Faculty Bibliography

OBJECTIVE: Gross-total resection of craniopharyngioma is associated with complications that potentially affect quality of life. This study was designed to investigate the impact of gross-total resection on the long-termquality of life and sexual functioning in adulthood. MATERIAL-METHODS:55 consecutive pediatric patients treated with primary gross-total resection for craniopharyngioma were included in this retrospective fixed cohort study. Amultidimensional questionnaire-based quality of life instrument, the SF36v1 and the Medical Outcomes Study family and sexual functioning scale, was chosen to analyze follow-up data. Additionally, patients were asked to fill out a Questionnaire about medication, visual impairment, education and family life. RESULTS: Of 43 mailed questionnaires 23 were returned (response rate 55%); 17 patients were lost to follow up, 3 individuals were reluctant to participate, 7 patients died and 5 patients were minors at the time of study. The median length of follow up was 19 years (range 10-31). BMI was underweight in 1 patient (4%), normal in 3 patients (13%), overweight in 8 patients (35%), obesity in 4 patients (17%) and severe obesity in 7 patients (31%). 18 out of 19 patients reported about sexual functioning, of whom 53% reported at least 'a little of a problem' in one or more areas of sexual functioning. The mean SF 36v total score was 51.9 for PCS (physical health) and 48.5 for MCS (mental health), no significant difference between the patient cohort and the normal population. No significant correlation between BMI and PCS, but significant correlation between BMI and MCS. 44% Patients reported to have excellent or very good health in general. CONCLUSIONS: In a cohort of adults who underwent gross-total resection for craniopharyngioma in childhood, quality of life scores according to the SF 36 instrument were not different from those in a normal sample population. Sexual dysfunction is slightly more prevalent in this population

OBJECTIVE: Pediatric optic pathway gliomas (OPGs) are often considered benign, but can have detrimental effects on the quality of life, impair vision and are a potentially lethal disease. The aim of this study is to report the characteristics and outcomes of surgically treated OPGs and to identify candidates for different treatment strategies. MATERIAL-METHODS: Retrospective chart review of consecutive pediatric patients with surgically treated OPGs by a single surgeon at our institution from 1985-2015. Three treatment pathways were defined: surgery without planned adjuvant therapy (1), surgery with planned adjuvant therapy (2) and patients with prior treatment (3). RESULTS:88 patients - 49 male and 39 female - were included in analysis. 8 patients had NF1. Pathology revealed pilocytic astrocytoma (85.2%), pilomyxoid astrocytoma (8%), and pilocytic/pilomyxoid astrocytoma (5.7%). Radiologic location of the tumor was: hypothalamic (87%), and involvement of only chiasmand/or tract in (13%).Median age at diagnosiswas 4 years, median age at surgery was 6 years, and median time from diagnosis to surgery was 1 year. At the time of the study: Pathway 1: 37 patients; median PFS 84 +/- 33.4; median OS of 118 months (range: 24 - 337 months); OS rate 68%. Pathway 2: 9 patients; median PFS 45 +/- 10.9 months; median OS of 127 months (range: 23 - 368 months); OS rate 67%. Pathway 3: 42 patients; median PFS 74 +/- 13.3 months; median OS of 69 months (range: 7 - 356) months; OS rate 76%.. CONCLUSIONS: The role of surgery in the treatment of pediatric OPGs depends on patient characteristics and tumor biology. With the adequate therapeutic strategy, long-term PFS and OS can be achieved

OBJECTIVE: The need of duraplasty for adequate decompression of Chiari 1 malformation remains highly controversial. Although proponents of dural opening contend that duraplasty increases the likelihood of symptom and syrinx improvement while concurrently decreasing reoperation rates, opponents reference the risks associated with dural opening: CSF leakage, bacterial meningitis, aseptic meningitis, increased bleeding, pseudomeningocele, and hydrocephalus. In this study we retrospectively investigated the outcomes for pediatric patients who underwent surgery for treatment of symptomatic Chiari Malformation. We limited our investigation to patients who were treated with bony decompression and duraplasty in an effort to describe the clinical outcomes and post-operative course associated with this posterior fossa decompression variant. MATERIAL-METHODS: This is a retrospective chart review of all patients who underwent surgical decompression of symptomatic Chiari Malformation with dural opening by a single surgeon at New York University Medical Center between the years of 1985 and 2015. RESULTS:107 patients, median age at surgery 10 years (range: 1-20). Presentation was typical tussive headaches in15.9%, mixed headache in 11.2%, atypical headache in 18.7%, serendipitous finding in 22.4%, scoliosis workup in 22.4%, neurologic deficit in 3.7%, ataxia in 2.8%, other in 3.7%. Focal neurologic deficits at presentation was sensory in19.6%, motor in 6.5%, mixed in 10.3%, CN involvement in 2.8%, none in 57.9% Headache Resolved in 46/48 patients(95.8%). Syrinx resolved in 63.8%, decreased in 28.8%, stable in 5%, progressive in 1.3%. Complications were aseptic meningitis in 15%, Infection in0.9%,dural leaks in0.9% No resurgery in 30 days, total resurgeries: 11 (10.3%). No mortality. CONCLUSIONS: Suboccipital decompression with duraplasty for Chiari 1 malformation can be achieved with a high success rate and a low complication rate in selected patients. Headache resolved in 96% and Syrinx resolved or improved in 93% of the patients. The most common complication was aseptic meningitis

Patients with marker-positive central nervous system (CNS) germ cell tumors are typically monitored for tumor recurrence with both tumor markers (AFP and b-hCG) and MRI. We hypothesize that the recurrence of these tumors will always be accompanied by an elevation in tumor markers, and that surveillance MRI may not be necessary. We retrospectively identified 28 patients with CNS germ cell tumors treated at our institution that presented with an elevated serum or cerebrospinal fluid (CSF) tumor marker at the time of diagnosis. We then identified those who had a tumor recurrence after having been in remission and whether each recurrence was detected via MRI changes, elevated tumor markers, or both. Four patients suffered a tumor recurrence. Only one patient had simultaneously elevated tumor markers and MRI evidence of recurrence. Two patients had evidence of recurrence on MRI without corresponding elevations in serum or CSF tumor markers. One patient had abnormal tumor markers with no evidence of recurrence on MRI until 6 months later. We conclude that in patients with marker-positive CNS germ cell tumors who achieve complete remission, continued surveillance imaging in addition to measurement of tumor markers is indicated to detect recurrences.

INTRODUCTION: Confusion has surrounded the description of post-operative mutism and associated morbidity in pediatric patients with cerebellar tumors for years. The heterogeneity of definitions and diagnostic features has hampered research progress within the field, and to date, no international guidelines exist on diagnosis, prevention, treatment, or follow-up of this debilitating condition. An international group of clinicians and researchers from multiple relevant disciplines recently formed a cohesive panel to formulate a new working definition and agree upon standardized methods for diagnosis and follow-up. METHODS: Consensus was obtained using the modified nominal group technique, involving four rounds of online Delphi questionnaires interspersed with a structured consensus conference with lectures, group work, and open discussion sessions. RESULTS: A new, proposed definition of "post-operative pediatric CMS" was formed, preliminary recommendations for diagnostic and follow-up procedures were created, two working groups on a new scoring scale and risk prediction and prevention were established, and areas were identified where further information is needed. DISCUSSION: The consensus process was motivated by desire to further research and improve quality of life for pediatric brain tumor patients. The Delphi rounds identified relevant topics and established basic agreement, while face-to-face engagement helped resolve matters of conflict and refine terminology. The new definition is intended to provide a more solid foundation for future clinical and research work. It is thought as a consensus for moving forward and hopefully paves the way to developing a standard approach to this challenging problem with the advent of better scoring methods and ultimate goal of reducing the risk of CMS.

INTRODUCTION: Optic gliomas are classified as pilocytic astrocytoma (PA) or pilomyxoid astrocytoma (PMXA). Abundant bluish chondroid myxoid matrix is characteristic of PMXA but not PA. We sought to investigate the molecular composition of myxoid matrix and its biologic role in angiogenesis of optic gliomas. We reviewed clinical and pathological data on a cohort of 120 patients with optic glioma diagnosed at NYU Langone Medical Center from 1996 to 2014. We analyzed microvascular density (MVD), perfusion, hypoxia and proliferation by immunohistochemistry and ultrastructural features by electron microscopy. To identify the composition of the myxoid matrix in PMXA we performed liquid chromatography-mass spectrometry (LC-MS) without sample fractionation quantified using peptide spectral counts. PMXA showed significantly lower MVD by CD34 (8.1 vs 14.5, p-value < 0.002) and Erg (7 vs. 13.6, p-value 0.003) than PA, however GLUT-1 showed equal perfusion. Electron microscopy showed that PMXA contain both regular blood vessels with endothelial lining and channels completely lacking endothelial and smooth muscle cells. LC-MS stratified optic gliomas into three distinct groups. We identified 5389 proteins of which 188 were differentially expressed in the three groups (p<0.05, Benjamini-Hochberg adjustment). Between PA and PMXA, we found that most of differentially expressed proteins (146/188) displayed a positive fold change (increasing in PMXA relative to PA), and a minority (42/188) showed a negative fold change. The most abundant extracellular matrix proteins were a chondroitin sulfate proteoglycan versican (VCAN 3.7-fold increase Q=0.000463) and its paralog vertebrate Hyaluronan And Proteoglycan Link Protein 1 (HAPLN1, 22-fold increase from the PA to the PMXA group Q=4.60x10-7). Optic gliomas can develop endothelium-independent channels reminiscent of those in invertebrates to maintain blood supply. The myxoid matrix is composed of VCAN and its linking paralog HAPLN1. Targeting the myxoid matrix may provide novel avenues for therapy of optic gliom

Introduction: Pediatric optic pathway gliomas (OPGs) are often considered benign, but can have detrimental effects on the quality of life, impair vision and are a potentially lethal disease. The aim of this study is to report the characteristics and outcomes of surgically treated pediatric OPGs and to identify candidates for different treatment strategies. Methods: Retrospective chart review of consecutive pediatric patients with surgically treated OPGs by a single surgeon at our institution from 1985-2015. Three treatment pathways were defined: (1) surgery without planned adjuvant therapy; (2) surgery with planned adjuvant therapy; and, (3) patients with prior treatment.Results: 100 patients-55 male and 45 female-were included in analysis. 8 patients had NF1. Pathology revealed pilocytic astrocytoma (45%), pilomyxoid astrocytoma (9%), ganglioglioma (3%), and unknown (35%). Radiologic location of the tumor was: hypothalamic 86%, involvement of only chiasm and/or tract in 12%. Median age at diagnosis was 4 years, median age at surgery was 6 years, and median time from diagnosis to surgery was 1 year. Pathway 1: 39 patients; median PFS 73+17 months; OS rate 74%; median follow-up 117 months. Pathway 2: 10 patients; median PFS 29+15 months; OS rate 70%; median follow-up 59 months. Pathway 3: 51 patients; median PFS 33+8 months; OS rate 80%; median follow-up was 73 months. Conclusion: The role of surgery in the treatment of pediatric OPGs depends on patient characteristics and tumor biology. With the adequate therapeutic strategy, long-term PFS and OS can be achieved