Publications (25)61.96 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
Chapter: Subependymal Giant Cell Astrocytoma[Show abstract] [Hide abstract] ABSTRACT: Subependymal giant cell astrocytomas (SEGAs) are benign tumors (WHO grade I) that occur almost exclusively in the setting of tuberous sclerosis (TS), a well-defined, multi-system genetic syndrome. Most commonly originating from the region of the caudate nucleus, these tumors may cause obstruction of cerebrospinal fluid circulation leading to hydrocephalus. Less frequently, they may hemorrhage spontaneously, causing precipitous neurological impairment . Mutations of the TSC-1 and TSC-2 genes, both effectors of the mTOR pathway (originally mammalian Target of Rapamycin, now formally mechanistic Target of Rapamycin), lead to the variably expressed systemic manifestations of TS; cardiac rhabdomyoma, renal angiolipomas, facial adenoma sebaceum, cortical tubers of the brain, and SEGAs. The standard treatment of symptomatic or enlarging SEGAs is surgical excision. Pharmacological effectors of the mTOR pathway, rapamycin (aka sirolimus) and its analogs have recently been shown to induce rapid involution of SEGAs; however, the optimal timing, dosage, safety, and duration of treatment remain areas of active clinical research. SEGAs in the context of TS represent an example of an emerging paradigm: targeted molecular-oncologic therapy.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Glioblastoma multiforme (GBM) is the most common and lethal primary malignancy of the central nervous system (CNS). Despite the proven benefit of surgical resection and aggressive treatment with chemo- and radiotherapy, the prognosis remains very poor. Recent advances of our understanding of the biology and pathophysiology of GBM have allowed the development of a wide array of novel therapeutic approaches, which have been developed. These novel approaches include molecularly targeted therapies, immunotherapies, and gene therapy. Methods: We offer a brief review of the current standard of care, and a survey of novel therapeutic approaches for treatment of GBM. Results: Despite promising results in preclinical trials, many of these therapies have demonstrated limited therapeutic efficacy in human clinical trials. Thus, although survival of patients with GBM continues to slowly improve, treatment of GBM remains extremely challenging. Conclusion: Continued research and development of targeted therapies, based on a detailed understanding of molecular pathogenesis can reasonably be expected to yield improved outcomes for patients with GBM.
- [Show abstract] [Hide abstract] ABSTRACT: 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. 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/m(2)/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. 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. 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.
- [Show abstract] [Hide abstract] ABSTRACT: Object: Subependymal giant cell astrocytomas (SEGAs) are benign tumors, most commonly associated with tuberous sclerosis complex (TSC). The vast majority of these tumors arise from the lateral ependymal surface adjacent to the foramen of Monro, therefore potentially encroaching on one or both foramina, and resulting in obstructive hydrocephalus that necessitates surgical decompression. The indications for surgery, intraoperative considerations, and evolution of the authors' management paradigm are presented. Methods: Patients with TSC who underwent craniotomy for SEGA resection at New York University Langone Medical Center between January 1997 and March 2011 were identified. Preoperative imaging, clinical characteristics, management decisions, operative procedures, and outcomes were reviewed. Results: Eighteen patients with TSC underwent 22 primary tumor resections for SEGAs. The indication for surgery was meaningful radiographic tumor progression in 16 of 21 cases. The average age at the time of operation was 10.3 years. Average follow-up duration was 52 months (range 12-124 months). The operative approach was intrahemispheric-transcallosal in 16 cases, transcortical-transventricular in 5, and neuroendoscopic in 1. Nine tumors were on the right, 9 on the left, and 3 were bilateral. Gross-total resection was documented in 16 of 22 cases in our series, with radical subtotal resection achieved in 4 cases, and subtotal resection (STR) in 2 cases. Two patients had undergone ventriculoperitoneal shunt placement preoperatively and 7 patients required shunt placement after surgery for moderate to severe ventriculomegaly. Two patients experienced tumor progression requiring reoperation; both of these patients had initially undergone STR. Conclusions: The authors present their management strategy for TSC patients with SEGAs. Select patients underwent microsurgical resection of SEGAs with acceptable morbidity. Gross-total resection or radical STR was achieved in 90.9% of our series (20 of 22 primary tumor resections), with no recurrences in this group. Approximately half of our patient series required CSF diversionary procedures. There were no instances of permanent neurological morbidity associated with surgery.
- [Show abstract] [Hide abstract] ABSTRACT: Surgical resection of epileptic foci relies on accurate localization of the epileptogenic zone, often achieved by subdural and depth electrodes. Our epilepsy center has treated selected children with poorly localized medically refractory epilepsy with a staged surgical protocol, with at least one phase of invasive monitoring for localization and resection of epileptic foci. To evaluate the safety of staged surgical treatments for refractory epilepsy among children. Data were retrospectively collected, including surgical details and complications of all patients who underwent invasive monitoring. 161 children underwent 200 admissions including staged procedures (>1 surgery during one hospital admission), and 496 total surgeries. Average age at surgery was 7y (8m-16.5y). 250 surgeries included resections (and invasive monitoring), and 189 involved electrode placement only. Cumulative total number of surgeries per patient was 2-10 (average 3). Average duration of monitoring was 10 days (1-30). There were no deaths. Follow-up ranged from 1m to 10y. Major complications included unexpected new permanent mild neurological deficits (2%/admission), CNS or bone flap infections (1.5%/admission), intracranial hemorrhage, CSF leak, and a retained strip (each 0.5%/admission). Minor complications included bone absorption (5%/admission), positive surveillance sub/epidural cultures in asymptomatic patients (5.5%/admission), non-infectious fever (5%/admission), and wound complications (3%/admission). 30 complications necessitated additional surgical treatment. Staged epilepsy surgery, with invasive electrode monitoring, is safe in children with poorly localized medically refractory epilepsy. The rate of major complications is low, and appears comparable to that associated with other elective neurosurgical procedures.
- [Show abstract] [Hide abstract] ABSTRACT: A 7-year-old white girl presented with left hemiparesis and ischemic stroke secondary to moyamoya syndrome, a progressive cerebrovascular occlusive disorder of uncertain but likely multifactorial etiology. Past medical history revealed hearing loss and developmental delay/intellectual disability. Routine karyotype demonstrated extra chromosomal material on 6p. Single nucleotide polymorphism microarray revealed a previously unreported complex de novo genetic rearrangement involving subtelomeric segments on chromosomes 6p and 12q. The duplicated/deleted regions included several known OMIM-annotated genes. This novel phenotype and genotype provides information about a possible association of genomic copy number variation and moyamoya syndrome. Dosage-sensitive genes in the deleted and duplicated segments may be involved in aberrant vascular proliferation. Our case also emphasizes the importance of comprehensive evaluation of both developmental delay and congenital anomalies such as moyamoya.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
Article: CLIN-ONGOING CLINICAL TRIALS[Show abstract] [Hide abstract] ABSTRACT: INTRODUCTION: Bevacizumab has been reported to be an effective treatment for symptomatic radiation necrosis and to decrease focal edema around areas of radiation necrosis. We report our preliminary results and ongoing clinical trial of bevacizumab treatment for radiation necrosis. METHODS: Thirteen patients with symptomatic radiation necrosis were treated with bevacizumab. Radiation necrosis was diagnosed according to the patients' clinical courses, magnetic resonance images, and fluoride-labeled boronophenylalanine-positron emission tomography (F-BPA-PET). Lesion/normal (L/N) ratios less than 2.0 and 2.5 on F-BPA-PET were defined as absolute and relative indications for bevacizumab treatment, respectively. The patients were treated with bevacizumab at a dose of 5 mg/kg every 2 weeks, 6 cycles in total. RESULTS: Two patients were excluded from analysis because of adverse events. Eleven patients underwent 3 to 6 cycles of bevacizumab treatment. The median rate of the reduction in peri-lesional edema was 65.5% (range: 2.0% to 81.0%). The Karnofsky performance status (KPS) improved in 6 patients after bevacizumab treatment, and in 5 patients the status did not change. The L/N ratio on F-BPA-PET (P = 0.0084) and the improvement of KPS after bevacizumab (P = 0.0228) were significantly associated with the reduction rate of peri-lesional edema after bevacizumab treatment. CONCLUSION: Bevacizumab is a very effective treatment for radiation necrosis, irrespective of the original tumor histology. F-BPA-PET could be useful for diagnosing radiation necrosis and for making the decision as to whether or not to treat symptomatic radiation necrosis with bevacizumab. The clinical trial “Intra-venous administration of bevacizumab for the treatment of radiation necrosis in the brain” has been approved as Investigational Medical Care System by the Japanese Ministry of Health, Labour and Welfare. This trial has been ongoing since April, 2011.
Article: Cervical ependymoma resection[Show abstract] [Hide abstract] ABSTRACT: Intradural intramedullary cervical spinal cord tumors pose a significant challenge for the neurosurgeon to resect with minimal morbidity. We present the case of a 12-year-old male with a cervical ependymoma and demonstrate our resection technique. The video can be found here: http://youtu.be/5DHlnxdggU0 .
- [Show abstract] [Hide abstract] ABSTRACT: Subependymal giant cell astrocytomas (SEGAs) are benign tumors, most commonly associated with tuberous sclerosis complex (TSC). Arising from the lateral ependymal surface, these tumors may obstruct one or both foramina of Monro, resulting in hydrocephalus and often requiring treatment. Although interhemispheric-transcallosal and transcortical-transventricular approaches have been the standard methods for resecting these tumors, advances in neuroendoscopic techniques have expanded SEGAs as a potential target for endoscopic resection. The authors present a case of an endoscopically resected SEGA with stereotactic guidance in a 4-year-old girl with TSC. A gross-total resection of an enlarging SEGA was achieved. This represents one of the early case reports of endoscopically resected SEGAs. Although recent advances in medical treatment for SEGAs with mammalian target of rapamycin (mTOR) pathway inhibitors have shown promising initial results, the long-term safety and efficacy of mTOR inhibitors has yet to be determined. The propensity of these tumors to cause obstructive hydrocephalus requires that a surgical option remain. Neuroendoscopic approaches may allow a safe and effective technique.
- [Show abstract] [Hide abstract] ABSTRACT: Intracranial monitoring (IM) is a key diagnostic procedure for select patients with treatment-resistant epilepsy (TRE). Seizure focus resection may improve seizure control in both lesional and nonlesional TRE. IM itself is not considered to have therapeutic potential. We describe a cohort of patients with improved seizure control following IM without resective surgery. Over 12.5 years, 161 children underwent 496 surgeries including intracranial monitoring. We retrospectively reviewed the patients' charts, operative reports, and radiologic scans, under an institutional review board-approved protocol. Seventeen patients underwent only IM, without additional resective surgery, and seven had a dramatic improvement in their epilepsy; six of the seven patients are seizure-free (Engel class I), and one rarely has seizures (Engel class II). All seven patients had frequent seizures that led to IM: either daily (five patients) or 1-2 per week (two patients). The mean age (± standard deviation, SD) at seizure onset was 1.6 ± 1.3 years (range 0.5-4 years). Etiologies were tuberous sclerosis (3 patients), trauma (1 patient), and unknown (3 patients). Mean age at surgery (± SD) was 4.1 ± 2 years (range 1-7 years), and duration of epilepsy 2.5 ± 1.1 years (range 0.5-4 years). Duration of IM was 11.7 ± 5.6 days (5-19 days). Six patients had bilateral and one unilateral invasive electrodes. At last follow-up, four patients required fewer antiepileptic drugs (AEDs), one had the same medication but a higher dose, and two patients were taking additional AEDs. Follow-up was 30.6 ± 9.5 months (range 19-41 months). Although uncommon, patients with TRE may improve after IM alone. The explanation for this observation remains unclear; however, perioperative medications including steroids, direct cortical manipulation, or other factors may influence the epileptogenic network.
- [Show abstract] [Hide abstract] ABSTRACT: Techniques for the placement of intrathecal baclofen (ITB) systems have been described in detail, with special consideration given to complications from hardware placement. Risks including catheter kinking and migration, hardware erosion through the skin, and lumbar CSF leak are elevated given the often-low body mass index and poor nutritional status of this patient population. The bulk of a spinal catheter and fascial connector within the lumbar wound may increase the potential for the aforementioned risks, leading to potential risks for wound infection and breakdown. The authors' experience has led them to develop a novel method of paraspinal subfascial lumbar catheter placement to address these risks. The authors describe a novel lumbar intrathecal catheter placement technique as part of the ITB system. All patients undergoing placement of an ITB system by the senior author at New York University Langone Medical Center between July 2010 and March 2011 underwent paraspinal subfascial lumbar catheter placement. Patients were followed-up by the surgeon 2 weeks after implantation and followed up and managed by their physiatrist thereafter, for an average of 5 months (range 0.5-9 months). Results Of the 20 patients who underwent this method of intrathecal catheter placement, none developed any hardware erosion, catheter migration, or CSF leak. One patient developed an abdominal wound infection 3 weeks after implantation, necessitating pump removal. In this initial short-term experience, subfascial placement of the lumbar spine intrathecal catheter may be an improvement over the traditional method of catheter placement. There is reduced risk of catheter migration or kinking, hardware erosion, CSF leak, and decreased operative time, all yielding a decreased reoperation rate in this vulnerable population.
- [Show abstract] [Hide abstract] ABSTRACT: Although rarely encountered, pediatric patients with severe cervical spine deformities and instability may occasionally require occipitocervicothoracic instrumentation and fusion. This case series reports the experience of 4 pediatric centers in managing this condition. Occipitocervical fixation is the treatment of choice for craniocervical instability that is symptomatic or threatens neurological function. In children, the most common distal fixation level with modern techniques is C-2. Treated patients maintain a significant amount of neck motion due to the flexibility of the subaxial cervical spine. Distal fixation to the thoracic spine has been reported in adult case series. This procedure is to be avoided due to the morbidity of complete loss of head and neck motion. Unfortunately, in rare cases, the pathological condition or highly aberrant anatomy may require occipitocervical constructs to include the thoracic spine. The authors identified 13 patients who underwent occipitocervicothoracic fixation. Demographic, radiological, and clinical data were gathered through retrospective review of patient records from 4 institutions. Patients ranged from 1 to 14 years of age. There were 7 girls and 6 boys. Diagnoses included Klippel-Feil, Larsen, Morquio, and VATER syndromes as well as postlaminectomy kyphosis and severe skeletal dysplasia. Four patients were neurologically intact and 9 had myelopathy. Five children were treated with preoperative traction prior to instrumentation; 5 underwent both anterior and posterior spinal reconstruction. Two patients underwent instrumentation beyond the thoracic spine. Allograft was used anteriorly, and autologous rib grafts were used in the majority for posterior arthrodesis. Follow-up ranged from 0 to 43 months. Computed tomography confirmed fusion in 9 patients; the remaining patients were lost to follow-up or had not undergone repeat imaging at the time of writing. Patients with myelopathy either improved or stabilized. One child had mild postoperative unilateral upper-extremity weakness, and a second child died due to a tracheostomy infection. All patients had severe movement restriction as expected. Occipitocervicothoracic stabilization may be employed to stabilize and reconstruct complex pediatric spinal deformities. Neurological function can be maintained or improved. The long-term morbidity of loss of cervical motion remains to be elucidated.
- [Show abstract] [Hide abstract] ABSTRACT: Hydrocephalus caused by stenosis of the foramen of Monro is rare. The authors describe a 28-year-old female patient with bilateral foraminal stenosis treated using endoscopic septostomy and unilateral foraminal balloon plasty (foraminoplasty). The patient's hydrocephalus and symptoms resolved postoperatively. Endoscopic strategies may be employed as first-line therapy in this condition.
- [Show abstract] [Hide abstract] ABSTRACT: Intrathecal baclofen (ITB) therapy is an accepted treatment modality for spasticity and dystonia. Several complications related to ITB have been described, including mechanical malfunctions, infections, cerebrospinal fluid fistula, and baclofen withdrawal or overdose. In this study, we present our institutional experience with ITB therapy, emphasizing complication avoidance and lessons learned. The charts of 87 patients treated with ITB therapy were retrospectively reviewed. The primary surgical technique, complication type and timing, method of treatment, and outcome were analyzed. Thirteen out of 76 (17.1%) patients primarily treated at our department had 25 complications. The first complication occurred 17.5-30.9 months (mean 24.2±6.7) after the pump implantation. Additional four patients with pumps placed elsewhere had six complications and were subsequently treated by our group. The main complications were: catheter fracture (11), subcutaneous fluid collection (5), lumbar wound/CSF infection (3), lumbar catheter or connector protrusion (3), pump malfunction (3), distal catheter migration outside the thecal sac (2), and baclofen withdrawal (1). Of the patients in the NYULMC group, six were treated by a single surgical procedure, six underwent multiple surgical procedures, and one was managed conservatively. In retrospect, changing the surgical technique, or adding an abdominal binder may have prevented 17 complications (54.8%). There were two deaths that were unrelated to the ITB therapy. ITB therapy is associated with complications, many of which require additional surgery. Some of these complications are avoidable by adhering to a strict surgical technique and a proper criterion for patient selection.
NYU Langone Medical CenterNew York, New York, United States