Magnetic Resonance Imaging-Based Distribution and Reversibility of Lesions in Pediatric Vigabatrin-Related Brain Toxicity.

BACKGROUND: We aimed to systematically characterize the magnetic resonance imaging (MRI) findings in vigabatrin-related neurotoxicity in children and determine the reversibility of lesions based on follow-up images. METHODS: We evaluated children with a history of refractory seizures who had a brain MRI while on vigabatrin therapy. We included available brain MRI studies before vigabatrin therapy initiation, during vigabatrin treatment, and after vigabatrin was discontinued. A pediatric neuroradiologist systematically assessed images on T2/fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging /apparent diffusion coefficient sequences to identify hyperintense lesions and/or restricted diffusion. The frequency of abnormal signal at each location was determined, as well as the reversibility of these after vigabatrin discontinuation. RESULTS: MRIs of 43 patients were reviewed: 13 before vigabatrin initiation, 18 during treatment, and 12 after vigabatrin discontinuation. In the MRIs acquired during vigabatrin treatment, most lesions on T2/FLAIR occurred in the globus pallidi, thalami, and midbrain. Correspondingly, the most common locations for restricted diffusion were the globus pallidi, thalami, and subthalamic nuclei. On MRI after vigabatrin discontinuation, complete resolution of lesions on T2/FLAIR in all patients was seen in the midbrain, dentate nuclei, subthalamic nuclei, and hypothalami. Complete resolution of restricted diffusion was observed in the globus pallidi, midbrain, dentate nuclei, hippocampi, anterior commissure, and hypothalami. CONCLUSION: Globus pallidi and thalami are the most commonly affected structures in vigabatrin-related toxicity, and most vigabatrin-related neuroimaging findings are reversible.

Distribution of IntraThalamic Injury According to Nuclei and Vascular Territories in Children With Term Hypoxic-Ischemic Injury.

BACKGROUND: Term hypoxic-ischemic injury (HII) on magnetic resonance imaging (MRI) is described as the basal ganglia thalamus [BGT], watershed [WS], or combined [BGT/WS] groups. We aimed to determine differences between HII groups in intrathalamic distribution. METHODS: Delayed MRIs of children with HII and thalamic injury were reviewed. Custom tools were placed over T2-weighted and/or fluid-attenuated inversion recovery axial images to determine distribution of intrathalamic injury: (1) six subjective (whole/near-whole, central, anterior, posterior, lateral, medial); (2) four nuclear (anterior [AN], ventrolateral [VLN], medial [MN], and pulvinar [PN]); and (3) three arterial (thalamoperforating arteries [TPA], thalamogeniculate arteries [TGA], and posterior choroidal arteries [PCA]) locations. We compared the frequency of injury of the aforementioned intrathalamic locations between HII groups. RESULTS: The 128 children (mean age at MRI 7.35 ± 3.6 years) comprised 41% (n = 53) BGT, 26% (n = 33) WS, and 33% (n = 42) BGT/WS. The VLN was the most frequent injured nuclear region (66%, n = 85), and the TGA (93%, n = 128) was the most frequent arterial region involved. VLN injury occurred more frequently in the BGT group (P < 0.001), PN in the WS group (P < 0.001), and AN (P < 0.001), MN (P < 0.001), PN (P = 0.001), and all nuclei together (P < 0.001) in the BGT/WS group. The combination of all vascular territories was significantly associated with BGT/WS (P < 0.001). CONCLUSIONS: There are significant differences in intrathalamic nuclear and arterial injuries between the different types of HII.

Atypical Triplane Fracture-Anteromedial Epiphyseal Sleeve Avulsion Pattern.

Atypical triplane fractures are unusual, but when they occur, the anteromedial epiphyseal sleeve avulsion pattern appears to be the most frequent. We present a classic case of the latter, which supports the introduction of an additional category to the classification of these fractures.

Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions.

Uncharacterized and unannotated open-reading frames, which we refer to as novel open reading frames (nORFs), may sometimes encode peptides that remain unexplored for novel therapeutic opportunities. To our knowledge, no systematic identification and characterization of transcripts encoding nORFs or their translation products in cancer, or in any other physiological process has been performed. We use our curated nORFs database (nORFs.org), together with RNA-Seq data from The Cancer Genome Atlas (TCGA) and Genotype-Expression (GTEx) consortiums, to identify transcripts containing nORFs that are expressed frequently in cancer or matched normal tissue across 22 cancer types. We show nORFs are subject to extensive dysregulation at the transcript level in cancer tissue and that a small subset of nORFs are associated with overall patient survival, suggesting that nORFs may have prognostic value. We also show that nORF products can form protein-like structures with post-translational modifications. Finally, we perform in silico screening for inhibitors against nORF-encoded proteins that are disrupted in stomach and esophageal cancer, showing that they can potentially be targeted by inhibitors. We hope this work will guide and motivate future studies that perform in-depth characterization of nORF functions in cancer and other diseases.