Cerebellar Watershed Injury in Children.

BACKGROUND AND PURPOSE: Focal signal abnormalities at the depth of the cerebellar fissures in children have recently been reported to represent a novel pattern of bottom-of-fissure dysplasia. We describe a series of patients with a similar distribution and appearance of cerebellar signal abnormality attributable to watershed injury. MATERIALS AND METHODS: Twenty-three children with MR imaging findings of focal T2 prolongation in the cerebellar gray matter and immediate subjacent white matter at the depth of the fissures were included. MR imaging examinations were qualitatively analyzed for the characteristics and distribution of signal abnormality within posterior fossa structures, the presence and distribution of volume loss, the presence of abnormal contrast enhancement, and the presence and pattern of supratentorial injury. RESULTS: T2 prolongation was observed at the depths of the cerebellar fissures bilaterally in all 23 patients, centered at the expected location of the deep cerebellar vascular borderzone. Diffusion restriction was associated with MR imaging performed during acute injury in 13/16 patients. Five of 23 patients had prior imaging, all demonstrating a normal cerebellum. The etiology of injury was hypoxic-ischemic injury in 17/23 patients, posterior reversible encephalopathy syndrome in 3/23 patients, and indeterminate in 3/23 patients. Twenty of 23 patients demonstrated an associated classic parasagittal watershed pattern of supratentorial cortical injury. Injury in the chronic phase was associated with relatively preserved gray matter volume in 8/15 patients, closely matching the published appearance of bottom-of-fissure dysplasia. CONCLUSIONS: In a series of patients with findings similar in appearance to the recently described bottom-of-fissure dysplasia, we have demonstrated a stereotyped pattern of injury attributable to cerebellar watershed injury.

Tract-based spatial statistical analysis of diffusion tensor imaging in pediatric patients with mitochondrial disease: widespread reduction in fractional anisotropy of white matter tracts.

BACKGROUND AND PURPOSE: Often diagnosed at birth or in early childhood, mitochondrial disease presents with a variety of clinical symptoms, particularly in organs and tissues that require high energetic demand such as brain, heart, liver, and skeletal muscles. In a group of pediatric patients identified as having complex I or I/III deficits on muscle biopsy but with white matter tissue appearing qualitatively normal for age, we hypothesized that quantitative DTI analyses might unmask disturbance in microstructural integrity. MATERIALS AND METHODS: In a retrospective study, DTI and structural MR brain imaging data from 10 pediatric patients with confirmed mitochondrial disease and 10 clinical control subjects were matched for age, sex, scanning parameters, and date of examination. Paired TBSS was performed to evaluate differences in FA, MD, and the separate diffusion direction terms (λr and λa). RESULTS: In patients with mitochondrial disease, significant widespread reductions in FA values were shown in white matter tracts. Mean diffusivity values were significantly increased in patients, having a sparser distribution of affected regions compared with FA. Separate diffusion maps showed significant increase in λr and no significant changes in λa. CONCLUSIONS: Despite qualitatively normal-appearing white matter tissues, patients with complex I or I/III deficiency have widespread microstructural changes measurable with quantitative DTI.

Gray matter abnormalities in autism spectrum disorder revealed by T2 relaxation.

OBJECTIVE: To perform quantitative T2 relaxation measurements to evaluate cerebral water content in children with autism. METHODS: Sixty 2- to 4-year-old children with autism spectrum disorder (ASD), 16 age-matched children with idiopathic developmental delay (DD), and 10 children with typical development (TD) were scanned on a 1.5 T GE MRI scanner to obtain dual-echo fast spin echo images (2.5 mm thick, 0-mm gap). Images were segmented into gray and white matter and used to mask regions of interest for calculating T2 for each tissue type. Analysis of variance, covarying for age and sex, was used to compare T2 between groups, and correlations were used to compare T2 to IQ measures. RESULTS: Children with ASD had prolonged cortical gray matter T2, but white matter T2 was not significantly different, compared with the children with TD. T2 was prolonged in cortical gray matter and white matter in children with DD compared with children with ASD or TD. Significant interactions between T2 measures and IQ were not observed. CONCLUSIONS: Prolonged gray and white matter T2 in the children with developmental delay likely represents a delay in neuronal development and maturation. Prolonged T2 in gray matter, but not white matter, observed in children with autism spectrum disorder may signify abnormal developmental processes specific to autism.

AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome.

BACKGROUND: Joubert syndrome (JS) is an autosomal recessive disorder characterised by hypotonia, ataxia, mental retardation, altered respiratory pattern, abnormal eye movements, and a brain malformation known as the molar tooth sign (MTS) on cranial MRI. Four genetic loci have been mapped, with two genes identified (AHI1 and NPHP1). METHODS: We screened a cohort of 117 JS subjects for AHI1 mutations by a combination of haplotype analysis and sequencing of the gene, and for the homozygous NPHP1 deletion by sequencing and marker analysis. RESULTS: We identified a total of 15 novel AHI1 mutations in 13 families, including nonsense, missense, splice site, and insertion mutations, with some clustering in the WD40 domains. Eight families were consanguineous, but no single founder mutation was apparent. In addition to the MTS, retinal dystrophy was present in 11 of 12 informative families; however, no subjects exhibited variable features of JS such as polydactyly, encephalocele, colobomas, or liver fibrosis. In contrast to previous reports, we identified two families with affected siblings who developed renal disease consistent with nephronophthisis (NPH) in their 20s. In addition, two individuals with classic NPH were found to have homozygous NPHP1 deletions. CONCLUSIONS: Overall, 11% of subjects had AHI1 mutations, while approximately 2% had the NPHP1 deletion, representing a total of less than 15% in a large JS cohort. Some preliminary genotype-phenotype correlations are possible, notably the association of renal impairment, specifically NPH, in those with NPHP1 deletions. Subjects with AHI1 mutations may be at risk of developing both retinal dystrophy and progressive kidney disease.