Faculty Bibliography

INTRODUCTION: Tuberous Sclerosis Complex (TSC) has an incidence of 1/6,000 in the general population. Overall care may be very complex and costly. We examine trends in healthcare utilization and outcomes of TSC patients over the last decade. METHODS: The National Inpatient Sample (NIS) database for inpatient hospitalizations was searched for admission of patients with TSC. RESULTS: During 2000-2010, the NIS captured 5655 TSC patients. The majority patients were admitted to teaching hospitals (71.7%). Over time, the percentage of craniotomies performed per year remained stable (p = 0.351). Relevant diagnoses included neuro-oncologic pathology (5.4%), hydrocephalus (6.5%), and epilepsy (41.2%). Hydrocephalus significantly increased length of stay and hospital charges. A higher percentage of patients who underwent craniotomy had hydrocephalus (29.8% versus 5.3%; p < 0.001), neuro-oncologic pathology (43.5% versus 3.4%; p < 0.001), other cranial pathologies (4.2% versus 1.2%; p < 0.001), and epilepsy (61.4% versus 40.1%; p < 0.001). CONCLUSION: Our study identifies aspects of inpatient healthcare utilization, outcomes, and cost of a large number of patients with TSC. These aspects include related diagnoses and procedures that contribute to longer length of stay, increased hospital cost, and increased in-hospital mortality, which can inform strategies to reduce costs and improve care of patients with TSC.

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

Treatment for intracranial germ cell tumors includes platinum-based chemotherapy and external beam radiation therapy, which are risk factors for hearing loss. In patients who experience significant sensorineural ototoxicity due to cochlear hair cell injury, dose reduction of chemotherapy may be necessary. This report describes an adolescent male, with excellent treatment response for an intracranial nongerminomatous germ cell tumor, who developed sensorineural hearing loss, which was central rather than cochlear in origin and unrelated to carboplatin. This patient highlights the need to carefully differentiate the type and etiology of sensorineural hearing loss in patients with brain tumors receiving ototoxic chemotherapy.

OBJECTIVE: Neuroendoscopy is increasingly being used in the management of intraventricular brain tumors. The role of endoscopy in diagnostic biopsy is well established. Expansion of these techniques may allow for definitive resection of intraventricular tumors. We report the feasibility and outcomes of endoscopic resection of select intraventricular tumors in children. METHODS: The clinical characteristics of 11 children with solid intraventricular tumors who underwent tumor resection were reviewed. Twelve procedures were performed. RESULTS: Gross-total resection was achieved in 11 of 12 cases (92%). Maximal tumor diameter ranged from 9 to 26 mm (mean, 16.6 mm). Pathologic results included subependymal giant cell astrocytomas, ependymomas, nongerminomatous germ cell tumors, and pilocytic astrocytomas. Mean follow-up was 35 months (range, 10-109 months). All patients returned to their neurologic baselines after surgery. Local tumor recurrence occurred in 1 patient and distant recurrence in another. In 1 patient, a transitory intraoperative increase of intracranial pressure without clinical implications occurred. There was no permanent morbidity or mortality in this series. Hydrocephalus was present preoperatively in 5 cases and was treated either with tumor removal alone or with an additional endoscopic third ventriculostomy. No patient required a ventriculoperitoneal shunt. CONCLUSIONS: Neuroendoscopic gross-total resection of solid intraventricular tumors is a safe and efficacious procedure in carefully selected pediatric patients.

OBJECT Intrathecal baclofen (ITB) is a valuable therapeutic option for patients with spasticity and dystonia. The techniques that place an ITB pump catheter into the subcutaneous fat of a lumbar incision are well described. Because patients who require ITB often have low body fat content, they may be predisposed to catheter-related complications. The senior author used a novel technique to place the catheter in a paraspinal subfascial fashion, and the short-term results were previously published. That study demonstrated no development of hardware erosions, catheter migrations, or CSF leaks within an average follow-up of 5 months. This study followed up on those initial findings by looking at the long-term outcomes since this technique was introduced. METHODS Using the institutional review board-approved protocol, the electronic medical records were reviewed retrospectively for all patients who underwent paraspinal subfascial catheter placement by the senior author. Patients received follow-up with the surgeon at 2 weeks postoperatively and were followed routinely by their physiatrist thereafter. RESULTS Of the 43 patients identified as having undergone surgery by the senior author using the paraspinal subfascial technique between July 2010 and February 2014, 12 patients (27.9%) required reoperation. There were 5 patients (11.6%) who had complications related to the catheter or lumbar incision. No hardware erosions or CSF leaks were identified. These patients received a median follow-up of 3.0 years, with 30 of 43 patients receiving follow-up over 2.0 years. CONCLUSION This follow-up study suggests that the technique of paraspinal subfascial catheter placement translates to long-term decreases in CSF leakage and complications from erosion, infection, and also catheter malfunctions. It does not seem to affect the overall rate of complications.

Objective: We report the feasibility and outcomes of endoscopic resection of select intraventricular tumors in children. Methods: The clinical characteristics of 11 children with solid intraventricular tumors who underwent tumor resection were reviewed. 12 procedures were performed. Results: Gross total resection was achieved in 11 of 12 cases (92%). Maximal diameter ranged from 9-26 mm (mean 16.6 mm). Pathology included subependymal giant cell astrocytomas (SEGA), ependymomas, non-germinomatous germ cell tumor (NGGCT) and pilocytic astrocytoma. Mean follow-up was 35 months (range 10-109 months). All patients returned to their neurological baseline following surgery. Local tumor recurrence occurred in one patient and distant recurrence in another. Complications occurred in one patient, no permanent morbidity or mortality occurred. Hydrocephalus was present preoperatively in 5 cases and was treated with tumor removal alone or with additional endoscopic third ventriculostomy. No patient required a ventriculoperitoneal shunt. Conclusion: Neuroendoscopic gross-total resection of solid intraventricular tumors is a safe procedure in carefully selected pediatric patients

A 4-year-old girl with a history of thoracic meningocele repair at the age of 3 months presented with progressive myelopathy. An intramedullary thoracic epidermoid was identified on MRI. The patient underwent excision of the epidermoid and subsequently returned to neurological baseline. This case illustrates the potential for delayed development of intraspinal epidermoid after initial repair of a simple meningocele.

We present the first case of pediatric intracranial M abscessus infection in a 16-month-old female with neurofibromatosis type-1. We describe a successful treatment regimen including excisional biopsy combined with high dose steroids and 16 weeks of triple antimicrobial therapy that resulted in clinical cure and an excellent neurologic outcome.

BACKGROUND: Activation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver of pediatric low-grade astrocytoma (PLGA) growth. Sorafenib is a multikinase inhibitor targeting BRAF, VEGFR, PDGFR, and c-kit. This multicenter phase II study was conducted to determine the response rate to sorafenib in patients with recurrent or progressive PLGA. METHODS: Key eligibility criteria included age >/=2 years, progressive PLGA evaluable on MRI, and at least one prior chemotherapy treatment. Sorafenib was administered twice daily at 200 mg/m2/dose (maximum of 400 mg/dose) in continuous 28-day cycles. MRI, including 3-dimensional volumetric tumor analysis, was performed every 12 weeks. BRAF molecular testing was performed on tumor tissue when available. RESULTS: Eleven patients, including 3 with neurofibromatosis type 1 (NF1), were evaluable for response; 5 tested positive for BRAF duplication. Nine patients (82%) came off trial due to radiological tumor progression after 2 or 3 cycles, including 3 patients with confirmed BRAF duplication. Median time to progression was 2.8 months (95% CI, 2.1-31.0 months). Enrollment was terminated early due to this rapid and unexpectedly high progression rate. Tumor tissue obtained from 4 patients after termination of the study showed viable pilocytic or pilomyxoid astrocytoma. CONCLUSIONS: Sorafenib produced unexpected and unprecedented acceleration of tumor growth in children with PLGA, irrespective of NF1 or tumor BRAF status. In vitro studies with sorafenib indicate that this effect is likely related to paradoxical ERK activation. Close monitoring for early tumor progression should be included in trials of novel agents that modulate signal transduction.