Posterior fossa syndrome and long-term neuropsychological outcomes among children treated for medulloblastoma on a multi-institutional, prospective study.

BACKGROUND: Patients treated for medulloblastoma who experience posterior fossa syndrome (PFS) demonstrate increased risk for neurocognitive impairment at one year post diagnosis. The aim of the study was to examine longitudinal trajectories of neuropsychological outcomes in patients who experienced PFS compared with patients who did not. METHODS: Participants were 36 patients (22 males) who experienced PFS and 36 comparison patients (21 males) who were matched on age at diagnosis and treatment exposure but did not experience PFS. All patients underwent serial evaluation of neurocognitive functioning spanning 1 to 5 years post diagnosis. RESULTS: The PFS group demonstrated lower estimated mean scores at 1, 3, and 5 years post diagnosis on measures of general intellectual ability, processing speed, broad attention, working memory, and spatial relations compared with the non-PFS group. The PFS group exhibited estimated mean scores that were at least one standard deviation below the mean for intellectual ability, processing speed, and broad attention across all time points and for working memory by 5 years post diagnosis. Processing speed was stable over time. Attention and working memory declined over time. Despite some change over time, caregiver ratings of executive function and behavior problem symptoms remained within the average range. CONCLUSION: Compared with patients who do not experience PFS, patients who experience PFS exhibit greater neurocognitive impairment, show little recovery over time, and decline further in some domains. Findings highlight the particularly high risk for long-term neurocognitive problems in patients who experience PFS and the need for close follow-up and intervention.

Altered MicroRNA Expression Is Associated with Tumor Grade, Molecular Background and Outcome in Childhood Infratentorial Ependymoma.

BACKGROUND: Ependymal tumors are the third most common group of brain tumors in children, accounting for about 10% of all primary brain neoplasms. According to the current WHO classification, they comprise four entities with the most frequent ependymoma and anaplastic ependymoma. The most of pediatric tumors are located within the posterior fossa, with a tendency to infiltrate the vital brain structures. This limits surgical resection and poses a considerable clinical problem. Moreover, there are no appropriate outcome prognostic factors besides the extent of surgical resection. Despite definition of molecular subgroups, the majority of childhood ependymomas present a balanced genome, which makes it difficult to establish molecular prognostic factors. METHODS: The purpose of our study was to explore whether miRNA expression could be used as prognostic markers in pediatric infratentorial ependymomas. We also performed a mRNA expression pattern analysis of NELL2 and LAMA2 genes, with immunohistochemical illustrations of representative cases. The miRNA and mRNA expression was measured in 53 pediatric infratentorial ependymomas using a real-time quantitative PCR. RESULTS: Three miRNAs were shown to efficiently differentiate between grade II and III ependymomas: miR-17-5p, miR-19a-3p, and miR-106b-5p. Survival analysis showed that the probabilities of overall (p = 0.036) and event-free survival (p = 0.002) were reduced with higher than median miRNA expression levels of miR-17-5p. Using multivariate analysis adjusted for patient's age, sex, tumor grade and localization, we showed statistically significant associations with event-free survival (p = 0004) and borderline statistical significance with overall survival (p = 0.057) for miR-17-5p. Correlation analysis of miR-19a, miR-17-5p, miR-106b revealed that their expression levels were significantly correlated with EZH2 expression, suggested marker of PFA ependymomas. Furthermore, lower expression level of LAMA2 mRNA was shown to be associated with an increased risk of death in covariate-adjusted analyses. CONCLUSIONS: Our data provide a better understanding of pediatric ependymoma and suggests the presence of plausible molecular biomarkers connected with the outcome.

Posterior fossa syndrome following brain tumour resection: review of pathophysiology and a new hypothesis on its pathogenesis.

INTRODUCTION: Posterior fossa syndrome (PFS), also known as cerebellar mutism syndrome (CMS), is a severe complication affecting children following surgery for posterior fossa brain tumours. Its incidence varies between 8 and 31 %, and its exact pathogenesis remains unclear. In this article, we aim to review the existing theories on its pathogenesis and propose a new hypothesis. DISCUSSION: There is varying level of evidence on existing theories on the pathogenesis of PFS following surgery. These include cerebellar perfusion deficits due to vasospasm, oedema or axonal injury due to direct surgical injury and neuronal dysfunction. There is emerging evidence that interruption of the dentato-thalamo-cortical (DTC) pathway is responsible for PFS. Based on our experience with intraoperative MRI, radiological and pathological evidence on heat-related brain injury, we propose a new hypothesis implicating thermal injury resulting from the use of the Cavitron Ultrasonic Aspirator (CUSA) as an important mechanism in the pathogenesis of PFS. CONCLUSION: The pathogenesis of PFS is likely to be multifactorial with direct injury from surgery being a major factor. We believe that thermal injury in addition to mechanical injury to the proximal segment of the DTC plays an important role in the pathogenesis of PFS and should be considered in future research related to the aetiology, prevention and management of PFS.

[Epidemiology and etiology of posterior fossa tumors with particular emphasis on astrocytomas from the Malopolska and Podkarpacki regions]. / Epidemiologia i etiologia guzów tylnej jamy czaszki ze szczególnym uwzglednieniem gwiazdziaków z terenu województw malopolskiego i podkarpackiego.

Brain tumors in children are rare compared with other diseases childhood. Virtually every pediatrician working at the local hospital has been in contact or brain tumor diagnosis was that more half of them recognized the posterior fossa tumor. Analysis of surveys showed difficulties in the interpretation of basic neurological symptoms. Lessons learned from these studies point to the fact that the success of the surgery affects mainly the histological type of tumor and its location. It is extremely important to analyze complaints and symptoms young patients, we should listen to the parents of children with, because usually just parents are the first to notice that their offspring something was wrong.

Infratentorial craniospinal irradiation for von Hippel-Lindau: a retrospective study supporting a new treatment for patients with CNS hemangioblastomas.

Patients with von Hippel-Lindau (VHL) syndrome with diffuse CNS hemangioblastomas have morbidity related to their disease and require a lifetime of surgical resections. Ninety-seven percent of tumors progress, and 5-year surgery rates are 20%-60%. Stereotactic radiosurgery and fractionated radiotherapy have had limited success. For the first time, we have used infratentorial craniospinal radiation therapy (ICSRT) for VHL patients with CNS hemangioblastomas. Consecutive VHL patients treated at the National Institutes of Health with radiographic evidence of hemangioblastomas were included if they received ICSRT. Patients underwent neurologic examinations and imaging at 3- to 12-month intervals. Seven patients with 84 hemangioblastomas met eligibility criteria. ICSRT was commonly administered to 43.2 Gy in 24 fractions. Mean pre-ICSRT tumor volume was 5.48 cm(3). At a mean follow-up of 73.8 months, mean post-ICSRT tumor volume was 6.87 cm(3), and 91 tumors were identified. Complete radiographic resolution was achieved in 17.9% of lesions. Although many patients were no longer optimal surgical candidates, only 4 surgeries were needed for symptomatic lesions after ICSRT, compared with 33 prior. Acute toxicity was mild and no patient developed grade ≥1 late spinal cord toxicity according to the criteria of the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer, despite the high dose that the entire spinal cord received. Clinical and radiographic stability or resolution was demonstrated in the majority of tumors. Tumor growth rate in this study was less than reported in natural history studies, and the rate of surgical intervention was reduced. ICSRT was well tolerated, can decrease hemangioblastoma growth rate, and is a potential therapeutic option for VHL patients that warrants further investigation.

Posterior fossa neoplasm and PHACES syndrome: a case report.

A 4-year-old girl with PHACES syndrome (posterior fossa brain malformations, hemangiomas, arterial anomalies, cardiac anomalies/coarctation of the aorta, eye abnormalities, and sternal clefting/supraumbilical raphe) developed a cerebellar pilocytic astrocytoma 18 months after resolution of her neck, ear, and thoracic hemangiomas. Because cutaneous hemangiomas may have involuted by the time a patient is diagnosed with a central nervous system neoplasm, it seems possible that in other such patients the association may have gone unrecognized. Cerebellar pilocytic astrocytoma may be a rare manifestation of the posterior fossa malformations of PHACES.

Ependymoma.

Ependymomas are rare tumours of neuroectodermal origin classified as myxopapillary ependymoma and subependymoma (grade I), ependymoma (grade II) and anaplastic ependymoma (grade III). The more common location is infratentorial (60%). Age <40 years and extent of surgery appear related to better prognosis, while the role of other prognostic factors, such as tumour grade and tumour site are equivocal. This emphasizes the role of surgery as the standard treatment. Postoperative radiotherapy is indicated in high-grade ependymomas, and is recommended in low-grade ependymomas after subtotal or incomplete resection (confirmed by postoperative MR). Deferral of radiotherapy until recurrence may be considered on an individual basis for patients with MR confirmation of a radical resection. Recommended dose to involved fields is 45-54 Gy for low-grade (grade II) and 54-60 Gy for high-grade ependymomas (grade III). There is no proof that postoperative chemotherapy improves the outcome. At recurrence, platinum-, nitrosourea- or temozolomide-based chemotherapy can be administered, although there is no evidence of efficacy.

Familial incidence of obstructive hydrocephalus due to posterior fossa tumours leading to the diagnosis of von Hippel-Lindau disease--a case report.

Von Hippel-Lindau disease (VHLD) is an autosomal dominant disorder predisposing to the development of different histological types of tumours with predominance of CNS haemangioblastomas in the majority of cases. We present a case of a 35-year-old man with obstructive hydrocephalus due to multiple posterior fossa tumours. Familial history revealed two relatives operated on previously because of a posterior fossa tumour (in one case haemangioblastoma was diagnosed). During surgery two cerebellar tumours were removed radically via the suboccipital approach. On a histopathological examination the typical features of haemangioblastoma were found in both tumours composed of stromal cells and a dense network of vessels, mostly capillaries. The presence of neoplastic infiltration with angiogenesis in the surrounding cerebellar tissue was evidenced in the presented case. Based on the clinical and histopathological data VHLD was diagnosed. Genetic analysis confirmed the presence of the von Hippel-Lindau gene mutation. The case presented suggests that genetic disregulation in VHLD may be responsible for a more aggressive behaviour of VHLD-related haemangioblastomas in comparison with sporadic disease.