Pediatric and Adult Low-Grade Gliomas: Where Do the Differences Lie?

Two thirds of pediatric gliomas are classified as low-grade (LGG), while in adults only around 20% of gliomas are low-grade. However, these tumors do not only differ in their incidence but also in their location, behavior and, subsequently, treatment. Pediatric LGG constitute 65% of pilocytic astrocytomas, while in adults the most commonly found histology is diffuse low-grade glioma (WHO II), which mostly occurs in eloquent regions of the brain, while its pediatric counterpart is frequently found in the infratentorial compartment. The different tumor locations require different skillsets from neurosurgeons. In adult LGG, a common practice is awake surgery, which is rarely performed on children. On the other hand, pediatric neurosurgeons are more commonly confronted with infratentorial tumors causing hydrocephalus, which more often require endoscopic or shunt procedures to restore the cerebrospinal fluid flow. In adult and pediatric LGG surgery, gross total excision is the primary treatment strategy. Only tumor recurrences or progression warrant adjuvant therapy with either chemo- or radiotherapy. In pediatric LGG, MEK inhibitors have shown promising initial results in treating recurrent LGG and several ongoing trials are investigating their role and safety. Moreover, predisposition syndromes, such as neurofibromatosis or tuberous sclerosis complex, can increase the risk of developing LGG in children, while in adults, usually no tumor growth in these syndromes is observed. In this review, we discuss and compare the differences between pediatric and adult LGG, emphasizing that pediatric LGG should not be approached and managed in the same way as adult LCG.

ROLE OF DIFFUSION WEIGHTED MRI IN DIFFERENTIAL DIAGNOSIS OF PAEDIATRIC POSTERIOR FOSSA TUMORS

Background: Infratentorial tumors accounts for 65% of all paediatric tumors, and most common infratentorial tumors in children include juvenile pilocytic astrocytoma (JPA), medulloblastoma, ependymoma and brainstem glioma. An accurate diagnosis has important clinical implications related to treatment and prognosis. DWI and ADC maps provide information regarding the cellularity of tumors and have an important role in the preoperative differentiation of different tumor types. Aim: To evaluate the role of DWI and ADC measurement in distinguishing between the most common pediatric posterior fossa tumors. Methods: In this study, we evaluated 25 paediatric patients aged between 1 to 15 years suspected to have posterior fossa mass on the CT referred from neurosurgery department to our department for MRI brain. All these patients subjected to conventional MRI followed by diffusion MR imaging and calculation of the ADC values. Written consent was taken from the guardians. Results: In juvenile pilocytic astrocytoma ( n = 10), ADC values ranged between 1.3 and 1.9 × 10?3 mm2/s, ependymoma (n = 8), ADC values ranged between 1.1 and 1.5 × 10?3 mm2/s and medulloblastoma (n = 7), ADC values ranged between 0.45 and 0.9 × 10?3 mm2/s. Statistically significant difference in ADC value was detected between JPA, ependymomas and medulloblastomas, while no statistically significant difference was detected between JPA and ependymomas. Conclusion: Diffusion Imaging plays an important role in demonstrating the features of posterior fossa brain tumours for appropriate diagnosis of medulloblastomas, ependymomas, and pilocytic astrocytoma. Keywords: DWI, MRI, Posterior fossa

Neuroimaging of pediatric infratentorial tumors and the value of diffusion-weighted imaging (DWI) in determining tumor grade

Background Diffusion-weighted imaging (DWI) provides information about the cellular density of tumors. This feature is useful in grading and identifying different tumor types. Purpose To assess the value of diffusion restriction and apparent diffusion coefficient (ADC) values in differentiating pediatric infratentorial tumors. Material and Methods This was a retrospective review of the magnetic resonance imaging (MRI) of 82 children (age range 1–16 years) with infratentorial tumors. Histopathological grading after surgical excision/biopsy was categorized as low grade (WHO grades I and II) (n = 31; 29 pilocytic astrocytomas, 2 ependymomas) and high grade (WHO grade III and IV) (n = 51; 40 medulloblastomas, 8 anaplastic ependymomas, 1 anaplastic astrocytoma, 2 atypical rhabdoid teratoid tumors [ATRT]). MRI features and ADC values were compared among tumor types and grades using a two-tailed t test, Mann–Whitney U test for continuous data and Chi-square test for categorical variables. Results Diffusion restriction and low ADC value was a feature of high-grade tumors ( P<0.001). The mean ADC values of the low-grade and high-grade tumors were 1.567 × 10−3mm2/s and 0.661 × 10−3mm2/s, respectively. Using 0.9 × 10−3mm2/s as the cut-off value, the sensitivity, specificity, positive and negative predictive values for differentiating the grades was 87%, 100%, 100%, and 81.8%, respectively. Significant differences were found between the mean ADC values of the individual tumor types ( P<0.05), except between medulloblastoma and ATRT. Conclusion ADC values and visual assessment of diffusion restriction are useful in tumor grading. The individual tumor types can be identified by an algorithmic approach, using DWI in conjunction with other described MRI features.

Conformal Radiation Therapy for Pediatric Ependymoma, Chemotherapy for Incompletely Resected Ependymoma, and Observation for Completely Resected, Supratentorial Ependymoma

PURPOSE The Children’s Oncology Group trial ACNS0121 estimated event-free survival (EFS) and overall survival for children with intracranial ependymoma treated with surgery, radiation therapy, and—selectively—with chemotherapy. Treatment was administered according to tumor location, histologic grade, and extent of resection. The impacts of histologic grade, focal copy number gain on chromosome 1q, and DNA methylation profiles were studied for those undergoing surgery and immediate postoperative conformal radiation therapy (CRT). METHODS ACNS0121 included 356 newly diagnosed patients (ages 1 to 21 years). Patients with classic supratentorial ependymoma were observed after gross total resection (GTR). Those undergoing subtotal resection received chemotherapy, second surgery, and CRT. The remaining patients received immediate postoperative CRT after near-total resection or GTR. CRT was administered with a 1.0-cm clinical target volume margin. The cumulative total dose was 59.4 Gy, except for patients who underwent GTR and were younger than age 18 months (who received 54 Gy). Patients were enrolled between October 2003 and September 2007 and were observed for 5 years. Supratentorial tumors were evaluated for RELA fusion; infratentorial tumors, for chromosome 1q gain. Classification of posterior fossa groups A and B was made by methylation profiles. RESULTS The 5-year EFS rates were 61.4% (95% CI, 34.5% to 89.6%), 37.2% (95% CI, 24.8% to 49.6%), and 68.5% (95% CI, 62.8% to 74.2%) for observation, subtotal resection, and near-total resection/GTR groups given immediate postoperative CRT, respectively. The 5-year EFS rates differed significantly by tumor grade ( P = .0044) but not by age, location, RELA fusion status, or posterior fossa A/posterior fossa B grouping. EFS was higher for patients with infratentorial tumors without 1q gain than with 1q gain (82.8% [95% CI, 74.4% to 91.2%] v 47.4% [95% CI, 26.0% to 68.8%]; P = .0013). CONCLUSION The EFS for patients with ependymoma younger than 3 years of age who received immediate postoperative CRT and for older patients is similar. Irradiation should remain the mainstay of care for most subtypes.

Incidence of intraoperative seizures during motor evoked potential monitoring in a large cohort of patients undergoing different surgical procedures

OBJECTIVE The purpose of this study was to investigate the incidence of seizures during the intraoperative monitoring of motor evoked potentials (MEPs) elicited by electrical brain stimulation in a wide spectrum of surgeries such as those of the orthopedic spine, spinal cord, and peripheral nerves, interventional radiology procedures, and craniotomies for supra- and infratentorial tumors and vascular lesions. METHODS The authors retrospectively analyzed data from 4179 consecutive patients who underwent surgery or an interventional radiology procedure with MEP monitoring. RESULTS Of 4179 patients, only 32 (0.8%) had 1 or more intraoperative seizures. The incidence of seizures in cranial procedures, including craniotomies and interventional neuroradiology, was 1.8%. In craniotomies in which transcranial electrical stimulation (TES) was applied to elicit MEPs, the incidence of seizures was 0.7% (6/850). When direct cortical stimulation was additionally applied, the incidence of seizures increased to 5.4% (23/422). Patients undergoing craniotomies for the excision of extraaxial brain tumors, particularly meningiomas (15 patients), exhibited the highest risk of developing an intraoperative seizure (16 patients). The incidence of seizures in orthopedic spine surgeries was 0.2% (3/1664). None of the patients who underwent surgery for conditions of the spinal cord, neck, or peripheral nerves or who underwent cranial or noncranial interventional radiology procedures had intraoperative seizures elicited by TES during MEP monitoring. CONCLUSIONS In this largest such study to date, the authors report the incidence of intraoperative seizures in patients who underwent MEP monitoring during a wide spectrum of surgeries such as those of the orthopedic spine, spinal cord, and peripheral nerves, interventional radiology procedures, and craniotomies for supra- and infratentorial tumors and vascular lesions. The low incidence of seizures induced by electrical brain stimulation, particularly short-train TES, demonstrates that MEP monitoring is a safe technique that should not be avoided due to the risk of inducing seizures.

Postoperative Hematoma Requiring Recraniotomy in 1149 Consecutive Patients With Intracranial Tumors

BACKGROUND: The reported 30-day mortality rate after brain tumor surgery is 2.2% to 2.9%, with a postoperative hematoma (POH) as the most frequent cause of death. OBJECTIVE: To investigate the risk factors for a POH requiring a recraniotomy after brain tumor surgery in a large, contemporary, single-institution consecutive series. METHODS: We included 1149 patients who underwent surgery for intracranial tumors at the Tokushima University Hospital from 1997 to 2014. The patient charts were retrospectively studied from our prospectively collected database. We analyzed the risk factors, type of hemorrhage, time to reoperation, and outcomes. RESULTS: The incidence of a POH requiring a recraniotomy was 2.09%. Among the patients with a POH requiring a recraniotomy, 12.5% died within 30 days of the first surgery. The incidence of a POH requiring a recraniotomy significantly correlated with the incidence of a hemangioblastoma, infratentorial tumors, and a prolonged operative time (&gt;10 h), but not with the patient age or sex, surgical procedure (biopsy or craniotomy), surgical type (primary or secondary), bleeding volume, or intraoperative blood transfusion requirement. A recraniotomy for a POH was performed in 54% of the patients just after the first operation, and within 24 h for 79% of the patients. The clinical status at the time of discharge deteriorated in 52% of the patients. CONCLUSION: Hemangioblastomas, infratentorial tumors, and an operative time exceeding 10 h were significantly correlated with an increased risk of a POH; these factors were responsible for 12.5% of the 30-day surgical mortality rate.