Atypical Molecular Features of Pediatric Tectal Glioma: A Single Institutional Series.

We present 4 children (diagnosed between 1 and 8 y, 3 females and 1 male) with molecularly distinct tectal gliomas (2 KRAS mutant, 1 EGFR mutant, 1 SRGAP3-RAF-1 fusion) that contributes to the growing literature of this uncommonly biopsied tumor. The patient with EGFR R222C mutation had a more severe course, earlier diagnosis, subsequent leptomeningeal metastatic disease, required more aggressive therapies, and died 9 years after diagnosis. Patients with KRAS mutations and SRGAP3-RAF-1 fusion had a more indolent course. Our series expands the molecular phenotype of tectal glioma with the potential for leptomeningeal dissemination. Future studies on establishing genotypic/phenotypic correlation from those who undergo biopsy are needed.

Use of hyperbaric oxygen therapy in pediatric neuro-oncology: a single institutional experience.

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) has been utilized as adjunctive treatment of CNS tumors and for radiation necrosis (RN) with reported success. The safety and efficacy in pediatric patients is less understood. METHODS: Seven patients (ages 10-23 years, six females) were treated with HBOT (3-60 sessions) for either RN (n = 5) or tumor-associated edema (n = 2). Tumor diagnosis included low-grade glioma (n = 4, two with neurofibromatosis type 1), meningioma (n = 1), medulloblastoma (n = 1) and secondary high grade glioma (n = 1). Prior therapies included: surgery (n = 4), chemotherapy (n = 4) and radiation (N = 5: four focal, one craniospinal). Three underwent biopsy: one confirming RN, one high-grade glioma, and one low-grade glioma. Patients were assessed for clinical and radiographic changes post HBOT. RESULTS: Median time to clinical and radiographic presentation was 8.5 months (range 6 months-11 years) in those who had prior radiation. Clinical improvement after HBOT (median: 40 sessions) was observed in four of seven patients. Symptoms were stable in two and worsened in one patient. Radiographic improvement was seen in four patients; three had radiographic disease progression. In the subgroup treated for presumed and biopsy-confirmed RN (n = 5), four of five (80%) had clinical and radiographic improvement. There were no long-term adverse events due to HBOT. CONCLUSIONS: HBOT is safe and well-tolerated in pediatric and young adult patients with CNS tumors. Clinical and radiographic improvements were observed in over half of patients. Clinical trials are needed to establish safety and efficacy of HBOT as adjunct therapy in pediatric CNS tumors.

Neuroimaging features of accidental fentanyl overdose in a toddler.

The opioid epidemic has become a significant public health crisis worldwide. With the rise in popularity of fentanyl, opioid overdoses continue to rise at unprecedented rates. Unfortunately, young children have become collateral damage in the face of the opioid epidemic. Accidental exposures and ingestions are the leading cause of opioid overdose in this age group and can result in significant acute complications, long-term sequelae and even death. We present the case of a toddler with accidental fentanyl ingestion who experienced seizures and required intubation for respiratory distress. He was found to have notable diffusion restriction cerebellar changes on MRI and ultimately discharged with normal neurological function. Our case adds to the growing literature of the clinical presentation and neuroimaging features associated with opioid toxicity in young children.

Pediatric Paraneoplastic Necrotizing Encephalitis Associated With Acute Lymphoblastic Leukemia.

BACKGROUND: Paraneoplastic encephalitis encompasses a diverse spectrum of neurological disorders associated with a variety of pediatric tumor types. METHODS: We describe a seven-year-old boy with paraneoplastic necrotizing encephalitis associated with precursor B-cell acute lymphoblastic leukemia. RESULTS: The initial presentation involved acute-onset upper extremity weakness, seizure-like activity, and agitation. Extensive evaluation revealed pancytopenia, elevated protein in the cerebrospinal fluid, and normal magnetic resonance imaging (MRI) consistent with a clinical diagnosis of encephalitis of presumed viral etiology. He was treated with antimicrobials and intravenous immunoglobulin and returned to his neurological baseline before discharge. One month later, he was diagnosed with precursor B-cell acute lymphoblastic leukemia. Before chemotherapy initiation, he again became encephalopathic. Repeat cerebrospinal fluid evaluation showed elevated protein, and MRI revealed findings consistent with diffuse necrotizing encephalitis. He received standard chemotherapy as well as immunotherapy with intravenous immunoglobulin and plasmapheresis, with resolution of MRI abnormalities and improvement in neurological status. At six years postpresentation, he is in remission for acute lymphoblastic leukemia, without significant neurocognitive deficits and mild right spastic hemiparesis. CONCLUSION: This is the first report of paraneoplastic encephalitis associated with pediatric leukemia. A hematologic malignancy should be considered in the differential diagnosis of paraneoplastic encephalitis.

Atypical anaplastic astrocytoma with unique molecular features and diffuse leptomeningeal spread in a child with long-term survival.

Paediatric high-grade gliomas, including glioblastoma and anaplastic astrocytoma, make up 8%-12% of paediatric central nervous system tumours 1 and have poor prognosis, with 2-year survival less than 30% 2 and overall survival less than 10%. The only known prognostic factors in this population include extent of resection and tumour histological grade. We present the case of a 9-year-old boy with disseminated anaplastic astrocytoma treated with subtotal resection, craniospinal radiation and temozolomide, with 8-year survival despite metastatic disease at presentation and subtotal resection. Next generation cancer gene panel sequencing revealed an usual pattern of 12 amplifications and four mutations not previously described.

Atypical central neurocytoma with novel EWSR1-ATF1 fusion and MUTYH mutation detected by next-generation sequencing.

We present the case of a 13-year-old boy with a very unusual periventricular atypical central neurocytoma with unique molecular features treated with subtotal surgical resection and photon intensity-modulated radiotherapy. Histological features were most consistent with atypical central neurocytoma. However, next-generation sequencing analysis revealed a novel EWSR1-ATF1 gene fusion (EWSR1-ATF1) as well as a MUTYH mutation. The EWSR1-ATF1 raised the possibility of Ewing sarcoma or angiomatoid fibrous histiocytoma, however, FLI-1 immunohistochemistry was negative. MUTYH mutations have been reported in diffuse midline paediatric glioma. The role of EWSR1-ATF1 and MUTYH mutations in central nervous system tumours is not well established. We present the first case of EWSR1-ATF1 and MUTYH mutation in a rare paediatric atypical central neurocytoma. Further studies are indicated to elucidate the consequences of these gene alterations in the context of paediatric central nervous system tumours as well as to investigate the potential role for targeted therapies.

Severe vincristine-induced polyneuropathy in a teenager with anaplastic medulloblastoma and undiagnosed Charcot-Marie-Tooth disease.

Severe neuropathy is a known adverse effect of vincristine in patients with Charcot-Marie-Tooth disease (CMT). We present the case of a 16-year-old girl with anaplastic medulloblastoma treated with gross total resection and high-dose craniospinal radiation with adjuvant vincristine chemotherapy who developed acute-onset severe quadriplegia and vocal cord paralysis. Vincristine and radiation therapy were discontinued. Although her neuropathy slowly improved over several weeks, she developed metastatic extraneural medulloblastoma and died 5 months after diagnosis. Subsequent genetic testing revealed previously asymptomatic and undiagnosed CMT1A. Our case highlights the importance of early recognition of acute vincristine neurotoxicity that should raise suspicion of an underlying hereditary neuropathy.