Chromosome band 7q34 deletions resulting in KIAA1549-BRAF and FAM131B-BRAF fusions in pediatric low-grade Gliomas.

The majority of pediatric low-grade gliomas (LGGs) are characterized by constitutive activation of the mitogen-activated protein kinase (MAPK) pathway through various mechanisms including BRAF mutations, inactivation of NF1, and KIAA1549-BRAF and FAM131B-BRAF fusions. The KIAA1549-BRAF fusion typically results from a 2.0 Mb tandem duplication in chromosome band 7q34. In the present study, single nucleotide polymorphism (SNP)-based array analysis of three LGGs demonstrated deletions in 7q34 that resulted in a BRAF fusion. Case 1 was likely a pilocytic astrocytoma (PA) with three deletions in 7q33q34 and an exon 15-9 KIAA1549-BRAF fusion. SNP array analysis of case 2, a possible dysembryoplastic neuroepithelial tumor (DNT), revealed a 2.6 Mb deletion, which included the 5' end of BRAF and extended to the 3' end of FAM131B. In case 3, deletions involving BRAF and FAM131B were observed in both a primary and a recurrent PA. RNA-based sequence analysis of cases 2 and 3 confirmed a fusion between FAM131B exon 2 and BRAF exon 9. The presence of fusion transcripts in these three LGGs highlights the utility of SNP array analysis to identify deletions that are suggestive of fusion proteins. BRAF fusions can result from multiple non-overlapping deletions, suggesting various complex mechanisms of formation.

Early prediction of postmeningitic hearing loss in children using magnetic resonance imaging.

OBJECTIVE: To determine whether early gadolinium-enhanced magnetic resonance imaging (GdMRI) can reliably detect meningitic labyrinthitis and thereby predict which children are at high risk for hearing loss. Permanent sensorineural hearing loss (SNHL) remains a common sequela of bacterial meningitis, and early diagnosis of the associated suppurative labyrinthitis can be difficult, especially in critically ill, sedated patients and young children. DESIGN: Retrospective cohort study. SETTING: Tertiary pediatric hospital. PARTICIPANTS: Twenty-three survivors of bacterial meningitis (median age, 15 months [range, 3 months-14 years]) who had undergone brain GdMRI during the acute disease and had subsequent ear-specific audiometric data. MAIN OUTCOME MEASURE: Blinded to disease and outcome, a neuroradiologist rated the relative enhancement of each cochlea on T1-weighted images using a 4-point scale. Scores were then correlated with the degree of hearing loss on subsequent testing. RESULTS: Sensorineural hearing loss occurred in 15 of 46 ears (8 of 23 patients). Enhancement on GdMRI was detected in 13 of the 15 ears that later developed SNHL but was absent in all 31 unaffected ears. Thus, GdMRI was 87% sensitive and 100% specific for predicting which ears would develop permanent SNHL. In the subgroup with pneumococcal meningitis (n = 15), GdMRI was 100% sensitive and 100% specific. Labyrinthine enhancement was detectable as early as 1 day after diagnosis. CONCLUSION: Gadolinium-enhanced MRI detected meningitic labyrinthitis at early stages and accurately predicted which patients would later develop hearing loss.

Takayasu arteritis presenting as cerebral aneurysms in an 18 month old: A case report.

BACKGROUND: Central nervous system involvement occurs in as many as twenty percent of Takayasu arteritis cases. When central nervous system disease is present, it typically manifests as cerebral ischemia or stroke. There are rare reports of intracranial aneurysms in adults with Takayasu arteritis, but none in children. CASE PRESENTATION: We describe a case of Takayasu arteritis in an 18 month old girl who presented with a ruptured cerebral aneurysm. Full body magnetic resonance angiography revealed bilateral iliac, pelvic and intragluteal aneurysms, irregular terminal aorta, and stenotic renal arteries. Iliac vessel biopsy showed a lymphocytic infiltrate and giant cells localized to the internal elastica. CONCLUSION: This case highlights cerebral aneurysm as a highly unusual initial manifestation of Takayasu arteritis and demonstrates the challenges of diagnosis, treatment, and assessment of response to therapy in TA in children.

The role of [18F]-fluorodeoxyglucose positron emission tomography in predicting plexiform neurofibroma progression.

BACKGROUND: The role of FDG-PET for managing patients with plexiform neurofibromas (PN) is unclear. While many PN tumors exhibit periods of rapid growth, others grow slowly or unpredictably and may have periods of relative quiescence. The ability to predict which PN are likely to progress should facilitate a more timely initiation of medical treatments. Since conventional radiographic techniques have limited prognostic value, the use of a functional imaging modality to predict tumor progression is desirable. We hypothesized that PN tumors with high metabolic activity as demonstrated by FDG-PET are more likely to progress in the following year. METHODS: All patients were clinically stable, but were considered at high-risk for progression based on anatomical location of PN. FDG-PET scans were performed within two weeks of the baseline MRI study. Standardized uptake values (SUV) were calculated for all focally active index lesions and analyzed for correlation with changes in quantitative MRI over the ensuing year. RESULTS: Fifteen of the 18 enrolled patients showed various degrees of FDG uptake as focal abnormalities, and these abnormalities corresponded to those noted on the MRI scans. Thirteen patients and 19 lesions were evaluable for PN volume change. The SUVmax ranged from 0.9 to 4 (median 1.5). There was a significant difference in the percent increase in PN volume in the following year for lesions that had an SUV > 2 compared to those with lower values (P = 0.016). CONCLUSIONS: These findings support the hypothesis that FDG-PET imaging predicts PN growth rate, and, therefore, may assist clinician decision making with regard to treatment of PN and enrollment in clinical trials.

Occipitalization of the atlas in children. Morphologic classification, associations, and clinical relevance.

BACKGROUND: Occipitalization is defined as a congenital fusion of the atlas to the base of the occiput. We are not aware of any previous studies addressing the morphologic patterns of occipitalization or the implications of occipitalization in children. We present data on what we believe is the largest reported series of children with occipitalization studied with computed tomography and/or magnetic resonance imaging, and we provide a description of their clinical characteristics. METHODS: We retrospectively reviewed all cases of occipitalization in children included in our spine database. Patient charts and imaging studies were reviewed. A new morphologic classification of occipitalization was developed from the two-dimensional sagittal and coronal reformatted computed tomographic reconstructions and/or magnetic resonance images. The classification includes four patterns according to the anatomic site of occipitalization (Zones 1, 2, and 3 and a combination of those zones), and it was applied to this group of patients. Imaging studies were also reviewed for evidence of cervical instability and for other anomalies of the craniovertebral junction. RESULTS: Thirty patients with occipitalization were identified. There were twenty-four boys and six girls with a mean age of 6.5 years. The morphologic categorization was Zone 1 (a fused anterior arch) in six patients, Zone 2 (fused lateral masses) in five, Zone 3 (a fused posterior arch) in four, and a combination of fused zones in fifteen. Seventeen patients (57%) had atlantoaxial instability, and eight of them had an associated C2-C3 fusion. Eleven patients (37%) had spinal canal encroachment, and five of them had clinical findings of myelopathy. The highest prevalence of spinal canal encroachment (63%) was noted in patients with occipitalization in Zone 2. CONCLUSIONS: Occipitalization is associated with abnormalities that lead to narrowing of the space available for the spinal cord or brainstem. The risk of atlantoaxial instability developing is particularly high when there is an associated congenital C2-C3 fusion. Two-dimensional sagittal and coronal reformatted computed tomographic reconstructions and/or magnetic resonance images can help to establish the diagnosis and permit categorization of occipitalization in three zones, each of which may have a different prognostic implication.