Bradley E. Weprin

Imaging Characteristics of Atypical Teratoid–Rhabdoid Tumor in Children Compared with Medulloblastoma

OBJECTIVE The purpose of our study was to compare the imaging characteristics of atypical teratoid-rhabdoid tumor with medulloblastoma and seek distinguishing features that can aid in preoperative diagnosis. MATERIALS AND METHODS Preoperative MRI examinations of 55 patients (36 medulloblastomas and 19 atypical teratoid-rhabdoid tumors) were analyzed retrospectively. Imaging characteristics of atypical teratoid-rhabdoid tumor and medulloblastoma were assessed with conventional MRI and CT. Diffusion-weighted imaging (DWI) was available in 27 patients (19 medulloblastomas and eight atypical teratoid-rhabdoid tumors). Apparent diffusion coefficient (ADC) values were calculated for 14 medulloblastomas and six atypical teratoid-rhabdoid tumors. RESULTS Both atypical teratoid-rhabdoid tumors in general and infratentorial atypical teratoid-rhabdoid tumors presented at a younger age than medulloblastomas. Eleven of 19 atypical teratoid-rhabdoid tumors were infratentorial. Cerebellopontine angle (CPA) involvement was more frequent (8/11, 72.7%) in atypical teratoid-rhabdoid tumor than in medulloblastoma (4/36, 11.1%) (p < 0.001). Intratumoral hemorrhage was more common in atypical teratoid-rhabdoid tumor (9/19, 47.4%) than in medulloblastoma (2/36, 5.6%) (p < 0.0001). All atypical teratoid-rhabdoid tumors and all medulloblastomas for which DWI was available displayed increased signal intensity on DWI compared with normal brain parenchyma. The mean ADC values for tumor types were not significantly different. CONCLUSION Atypical teratoid-rhabdoid tumor presents at a younger age than medulloblastoma. Although atypical teratoid-rhabdoid tumor and medulloblastoma display similar imaging characteristics on conventional MRI, CPA involvement and intratumoral hemorrhage are more common in atypical teratoid-rhabdoid tumor. If a pediatric posterior fossa mass that displays restricted diffusion is involving the CPA, atypical teratoid-rhabdoid tumor is a more likely consideration than medulloblastoma.

Robotically guided radiosurgery for children

A robotically guided linear accelerator has recently been developed which provides frameless radiosurgery with high precision. Potential advantages for the pediatric population include the avoidance of the cognitive decline associated with whole brain radiotherapy, the ability to treat young children with thin skulls unsuitable for frame‐based methods, and the possible avoidance of general anesthesia. We report our experience with this system (the “Cyberknife”) in the treatment of 21 children.

A new approach to closure of large lumbosacral myelomeningoceles: the superior gluteal artery perforator flap.

The most common form of neural tube defect is the myelomeningocele, developing during the fourth week of gestation. The era of early closure of myelomeningoceles began in the sixties with the demonstration that these patients had a lower rate of mortality.1 The goals of early surgical closure are to (1) prevent infection, (2) eliminate cerebrospinal fluid leaks, (3) preserve neural function, and (4) diminish negative late sequelae such as pain over the closure site and possibly even tethered cord.2 After closure of the neural tube and dura, the majority of these patients have enough local skin to allow for simple closure of the skin over the dural closure. When the skin defect is large or the surrounding skin quality is poor, more elaborate methods of obtaining stable skin closure over the dural closure must be devised.3 Multiple methods of soft-tissue closure for larger lumbosacral myelomeningocele defects have been described, including skin grafting,4 random flaps,5 skin undermining with relaxing incisions,6 and musculocutaneous flaps.7,8 None of these approaches are ideal, however, particularly when the skin defect is large and/or the quality of the surrounding skin is poor. We have developed a new approach to closure of large lumbosacral defects with superior gluteal artery perforator flaps.

Complications of ventricular shunts

Abstract:Ventricular shunting is the most widely accepted form of treatment of hydrocephalus. The placement of cerebrospinal fluid shunts has become one of the most common procedures in modern neurologic surgery. Despite significant improvements in shunt procedures, shunt complications remain common

Common Pediatric Cerebellar Tumors: Correlation between Cell Densities and Apparent Diffusion Coefficient Metrics

PURPOSE To test whether there is correlation between cell densities and apparent diffusion coefficient (ADC) metrics of common pediatric cerebellar tumors. MATERIALS AND METHODS This study was reviewed for issues of patient safety and confidentiality and was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center and was compliant with HIPAA. The need for informed consent was waived. Ninety-five patients who had preoperative magnetic resonance imaging and surgical pathologic findings available between January 2003 and June 2011 were included. There were 37 pilocytic astrocytomas, 34 medulloblastomas (23 classic, eight desmoplastic-nodular, two large cell, one anaplastic), 17 ependymomas (13 World Health Organization [WHO] grade II, four WHO grade III), and seven atypical teratoid rhabdoid tumors. ADCs of solid tumor components and normal cerebellum were measured. Tumor-to-normal brain ADC ratios (hereafter, ADC ratio) were calculated. The medulloblastomas and ependymomas were subcategorized according to the latest WHO classification, and tumor cellularity was calculated. Correlation was sought between cell densities and mean tumor ADCs, minimum tumor ADCs, and ADC ratio. RESULTS When all tumors were considered together, negative correlation was found between cellularity and mean tumor ADCs (ρ = -0.737, P < .05) and minimum tumor ADCs (ρ = -0.736, P < .05) of common pediatric cerebellar tumors. There was no correlation between cellularity and ADC ratio. Negative correlation was found between cellularity and minimum tumor ADC in atypical teratoid rhabdoid tumors (ρ = -0.786, P < .05). In atypical teratoid rhabdoid tumors, no correlation was found between cellularity and mean tumor ADC and ADC ratio. There was no correlation between the ADC metrics and cellularity of the pilocytic astrocytomas, medulloblastomas, and ependymomas. CONCLUSION Negative correlation was found between cellularity and ADC metrics of common pediatric cerebellar tumors. Although ADC metrics are useful in the preoperative diagnosis of common pediatric cerebellar tumors and this utility is generally attributed to differences in cellularity of tumors, tumor cellularity may not be the sole determinant of the differences in diffusivity.

Predictors of tumor progression among children with gangliogliomas. Clinical article.

OBJECT Few reports describe the outcome and prognostic factors for children with gangliogliomas. The objective of this report was to describe the progression-free survival (PFS) for children with low-grade gangliogliomas and identify risk factors for tumor progression. METHODS A retrospective study was performed in children with low-grade gangliogliomas who were evaluated and treated in the neuro-oncology department between 1986 and 2006 to determine risk factors for subsequent tumor progression. RESULTS A total of 38 children with newly diagnosed gangliogliomas were included in this report. Thirty-four children were treated with surgery alone, 3 with subtotal resection and radiation therapy, and 1 with subtotal resection and chemotherapy. The follow-up ranged from 4 months to 15.8 years (mean 5.7+/-4.2 years [+/-SD]). Seven children have experienced tumor progression, and 1 child died after his tumor subsequently underwent malignant transformation. The 5-year PFS was calculated to be 81.2% using Kaplan-Meier survival analysis. Initial presentation with seizures (p=0.004), tumor location in the cerebral hemisphere (p=0.020), and complete tumor resection (p=0.035) were associated with prolonged PFS. Further analysis of the above significant variables by a Cox regression model identified initial presentation with seizures as being associated with prolonged PFS (p=0.028). CONCLUSIONS The PFS and overall survival of children with gangliogliomas are good. Tumors located in the cerebral hemispheres, the achievement of total resection, and seizures at presentation were associated with prolonged PFS. Cox regression analysis identified presenting symptoms including seizures as significant predictive factors of PFS. Prospective studies with larger numbers of children are needed to define the significant factors of tumor progression.

Feasibility of radiosurgery for malignant brain tumors in infants by use of image-guided robotic radiosurgery: preliminary report.

OBJECTIVE:The benefits of radiation therapy are generally denied to infants with malignant brain tumors because of the risk of devastating cognitive decline. Efforts to limit this morbidity with radiosurgical techniques have not been feasible for infants because of the dual requirements of rigid head fixation and high precision. We report the radiosurgical treatment of five infants by use of a robotically controlled system without rigid head fixation. METHODS:Five infants with malignant brain tumors received radiosurgical treatment with a robotically driven linear accelerator. Immobilization was aided by general anesthesia, form-fitting head supports, face masks, and body molds. The average marginal dose was 17 ± 2 Gy, and the average treatment volume was 18 ± 22 ml. RESULTS:X-rays obtained during treatment revealed acceptable agreement with preoperative computed tomographic scans in all patients. In one patient, the lesion did not progress, but a distant recurrence occurred 15 months after radiosurgery and also was treated with radiosurgery. In another patient, tumor in the treated region did not progress, but recurrence elsewhere led to death 7 months after treatment. Tumor enlargement occurred in Patient 3 at 3 months posttreatment, leading to death 2 months later. Tumor size was smaller in the remaining two patients at 9 and 11 months after treatment. There has been no toxicity attributed to treatment. CONCLUSION:Radiosurgery with minimal toxicity can be delivered to infants by use of a robotically controlled system that does not require rigid fixation. A formal dose-escalation trial is under way to address dose and toxicity for infants more thoroughly.

Stereotactic radiosurgery in pediatric patients

Although stereotactic radiosurgery has been studied extensively in adults, the data demonstrating its efficacy in children is limited. Medical records were reviewed to identify the indications for and outcomes of patients treated with this modality. Linear accelerator-based radiosurgery was used to treat 11 recurrent brain tumors and one posterior fossa arteriovenous malformation over 3 years. The mean and median age of those treated was 10 and 8 years, respectively (range 1-20 years). Patients received 700 to 3,000 cGy delivered to the 50-90% isodose line in a single fraction. The mean and median follow-up was 15 and 17 months, respectively. Three of the four children with malignant disease died 6 to 9 months after treatment. One patient died of recurrence outside the treatment field. Another child died of complications related to radiation injury, and the third died of disease progression. All children with low-grade tumors remain alive without complications. Six of eight (75%) children exhibit substantial radiographic reductions in tumor size. The child with a vascular malformation has been followed for 26 months, without hemorrhage and with a radiographically proved decrease in size. Our series suggests that radiosurgery has limited usefulness in malignant disease. Therapeutic response is influenced by lesion size and/or location. Stereotactic radiosurgery appears to be effective in children with low-grade intracranial tumors or arteriovenous malformations. Further experience is required to establish the role and long term side effects of radiosurgery in pediatric patients.

Prognostic factors in children and adolescents with low-grade oligodendrogliomas.

Few reports exist describing the progression-free and overall survival of children with low-grade (WHO grade II) oligodendrogliomas treated uniformly with aggressive surgery but without adjuvant chemotherapy or radiation therapy. Furthermore, significant prognostic features, including the MIB-1 labeling index (LI), have not been reported for children with oligodendrogliomas. The medical records of 20 consecutive patients with low-grade oligodendrogliomas were reviewed. All patients had been treated with aggressive surgical resection. Adjuvant chemotherapy and radiation therapy were reserved for radiographic or clinical progression. These patients have been followed for a median of 5.5 years (range 0.5–11.5 years) after diagnosis. To date, there have been no patient deaths. Six of the 20 patients experienced tumor progression at a median of 2.2 years (range 0.4–4.8 years) following the initial surgery. The MIB-1 LI was infrequently greater than 5. Of several prognostic factors for subsequent tumor progression that were examined, only tumors located within the parietal lobes were associated with a worse progression-free survival. Other risk factors, including presenting symptoms, age at diagnosis, MIB-1 LI and the extent of tumor resection, were not associated with an increased frequency of tumor progression.

Effect of recombinant human bone morphogenetic protein–2 on bone regeneration in large defects of the growing canine skull after dura mater replacement with a dura mater substitute

OBJECT This study was designed to evaluate the bone regeneration potential of the dura mater and dura mater substitute (Durepair) in the presence of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a collagen sponge-collagen-ceramic matrix (CCM; MasterGraft Matrix) in a large skull defect in growing canines. METHODS Forty immature male beagles were used to create two 2.5 x 4-cm cranial defects on each side of the sagittal suture. The dura mater on the left side was cut to make a 1 x 3-cm defect and replaced with bovine skin collagen (Durepair). The dura mater on the right side remained intact. Different doses of rhBMP-2 (none [8 animals], 0.11 mg/ml [4 animals], 0.21 mg/ml [4 animals], and 0.43 mg/ml [8 animals]) were infused on 2 Type I bovine absorbable collagen sponge (ACS) strips. The strips were layered with the CCM (15% hydroxyapatite [HA]/85% tricalcium phosphate [TCP]) to reconstruct both cranial defects. In a fifth group (8 animals), 0.43 mg/ml rhBMP-2 was directly infused into the CCM. Demineralized canine cancellous freeze-dried demineralized bone matrix (DBM; 8 animals) was used as a control in a sixth group. All materials were fixed under 2 resorbable protective sheets (MacroPore). Skulls were resected 16 weeks after operation. Histological and histomorphometric analyses on the percentage of the defect spanned by bone, and the percentage of residual HA-TCP granules and collagen were analyzed. RESULTS Calcified seroma was the only complication observed and only occurred in the 0.43-mg/ml rhBMP-2 groups (Groups 4 and 5). Dura mater repair appeared complete at 4 months in all animals. New bone was formed sporadically throughout the skull defect in the ACS+CCM and DBM groups without rhBMP-2. In all rhBMP-2 groups, mature new bone (compact and trabecular) was uniformly formed across the defect on both the repaired and intact dura mater sides. There was significant new compact bone formation on top of the repaired dura mater, which did not appear in the ACS+CCM and DBM groups lacking rhBMP-2. Greater HA-TCP and collagen scaffold resorption was noted in rhBMP-2 groups compared with non-rhBMP-2 groups. Statistical analysis showed there was a significantly lower percentage of bone spanning the defect in the ACS+CCM group compared with groups with rhBMP-2, with more residual HA-TCP and collagen on the repaired dura mater side than the intact dura mater side (p < 0.05). In all rhBMP-2 groups, there were no significant differences in new bone formation between the repaired and intact dura mater sides (p > 0.05). CONCLUSIONS The ACS+CCM combination had an effect similar to demineralized bone-on-bone regeneration in craniofacial reconstruction. The addition of rhBMP-2 to CCM directly or with ACS induces mature new bone formation in large cranial defects both in the presence of intact dura mater and repaired dura mater.