Novel predictive scoring system for morbid hypothalamic obesity in patients with pediatric craniopharyngioma.

PURPOSE: To identify the independent risk factors for developing morbid hypothalamic obesity, to propose a predictive scoring system for morbid hypothalamic obesity, and to propose an algorithm for management in order to minimize the risk of developing morbid hypothalamic obesity in patients with pediatric craniopharyngioma. METHODS: A retrospective analysis of all pediatric craniopharyngioma patients diagnosed and treated at Boston Children's Hospital (BCH) between 1985 and 2017. Analysis of the data was conducted using IBM SPSS Statistics. RESULTS: We identified 105 patients, 90 (47 males and 43 females) fulfilled the inclusion criteria. The median age of patients at time of diagnosis was 8.4 years. The median follow-up was 10.6 years. Morbid hypothalamic obesity was evident in 28 (31.1%) patients at the last follow-up visit. Age of patients at time of diagnosis > 10 years (P = 0.023), preoperative body mass index (BMI) > 95th percentile (P = 0.006), and preoperative papilledema (P < 0.001) were the independent risk factors for developing morbid hypothalamic obesity. CONCLUSION: We developed a unique predictive scoring system in order to differentiate between patients with and without high risk for developing morbid hypothalamic obesity.

Analysis of 2141 pediatric craniopharyngioma admissions in the USA utilizing the Kids' Inpatient Database (KID): predictors of discharge disposition.

OBJECTIVES: To recognize the national trends in management of pediatric craniopharyngioma and to address the significant predictors of discharge disposition. METHODS: We utilized the Kids' Inpatient Database (KID), a pediatric inpatient sample generated by the Healthcare Cost and Utilization Project (HCUP) triennially from 1997 to 2016. RESULTS: KID contains 2141 pediatric craniopharyngioma admissions. Patient demographics had no effect on discharge disposition. Based on the multivariable logistic regression analysis, we confirmed a significantly higher non-routine discharge rate among patients with hydrocephalus (P = 0.01). Patients who developed diabetes insipidus were at higher risk for non-routine discharge (P = 0.02). Admission of patients to a freestanding children's hospital increased the likelihood of routine discharge (P = 0.001). CONCLUSION: Hydrocephalus, diabetes insipidus, and admission to a freestanding children's hospital are significant independent predictors of discharge disposition.

Sixty years single institutional experience with pediatric craniopharyngioma: between the past and the future.

PURPOSE: To demonstrate the paradigm shift in management strategies of pediatric craniopharyngioma at our institution over the past six decades. METHODS: Retrospective analysis of all pediatric patients with craniopharyngioma treated at Boston Children's Hospital between 1960 and 2017. RESULTS: One hundred seventy-eight patients with craniopharyngioma were treated between 1960 and 2017; 135 (70 males and 65 females) fulfilled the inclusion criteria. Forty-five patients were treated in the old era (1960-1984) and 90 patients were treated in the new era (1985-2017). Gross total resection (GTR) was achieved in 4% and 43% of patients in old and new eras respectively. Sub-total resection (STR) and radiotherapy (XRT) were performed in 27% and 28% of patients in old and new eras respectively. STR without XRT was performed in 20% and 29% of patients in old and new era respectively. Cyst drainage and adjuvant radiotherapy were performed in 49% of patients in the old era while no patients in the new era underwent such conservative management. Aggressive surgical resection was associated with a higher risk of worsening visual outcomes (20% vs 16%), panhypopituitarism and diabetes insipidus (86% vs 53%), psycho-social impairment (42% vs 26%), and new-onset obesity (33% vs 22%). The mortality rate was higher in the old era in comparison with that of the new one (9% vs 2%). CONCLUSION: There was a paradigm shift in management strategies of pediatric craniopharyngioma over the past six decades which in turn affected the long-term outcomes and quality of life of patients.

Brain tumors and epileptic spasms: Natural history and outcomes.

While brain tumors are a frequent cause of seizures, they rarely cause epileptic spasms (ES). The objective of this study was to investigate features of tumor-associated ES. We conducted a retrospective review of patients with ES and a brain tumor. Demographics; pathologic, radiologic, and EEG data; treatment response; and long-term outcome were collected. Twenty four patients were identified; 11 met inclusion criteria. Epileptic spasm (ES) onset occurred prior to tumor diagnosis in seven patients (63%), and after tumor resection in 4 patients (36%). Spasms and ictal EEG often had focal features (45%). Gross total tumor resection resulted in ES freedom in 3/7 patients. There was poor response to first-line therapy (ACTH/vigabatrin; 1/5 with ES freedom). Low grade tumors predominated (8/11) with dual pathology (associated cortical malformation) in 2 patients. All tumors involved cortex; half involved subcortical regions and/or brainstem. Ten patients developed other seizure types; eight experienced refractory epilepsy, and nine had a Modified Rankin Scale of >3. In summary, EEG in tumor-associated ES often has focal features of either the semiology or EEG. Complete tumor resection yielded ES freedom in only a subset of patients. Most patients developed refractory epilepsy and adverse developmental outcomes.

Long-term visual outcomes of optic pathway gliomas in pediatric patients without neurofibromatosis type 1.

Sporadic optic pathway gliomas (OPGs) have been reported to cause more vision loss than OPGs associated with neurofibromatosis type-1, but long-term visual outcome data are limited. The purpose of this study was to report the visual outcomes of a cohort of pediatric patients with sporadic OPGs. This was a retrospective, cohort study at a tertiary care pediatric hospital and cancer institute. The study included all patients with sporadic OPGs evaluated from 1990 to 2014. The primary outcome was visual acuity at final follow-up. Secondary outcomes were risk factors for a poor visual outcome and the rate of progression. There were 59 pediatric patients included in the study. Median age at presentation was 2.5 years old and median follow-up was 5.2 years. In the worse eye at final follow-up, 16 patients (27 %) were 20/30 or better, 9 patients (15 %) were between 20/40 and 20/80, and 34 patients (58 %) were 20/100 or worse. In the better eye at final follow-up, 33 patients (56 %) were 20/30 or better, 11 patients (19 %) were between 20/40 and 20/80, and 15 patients (25 %) were 20/100 or worse. Risk factors for a poor visual outcome included younger age at presentation, optic nerve pallor, and tumor extent. Of the 54 patients (92 %) who received treatment, 40 (74 %) experienced disease progression during or after treatment. A majority of pediatric patients with sporadic OPGs had significant long-term visual impairment. In spite of treatment, tumor progression is common. Serial ophthalmic examinations with quantitative vision measurements are essential in the management of sporadic OPGs.

Myxopapillary ependymomas in children: imaging, treatment and outcomes.

Myxopapillary ependymomas (MPEs) are rare spinal tumors in children. The natural history and clinical course of pediatric MPEs are largely unknown and the indication for adjuvant therapy remains to be clarified. We performed an IRB-approved, retrospective review of children with MPEs treated at the Dana-Farber/Boston Children's Cancer and Blood Disorder Center between 1982 and 2013. Eighteen children (age range 8-21 years, median age 14 years) met inclusion criteria. We reviewed the histopathology, magnetic resonance imaging, tumor location and stage, surgical management, adjuvant therapy, and clinical outcomes. The median follow-up duration was 9.4 years (range 1-30 years). Children most commonly presented with pain, scoliosis, and urinary symptoms. All primary tumors were located in the lower thoracic or lumbar spine. Nine children (50%) had leptomeningeal tumor seeding at presentation, most commonly located within the distal thecal sac. A gross-total resection was achieved in nine children (50%). Three children were treated with irradiation following initial surgery. No child received adjuvant chemotherapy at diagnosis. The 10-year event-free survival (EFS) was 26% ± 14.8. Children with disseminated disease trended towards inferior EFS compared to those with localized disease (10-year EFS 12.7% ± 12 vs. 57 ± 25%, p value 0.07). The 10-year overall survival was 100%. The efficacy of adjuvant irradiation could not be assessed due to the small sample size. Although children with MPEs frequently present with disseminated tumor and/or develop recurrent or progressive disease, their overall survival is excellent. Treatment should aim to minimize both tumor- and therapy-related morbidity.

Incidence, risk factors, and longitudinal outcome of seizures in long-term survivors of pediatric brain tumors.

OBJECTIVE: Seizures are common during and after treatment for a primary brain tumor. Our objective was to describe the incidence and risk factors for seizures in long-term survivors of pediatric brain tumors. METHODS: In a retrospective, longitudinal study, we reviewed all consecutive patients during a 12-month period who were at least 2 years post initial diagnosis of a brain tumor. Data collection included age at diagnosis, length of follow-up, extent of initial resection, tumor histology, and treatment modalities. For patients who had experienced seizures at any time, the timing and frequency of seizures, seizure semiology, electroencephalography results, and anticonvulsant use were recorded. Univariate analyses and logistic regression were performed to assess risk factors. RESULTS: The cohort included 298 patients (140 female). Average duration of follow-up was 7.6 years. Initial surgical resection was gross-total in 109 patients, and subtotal for 143. Twenty-nine patients underwent biopsy alone and 17 had no surgical intervention. Tumor location included posterior fossa (104; 36%), midline (98; 34%), cortical (85; 29%), and other (11; 3%). Most frequent diagnoses were low grade glioma, medulloblastoma, and ependymoma. Other treatments included cranial irradiation (N = 163) and chemotherapy (n = 127). Tumor recurrence occurred in 92 patients (30%). Seventy-one patients had seizures (24%). Ongoing seizures at the time of most recent follow-up were present in 42 patients. Risk factors for seizures included tumor location, tumor histology, tumor recurrence, and incomplete resection at time of initial presentation. SIGNIFICANCE: Seizures are a frequent comorbidity in pediatric brain tumor survivors, seen at presentation in 24% of patients and ongoing in 14%. Factors predisposing to seizures include tumor pathology (low/high grade glioma, glioneuronal tumor), cortical location, and subtotal resection. These data may assist in identification and management of patients at highest risk for seizures as well as identification of patients for potential treatment trials with antiepileptogenic agents.

Long-term outcome of 4,040 children diagnosed with pediatric low-grade gliomas: an analysis of the Surveillance Epidemiology and End Results (SEER) database.

BACKGROUND: Children with pediatric low-grade gliomas (PLGG) are known to have excellent 10-year survival rates; however the outcomes of adult survivors of PLGG are unknown. We identified patients diagnosed with PLGG diagnosed between 1973 and 2008 through the Surveillance Epidemiology and End Results (SEER) database to examine outcomes of adult survivors of PLGG. PROCEDURE: Four thousand and forty patients with either WHO grade I or II PLGG were identified and outcome data retrieved. Two analyses were performed to assess survival and risk of death from tumor. Competing risks analysis was conducted and cumulative incidence curves of death due to disease were generated. Cox proportional hazards regression was performed, with adjustment for non-disease death. Kaplan-Meier curves for overall cancer specific survival (OS) were also generated. RESULTS: The 20-year OS was 87% ± 0.8% and the 20-year cumulative incidence of death due to glioma was 12% ± 0.8%. The incidence of death after transition to adulthood (age greater than 22 years) was slightly lower, with 20-year cumulative incidence of disease death of 7% ± 1.8%. Year of diagnosis, age of diagnosis, histology, WHO grade, primary site, radiation, and degree of initial resection were prognostic in univariate analysis, while the administration of radiation was the greatest risk of death in multivariate analysis of OS (hazard ratio = 3.9). CONCLUSIONS: PLGGs are associated with an excellent long-term survival, with a low likelihood of PLGG related death in adult survivors. Treatment strategies for pediatric tumors should therefore aim for disease control during childhood and adolescence with an emphasis on minimizing long-term treatment induced toxicities.

Sleep dysfunction in long term survivors of craniopharyngioma.

Craniopharyngiomas are slow growing tumors of the sellar and parasellar region and may also involve the hypothalamus. Treatment involves maximal surgical excision or subtotal resection followed by focal radiation therapy. Late effects of treatment include endocrinopathies, cognitive deficits, behavioral changes, obesity and sleep dysfunction. We conducted a retrospective review of all patients with craniopharyngioma more than 2 years off treatment and who were evaluated in the neuro-oncology survivorship clinic between 2003 and 2007. Clinical data, extent of resection, treatment modalities, endocrine status, patient symptom report and sleep study results were collected to evaluate the presence of patient reported daytime sleepiness and sleep disturbance and to determine possible risk factors. 28 patients were identified (25 %) female. 19/28 self-reported daytime fatigue or sleep disturbance; this included 4/6 patients with gross total resection and 15/22 with subtotal resection. 16/22 patients treated with cranial irradiation reported sleep-related abnormalities, compared to 3/6 patients who did not receive radiation. All but one patient had pituitary dysfunction requiring hormonal replacement. Patients with more than ≥2 sleep related complaints had a higher BMI (44.6 vs. 32.6, p = 0.0192). 8 patients underwent formal sleep evaluation. 3 patients had documented central or obstructive sleep apnea. The mean arousal index was 11.0/h (normal <5). Two patients were treated with melatonin for sleep disturbance and 2 were treated with stimulants for excessive daytime sleepiness. A majority of patients with craniopharyngioma have self-reported daytime fatigue and/or sleep dysfunction after treatment. Extent of resection did not increase the likelihood of patient-reported daytime sleepiness and/sleep dysfunction; however, patients who received radiation more frequently reported daytime sleepiness and/or sleep dysfunction. Patients with a higher BMI were more likely to experience sleep disturbance. Formal sleep evaluations should be considered in all patients with craniopharyngioma.

Structural variants shape driver combinations and outcomes in pediatric high-grade glioma.

We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an SV amplifying a MYC enhancer in 12% of diffuse midline gliomas (DMG), indicating an underappreciated role for MYC in pHGG. SV signature analysis revealed that tumors with simple signatures were TP53 wild type (TP53WT) but showed alterations in TP53 pathway members PPM1D and MDM4. Complex signatures were associated with direct aberrations in TP53, CDKN2A and RB1 early in tumor evolution and with later-occurring extrachromosomal amplicons. All pHGGs exhibited at least one simple-SV signature, but complex-SV signatures were primarily restricted to subsets of H3.3K27M DMGs and hemispheric pHGGs. Importantly, DMGs with complex-SV signatures were associated with shorter overall survival independent of histone mutation and TP53 status. These data provide insight into the impact of SVs on gliomagenesis and the mechanisms that shape them.

Long-term clinical outcomes following treatment of childhood craniopharyngioma.

PURPOSE: To review our institution's experience with treatment of craniopharyngioma in children, and to report long-term treatment outcomes stratified by treatment era to assess whether modern treatment techniques result in improvements in local control and survival. MATERIALS AND METHODS: We retrospectively reviewed the records of 100 children who underwent surgery for craniopharygioma at Children's Hospital Boston (CHB) from August 1976 to March 2003. Of these, 79 children (median age 8.5 years) had initial treatment at CHB and sufficient follow-up data to be included in this analysis. We report their treatment course, recurrence rates, and treatment-related morbidity. We compared the results in two different treatment eras based on changes in surgical approach at CHB. RESULTS: Thirty-six patients underwent initial treatment with surgery alone; 63% treated prior to 1988 recurred and 36% treated after 1988 recurred. Recurrence rates following combined modality therapy (CMT) with limited surgery followed by radiation were 21 and 5% in the pre- and post-1988 eras, respectively. Accounting for treatment era, patients treated with surgery alone were 7.7 times as likely to recur as those treated with CMT (95%CI: 2.0, 28.7). In the Cox regression model, there was no significant difference in local control or overall survival based on treatment era; initial treatment remained the only statistically significant variable (P = 0.02). CONCLUSIONS: Advancements in treatment techniques have improved local control in children diagnosed with craniopharyngioma. The excellent survival rates necessitate long-term patient follow-up to identify and manage any treatment-related effects, including second tumors, vascular abnormalities, and endocrinopathies.

Meningoencephalocele and other dural disruptions: complications of Le Fort III midfacial osteotomies and distraction.

OBJECTIVE: Complications of Le Fort III midfacial advancement include cerebrospinal fluid (CSF) rhinorrhea, meningitis, and ocular and cerebral injury. This report reviews our experience with Le Fort III distraction, highlighting complications of dural disruption, and correlates occurrences with the anatomy of the cranial base and prior cranial procedures. METHODS: This was a retrospective chart review of all patients who had Le Fort III subcranial osteotomies and midfacial advancement with distraction. Complications related to dural disruption were documented. The anatomy of the anterior cranial fossa was assessed with preoperative computed tomographic (CT) scans and compared with age- and sex-matched normal control scans, with particular attention paid to the anterior cranial fossa and fovea ethmoidalis (FE). On reconstructed midline sagittal images, the anterior cranial fossa was characterized as normal, sagging, or slanting. On reconstructed coronal images, immediately posterior to the plane of the lacrimal sac, each FE was characterized as normal, flattened, or depressed, relative to the adjacent cribriform plates. RESULTS: Thirty-one patients have had Le Fort III midfacial advancement with distraction at Children's Hospital Boston since 1995. Two patients underwent a second Le Fort III distraction. Two patients (6.5%) had postoperative CSF rhinorrhea, 2 had CSF leak at a pin site, and 1 patient had a late complication of meningoencephalocele. Twenty-six patients had 27 available preoperative three-dimensional reformatted CT scans. Seven of these had a normal sagittal anterior cranial fossa and normal coronal FE morphology. One of these 7 patients had a second CT at an older age showing development of bilateral FE flattening. Eleven patients had a sagging midline anterior cranial fossa including both patients who developed CSF rhinorrhea. Of these 11 patients, all had unilateral or bilateral flattening or depression of the FE, and 5 had abnormal slanting of the anterior cranial fossa. Eight patients had normal sagittal morphology, but bilateral or unilateral depression of the FE, including the patient who developed a meningoencephalocele. All patients with CSF leak had previously had a fronto-orbital advancement (FOA). Three of 4 patients with CSF leak did not have prior ventriculoperitoneal shunt placement. The patient with postoperative meningoencephalocele had prior FOA and shunt. CONCLUSIONS: We studied the abnormal position of the sagging or slanted anterior cranial base and depressed FE in patients with syndromic coronal synostosis. These findings may explain the risk for dural tear during osteotomies at the nasofrontal suture and superior-medial orbital wall. Attention to the morphology of the anterior cranial base, as seen on sagittal and coronal CT images, aids in preventing these complications. Patients who have a shunt are at lower risk for CSF leak; however, patients who have had an FOA are at higher risk.

Clinicopathologic study of glioblastoma in children with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is characterized by low-grade tumors of the central and peripheral nervous system. There is also an increased risk of developing malignant tumors. Glioblastoma is an uncommon, malignant tumor of children that is even less frequently observed in children with NF1. PROCEDURE: We performed a retrospective review of patients with NF1 and glioblastoma to determine specific clinical and pathologic indicators of overall prognosis. RESULTS: Five patients were identified from the CHB/DFCI database for whom pathologic and imaging studies were available. All pathologic specimens demonstrated vascular proliferation and necrosis. All samples stained positively for p53. Chromogenic in situ hybridization (CISH) for epidermal growth factor receptor (EGFR) copy numbers was increased, PTEN copy numbers were normal and the promoter of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene was unmethylated in the one patient evaluated. In the same time period, there were 56 patients without NF1 diagnosed with glioblastoma who were treated at our institution. Although the small sample size precludes formal statistical analysis, the 2-year survival of patients with NF1 is 60% with median overall survival of 9.25 years compared to non-NF1 patients with a 2-year survival of 25% and median overall survival 1.08 years. CONCLUSIONS: This study provides preliminary evidence that children with NF1 may be at risk for glioblastoma, but that these patients have an increased survival compared to children without NF1. Additional molecular studies will be required to determine if the pathogenesis of these tumors differs from glioblastoma in children without NF1.

A modified IRS-III chemotherapy regimen leads to prolonged survival in children with embryonal tumor with multilayer rosettes.

BACKGROUND: Embryonal tumor with multilayer rosettes (ETMR) is a rare CNS malignancy affecting young children that carries a very poor prognosis. Treatment with intensive surgical resection, radiotherapy, and high-dose chemotherapy is insufficient treatment in the vast majority of cases. Effective, biologically based therapies for this tumor are therefore desperately needed. The Dana-Farber Cancer Institute-modified IRS-III protocol incorporates preclinically active agents, such as doxorubicin and actinomycin D, into the treatment regimen for ETMR and may improve patient outcomes. METHODS: The authors present a case series of 5 children with ETMR treated with an IRS-III-based chemotherapy backbone. RESULTS: All 5 patients received a gross-total tumor resection. Patients received between 12 and 51 weeks of IRS-III therapy at the discretion of their treating physician. Four patients received focal radiation therapy, with the fifth patient instead receiving a cycle of high-dose chemotherapy with autologous stem cell rescue. Four patients have progression-free survival of more than 18 months. Chemotherapy treatment was reasonably tolerated by all 5 patients with one case of mild sinusoidal obstructive syndrome and one case of Grade 3 peripheral neuropathy. CONCLUSIONS: The patient outcomes in this small cohort are far better than would be expected based on the historical survival for this tumor. Given the tremendous need for effective therapy for ETMR, further investigation of this approach is warranted. An international consensus protocol based on the IRS-III regimen has been developed and will be available through a multicenter clinical trial and a global treatment registry.

Optimizing Postoperative Surveillance of Pediatric Low-Grade Glioma Using Tumor Behavior Patterns.

BACKGROUND: Pediatric low-grade gliomas are among the most common childhood neoplasms, yet their post-treatment surveillance remains nonstandardized, relying on arbitrarily chosen imaging intervals. OBJECTIVE: To optimize postoperative magnetic resonance imaging (MRI) surveillance protocols for pediatric low-grade gliomas. METHODS: Patients aged 0 to 21 yr with pediatric low-grade gliomas, treated between 1990 and 2016 were retrospectively analyzed. The timing of surveillance imaging and radiologic tumor outcomes were extracted, and the effect of patient age, tumor location, histology, and extent of resection as prognostic factors was studied. An algorithm was developed to analyze the detection efficacy and cost of all possible surveillance protocols. RESULTS: A total of 517 patients were included with a median follow-up of 7.7 yr (range: 2-25.1 yr) who underwent 8061 MRI scans (mean 15.6 scans per patient). Tumor recurrence was detected radiologically in 292 patients (56.5%), of whom, 143 underwent reoperation. The hazards ratio (HR) of recurrence was higher in patients who underwent biopsy (HR = 3.60; 95% confidence interval (CI): 2.45-5.30; P < .001), subtotal resection (HR = 2.97; 95% CI: 2.18-4.03; P < .001), and near-total resection (HR = 2.03; 95% CI: 1.16-3.54; P = .01), compared to patients with gross total resection (GTR). For all patients, an 8-image surveillance protocol at 0, 3, 6, 12, 24, 36, 60, and 72 mo (total cost: $13 672 per patient) yielded comparative detection rates to the current 15-image protocol ($25 635). For patients who underwent GTR, a 6-image protocol at 0, 3, 9, 24, 36, and 60 mo ($10 254) is sufficient. CONCLUSION: Our data suggest that postoperative surveillance of pediatric low-grade gliomas can be effectively performed using less frequent imaging compared to current practice, thereby improving adherence to follow-up, and quality-of-life, while reducing costs.

Natural History and Management of Incidentally Discovered Focal Brain Lesions Indeterminate for Tumor in Children.

BACKGROUND: The incidental discovery of brain lesions in children has increased due to greater utilization of neuroimaging. Standardized surveillance and management guidelines following the discovery of such lesions remain nonexistent. OBJECTIVE: To study the natural history and management of incidental brain lesions in children. METHODS: A retrospective analysis of pediatric patients who were treated at our institution between 2000 and 2016 with incidentally detected brain lesions that were indeterminate for neoplasm on MRI. RESULTS: We identified 445 patients with incidental brain abnormalities of whom 144 had lesions indeterminate for neoplasm. Average age at diagnosis was 11.2 (SD = 4.14) yr and average follow-up was 3.8 yr (range 1-13.2 yr). Lesions showed no progression in 112 patients (77.8%), whereas progression was detected in 31 patients (21.5%). Mean time to progression was 32.3 months (SD = 24.4). A change in management was made in 13/144 patients (9%), which included surgical resection (n = 11), biopsy (n = 1), and lumbar puncture (n = 1). Lesion size, location, multiplicity, new-onset symptoms, associated contrast enhancement, or edema were not predictive of radiologic progression. Larger lesions and those with contrast enhancement or edema were significantly more likely to undergo surgery (P < .001 each). Median geometric diameter of lesions that did not undergo surgery was 6.5 mm, whereas that of surgically resected lesions was 12.5 mm (P < .001). CONCLUSION: Most incidental brain lesions indeterminate for neoplasm have an indolent, benign course. For asymptomatic patients with radiologically stable lesions, we recommend conservative management with MRI and clinical surveillance at 6, 12, 24, 36, and 60 mo after detection.

Medical, psychological, cognitive and educational late-effects in pediatric low-grade glioma survivors treated with surgery only.

BACKGROUND: Surgical resection is often the only treatment necessary for pediatric low-grade gliomas (LGGs) and is thought to define a population with an excellent long-term prognosis. The goal of this study was to describe the multidimensional late-effects of pediatric LGG survivors treated exclusively with surgery. METHODS: A retrospective chart review of "surgery-only" LGG survivors followed at Dana-Farber/Children's Hospital Cancer Care was undertaken. Patients had to be diagnosed with an LGG before the age of 22 years, treated with "surgery-only" and be at least 2 years from diagnosis. RESULTS: Sixty survivors were eligible with a median age at the time of review of 16.3 years and the median time since diagnosis of 8.4 years. Tumor locations were predominantly posterior fossa (47%) or cortical (33%). Eighty-five percent of patients had at least one ongoing late-effect, and 28% had three or more. The most common late-effects consisted of motor dysfunction (43%), visual problems (32%), anxiety (19%), social difficulties (19%), seizure disorders (17%), depression (15%), poor coordination/ataxia (14%), behavioral problems (13%), and endocrinopathies (10%). Nine patients had a history of suicidal ideation; two with suicide attempts. The mean full-scale IQ was normal, however, the number of survivors scoring one standard deviation below the mean was twice the expected number. Special education services were utilized by more than half of the survivors. CONCLUSIONS: "Surgery-only" LGG survivors may be more affected by their tumor and its resection than previously appreciated. A prospective study is needed to address this survivor population.

The Impact of Intraoperative Electrocorticography on Seizure Outcome After Resection of Pediatric Brain Tumors: A Cohort Study.

BACKGROUND: Intraoperative electrocorticography (ECoG) has been utilized in patients with tumor-associated seizures; however, its effectiveness for seizure control remains controversial. OBJECTIVE: To evaluate clinical outcomes in pediatric patients undergoing lesionectomy with or without ECoG. METHODS: Patients undergoing brain tumor resection at Boston Children's Hospital were examined retrospectively (2005-2014). Inclusion criteria involved diagnosis of a supratentorial tumor, ≥2 unequivocal seizures, and ≥6 mo follow-up. Patients with isolated cortical dysplasia or posterior fossa tumors were excluded. Logistic regression models evaluated predictors of ECoG use, and the impact of ECoG, gross total resection, and focal cortical dysplasia with tumors on seizure freedom by Engel Class and anti-epileptic drug use (AED). RESULTS: A total of 119 pediatric patients were included (n = 69 males, 58%; median age, 11.3 yr). Forty-one patients (34.5%) had ECoG-guided surgery. Preoperative seizure duration and number and duration of AED use were significant predictors for undergoing ECoG. There were no differences in seizure freedom (Engel Class I) or improved Engel Score (Class I-II vs III-IV) in patients who did or did not have ECoG at 30 d, 6 mo, and 1, 2, or 5 yr. Patients undergoing ECoG required a greater number of AEDs at 6 mo (P = .01), although this difference disappeared at subsequent time intervals. Gross total resection predicted seizure freedom at 30 d and 6 mo postsurgery (P = .045). CONCLUSION: This retrospective study, one of the largest evaluating the use of ECoG during tumor resection, suggests that ECoG does not provide improved seizure freedom compared to lesionectomy alone for children.

Noninvasive Thermal Evaluation of Ventriculoperitoneal Shunt Patency and Cerebrospinal Fluid Flow Using a Flow Enhancing Device.

BACKGROUND: While a noninvasive flow determination would be desirable in the diagnosis of cerebrospinal fluid shunt malfunction, existing studies have not yet defined a role for thermal flow detection. OBJECTIVE: To evaluate a revised test protocol using a micropumper designed to transiently enhance flow during thermal testing to determine whether thermal detection of flow is associated with progression to shunt revision surgery. METHODS: Eighty-two unique tests were performed in 71 shunts. The primary outcome, need for revision within 7 d of testing, was compared with results of micropumper-augmented thermal flow detection. Statistical analysis was based on blind interpretation of test results and raw temperature data recorded during testing. RESULTS: The test was sensitive (73%) and specific (68%) in predicting need for revision, with 5.6-fold higher probability of revision when flow was not detected. Negative predictive value in our sample was 94.2%. The probability of not requiring revision increased with increasing total temperature drop. Analysis of various possible thresholds showed that the optimal temperature cutoff may be lower than suggested by the manufacturer (0.125°C vs 0.2°C). CONCLUSION: This is the first study to report a strong association between thermal flow evaluation and a clinical impression that a shunt is not malfunctioning. The current recommended threshold may increase the false positive rate unnecessarily, and as clinicians gain experience with the method, they may find value in examining the temperature curves themselves. Multicenter studies are suggested to further define a role for this diagnostic test.