Matei A. Banu

Endoscopic Endonasal Resection of Suprasellar Meningiomas: The Importance of Case Selection and Experience in Determining Extent of Resection, Visual Improvement, and Complications

OBJECTIVE Suprasellar meningiomas have been resected via various open cranial approaches. During the past 2 decades, the endoscopic endonasal approach has been shown to be an option in selected patients. We wished to examine the learning curve for parameters such as extent of resection, visual outcome, and complications. METHODS We retrospectively reviewed a consecutive series of patients in whom suprasellar meningiomas were resected via an endonasal endoscopic approach between 2005 and 2013 at our institution. After June 2008, our surgical technique matured. Using this time point, we divided our case series into 2 chronological groups, group 1 (n=8) and group 2 (n=12). This cut-off also was used to examine rates of gross total resection (GTR) and visual improvement. Case selection criteria in successful and unsuccessful cases were examined to determine important principals for case selection. RESULTS Mean patient age at surgery was 57.05 years (range, 31-81 years). Mean tumor volume was 11.98 cm3 (range, 0.43-28.93 cm3). Overall, GTR was achieved in 80%, and vision improved or normalized in 14 patients (82.4%) with no occurrence of postoperative visual deterioration. Rates of GTR increased from 62.5% (group 1) to 91.7% (group 2). Visual improvement increased from 75% (group 1) to 88.9% (group 2). Rates of cerebrospinal fluid leak were 25% in group 1 and 0% in group 2. Average follow-up was 51.5 month (range, 3-96 months). CONCLUSION Once the learning curve is overcome, surgeons performing endonasal endoscopic resection of suprasellar meningiomas can achieve high rates of GTR with low complication rates in well-selected cases.

Low-dose intrathecal fluorescein and etiology-based graft choice in endoscopic endonasal closure of CSF leaks

OBJECTIVE Skull base cerebrospinal fluid (CSF) leaks of various etiologies are increasingly repaired through the natural corridor using an endoscopic endonasal approach. Characteristics of the skull base defect significantly correlate with etiology, which should be ascertained to guide surgical management. The objectives of this study were to assess the long-term outcomes of patients that underwent endoscopic endonasal repair of CSF leak using low-dose intrathecal fluorescein (ITF) and an etiology-based algorithm for multi-layer graft closure. METHODS Patients were divided into 4 groups: A--congenital, B--post-traumatic, C--post-endonasal surgery, D--post-craniotomy. Low-dose ITF was utilized in all case series. Long-term clinical follow-up data, including perioperative complications associated with the use of intrathecal fluorescein and leak closure rates, were obtained retrospectively. Endoscopic visualization of fluorescein-stained CSF as well as the method of skull base closure and graft material is detailed. RESULTS We identified a total of 41 patients (N=24 in Group A, N=4 in Group B, N=12 in Group C and N=1 in Group D) that underwent 50 CSF leak repairs using the endoscopic endonasal approach with an average follow-up of 31.6 months. Nine patients (21.9%) had undergone a previous attempt at CSF leak repair. Lumbar drain was used intraoperatively in 26 patients (63.4%) and kept in place for an average duration of 3.25 days. ITF successfully identified the site of leak in 80.5% of cases regardless of etiology. Leaks were successfully closed in 92% of patients. One patient (2.4%) experienced transient leg weakness following lumbar drain placement. Another patient (2.4%) developed hydrocephalus requiring a ventriculoperitoneal shunt. CONCLUSION Low-dose ITF is a safe and useful adjunct to endoscopic endonasal repair of CSF leaks with minimal complications and successful localization of the leak in approximately 80%. An etiology-based approach to graft choice and duration of lumbar drain placement in CSF leak repair may optimize closure rates.

Impact of skull base development on endonasal endoscopic surgical corridors.

OBJECT Scarce morphometric data exist on the developing skull base as a corridor for endonasal endoscopic approaches (EEAs). Furthermore, the impact of skull base lesions on its development has not been assessed. The authors describe a novel set of anatomical parameters characterizing the developmental process as well as the utility of these parameters in preoperative planning and a feasibility assessment of EEAs for neurosurgical treatment of skull base lesions in children. METHODS Based on specific MRI sequences in 107 pediatric patients (2-16 years of age) without skull base lesions (referred to here as the normal population), 3 sets of anatomical parameters were analyzed according to age group and sex: drilling distance, restriction sites, and working distance parameters. A separate set of patients undergoing EEAs was analyzed in similar fashion to address the impact of skull base lesions on the developmental process. RESULTS The volume of the sphenoid sinus significantly increases with age, reaching 6866.4 mm(3) in the 14-16 years age group, and directly correlates with the pneumatization type (r = 0.533, p = 0.0001). The pneumatization process progresses slowly in a temporal-posterior direction, as demonstrated by the growth trend of the sellar width (r = 0.428, p = 0.0001). Nasal restriction sites do not change significantly with age, with little impact on EEAs. The intercarotid distance is significantly different only in the extreme age groups (3.9 mm, p = 0.038), and has an important impact on the transsphenoidal angle and the intracranial dissection limits (r = 0.443, p < 0.0001). The 14.9° transsphenoidal angle at 2-4 years has a 37.6% significant increase in the 11-13 years age group (p = 0.001) and is highly dependent on pneumatization type. Age-dependent differences between working parameters are mostly noted for the extreme age groups, such as the 8.6-mm increase in nare-vomer distance (p = 0.025). The nare-sellar distance is the only parameter with significant differences based on sex. Skull base lesions induce a high degree of variance in skull base measurements, delaying development and decreasing parameter values. Skull base parameters are interdependent. Nare-sellar distance can be used to assess global skull base development because it highly correlates with the intercarotid distance in both the normal population and in patients harboring skull base lesions. CONCLUSIONS Skull base development is a slow, gradual, age-dependent, sex-independent process significantly altering endonasal endoscopic corridors. Preoperative MRI measurements of the pediatric skull base are thus a useful adjunct in choosing the appropriate corridor and in assessing working angles and limits during dissection or reparative surgery. Skull base lesions can significantly impact normal skull base development and age-dependent growth patterns.

Sensitivity and specificity of intrathecal fluorescein and white light excitation for detecting intraoperative cerebrospinal fluid leak in endoscopic skull base surgery: a prospective study.

OBJECTIVE The intraoperative detection of CSF leaks during endonasal endoscopic skull base surgery is critical to preventing postoperative CSF leaks. Intrathecal fluorescein (ITF) has been used at varying doses to aid in the detection of intraoperative CSF leaks. However, the sensitivity and specificity of ITF at certain dosages is unknown. METHODS A prospective database of all endoscopic endonasal procedures was reviewed. All patients received 25 mg ITF diluted in 10 ml CSF and were pretreated with dexamethasone and Benadryl. Immediately after surgery, the operating surgeon prospectively noted if there was an intraoperative CSF leak and fluorescein was identified. The sensitivity, specificity, and positive and negative predictive power of ITF for detecting intraoperative CSF leak were calculated. Factors correlating with postoperative CSF leak were determined. RESULTS Of 419 patients, 35.8% of patients did not show a CSF leak. Fluorescein-tinted CSF (true positive) was noted in 59.7% of patients and 0 false positives were encountered. CSF without fluorescein staining (false negative) was noted in 4.5% of patients. The sensitivity and specificity of ITF were 92.9% and 100%, respectively. The negative and positive predictive values were 88.8% and 100%, respectively. Postoperative CSF leaks only occurred in true positives at a rate of 2.8%. CONCLUSIONS ITF is extremely specific and very sensitive for detecting intraoperative CSF leaks. Although false negatives can occur, these patients do not appear to be at risk for postoperative CSF leak. The use of ITF may help surgeons prevent postoperative CSF leaks by intraoperatively detecting and confirming a watertight repair.

Tight regulation between cell survival and programmed cell death in GBM stem-like cells by EGFR/GSK3b/PP2A signaling

Malignant gliomas represent one of the most aggressive forms of cancer, displaying high mortality rates and limited treatment options. Specific subpopulations of cells residing in the tumor niche with stem-like characteristics have been postulated to initiate and maintain neoplasticity while resisting conventional therapies. The study presented here aims to define the role of glycogen synthase kinase 3 beta (GSK3b) in patient-derived glioblastoma (GBM) stem-like cell (GSC) proliferation, apoptosis and invasion. To evaluate the potential role of GSK3b in GBM, protein profiles from 68 GBM patients and 20 normal brain samples were analyzed for EGFR-mediated PI3kinase/Akt and GSK3b signaling molecules including protein phosphatase 2A (PP2A). To better understand the function of GSK3b in GBM, GSCs were isolated from GBM patient samples. Blocking GSK3b phosphorylation at Serine 9 attenuated cell proliferation while concomitantly stimulating apoptosis through activation of Caspase-3 in patient-derived GSCs. Increasing GSK3b protein content resulted in the inhibition of cell proliferation, colony formation and stimulated programmed cell death. Depleting GSK3b in GSCs down regulated PP2A. Furthermore, knocking down PP2A or blocking its activity by okadaic acid inactivated GSK3b by increasing GSK3b phosphorylation at Serine 9. Our data suggests that GSK3b may function as a regulator of apoptosis and tumorigenesis in GSCs. Therapeutic approaches targeting GSK3b in glioblastoma stem-like cells may be a useful addition to our current therapeutic armamentarium.

Endoscopic lumbar foraminotomy.

Foraminal stenosis frequently causes radiculopathy in lumbar degenerative spondylosis. Endoscopic transforaminal techniques allow for foraminal access with minimal tissue disruption. However, the effectiveness of foraminal decompression by endoscopic techniques has yet to be studied. We evaluate radiographic outcome of endoscopic transforaminal foraminotomies performed at L3-L4, L4-L5, and L5-S1 on cadaveric specimens. Before and after the procedures, three dimensional CT scans were obtained to measure foraminal height and area. Following the foraminotomies, complete laminectomies and facetectomies were performed to assess for dural tears or nerve root damage. L3-L4 preoperative foraminal height increased by 8.9%, from 2.12±0.13cm to 2.27±0.14cm (p<0.01), and foraminal area increased by 24.8% from 2.21±0.18cm(2) to 2.72±0.19cm(2) (p<0.01). At L4-L5, preoperative foraminal height was 1.87±0.17cm and area was 1.78±0.18cm(2). Endoscopic foraminotomies resulted in a 15.3% increase of foraminal height (2.11±0.15cm, p<0.05) and 44.8% increase in area of (2.51±0.21cm(2), p<0.01). At L5-S1, spondylitic changes caused diminished foraminal height (1.26±0.14cm) and foraminal area (1.17±0.18cm(2)). Postoperatively, foraminal height increased by 41.6% (1.74±0.09cm, p<0.05) and area increased by 98.7% (2.08±0.17cm(2), p<0.01). Subsequent inspection via a standard midline approach revealed one dural tear of an S1 nerve root. Endoscopic foraminotomies allow for effective foraminal decompression, though clinical studies are necessary to further evaluate complications and efficacy.

Corridor-Based Endonasal Endoscopic Surgery for Pediatric Skull Base Pathology With Detailed Radioanatomic Measurements

BACKGROUND: Pediatric anatomy is more restricted, and the propagation of endonasal endoscopic approaches in the pediatric population has been limited. OBJECTIVE: To demonstrate the feasibility of the endonasal endoscopic approach in a variety of age groups and to perform measurements of the corridors and spaces available for surgery as a guide for case selection. METHODS: Only patients <18 years were included. The choice of operative corridor/approach is described in relation to pathological entity and location. Preoperative/postoperative visual fields and endocrine panels, extent of resection, as well as postoperative long-term complications are described. Prospective magnetic resonance image-based anatomic measurements of key distances were performed to determine age-dependent surgical indications and limitations. RESULTS: Forty purely endoscopic procedures were performed in 33 pediatric patients (5-18 years of age) harboring a variety of skull base lesions, from benign tumors to congenital malformations. For the 20 patients in whom gross total resection was the intended goal of surgery, gross total resection was attained in 15 (75%). There were 2 infections (5%) and no cerebrospinal fluid leaks. Significant improvement was shown in 58.3% of patients with visual deficits. Hormone overproduction resolved in 75% of patients, while preoperative hormone insufficiency only improved in 29.2%. Wider intercarotid distance at the superior clivus (P = .01) and shorter nare-dens working distance (P = .001) predicted improved outcomes and fewer postoperative complications. CONCLUSION: Endonasal endoscopic skull base approaches are viable in the pediatric population, they are not impeded by sphenoid sinus aeration, and they have minimal risk of cerebrospinal fluid leak and meningitis. Outcomes and complications can be predicted based on specific radio anatomical skull base measurements rather than age. ABBREVIATIONS: ASB, anterior sphenoid bone ASW, anterior sellar wall DI, diabetes insipidus EEA, endonasal endoscopic approach FSE, fast spin echo GH, growth hormone GTR, gross total resection ICD-CS, intercarotid distance at the level of the cavernous sinus ICD-SC, intercarotid distance at the superior clivus MaxWiT, maximum width between middle turbinates NDD, nare-dens distance NSD, nare-sellar distance NVD, nare-vomer distance SKB, skull base STR, subtotal resection TA, transsphenoidal angle VCD, vomer-clival distance

Expanding the borders: the evolution of neurosurgical approaches.

In this article the authors discuss the development of neurosurgical approaches and the advances in science and technology that influenced this development throughout history. They provide a broad overview of this interesting topic from the first attempts of trephination by ancient cultures to the work of the pioneers of neurosurgery and the introduction of microsurgery.

Industry progress report on neuro-oncology: Biotech update 2013

For the second time, The Brain Tumor Center of the Weill Cornell Brain and Spine Center, in collaboration with Voices Against Brain Cancer, hosted The Brain Tumor Biotech Summit in New York City in June 2013. After a very successful first summit in 2012, this innovative event has established a platform for intensive networking between neuro-oncologists, neurosurgeons, neuroscientists, members of the biotechnology and pharmaceutical communities, members of the financial community and leaders of non-profit organizations. This year’s summit highlighted dendritic cell vaccines, novel antibody, heat shock protein and targeted therapies as well as exosome technologies, MRI-guided therapies and other novel drug delivery tools. This report presents a short overview of the current progress in brain tumor research and therapy as presented at the 2013 Brain Tumor Biotech Summit.

Efficacy and outcomes of facial nerve–sparing treatment approach to cerebellopontine angle meningiomas

OBJECTIVE Advanced microsurgical techniques contribute to reduced morbidity and improved surgical management of meningiomas arising within the cerebellopontine angle (CPA). However, the goal of surgery has evolved to preserve the quality of the patients life, even if it means leaving residual tumor. Concurrently, Gamma Knife radiosurgery (GKRS) has become an acceptable and effective treatment modality for newly diagnosed, recurrent, or progressive meningiomas of the CPA. The authors review their institutional experience with CPA meningiomas treated with GKRS, surgery, or a combination of surgery and GKRS. They specifically focus on rates of facial nerve preservation and characterize specific anatomical features of tumor location with respect to the internal auditory canal (IAC). METHODS Medical records of 76 patients with radiographic evidence or a postoperative diagnosis of CPA meningioma, treated by a single surgeon between 1992 and 2016, were retrospectively reviewed. Patients with CPA meningiomas smaller than 2.5 cm in greatest dimension were treated with GKRS, while patients with tumors 2.5 cm or larger underwent facial nerve-sparing microsurgical resection where appropriate. Various patient, clinical, and tumor data were gathered. Anatomical features of the tumor origin as seen on preoperative imaging confirmed by intraoperative investigation were evaluated for prognostic significance. Facial nerve preservation rates were evaluated. RESULTS According to our treatment paradigm, 51 (67.1%) patients underwent microsurgical resection and 25 (32.9%) patients underwent GKRS. Gross-total resection (GTR) was achieved in 34 (66.7%) patients, and subtotal resection (STR) in 17 (33.3%) patients. Tumors recurred in 12 (23.5%) patients initially treated surgically, requiring additional surgery and/or GKRS. Facial nerve function was unchanged or improved in 68 (89.5%) patients. Worsening facial nerve function occurred in 8 (10.5%) patients, all of whom had undergone microsurgical resection. Upfront treatment with GKRS for CPA meningiomas smaller than 2.5 cm was associated with preservation of facial nerve function in all patients over a median follow-up of 46 months, regardless of IAC invasion and tumor origin. Anatomical origin was associated with extent of resection but did not correlate with postoperative facial nerve function. Tumor size, extent of resection, and the presence of an arachnoid plane separating the tumor and the contents of the IAC were associated with postoperative facial nerve outcomes. CONCLUSIONS CPA meningiomas remain challenging lesions to treat, given their proximity to critical neurovascular structures. GKRS is a safe and effective option for managing CPA meningiomas smaller than 2.5 cm without associated mass effect or acute neurological symptoms. Maximal safe resection with preservation of neurological function can be performed for tumors 2.5 cm or larger without significant risk of facial nerve dysfunction, and, when combined with GKRS for recurrence and/or progression, provides excellent disease control. Anatomical features of the tumor origin offer critical insights for optimizing facial nerve preservation in this cohort.