. Although changes in conventional MR imaging are typically not visually apparent in children aged <10 years, we previously found significant microstructural abnormalities by using diffusion MR imaging. Therefore, we hypothesized that the structural connectivity networks would also be affected in the disease. MATERIALS AND METHODS: We acquired diffusion MR imaging data from 14 children with juvenile neuronal ceroid lipofuscinosis (mean ± SD age, 9.6 ± 3.4 years; 10 boys) and 14 control subjects (mean ± SD age, 11.2 ± 2.3 years; 7 boys). A follow-up MR imaging was performed for 12 of the patients (mean ± SD age, 11.4 ± 3.2 years; 8 boys). We used graph theoretical analysis to investigate the global and local properties of the structural brain connectivity networks reconstructed with constrained spherical deconvolution-based whole-brain probabilistic tractography. RESULTS: We found significantly increased characteristic path length (P = .003) and decreased degree (P = .003), which indicated decreased network integration and centrality in children with juvenile neuronal ceroid lipofuscinosis. The findings were similar for the follow-up MR imaging, and there were no significant differences between the two acquisitions of the patients. In addition, we found that the disease severity correlated negatively (P < .007) with integration, segregation, centrality, and small-worldness of the networks. Moreover, we found significantly (P < .0003) decreased local efficiency in the left supramarginal gyrus and temporal plane, and decreased strength in the right lingual gyrus. CONCLUSIONS: We found significant global and local network alterations in juvenile neuronal ceroid lipofuscinosis that correlated with the disease severity and in areas related to the symptomatology.

Global and Widespread Local White Matter Abnormalities in Juvenile Neuronal Ceroid Lipofuscinosis.

BACKGROUND AND PURPOSE: Juvenile neuronal ceroid lipofuscinosis is a progressive neurodegenerative lysosomal storage disease of childhood. It manifests with loss of vision, seizures, and loss of cognitive and motor functions leading to premature death. Previous MR imaging studies have reported cerebral and cerebellar atrophy, progressive hippocampal atrophy, thalamic signal intensity alterations, and decreased white matter volume in the corona radiata. However, conventional MR imaging findings are usually normal at younger than 10 years of age. The purpose of our study was to investigate whether diffusion MR imaging could reveal changes in white matter microstructure already present at a younger age. MATERIALS AND METHODS: We investigated global and local white matter abnormalities in 14 children with juvenile neuronal ceroid lipofuscinosis (mean age, 9.6 ± 3.4 years; 10 boys) and 14 control subjects (mean age, 11.2 ± 2.3 years; 7 boys). Twelve patients underwent follow-up MR imaging after 2 years (mean age, 11.4 ± 3.2 years; 8 boys). We performed a global analysis using 2 approaches: white matter tract skeleton and constrained spherical deconvolution-based whole-brain tractography. Then, we investigated local microstructural abnormalities using Tract-Based Spatial Statistics. RESULTS: We found globally decreased anisotropy (P = .000001) and increased diffusivity (P = .001) in patients with juvenile neuronal ceroid lipofuscinosis. In addition, we found widespread increased diffusivity and decreased anisotropy in, for example, the corona radiata (P < .001) and posterior thalamic radiation (P < .001). However, we found no differences between the first and second acquisitions. CONCLUSIONS: The patients with juvenile neuronal ceroid lipofuscinosis exhibited global and local abnormalities in white matter microstructure. Future studies could apply more specific microstructural models and study whether these abnormalities are already present at a younger age.

Brain magnetic resonance imaging of siblings from families with two or more children with learning or intellectual disabilities and need for full-time special education.

BACKGROUND: Several factors are involved in determining a child's need for special education (SE). Thus, the value of brain magnetic resonance imaging (MRI) for subjects with learning and intellectual disabilities is uncertain. PURPOSE: To evaluate the usefulness of MRI in the diagnostic process of siblings with learning and intellectual disabilities and need for full-time SE. MATERIAL AND METHODS: Altogether, 119 siblings (mean age 11.9 years) from families in which two or more children attended/had previously attended full-time SE underwent prospective brain MRI. SE grouping included three levels, from specific learning disabilities (level 1) to global intellectual disabilities (level 3). Forty-three controls (level 0, mean age 12.0 years) attended mainstream education groups. Signal intensity and structural abnormalities were analyzed, and areas of the cerebrum, posterior fossa, corpus callosum, vermis and brain stem, and diameters of the corpus callosum were measured. In analyses, all area measurements were calculated in proportion to the total inner skull area. RESULTS: Abnormal finding in MRI was more common for siblings (n=62; 52%) in SE (58% for level 3; 49% for level 2; 35% for level 1) than for controls (n=13; 16%). The siblings showed enlarged supra- (P<0.001) and infratentorial (P=0.015) cerebrospinal fluid (CSF) spaces and mild corpus callosum abnormalities (P=0.003) compared to controls. Siblings in SE had smaller inner skull area than controls (P<0.001). Further, the relative area of the mesencephalon (P=0.027) and the diameter of the body of the corpus callosum (P=0.015) were significantly smaller than in controls. In binary logistic regression analysis, enlarged supratentorial CSF spaces increased the probability of SE (odds ratio 4.2; P=0.023). CONCLUSION: Subjects with learning and intellectual disabilities commonly have more MRI findings than controls. Enlarged supratentorial CSF spaces were a frequent finding in siblings in full-time SE.

Transdermal fentanyl therapy for pains in children with infantile neuronal ceroid lipofuscinosis.

We used infantile neuronal ceroid lipofuscinosis (INCL), in which deterioration of the central nervous system is extremely rapid, to study constant release of an opioid for pains of central origin in a metabolic disease. The effect of a transdermal fentanyl patch was studied in five children with INCL. In two of them, measurements of 17 fentanyl serum concentrations and also visual analogue pain scale were obtained during a 15-day study period. Low doses of transdermal fentanyl usually provided good pain relief for the first two days, but not for the third day, of the three-day patch change interval. Pain relief of this type seems mandatory for pains mostly of central origin.