Central Nervous System Tumor With BCL6 Corepressor Internal Tandem Duplication: Treatment Course of a Long-term Survivor.

Central nervous system (CNS) tumor with BCL6 corepressor (BCOR) internal tandem duplication (ITD) is a newly described CNS tumor, characterized by in-frame ITDs of the BCOR gene. There is no standard practice regarding the management of this tumor. We report the clinical course of a 6-year-old boy who presented to the hospital with worsening headaches. Computed tomography scan showed a large right-sided parietal supratentorial mass and brain magnetic resonance imaging confirmed a 6×8×6.7 cm lobulated, solid but heterogeneous mass in the right parieto-occipital region. While initial pathology suggested a WHO grade 3 anaplastic meningioma, additional investigation with molecular analysis confirmed the diagnosis of high-grade neuroepithelial tumor with BCOR exon 15 ITD. This diagnosis was renamed CNS tumor with BCOR ITD in the 2021 WHO CNS tumor classification. The patient received 54 Gy of focal radiation and has no evidence of disease recurrence after 48 months from the end of treatment. As this is a newly discovered entity with only a few previous reports in the scientific literature, this report presents a unique treatment for this CNS tumor compared with those previously described.

Does Severity of Brain Injury on Magnetic Resonance Imaging Predict Short-Term Outcome in Neonates Who Received Therapeutic Hypothermia?

OBJECTIVE: The National Institute of Child Health and Human Development (NICHD) magnetic resonance imaging (MRI) pattern of brain injury is a known biomarker of childhood outcome following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE). However, usefulness of this classification has not been evaluated to predict short-term outcomes. The study aimed to test the hypothesis that infants with NICHD MRI pattern of severe hypoxic-ischemic brain injury will be sicker with more severe asphyxia-induced multiorgan dysfunction resulting in prolonged length of stay (LOS) following therapeutic hypothermia. We also evaluated the role of other risk factors which may prolong LOS. STUDY DESIGN: We retrospectively reviewed the medical records of 71 consecutively cooled neonates to examine the ability of MRI patterns of brain injury to predict the LOS. A neuroradiologist masked to outcomes classified the patterns of brain injury on MRI as per NICHD. Pattern 2A (basal ganglia thalamic, internal capsule, or watershed infarction), 2B (2A with cerebral lesions), and 3 (hemispheric devastation) of brain injury was deemed "severe injury." RESULTS: Out of 71 infants, 59 surviving infants had both MRI and LOS data. LOS was higher for infants who had Apgar's score of ≤5 at 10 minutes, severe HIE, seizures, coagulopathy, or needed vasopressors or inhaled nitric oxide, or had persistent feeding difficulty, or remained intubated following cooling. However, median LOS did not differ between the infants with and without MRI pattern of severe injury (15 days, interquartile range [IQR]: 9-28 vs. 12 days, IQR: 10-20; p = 0.4294). On multivariate linear regression analysis, only persistent feeding difficulty (ß coefficient = 11, p = 0.001; or LOS = 11 days longer if had feeding difficulty) and ventilator days (ß coefficient 1.7, p < 0.001; or LOS increased 1.7 times for each day of ventilator support) but not the severity of brain injury predicted LOS. CONCLUSION: Unlike neurodevelopmental outcome, LOS is not related to severity of brain injury as defined by the NICHD. KEY POINTS: · The NICHD pattern of brain injury on MRI predicts neurodevelopmental outcome following hypothermia treatment for neonatal HIE.. · LOS did not differ between the infants with and without MRI patterns of severe injury.. · The severity of brain injury as defined by the NICHD was not predictive of the LOS following therapeutic hypothermia..

Pineal Parenchymal Tumor of Intermediate Differentiation and DICER1 Syndrome: A Case Report.

DICER1 syndrome is a rare inherited tumor predisposition syndrome associated with an increased risk for several malignant and benign tumors. We present a patient with pineal parenchymal tumor of intermediate differentiation who was found to have a germline pathogenic variant in DICER1 gene. Pineoblastoma is a known DICER1-related tumor; however, the association between pineal parenchymal tumor of intermediate differentiation and DICER1 mutation is rare with only 1 recent large molecular study that has reported this association. This report adds to the evolving tumor spectrum of DICER1 and highlights the importance of molecular evaluation of pediatric brain tumors, for both therapeutic decisions and long-term surveillance.

A Rare Case of Type B Neonatal Pyruvate Carboxylase Enzyme Deficiency Presenting With Refractory Lactic Acidosis in the Early Neonatal Period.

Pyruvate carboxylase (PC) enzyme deficiency is a rare genetic disorder inherited in an autosomal recessive (AR) manner. PC, a mitochondrial enzyme, converts pyruvate to oxaloacetate (OAA), which enters the tricarboxylic acid (TCA) cycle. Based on the tissue type, intermediate metabolites of the TCA cycle play a vital role in gluconeogenesis, lipogenesis, synthesis of nicotinamide adenine dinucleotide phosphate (NADPH), and neurotransmitter glutamate in the astrocytes. The severity of clinical presentation depends on the type of PC deficiency and on the residual enzyme activity. We present a term female infant admitted with refractory lactic acidosis that developed soon after birth. On biochemical evaluation, serum ammonia was 125 µmol/L; plasma amino acid analysis showed elevated citrulline, lysine, proline, decreased glutamine, and aspartic acid; urine organic acid analysis showed markedly increased lactic acid, and moderately elevated 3-hydroxy-butyric and acetoacetic acid. MRI brain demonstrated abnormal diffuse white matter edema, loculated and septate large cysts along the caudothalamic notch as well as lateral aspect of the frontal horn bilaterally. Magnetic resonance (MR) spectroscopy showed large amounts of lactate peak. Molecular genetic analysis showed two pathogenic variants in the PC gene confirming the diagnosis of PC enzyme deficiency. The infant was discharged home on palliative and hospice care, and she died on the 22nd day after birth.

Ongoing Response in a Multiply Relapsed Metastatic Posterior Fossa Ependymoma A After Vorinostat and Concomitant Irradiation.

Posterior fossa ependymomas A confer the worst prognosis among all subtypes. They demonstrate distinct epigenetic changes, which can be targeted with epigenetic modifiers like histone deacetylase inhibitors (Vorinostat). We describe a 3-year-old male diagnosed with a posterior fossa ependymoma who had a number of recurrences requiring multimodal therapy. Molecular analysis demonstrated a BCL-6 corepressor mutation, and methylation profiling matched with posterior fossa ependymomas A. He received craniospinal irradiation and focal boost with Vorinostat. Serial imaging after irradiation revealed a progressively decreasing tumor burden with nearly complete resolution of disease at 15 months. Histone deacetylase inhibitors demonstrate promise in treatment of carefully selected cases of ependymoma.

Reversible Cerebral Vasoconstriction Syndrome and Sickle Cell Disease: A Case Report.

Reversible cerebral vasoconstriction syndrome (RCVS), is rare in the pediatric population and is characterized by severe headaches and other neurologic symptoms. We present a case of RCVS occurring concomitantly with posterior reversible encephalopathy syndrome in an 8-year-old African American child with sickle cell disease (HbSS). Imaging studies including computed tomography, magnetic resonance imaging and cerebral angiography of the brain showed acute hemorrhagic stroke and a beaded appearance of peripheral cerebral vessels. In this report, we focus on the typical features of RCVS and discuss the underlying risk factors that may increase the risk in patients with HbSS disease.

Term Infant with Cerebral Venous Sinus Thrombosis.

Hypernatremic dehydration in neonates is a common condition in an exclusively breastfed infant but often underdiagnosed. Any newborn who has lost more than 10% of birthweight should be carefully evaluated and monitored for clinical features of dehydration. Efforts such as frequent follow-up for weight check, and formula supplementation, if needed, should be provided to a neonate at risk of developing complications of dehydration. Adequate lactation consultation, both inpatient and outpatient, should also be provided, especially to the primigravida mother. Here, we present a case of a neonate with severe hypernatremic dehydration caused by inadequate lactation in a primigravida mother, which resulted in cerebral venous sinus thrombosis leading to significant intracerebral hemorrhage. The infant suffered permanent neurologic damage and was sent home on technological devices (tracheostomy and gastrostomy tubes). Further, we provide a brief review of hypernatremic dehydration and sinus venous thrombosis in neonates.

Pneumocephalus in a Pediatric Patient with Glioma Receiving Trametinib.

The mitogen-activated protein kinase (MAPK) pathway consists of the Ras/Raf/MEK/ERK signaling cascade, and its upregulation plays a major role in the pathogenesis of pediatric astrocytomas and molecular inhibitors of this pathway including trametinib and dabrafenib have been tested in early-phase clinical trials and used by pediatric oncologists in children with BRAF-mutated gliomas. We report a clinical case where a child with progressive BRAF-mutated glioma developed an uncommon and difficult to manage complication - pneumocephalus from intracranial air entry and trapping through dehisced surgical wounds and preexisting skull burr holes. The patient's wound breakdown coincided with skin toxicity from MEK inhibitor therapy. With increasing use of targeted molecular inhibitors in pediatric neuro-oncology, this case illustrates the potentially complicated course of MEK inhibitor therapy in patients with scalp surgical wounds and burr holes that were placed within few weeks from initiation of drug therapy, especially if patients have additional factors that can contribute to poor wound healing such as use of steroids and malnutrition.

Monozygotic twins with neuroblastoma MS have a similar molecular profile: a case of twin-to-twin metastasis.

Fetoplacental neuroblastoma metastasis has been postulated as a mechanism accounting for concordant cases where one twin develops a primary tumour and the second twin manifests the disease without an identifiable primary site. These tumours may originate and spread concomitantly due to the same genetic background shared by monozygotic twins. This study investigated the molecular profile of stage MS neuroblastoma presenting concomitantly in monozygotic twins. Comparative genomic hybridisation (aCGH) was done for each of the twin liver tumour and peripheral blood samples at diagnosis. Comparison of copy-number variation (CNV) regions revealed a set of CNVs that were common to both tumour specimens and not apparent in the blood. The CNV signature in both twins' tumours was highly similar, suggesting a common clonal origin. Additional findings included large deletion of chromosome 10 and amplification of chromosome 17. Notably, both liver samples had amplification of a short region involving DEIN (chromosome 4q34.1). Similar CNVs strongly support a common clonal origin and metastatic spread from one twin to the other. DEIN is a long-coding RNA (IncRNA) that has been found highly expressed in stage MS neuroblastoma and is likely involved in biological processes such as cell migration and metastasis.

In-hospital outcomes of neonates with hypoxic-ischemic encephalopathy receiving extracorporeal membrane oxygenation.

OBJECTIVE: To determine in-hospital outcomes of neonates with hypoxic ischemic encephalopathy (HIE) requiring extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: Single-center retrospective study from 2005 to 2016 of neonates ≥35 weeks gestation with moderate/severe HIE, requiring ECMO for persistent pulmonary hypertension of newborn (PPHN). RESULTS: Our cohort (n = 20) received therapeutic hypothermia for moderate (n = 12), severe (n = 5), or undocumented severity (n = 3) of HIE. During ECMO, 30% (n = 6) infants developed intracranial hemorrhage at a median (IQR) duration of 24 (20) hours. Sixteen (80%) infants survived to discharge, among which 15 had MRI performed; 47% (n = 7) had normal MRI, 20% (n = 3) had intracranial hemorrhage and 13% (n = 2), 13% (n = 2) and 7% (n = 1) had NICHD stage 1, 2, and 3 pattern of brain injury respectively. CONCLUSIONS: In this high-risk population of neonates, use of ECMO was safe and efficacious as demonstrated by survival and outcomes.

Concomitant Use of Panobinostat and Reirradiation in Progressive DIPG: Report of 2 Cases.

Diffuse intrinsic pontine glioma (DIPG) remains a devastating disease. Panobinostat has been shown to have therapeutic efficacy both in vitro and in DIPG orthotopic xenograft models; however, clinical data in patients with DIPG are lacking. We present 2 cases of DIPG, who were treated with panobinostat at 22 to 25 mg/m/dose, 3 times weekly for 2 weeks in 3-week cycles and concomitant reirradiation after disease progression. Two episodes of asymptomatic thrombocytopenia were observed in 1 patient. Hyperacetylation of histone H4 of peripheral blood mononuclear cells was evident following treatment. In our experience, panobinostat administered with reirradiation was well tolerated at a relatively higher dose than that used in adult studies.