Faculty Bibliography

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.

Craniofacial surgeons perform operations that involve exposure of the dura. Typical procedures include cranial vault remodeling (CVR), fronto-orbital advancement (FOA), Le Fort III, monobloc, bipartition advancement, or distraction. Cerebrospinal fluid (CSF) fistulas remain one of the most common complications encountered, occurring in up to 30% of patients. Cerebrospinal fluid fistulas can be encountered intraoperatively, acutely, or in the late postoperative period. Traditional management has been well described in the neurosurgical literature. While several studies of complications exist, there is a relative lack of adequate information for craniofacial surgeons. The authors review current literature and provide 3 patients to illustrate our management paradigm.The authors review 30 years of experience at our institution and the pertinent literature. The mean rate of CSF fistula was 11.2%; rates were lowest for FOA/CVR, 5.5%. Patients with fistulas persisting after 2 days of conservative therapy or whom were symptomatic prompted placement of a lumbar subarachnoid catheter. Failure of the leak to resolve with CSF diversion prompted exploration and therapy which could include a patch, pericranial flap, and/or endonasal repair with septal flaps. Three patients are used to illustrate the paradigm, all of which have had no recurrence thus far.Cerebrospinal fluid fistula remains one of most common complications craniofacial surgeons encounter. Although neurosurgeons are often part of the clinical team, the craniofacial surgeon should be familiar with all aspects of treatment. Prompt diagnosis and appropriate knowledgeable management may avoid morbidity and mortality.

Intrathecal baclofen therapy is widely accepted as a treatment option for patients with severe spasticity. The current treatment of spasticity in patients with Sjogren-Larsson syndrome is largely symptomatic, given that no effective causal therapy treatments are available. We report the outcome of 2 patients with Sjogren-Larsson syndrome who had pump implantation for intrathecal baclofen. We observed a positive response, with a decrease of spasticity, reflecting in the Modified Ashworth Scale, and parents and caregivers observed a functional improvement in both patients. One patient experienced skin irritation 15 months after surgery, necessitating pump repositioning. No infection occurred. Our report shows that intrathecal baclofen therapy can have a positive therapeutic effect on spasticity in patients with Sjogren-Larsson syndrome, and therefore may be a promising addition to current treatments.

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.

Utilizing advanced 3D printing techniques, a multimaterial model was created for the surgical planning of a complex deformity of the skull base and craniovertebral junction. The model contained bone anatomy as well as vasculature and the previously placed occipital cervical instrumentation. Careful evaluation allowed for a unique preoperative perspective of the craniovertebral deformity and instrumentation options. This patient-specific model was invaluable in choosing the most effective approach and correction strategy, which was not readily apparent from standard 2D imaging. Advanced 3D multimaterial printing provides a cost-effective method of presurgical planning, which can also be used for both patient and resident education.

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

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