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.

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.

Clinical, neurophysiological and morphological study of dominant intermediate Charcot-Marie-Tooth type C neuropathy.

Dominant intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) was associated with mutations in the YARS gene, encoding tyrosyl-tRNA synthetase, in two large unrelated Bulgarian and US pedigrees and one sporadic case. Here for the first time we describe the clinical, neurophysiological and histopathological features, and phenotypic differences between these two DI-CMTC families. Twenty-one affected individuals from the US family and 27 from the Bulgarian family were evaluated. The mean age of onset in US subjects was 10.7 years in men and 7.3 years in women, while in the Bulgarian participants it was 18.2 years in men and 33.7 years in women. The course was slowly progressive. Extensor digitorum brevis atrophy was uniform. Atrophy and/or weakness of upper and lower limb muscles were found in over 50 % of the subjects. Nerve conduction studies (NCS) were abnormal in all US adults and five of six children and all Bulgarian patients except one asymptomatic 25-year-old man. Median motor NCS were in the range of 29.5-45.6 m/s in the US family and 24.7-57.8 m/s in the Bulgarian family. Sural sensory nerve action potentials were absent in 14/21 and 4/12 NCS from adult US and Bulgarian participants, respectively. Analysis of sural nerve biopsies from US patients revealed age-dependent morphological changes of axonal degeneration, absence of onion bulbs, and <10 % fibers with segmental remyelination. Our findings provide further insights into the diagnosis and pathology of intermediate CMT. They also extend the phenotypic spectrum of peripheral neuropathies associated with aminoacyl-tRNA synthetase mutations.

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.

Infantile Alexander's disease: serial neuroradiologic findings.

Serial neuroimaging studies in Alexander's disease were obtained on an African-American girl who died at 4z\x years of age. She presented with macrocephaly, psychomotor retardation, spasticity, a seizure disorder, and hydrocephalus. A thorough metabolic evaluation of defined leukodystrophies, including Krabbe's disease, adrenoleukodystrophy, metachromatic leukodystrophy, Canavan's disease, and Leigh disease, was negative. A diagnosis of Alexander's disease was made based on the clinical features and ruling out all other possible causes. It was confirmed by pathologic findings of numerous subpial, subependymal, and perivascular Rosenthal fibers throughout the entire cerebrum. Interestingly, autopsy also identified the stenotic sylvian aqueduct owing to Rosenthal fiber accumulation, explaining the origin of hydrocephalus. The evolution of magnetic resonance imaging findings appears to be unique in this disease.

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.

Cerebral FDG Metabolic Pattern in Pediatric Patients with Neurofibromatosis Type 1: A Retrospective Study.

Aims: Learning disabilities represent the most significant cause of lifetime morbidity in neurofibromatosis type 1 (NF1) patients. The cognitive phenotype of NF1 pediatric patients is not well understood. The purpose of this study was to examine the cerebral glucose metabolic pattern in NF1 pediatric patients. Study Design: Retrospective. Place and Duration of Study: Saint Louis University Hospital, Saint Louis, Missouri, United States, between May 2011 and May 2012. Methodology: Six NF1 pediatric patients underwent FDG PET/CT including the brain, for evaluation of extracranial neoplasm. Their brain PET images were compared with a pediatric comparison set (21 subjects) using Statistical Parametric Mapping. Significant differences between groups were examined at p<0.001, uncorrected for voxel height and p<0.05, corrected for cluster extent. Results: Compared with the comparison set, the 6 NF1 patients showed the largest cluster of reduced FDG uptake (3966 voxels) in the medial dorsal nucleus of bilateral thalami. Additional clusters of metabolism in the range from 415 to 926 voxels were noticed in the right cingulate gyrus (Brodmann area (BA) 8 and 24), left occipital lobe (BA 17 and 18) and right fronto-parietal lobe (BA 43). Conclusion: The FDG reduction of the bilateral thalami is compelling and may be most pathognomonic for NF1. This and other areas of FDG reduction found within the brain may contribute to a better understanding of the NF1 cognitive phenotype.