Faculty Bibliography

BACKGROUND: Hydrocephalus in patients with neurofibromatosis type I (NF1) is usually obstructive, and may arise secondary to tumoral or non-tumoral causes. The treatment of hydrocephalus in these patients is often challenging due to combined pathologies and unique anatomical changes. The use of endoscopic third ventriculostomy (ETV) as treatment has rarely been described in this group. In this study we aimed to characterize the indications, considerations and outcome of ETV in patients with NF1 gathered in a multicenter international cohort. METHODS: Five centers participated in this retrospective study. Following an IRB approval, data and images were collected. Inclusion criteria were patients of all ages with NF1 who underwent an ETV for the treatment of obstructive hydrocephalus. Exclusion criteria were patients who had no post-operative radiological or clinical follow up. ETV failure was defined as recurrent clinical or radiological signs of hydrocephalus. RESULTS: Forty-two patients were included in this study. Common etiologies for hydrocephalus were aqueductal/tectal tumor (31%), aqueductal web (26%), and aqueductal stenosis due to neurofibromatosis related changes (14%). Ten patients had a preoperative diagnosis of optic pathway glioma. Six patients were defined as ETV failure within 1 month, 3 more within 9 months and 1 more within 4 years. ETV was defined as successful in 32 patients (76%) with a mean follow up of 59.4 +/- 50.9 months (4 months - 15 years). CONCLUSION: ETV is a safe treatment for selected patients with NF1 and obstructive hydrocephalus. Individual anatomical and pathological aspects should be taken into consideration.

Optic gliomas are brain tumors characterized by slow growth, progressive loss of vision, and limited therapeutic options. Optic gliomas contain various amounts of myxoid matrix, which can represent most of the tumor mass. We sought to investigate biological function and protein structure of the myxoid matrix in optic gliomas to identify novel therapeutic targets. We reviewed histological features and clinical imaging properties, analyzed vasculature by immunohistochemistry and electron microscopy, and performed liquid chromatography-mass spectrometry on optic gliomas, which varied in the amount of myxoid matrix. We found that although subtypes of optic gliomas are indistinguishable on imaging, the microvascular network of pilomyxoid astrocytoma, a subtype of optic glioma with abundant myxoid matrix, is characterized by the presence of endothelium-free channels in the myxoid matrix. These tumors show normal perfusion by clinical imaging and lack histological evidence of hemorrhage organization or thrombosis. The myxoid matrix is composed predominantly of the proteoglycan versican and its linking protein, a vertebrate hyaluronan and proteoglycan link protein 1. We propose that pediatric optic gliomas can maintain blood supply without endothelial cells by using invertebrate-like channels, which we termed primitive myxoid vascularization. Enzymatic targeting of the proteoglycan versican/hyaluronan and proteoglycan link protein 1 rich myxoid matrix, which is in direct contact with circulating blood, can provide novel therapeutic avenues for optic gliomas of childhood.

OBJECTIVE: Dermoid and epidermoid cysts rank among the most common pediatric tumors. We analyzed the outcomes of surgical excision of dermal and epidermal inclusion cysts in a large consecutive series of children. METHODS: We retrospectively reviewed 128 consecutive children who underwent calvarial inclusion cyst resection between 2000 and 2010 at NYU Langone Medical Center. Demographic information, neurological exam, lesion location, lesion diameter, type of treatment, extent of resection, time of follow-up, and recurrence were collected. RESULTS: The cohort includes 67 girls (52.3 %) and 61 boys (47.7 %). Age at diagnosis ranged from birth to 6.5 years (mean of 1.2 years) with surgical intervention between 1 month and 20 years of age (1.5 +/- 2.1). Of the 128 patients, 107 underwent open resection. Surgical approach was determined by the senior surgeon. Location, postoperative cosmesis, and family preference were the determining factors. Endoscopic resection was favored with supraorbital and glabellar lesions (75 % endoscopic versus 25 % open) using a rigid scope via a single incision. Erosion of the outer table and involvement of the inner table was noted in 20 patients (15 %), 14 of which were reconstructed using a split thickness calvarial graft. These lesions were noted to be significantly larger than lesions where cranioplasty was not used (1.9 +/- 2.81 cm versus 1.23 +/- 0.98 cm, p = 0.022). Gross total resection was achieved in all cases. DISCUSSION: Complete removal and cure from dermoid and epidermoid inclusion cysts are possible. Complications are few. Endoscopic approaches are useful to improve cosmesis and limit tissue damage for lesions near the orbits.

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: Optic gliomas are characterized as pilocytic astrocytoma (PA) or pilomyxoid astrocytoma (PMXA). Prominent chondroid myxoid matrix is typical of PMXA but not PA. We investigated the composition of myxoid matrix and its role in vasculariztion of optic gliomas. MATERIAL-METHODS: We reviewed clinicopathological data 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. Liquid chromatography-mass spectrometry (LC-MS) was performed to identify components of the myxoid matrix in PMXA. RESULTS: PMXA showed significantly lowerMVD by CD34 (8.1 vs 14.5, pvalue < 0.002) and Erg (7 vs. 13.6, p-value 0.003) than PA, however GLUT-1 showed equal distribution. Electron microscopy showed that PMXA contains both regular blood vessels with endothelial lining and channels completely lacking endothelia and smooth muscle. 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 PAand PMXA,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. 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). CONCLUSIONS: Optic gliomas develop endothelium-independent channels evocative invertebrate blood supply. The myxoid matrix is composed of VCAN and linking paralog HAPLN1. Targeting the myxoid matrix may provide novel avenues for therapy of optic gliomas and PMA

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

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