Rosette-Forming Glioneuronal Tumor of the Fourth Ventricle in Children: Case Report and Literature Review.

BACKGROUND: Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a rare World Health Organization (WHO) grade I neoplasm. Gross total resection (GTR) is the treatment of choice, and there is no firm evidence supporting other treatment options when GTR is not feasible. CASE DESCRIPTION: We report a 6-year-old boy who, following an initial subtotal resection of a fourth ventricular RGNT, received an individualized chemotherapy protocol with vincristine, etoposide, and carboplatin for 3 cycles. The tumor was stable for 2 years after the completion of chemotherapy but then began to progress, at which point GTR was successfully performed. In addition, we completed a comprehensive literature review of RGNT cases. To date, a total of 104 cases have been reported, 33 of which are pediatric cases. Recurrence has been reported in only 7 cases of all ages (4 in the pediatric population). Radiotherapy has been used in several cases, but adjuvant chemotherapy has been reported only once following a recurrence. CONCLUSIONS: We report a case of chemotherapy administration as a first-line treatment for a subtotally resected RGNT. Chemotherapy may be considered as an adjuvant therapy option for RGNT when GTR cannot be achieved. Furthermore, increased incidence of recurrence in the pediatric population may suggest that the tumor biology of RGNT in children differs from that in adults.

Basal cell nevus syndrome or Gorlin syndrome.

Basal cell nevus syndrome (BCNS) or Gorlin syndrome is a rare neurocutaneous syndrome sometimes known as the fifth phacomatosis, inherited in autosomal dominant fashion with complete penetrance and variable expressivity. Gorlin syndrome is characterized by development of multiple basal cell carcinomas (BCCs), jaw cysts, palmar or plantar pits, calcification of falx cerebri, various developmental skeletal abnormalities such as bifid rib, hemi- or bifid vertebra and predisposition to the development of various tumors. BCNS is caused by a mutation in the PTCH1 gene localized to 9q22.3. Its estimated prevalence varies between 1/55600 and 1/256000 with an equal male to female ratio. The medulloblastoma variant seen in Gorlin syndrome patients is of the desmoplastic type, characteristically presenting during the first 3 years of life. Therefore, children with desmoplastic medulloblastoma should be carefully screened for other features of BCNS. Radiation therapy for desmoplastic medulloblastoma should be avoided in BCNS patients as it may induce development of invasive BCCs and other tumors in the skin area exposed to radiation. This syndrome is a multisystem disorder so involvement of multiple specialists with a multimodal approach to detect and treat various manifestations at early stages will reduce the long-term sequelae and severity of the condition. Life expectancy is not significantly altered but morbidity from complications and cosmetic scarring can be substantial.

A systematic review of neuropsychological outcomes following posterior fossa tumor surgery in children.

PURPOSE: Central nervous system tumors are the most common solid tumors in the pediatric population. As children with central nervous system (CNS) tumors are surviving into adolescence and adulthood, more research is being focused on the long-term cognitive outcomes of the survivors. This review examines the literature on different cognitive outcomes of survivors of different childhood posterior fossa CNS tumor types. METHODS: The authors reviewed the literature for articles published from 2000 to 2012 about long-term neuropsychological outcomes of children diagnosed with posterior fossa brain tumors before the age of 18, which distinguished between histological tumor types, and had a minimum follow-up of 3 years. RESULTS: The literature search returned 13 articles, and a descriptive analysis was performed comparing intelligence quotient (IQ), attention/executive function, and memory components of 456 survivors of childhood posterior fossa tumors. Four articles directly compared astrocytoma and medulloblastoma survivors and showed medulloblastoma survivors fared worse in IQ, attention/executive function, and memory measurements. Five articles reporting medulloblastomas found IQ, attention, and memory scores to be significantly below the standardized means. Articles examining astrocytoma survivors found IQ scores within the normal range for the population. Survivors of ependymomas reported 2/23 survivors impaired on IQ scores, while a second study reported a significant number of ependymoma survivors lower than the expected population norm. CONCLUSIONS: Tumor histopathology and the type of postoperative adjuvant therapy seem to have a significant impact on the long-term neuropsychological complications of pediatric posterior fossa CNS tumor survivors. Age at diagnosis and treatment factors are important variables that affect the outcomes of the survivors.

Resolution of precocious puberty following resection of fourth ventricular medulloblastoma: case report.

Medulloblastoma is a malignant embryonal tumor that arises in the cerebellum and invades the fourth ventricle, often resulting in obstructive hydrocephalus. Patients typically present with symptoms related to increased intracranial pressure and cerebellar dysfunction. The authors report a rare case of classic medulloblastoma with central precocious puberty (CPP) as its only presenting symptom. A 7-year-old boy with no prior history of medulloblastoma presented with Tanner Stage IV testicular enlargement and a 4-month history of acne and pubic hair. Laboratory tests of blood samples demonstrated highly elevated luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Admission MRI of the brain revealed a mass in the posterior fossa, which bordered and compressed the fourth ventricle. The patient also exhibited mild lateral and third ventriculomegaly. Surgical options were discussed with the neurosurgical department. A suboccipital craniotomy and C-1 laminectomy were performed. A large mass was seen arising from the inferior surface of the vermis, and lying within the fourth ventricle. Gross-total microsurgical resection of the mass was performed. Histopathological investigation characterized the tumor as classic medulloblastoma. Follow-up laboratory tests of blood samples demonstrated a reduction of LH, FSH, and testosterone back to prepubertal levels. The patient then began radiation and chemotherapy. This report demonstrates that mild obstructive hydrocephalus due to a posterior fossa tumor may present with unexpected symptoms, such as CPP. To the authors' knowledge, precocious puberty has not yet been associated with medulloblastoma, although it has been found with other posterior fossa tumors. Extensive imaging of the CNS for patients presenting with CPP is recommended.

Glutamic acid not beneficial for the prevention of vincristine neurotoxicity in children with cancer.

BACKGROUND: Vincristine causes known side effects of peripheral sensory, motor, autonomic and cranial neuropathies. No preventive interventions are known. PROCEDURE: We performed a randomized, placebo-controlled, double-blind trial of oral glutamic acid as a preventive agent in pediatric patients with cancer who would be receiving vincristine therapy for at least 9 consecutive weeks (Stratum 1 = Wilms tumor and rhabdomyosarcoma) or 4 consecutive weeks in conjunction with steroids (Stratum 2 = Acute lymphoblastic leukemia and non-Hodgkin lymphoma). At designated time points, a scored neurologic exam using the Modified Balis Pediatric Scale of Peripheral Neuropathies was performed to document neurologic toxicity. RESULTS: Between 2007 and 2012, 250 patients were enrolled (Stratum 1 = 50, Stratum 2 = 200). The glutamic acid treated group did not have a significantly lower percentage of neurotoxicity compared to placebo treated group either overall or within stratum or age subgroups. The only subgroup which was suggestive of treatment effect was for age. Patients 13 years or older showed a larger benefit in favor of glutamic acid (P = 0.055) compared to patients less than 13 years (P = 1.00). Constipation was the most frequently reported (14%) Grade II or higher neurotoxicity. CONCLUSION: Vincristine-associated neurotoxicity in pediatric oncology remains a frequent complication of chemotherapy for multiple diagnoses with an approximate 30% of patients affected. Glutamic acid is not effective for prevention in pre-adolescents. There is a suggestion of benefit in patients 13 years or older, but the study was not designed to provide adequate power to test the treatment effect within this age group alone.

Malignant transformation of a desmoplastic infantile ganglioglioma in an infant carrier of a nonsynonymous TP53 mutation.

INTRODUCTION: Desmoplastic infantile ganglioglioma is a rare intracranial neoplasm classified as World Health Organization grade I tumor under neuronal and mixed neuronal-glial tumors (2007 World Health Organization brain tumor classification). It is usually a good prognosis, but 40% of patients require further medical, radiation, and/or surgical intervention, and 15% develop leptomeningeal spread or die from desmoplastic infantile ganglioglioma. Transformation to malignant glioblastoma occurs, but the genetic alterations associated with the transformation are generally unknown. METHODS: We describe a desmoplastic infantile ganglioglioma in a 2-month-old boy, which showed aggressive behavior, requiring debulking at 2.5 months of age and chemotherapy at 10 months of age after tumor progression. At 8.5 years of age he developed malignant transformation to glioblastoma. Chromosome microarray analysis using oligo array and genomic sequencing was performed on the biopsy specimen from 2 months of age and on the subsequent transformed malignant glioblastoma. RESULTS: After being clinically stable for 7.5-years, transformation to glioblastoma transformation occurred. He did well for 1 year but subsequently died from tumor progression. Chromosome microarray analysis using oligo array performed on the biopsy specimen obtained at 2 months of age did not reveal significant abnormalities; but there were significant genomic deletions and duplications associated with the glioblastoma. These included multiple genomic losses involving 4q and Y, gains of 5q, and amplification of 12q14. Genomic sequencing revealed a single nucleotide variant, p.R248Q in exon 7 of TP53, in the primary desmoplastic infantile ganglioglioma and the glioblastoma multiforme. CONCLUSIONS: The nonsynonymous variant (p.R248Q in exon 7) of the TP53 gene is predicted to alter the structure of the L2/L3 motif of the DNA binding domain of p53 protein. It was detected in the primary desmoplastic infantile ganglioglioma and glioblastoma multiforme. This child illustrates the rare recurrence of desmoplastic infantile ganglioglioma with malignant transformation to glioblastoma caused by a nonsynonymous TP53 mutation, providing explanation for other rare benign tumor transformations. The TP53 gene is a known primary site of genetic alteration that predisposes to malignant tumors, and this case indicates that it might also be involved in the behavior and outcome of desmoplastic infantile ganglioglioma. Therefore more genetic testing is recommended on desmoplastic infantile ganglioglioma tumors, which may provide biologic prognostic markers.

Rapidly progressive primary leptomeningeal atypical teratoid/rhabdoid tumor: a report of 2 cases.

Atypical teratoid/rhabdoid tumor is a rare, highly malignant central nervous system tumor most commonly occurring in very young children. Atypical teratoid/rhabdoid tumor most often presents as an expanding mass with symptoms consistent with the location of the tumor and may present with metastatic leptomeningeal disease. The authors describe 2 cases of rapidly progressive, diffuse leptomeningeal atypical teratoid/rhabdoid tumor without a solid primary mass. These cases demonstrate a clinical picture that can easily be confused with a basilar meningitis, encephalomyelitis, or vasculitis.

Cannabis-related stroke: case series and review of literature.

Marijuana, or cannabis, is one of the most commonly used illicit drugs worldwide. Although there are some case reports of stroke associated with cannabis use, there is no information on a causal role of cannabis in stroke. We identified 14 patients admitted to St Louis University Hospital between January 2004 and July 2007 with ischemic stroke who had documented clear exposure to cannabis during or before symptom onset and a positive urine screen for cannabis. We report this series, along with 3 cases previously reported by our group, for a total of 17 patients (13 men and 4 women), with a mean age of 41 years (range, 15-63 years). Nine patients were under age 45 years, 4 had a history of hypertension, and 10 sustained stroke in the posterior circulation. Headache, dysarthria, and ataxia were the most common presenting symptoms. Five patients had recurrent stroke with reexposure to cannabis. No patient had a prothrombotic state or cardiac source of embolism. Autopsy performed in 2 patients revealed hemorrhagic infarct with no evidence of vasculitis or embolus. The absence of other vascular risk factors in most of our patients, the temporal relation of symptom onset to cannabis exposure, and the recurrence of symptoms in a few patients with reexposure suggest a causal role of cannabis in these cases of ischemic stroke. However, this causal association cannot be definitely ascertained, given the descriptive nature of our series. More research is needed to explore this possible causal association.

Sleep in children with cancer.

PURPOSE OF REVIEW: Advances in cancer treatment have improved the 5-year survival rate for childhood cancers to over 78%, resulting in a large population of pediatric cancer survivors. There is increasing recognition that sleep intersects with cancer through the circadian control of the cell cycle and that sleep problems are one of the 'effects' of cancer, its treatments, or both. Recognition of these intersections will facilitate new areas of treatment and the use of proven clinical interventions for sleep problems in cancer survivors. RECENT FINDINGS: Discoveries in circadian biology have revealed that the biologic clocks, which control sleep/wake rhythms, are present in all cells and exert considerable control over the cell cycle. This has opened new opportunities for improving efficacy, decreasing toxicity, or both of cancer therapy through circadian timing of chemotherapy. Excessive daytime sleepiness has emerged as one of the most common, but often unrecognized, sleep symptoms in cancer survivors. SUMMARY: Sleep complaints are especially common in survivors of childhood cancer who have sustained an injury to the hypothalamus or brainstem, have evidence of endocrine dysfunction, are obese, or have been treated with cranial radiation. If recognized and treated appropriately, sleep problems can be successfully managed.

Cerebellar infarction in adolescent males associated with acute marijuana use.

OBJECTIVE: To demonstrate the clinical characteristics, radiologic findings, and neuropathological features of tetrahydrocannabinol-related posterior fossa ischemic stroke in adolescent patients. DESIGN: A retrospective case and chart review of 3 cases encountered at a tertiary care institution over a span of 5 years. SETTING: Inpatient and intensive care hospitalization units managing children and adolescents. SUBJECTS: Male adolescent patients with ischemic cerebellar stroke after use of marijuana. DIAGNOSTIC INVESTIGATIONS: Computed tomography brain scans (3 subjects), magnetic resonance imaging brain study (1 subject), cerebral arteriography (1 subject), cerebellar biopsy (1 subject), and necropsy (2 subjects). RESULTS: Three adolescent males had similar presentations of headache, fluctuating level of consciousness or lethargy, visual disturbance, and variable ataxia after self-administration of marijuana. They developed primary cerebellar infarctions within days after the exposure that could not be attributed to supratentorial herniation syndromes and only minimally involved brainstem structures. CONCLUSIONS: Episodic marijuana use may represent a risk factor for stroke in childhood, particularly in the posterior circulation. Early recognition of the cerebellar stroke syndrome may allow prompt neurosurgical intervention, reducing morbidity.