Radiation-Induced Moyamoya Syndrome after Proton Beam Therapy in the Pediatric Patient: A Case Series.

Minimizing normal-tissue radiation exposure is especially important in the pediatric population as children appear to be particularly sensitive to postradiation vasculopathies after conventional photon radiotherapy. Given the limited scattering effect and low-dose radiation delivery to the surrounding tissues with proton beam radiotherapy, this modality is considered to be an effective treatment for pediatric skull-base tumors compared to conventional radiotherapy, and to have fewer adverse side effects. We report 2 cases of radiation-induced moyamoya syndrome following proton beam therapy in pediatric patients. To our knowledge, only a few other reported cases of radiation-induced moyamoya syndrome following proton beam therapy exist in the current literature. While rare, radiation-induced moyamoya syndrome can occur in the pediatric population with newer techniques like proton beam radiotherapy. Accordingly, patients and their families should be informed about this potential complication prior to all forms of radiation treatment.

BRAF(V600E) mutation is a negative prognosticator in pediatric ganglioglioma.

Gangliogliomas are typically low-grade neuroepithelial tumors seen in the pediatric and young adult populations. Despite their often bland histologic appearance, these tumors recur with varying frequencies; however, little data exist that adequately predict ganglioglioma recurrence in children. To identify potential histopathologic features predictive of recurrence-free survival, a series of 53 patients with World Health Organization (WHO) grade I gangliogliomas were evaluated, representing the largest cohort of pediatric gangliogliomas with accompanying histopathologic and survival data. Fifteen patients (28 %) exhibited disease recurrence during the study period. BRAF(V600E) immunohistochemistry was performed on 47 of these tumors. Histopathologic features associated with shorter recurrence-free survival included an absence of oligodendroglial morphology, higher glial cell density, microvascular proliferation, and the presence of a high lymphoplasmacytic inflammatory infiltrate. Eighteen tumors (38.3 %) had positive BRAF(V600E) staining, which was associated with shorter recurrence-free survival. Collectively, the combined use of histopathologic and molecular features to stratify grade I gangliogliomas into low and high-risk groups provides important information relevant to the management of children and young adults with these rare tumors.

Pontine extraventricular neurocytoma in a child.

Extraventricular neurocytomas mimic central neurocytomas histologically but are located outside the lateral and/or third ventricles. Pontine neurocytomas represent an extremely rare subset of extraventricular neurocytomas, and reports are limited to 2 adults followed under 28 months. The authors present the case of a 14-year-old boy who initially underwent near-total resection of a pontine extraventricular neurocytoma. One-year postoperative surveillance imaging revealed a small, local recurrence treated with intensity-modulated radiation therapy. This case details the diagnosis and management of the first reported pontine extraventricular neurocytoma in a child with 4.5-year follow-up data.

Greater extent of resection improves ganglioglioma recurrence-free survival in children: a volumetric analysis.

BACKGROUND: Gangliogliomas are rare, low-grade, glial-neural tumors that are most often found in children. They can recur with varying frequency; yet few data are available that adequately predict such events. OBJECTIVE: To review our institution's large series of gangliogliomas in children and identify clinical features that predict recurrence-free survival. METHODS: Clinical records were retrospectively reviewed from 1990 to 2011. Fifty-three children were identified, and pertinent clinical features were analyzed against survival data to categorize lesions at high risk of recurrence. RESULTS: Fifteen children (28%) experienced a recurrence during the study period with a median time to recurrence of 8.8 months and a mean follow-up of 4.2 years. The 5-year recurrence-free survival rate was 70.5%, whereas the overall survival rate was 98.1%. Older age at diagnosis (P = .02), seizure history (P < .001), supratentorial tumor location (P < .001), and greater extent of surgical resection (P < .001) were all associated with improved recurrence-free survival on univariate analysis. Extent of surgical resection was the only clinical variable that retained its significance in multivariate models (P = .01). Patients who received 94% or greater volumetric extent of resection had prolonged recurrence-free survival compared with those individuals who received a less than 94% resection (P = .02). CONCLUSION: Attention to specific clinical variables, most notably the extent of surgical resection, can further stratify grade I gangliogliomas into low- and high-risk groups among children. Although 100% resection should remain an operative goal for surgically accessible gangliogliomas, a thorough yet subtotal resection may improve recurrence-free survival.

Intraoperative magnetic resonance imaging to reduce the rate of early reoperation for lesion resection in pediatric neurosurgery.

OBJECT: This study describes the pediatric experience with a dual-multifunction-room IMRIS 1.5-T intraoperative magnetic resonance imaging (iMRI) suite and analyzes its impact on clinical variables associated with neurosurgical resection of intracranial lesions, including safety and efficacy. METHODS: Since the inception of the iMRI-guided resection program in April 2008 at both Barnes-Jewish and St. Louis Children's Hospital, a prospective database recorded the clinical variables associated with demographics and outcome with institutional review board approval. A similarly approved retrospective database was constructed from February 2006 to March 2010 for non-iMRI resections. These databases were retrospectively reviewed for clinical variables associated with resection of pediatric (age 20 months-21 years) intracranial lesions including brain tumors and focal cortical dysplasia. Patient demographics, operative time, estimated blood loss, additional resection, length of stay, pathology, and complications were analyzed. RESULTS: The authors found that 42 iMRI-guided resections were performed, whereas 103 conventional resections had been performed without the iMRI. The mean patient age was 10.5 years (range 20 months-20 years) in the iMRI group and 9.8 years (range 2-21 years) in the conventional group (p = 0.41). The mean duration of surgery was 350 minutes in the iMRI group and 243 minutes in the conventional group (p < 0.0001). The mean hospital stay was 8.2 days in the iMRI group, and 6.6 days in the conventional group, and this trended toward significance (p = 0.05). In the first 2 weeks postoperatively, there were 8 reoperations (7.77%) in the conventional group compared with none in the iMRI group, which was not significant in a 2-tailed test (p = 0.11) but trended toward significance in a 1-tailed test (p = 0.06). The significant complications included reoperation for hydrocephalus or infection: 6.8% (conventional) versus 4.8% (iMRI). CONCLUSIONS: Intraoperative MR imaging-guided resections resulted in a trend toward reduction in the need for repeat surgery in the immediate 2-week postoperative period compared with conventional pediatric neurosurgical resections for tumor or focal cortical dysplasia. Although there is an increased operative time, the iMRI suite offers a comparable safety and efficacy profile while potentially reducing the per-case cost by diminishing the need for early reoperation.

Ability of Sit4p to promote K+ efflux via Nha1p is modulated by Sap155p and Sap185p.

We demonstrate here that SAP155 encodes a negative modulator of K+ efflux in the yeast Saccharomyces cerevisiae. Overexpression of SAP155 decreases efflux, whereas deletion increases efflux. In contrast, a homolog of SAP155, called SAP185, encodes a positive modulator of K+ efflux: overexpression of SAP185 increases efflux, whereas deletion decreases efflux. Two other homologs, SAP4 and SAP190, are without effect on K+ homeostasis. Both SAP155 and SAP185 require the presence of SIT4 for function, which encodes a PP2A-like phosphatase important for the G1-S transition through the cell cycle. Overexpression of either the outwardly rectifying K+ channel, Tok1p, or the putative plasma membrane K+/H+ antiporter, Kha1p, increases efflux in both wild-type and sit4Delta strains. However, overexpression of the Na+-K+/H+ antiporter, Nha1p, is without effect in a sit4Delta strain, suggesting that Sit4p signals to Nha1p. In summary, the combined activities of Sap155p and Sap185p appear to control the function of Nha1p in K+ homeostasis via Sit4p.

Yeast ARL1 encodes a regulator of K+ influx.

A molecular genetic approach was undertaken in Saccharomyces cerevisiae to examine the functions of ARL1, encoding a G protein of the Ras superfamily. We show here that ARL1 is an important component of the control of intracellular K(+). The arl1 mutant was sensitive to toxic cations, including hygromycin B and other aminoglycoside antibiotics, tetramethylammonium ions, methylammonium ions and protons. The hygromycin-B-sensitive phenotype was suppressed by the inclusion of K(+) and complemented by wild-type ARL1 and an allele of ARL1 predicted to be unbound to nucleotide in vivo. The arl1 mutant strain internalized approximately 25% more [(14)C]-methylammonium ion than did the wild type, consistent with hyperpolarization of the plasma membrane. The arl1 strain took up 30-40% less (86)Rb(+) than did the wild type, showing an inability to regulate K(+) import properly, contributing to membrane hyperpolarity. By contrast, K(+) and H(+) efflux were undisturbed. The loss of ARL1 had no effect on the steady-state level or the localization of a tagged version of Trk1p. High copy suppressors of the hygromycin-B phenotype included SAP155, encoding a protein that interacts with the cell cycle regulator Sit4p, and HAL4 and HAL5, encoding Ser/Thr kinases that regulate the K(+)-influx mediators Trk1p and Trk2p. These results are consistent with a model in which ARL1, via regulation of HAL4/HAL5, governs K(+) homeostasis in cells.