Publications by authors named "Peter Morgenstern"

34 Publications

Three-dimensional printing and craniosynostosis surgery.

Childs Nerv Syst 2021 Mar 29. Epub 2021 Mar 29.

Department of Neurological Surgery, University of Virginia Health System, P.O. Box 800212, Charlottesville, VA, 22908, USA.

Overview: The goal of this study was to review the current application and status of three-dimensional printing for craniosynostosis surgery.

Methods: A literature review was performed using the PubMed/MEDLINE databases for studies published between 2010 and 2020. All studies demonstrating the utilization of three-dimensional printing for craniosynostosis surgery were included.

Results: A total of 15 studies were ultimately selected. This includes studies demonstrating novel three-dimensional simulation and printing workflows, studies utilizing three-dimensional printing for surgical simulation, as well as case reports describing prior experiences.

Conclusion: The incorporation of three-dimensional printing into the domain of craniosynostosis surgery has many potential benefits. This includes streamlining surgical planning, developing patient-specific template guides, enhancing residency training, as well as aiding in patient counseling. However, the current state of the literature remains in the validation stage. Further study with larger case series, direct comparisons with control groups, and prolonged follow-up times is necessary before more widespread implementation is justified.
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http://dx.doi.org/10.1007/s00381-021-05133-8DOI Listing
March 2021

A Review on Variability in Treatment Protocols With Posterior Cranial Vault Distraction.

J Craniofac Surg 2021 Mar 5. Epub 2021 Mar 5.

Division of Plastic and Reconstructive Surgery, Department of Surgery Department of Neurosurgery, Icahn School of Medicine at Mount Sinai Mount Sinai Kravis Children's Hospital Mount Sinai Cleft and Craniofacial Center, New York, NY.

Background: Prior studies have confirmed the ability of posterior cranial vault distraction osteogenesis (PVDO) to expand the intracranial volume in patients with craniosynostosis. To date, there is scant literature on the optimal distraction protocol for PVDO. The authors sought to review the literature and define a common protocol for posterior cranial vault distraction.

Methods: The authors performed a systematic review for published PVDO protocols. The data collected from these studies included age at the time of PVDO, number of distraction devices placed, time for latency, rate and rhythm of distraction, distraction length, time for consolidation, and surgical outcomes.

Results: A total of 286 patients were identified within 24 studies from 2011 to 2019. The mean age of patients identified was 25.34 months. After application of distractors, latency period ranged between 1 and 7 days, with most patients undergoing 5 to 7 days of latency. Once distraction was begun, the majority of patients (77.4%) underwent 1 mm of distraction daily. Total lengths of distraction ranged between 13 and 35 mm, with the largest cohort of patients undergoing 26 to 30 mm of total distraction. A total of 60 complications were reported for a total of 212 patients, yielding an overall complication rate of 28.3%.

Conclusions: Although there is variability in reported PVDO protocols, the majority are similar to distraction osteogenesis protocols described for long bone sites. Increased patient age correlates with selection of a greater latency period and total distraction length, while frequency of complications is also increased.
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http://dx.doi.org/10.1097/SCS.0000000000007340DOI Listing
March 2021

Idiopathic membranous occlusion of the foramen of Monro: an unusual cause of hydrocephalus and headache in adults.

Br J Neurosurg 2021 Jan 7:1-3. Epub 2021 Jan 7.

Department Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.

Occlusion of foramen of Monro is an uncommon clinical entity that usually presents in children. Common causes are obstructing mass, infectious etiologies or vascular malformation. Rarely, it may be an idiopathic stricture or membrane. We report a case of idiopathic membranous obstruction of the foramen of Monro in a 45-year-old male with no past medical or surgical history. He presented with new intermittent dull and burning bifrontal severe headache for 2 d, which was alleviated slightly by non-steroidal anti-inflammatory medication. Imaging showed marked dilation of the lateral ventricles with normal third and fourth ventricles. The patient was discharged initially with conservative medical management and close follows up; however, the headache continued to progress and neurosurgical intervention was offered. The patient underwent endoscopic exploration, fenestration of the septum pellucidum, and right ventriculoperitoneal shunt placement. Bilateral membranous obstruction of foramina of Monro and an auto-fenestrated cavum septum pellucidum were identified intraoperatively. The patient reported resolution of headache post-operatively without recurrence on 1-month follow up. This case is unusual in that the patient presented without any known neurologic history or prior intracranial infections. It became apparent at the time of surgery that chronic obstruction of the bilateral foramina with collapse of the third ventricle had developed, and the safest durable treatment for him was septostomy and cerebrospinal fluid (CSF) shunt placement.
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http://dx.doi.org/10.1080/02688697.2020.1866167DOI Listing
January 2021

Repeat convection-enhanced delivery for diffuse intrinsic pontine glioma.

J Neurosurg Pediatr 2020 Sep 25:1-6. Epub 2020 Sep 25.

1Department of Neurological Surgery, NewYork-Presbyterian Hospital, Weill Cornell Medicine, New York.

Objective: While the safety and efficacy of convection-enhanced delivery (CED) have been studied in patients receiving single-dose drug infusions, agents for oncological therapy may require repeated or chronic infusions to maintain therapeutic drug concentrations. Repeat and chronic CED infusions have rarely been described for oncological purposes. Currently available CED devices are not approved for extended indwelling use, and the only potential at this time is for sequential treatments through multiple procedures. The authors report on the safety and experience in a group of pediatric patients who received sequential CED into the brainstem for the treatment of diffuse intrinsic pontine glioma.

Methods: Patients in this study were enrolled in a phase I single-center clinical trial using 124I-8H9 monoclonal antibody (124I-omburtamab) administered by CED (clinicaltrials.gov identifier NCT01502917). A retrospective chart and imaging review were used to assess demographic data, CED infusion data, and postoperative neurological and surgical outcomes. MRI scans were analyzed using iPlan Flow software for volumetric measurements. Target and catheter coordinates as well as radial, depth, and absolute error in MRI space were calculated with the ClearPoint imaging software.

Results: Seven patients underwent 2 or more sequential CED infusions. No patients experienced Clinical Terminology Criteria for Adverse Events grade 3 or greater deficits. One patient had a persistent grade 2 cranial nerve deficit after a second infusion. No patient experienced hemorrhage or stroke postoperatively. There was a statistically significant decrease in radial error (p = 0.005) and absolute tip error (p = 0.008) for the second infusion compared with the initial infusion. Sequential infusions did not result in significantly different distribution capacities between the first and second infusions (volume of distribution determined by the PET signal/volume of infusion ratio [mean ± SD]: 2.66 ± 0.35 vs 2.42 ± 0.75; p = 0.45).

Conclusions: This series demonstrates the ability to safely perform sequential CED infusions into the pediatric brainstem. Past treatments did not negatively influence the procedural workflow, technical application of the targeting interface, or distribution capacity. This limited experience provides a foundation for using repeat CED for oncological purposes.
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http://dx.doi.org/10.3171/2020.6.PEDS20280DOI Listing
September 2020

Utility of invasive electroencephalography in children 3 years old and younger with refractory epilepsy.

J Neurosurg Pediatr 2020 Sep 18:1-6. Epub 2020 Sep 18.

1Department of Neurological Surgery, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York.

Objective: Early surgical intervention for pediatric refractory epilepsy is increasingly advocated as surgery has become safer and data have demonstrated improved outcomes with early seizure control. There is concern that the risks associated with staged invasive electroencephalography (EEG) in very young children outweigh the potential benefits. Here, the authors present a cohort of children with refractory epilepsy who were referred for invasive monitoring, and they evaluate the role and safety of staged invasive EEG in those 3 years old and younger.

Methods: The authors conducted a retrospective review of children 3 years and younger with epilepsy, who had been managed surgically at two institutions between 2001 and 2015. A cohort of pediatric patients older than 3 years of age was used for comparison. Demographics, seizure etiology, surgical management, surgical complications, and adverse events were recorded. Statistical analysis was completed using Stata version 13. A p < 0.05 was considered statistically significant. Fisher's exact test was used to compare proportions.

Results: Ninety-four patients (45 patients aged ≤ 3 [47.9%]) and 208 procedures were included for analysis. Eighty-six procedures (41.3%) were performed in children younger than 3 years versus 122 in the older cohort (58.7%). Forty-two patients underwent grid placement (14 patients aged ≤ 3 [33.3%]); 3 of them developed complications associated with the implant (3/42 [7.14%]), none of whom were among the younger cohort. Across all procedures, 11 complications occurred in the younger cohort versus 5 in the older patients (11/86 [12.8%] vs 5/122 [4.1%], p = 0.032). Two adverse events occurred in the younger group versus 1 in the older group (2/86 [2.32%] vs 1/122 [0.82%], p = 0.571). Following grid placement, 13/14 younger patients underwent guided resections compared to 20/28 older patients (92.9% vs 71.4%, p = 0.23).

Conclusions: While overall complication rates were higher in the younger cohort, subdural grid placement was not associated with an increased risk of surgical complications in that population. Invasive electrocorticography informs management in very young children with refractory, localization-related epilepsy and should therefore be used when clinically indicated.
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http://dx.doi.org/10.3171/2020.6.PEDS19504DOI Listing
September 2020

Fatal cerebral infarct in a child with COVID-19.

Pediatr Radiol 2020 09 23;50(10):1479-1480. Epub 2020 Jul 23.

Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1234, New York, NY, 10029, USA.

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http://dx.doi.org/10.1007/s00247-020-04779-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376273PMC
September 2020

The slope of the learning curve in 600 consecutive endoscopic transsphenoidal pituitary surgeries.

Acta Neurochir (Wien) 2020 10 1;162(10):2361-2370. Epub 2020 Jul 1.

Department of Neurosurgery, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA.

Background: Endonasal endoscopic transsphenoidal surgery (EETS) for pituitary adenoma has become a mainstay of treatment over the last two decades and it is generally accepted that once this learning curve is achieved, a plateau is reached with little incremental improvement.

Objective: The objective of this study was to assess the slope of the learning curve over a long period of time for a variety of outcomes measures.

Methods: We examined outcomes and complications in a consecutive series of 600 EETS for pituitary adenoma grouped into quartiles based on date of surgery.

Results: GTR significantly increased across quartiles from 55 to 79% in the last quartile (p < 0.005). The rate of intraoperative CSF leak significantly decreased from 60% in the first quartile to 33% in the last quartile and the rate of lumbar drain placement from 28% in the first quartile to 6% in the last quartile (p < 0.005). Hormonal remission for secreting adenomas increased from 68% in the first quartile to 90% in the last quartile (p < 0.05). The rate of post-operative CSF leak trended lower (3% in first quartile to 0.7% in last two quartiles). The greatest improvement in outcome occurred between the first and second quartiles (19.9%), but persistent improvement occurred between the second and third (6.7%) and third and fourth quartiles (8.0%).

Conclusion: Although the slope of the learning curve is steeper earlier in a surgeon's experience, the slope does not plateau and continues to increase even over more than a decade.
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http://dx.doi.org/10.1007/s00701-020-04471-xDOI Listing
October 2020

Neurological manifestations of pediatric multi-system inflammatory syndrome potentially associated with COVID-19.

Childs Nerv Syst 2020 08 25;36(8):1579-1580. Epub 2020 Jun 25.

Department of Neurosurgery, Mount Sinai Health System, 1468 Madison Avenue, Annenberg 8th Floor, New York, NY, 10029, USA.

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http://dx.doi.org/10.1007/s00381-020-04755-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314616PMC
August 2020

Endoscopic Skull Base Surgery Protocol From the Frontlines: Transnasal Surgery During the COVID-19 Pandemic.

Otolaryngol Head Neck Surg 2020 09 26;163(3):482-490. Epub 2020 May 26.

Department of Neurosurgery, The Mount Sinai Hospital/Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Objective: The coronavirus disease 2019 (COVID-19) pandemic disrupted the standard management paradigms for care of patients with sinus and skull base presentations due to concern for patient and health care provider safety, given the high aerosol-generating potential of endonasal procedures.

Data Sources: We reviewed the relevant literature complied from available sources, including PubMed, Google Scholar, and otolaryngology journals providing electronic manuscripts ahead of indexing or publication.

Review Methods: Incorporating available evidence and the projected infection control and resource limitations at our institution, we collectively authored a dynamic set of protocols guiding (1) case stratification, (2) preoperative assessment, (3) operative setup, and (4) postoperative care of patients with sinus or skull base presentations. Due to the rapidly evolving nature of COVID-19 publications, lack of rigorous data, and urgent necessity of standardized protocols, strict inclusion and exclusion criteria were not employed.

Conclusions: As scarce hospital resources are diverted to COVID-19 care and staff are redeployed to forward-facing roles, endonasal procedures have largely ceased, leaving patients with ongoing sinonasal and skull base complaints untreated. Skull base teams now weigh the urgency of surgery in this population with the regional availability of resources.

Implications For Practice: The COVID-19 pandemic will have an enduring and unpredictable impact on hospital operations and surgical skull base practices and will require a dynamic set of management protocols responsive to new evidence and changing resources. In the current resource-limited environment, clinicians may utilize these protocols to assist with stratifying patients by acuity, performing preoperative assessment, and guiding peri- and postoperative care.
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http://dx.doi.org/10.1177/0194599820931836DOI Listing
September 2020

Ventrolateral Tonsillar Position Defines Novel Chiari 0.5 Classification.

World Neurosurg 2020 Apr;136:444-453

Department of Neurological Surgery, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York, USA. Electronic address:

Background: Cervicomedullary compression in young children has been described in the context of Chiari type 1 malformation, with symptoms associated with the extent of tonsillar herniation below McRae line. Historically, Chiari type 1 malformation has been defined by tonsillar herniation of at least 5 mm. However, in certain populations, including very young children, Chiari symptoms may be present without this finding. A new Chiari classification is thus necessary.

Methods: Cases involving patients up to 5 years of age evaluated for possible posterior fossa decompression were retrospectively reviewed. Preoperative symptoms, magnetic resonance imaging findings, surgical management, and short- and long-term outcome and follow-up were recorded. Tonsillar descent and presence of ventral herniation (VH) were recorded. We define VH as the tonsils crossing a line that bisects the caudal medulla at the level of the foramen magnum, thus creating a novel entity, Chiari type 0.5 malformation. Patients with ventrally herniated tonsils were compared with patients exhibiting more typical Chiari morphology.

Results: Of 41 cases retrospectively reviewed, 20 met criteria for VH. These differed from cases without VH because of the predominance of medullary symptoms. In the VH cohort, 11 patients underwent surgical decompression with symptom resolution; 9 were initially managed conservatively, but 3 subsequently required surgery.

Conclusions: We define a novel Chiari entity, Chiari type 0.5 malformation, characterized by ventral tonsillar wrapping around the medulla in young children in the absence of classic Chiari type 1 malformation imaging findings. These patients are more likely to present with medullary symptoms than patients without VH. They are also more likely to require surgical decompression and respond favorably to intervention.
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http://dx.doi.org/10.1016/j.wneu.2020.01.147DOI Listing
April 2020

How long is the tail end of the learning curve? Results from 1000 consecutive endoscopic endonasal skull base cases following the initial 200 cases.

J Neurosurg 2020 Feb 7:1-11. Epub 2020 Feb 7.

Departments of2Neurosurgery.

Objective: Endoscopic endonasal approaches (EEAs) to the skull base have evolved over the last 20 years to become an essential component of a comprehensive skull base practice. Many case series show a learning curve from the earliest cases, in which the authors were inexperienced or were not using advanced closure techniques. It is generally accepted that once this learning curve is achieved, a plateau is reached with little incremental improvement. Cases performed during the early steep learning curve were eliminated to examine whether the continued improvement exists over the "tail end" of the curve.

Methods: A prospectively acquired database of all EEA cases performed by the senior authors at Weill Cornell Medicine/NewYork-Presbyterian Hospital was reviewed. The first 200 cases were eliminated and the next 1000 consecutive cases were examined to avoid the bias created by the early learning curve.

Results: Of the 1000 cases, the most common pathologies included pituitary adenoma (51%), meningoencephalocele or CSF leak repair (8.6%), meningioma (8.4%), craniopharyngioma (7.3%), basilar invagination (3.1%), Rathke's cleft cyst (2.8%), and chordoma (2.4%). Use of lumbar drains decreased from the first half to the second half of our series (p <0.05) as did the authors' use of fat alone (p <0.005) or gasket alone (p <0.005) for dural closure, while the use of a nasoseptal flap increased (p <0.005). Although mean tumor diameter was constant (on average), gross-total resection (GTR) increased from 60% in the first half to 73% in the second half (p <0.005). GTR increased for all pathologies but most significantly for chordoma (56% vs 100%, p <0.05), craniopharyngioma (47% vs 0.71%, p <0.05) and pituitary adenoma (67% vs 75%, p <0.05). Hormonal cure for secreting adenomas also increased from 83% in the first half to 89% in the second half (p <0.05). The rate of any complication was unchanged at 6.4% in the first half and 6.2% in the latter half of cases, and vascular injury occurred in only 0.6% of cases. Postoperative CSF leak occurred in 2% of cases and was unchanged between the first and second half of the series.

Conclusions: This study demonstrates that contrary to popular belief, the surgical learning curve does not plateau but can continue for several years depending on the complexity of the endpoints considered. These findings may have implications for clinical trial design, surgical education, and patient safety measures.
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http://dx.doi.org/10.3171/2019.12.JNS192600DOI Listing
February 2020

Adult Human Glioblastomas Harbor Radial Glia-like Cells.

Stem Cell Reports 2020 02 30;14(2):338-350. Epub 2020 Jan 30.

Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Radial glia (RG) cells are the first neural stem cells to appear during embryonic development. Adult human glioblastomas harbor a subpopulation of RG-like cells with typical RG morphology and markers. The cells exhibit the classic and unique mitotic behavior of normal RG in a cell-autonomous manner. Single-cell RNA sequencing analyses of glioblastoma cells reveal transcriptionally dynamic clusters of RG-like cells that share the profiles of normal human fetal radial glia and that reside in quiescent and cycling states. Functional assays show a role for interleukin in triggering exit from dormancy into active cycling, suggesting a role for inflammation in tumor progression. These data are consistent with the possibility of persistence of RG into adulthood and their involvement in tumor initiation or maintenance. They also provide a putative cellular basis for the persistence of normal developmental programs in adult tumors.
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http://dx.doi.org/10.1016/j.stemcr.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014025PMC
February 2020

Neurosurgical management of Currarino syndrome: A case series and review of literature.

Surg Neurol Int 2019 24;10:70. Epub 2019 Apr 24.

Department of Neurosurgery, University of Washington, Seattle.

Background: The Currarino syndrome (CS), defined by the triad of anorectal malformations, sacral bone deformities, and presacral masses, is rare. There are few surgical series that discuss conservative management versus the surgical approaches to these lesions. Here, we describe utilizing a combined anterior and posterior approach for resecting these lesions in four patients.

Methods: Four patients with CS were treated with two-stage approaches performed by a multidisciplinary team, including pediatric neurosurgery and general surgery. The first anterior laparoscopic approach mobilized the presacral mass from its ventral attachments. The second posterior procedure detethered the spinal cord, repaired the dural defect, and facilitated removal of the presacral mass.

Results: Gross total resection of all four presacral masses was accomplished without intraoperative complication; all patients clinically improved.

Conclusion: The CS is characterized by a large presacral mass. Here, one must rule out malignancy and also consider diagnosis/resection due to the risks for malignant transformation. The operative approach we described in four patients utilized standard anterior mobilization of the mass, followed by posterior detethering, dural repair, and ultimate resection.
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http://dx.doi.org/10.25259/SNI-26-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744743PMC
April 2019

Placement of cesium-131 permanent brachytherapy seeds using the endoscopic endonasal approach for recurrent anaplastic skull base meningioma: case report and technical note.

J Neurosurg 2019 Mar 1;132(3):921-926. Epub 2019 Mar 1.

Departments of3Neurosurgery.

There are few therapeutic options available for the treatment of recurrent meningiomas that have failed treatment with surgery and external-beam radiation therapy (EBRT). As additional EBRT is clinically risky, brachytherapy offers an important alternative for optimizing local control. In skull base meningiomas, the endoscopic endonasal approach (EEA) has demonstrated an excellent extent of resection. However, in the case of recurrent, atypical, or residual meningiomas, the EEA alone may not be adequate to address microscopic, residual, highly proliferative disease. In this situation, local radioactive seed brachytherapy has been shown to improve control, but few reports of this technique exist. A 48-year-old right-handed man presented on multiple occasions with recurrence of an anaplastic skull base meningioma, after multiple prior gross-total resections and multiple rounds of radiotherapy had failed. The authors performed a maximally safe neurosurgical tumor resection via EEA supplemented by the intraoperative implantation of 131Cs low-dose permanent brachytherapy seeds. They describe a technique for permanent implantation of brachytherapy seeds and provide operative video of this technique. The authors submit that utilizing this technique in combination with EEA tumor resection renders a minimally invasive approach to improving local control in a patient with a recurrent anaplastic or atypical meningioma of the skull base.
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http://dx.doi.org/10.3171/2018.11.JNS181943DOI Listing
March 2019

Lessons learned in the evolution of endoscopic skull base surgery.

J Neurosurg 2019 02;130(2):337-346

2Otorhinolaryngology, NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York; and.

OBJECTIVEEndoscopic skull base surgery (ESBS) is a relatively recent addition to the neurosurgical armamentarium. As with many new approaches, there has been significant controversy regarding its value compared with more traditional approaches to ventral skull base pathology. Although early enthusiasm for new approaches that appear less invasive is usually high, these new techniques require rigorous study to ensure that widespread implementation is in the best interest of patients.METHODSThe authors compared surgical results for ESBS with transcranial surgery (TCS) for several different pathologies over two different time periods (prior to 2012 and 2012-2017) to see how results have evolved over time. Pathologies examined were craniopharyngioma, anterior skull base meningioma, esthesioneuroblastoma, chordoma, and chondrosarcoma.RESULTSESBS offers clear advantages over TCS for most craniopharyngiomas and chordomas. For well-selected cases of planum sphenoidale and tuberculum sellae meningiomas, ESBS has similar rates of resection with higher rates of visual improvement, and more recent results with lower CSF leaks make the complication rates similar between the two approaches. TCS offers a higher rate of resection with fewer complications for olfactory groove meningiomas. ESBS is preferred for lower-grade esthesioneuroblastomas, but higher-grade tumors often still require a craniofacial approach. There are few data on chondrosarcomas, but early results show that ESBS appears to offer clear advantages for minimizing morbidity with similar rates of resection, as long as surgeons are familiar with more complex inferolateral approaches.CONCLUSIONSESBS is maturing into a well-established approach that is clearly in the patients' best interest when applied by experienced surgeons for appropriate pathology. Ongoing critical reevaluation of outcomes is essential for ensuring optimal results.
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http://dx.doi.org/10.3171/2018.10.JNS182154DOI Listing
February 2019

Clinical tolerance of corticospinal tracts in convection-enhanced delivery to the brainstem.

J Neurosurg 2018 Dec;131(6):1812-1818

Departments of1Neurological Surgery and.

Objective: Convection-enhanced delivery (CED) has been explored as a therapeutic strategy for diffuse intrinsic pontine glioma (DIPG). Variables that may affect tolerance include infusate volume, infusion rate, catheter trajectory, and target position. Supratentorial approaches for catheter placement and infusate distribution patterns may conflict with corticospinal tracts (CSTs). The clinical relevance of these anatomical constraints has not been described. The authors report their experience using CED in the brainstem as it relates to anatomical CST conflict and association with clinical tolerance.

Methods: In a phase I clinical trial of CED for DIPG (clinical trial registration no. NCT01502917, clinicaltrials.gov), a flexible infusion catheter was placed with MRI guidance for infusion of 124I-8H9, a radioimmunotherapeutic agent. Intra- and postprocedural MR images were analyzed to identify catheter trajectories and changes in T2-weighted signal intensity to approximate volume of distribution (Vd). Intersection of CST by the catheter and overlap between Vd and CST were recorded and their correlation with motor deficits was evaluated.

Results: Thirty-one patients with a mean age of 7.6 years (range 3.2-18 years) underwent 39 catheter insertions for CED between 2012 and 2017. Thirty catheter insertions had tractography data available for analysis. The mean trajectory length was 105.5 mm (range 92.7-121.6 mm). The mean number of intersections of CST by catheter was 2.2 (range 0-3) and the mean intersecting length was 18.9 mm (range 0-44.2 mm). The first 9 infusions in the highest dose level (range 3.84-4.54 ml infusate) were analyzed for Vd overlap with CST. In this group, the mean age was 7.6 years (range 5.8-10.3 years), the mean trajectory length was 109.5 mm (range 102.6-122.3 mm), and the mean overlap between Vd and CST was 5.5 cm3. For catheter placement-related adverse events, 1 patient (3%) had worsening of a contralateral facial nerve palsy following the procedure with two CST intersections, an intersecting distance of 31.7 mm, and an overlap between Vd and CST of 3.64 cm3. For infusion-related adverse events, transient postinfusion deficits were noted in 3 patients in the highest dose level, with a mean number of 2 intersections of CST by catheter, mean intersecting length of 12.9 mm, and mean overlap between Vd and CST of 6.3 cm3.

Conclusions: A supratentorial approach to the brainstem crossing the CST resulted in one worsened neurological deficit. There does not appear to be a significant risk requiring avoidance of dominant motor fiber tracts with catheter trajectory planning. There was no correlation between Vd-CST overlap and neurological adverse events in this cohort.Clinical trial registration no.: NCT01502917 (clinicaltrials.gov).
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http://dx.doi.org/10.3171/2018.6.JNS18854DOI Listing
December 2018

Beals syndrome with middle and inner ear dysplasia and encephalocele: A case report and review of imaging findings.

Int J Pediatr Otorhinolaryngol 2019 Feb 10;117:26-29. Epub 2018 Nov 10.

Department of Radiology, New York Presbyterian Hospital, Weill Cornell Medicine, 525 East 68th Street, New York, NY, 10065, USA.

A 10-year-old male with history of Beals syndrome presented with hearing loss and was found to have middle and inner ear dysplasia and left temporal encephalocele on imaging. Beals syndrome is a rare autosomal dominant connective tissue disorder caused by a mutation in the fibrillin-2 gene. Skeletal manifestations of Beals have been reported, including anomalies of the long bones, calvarium, and spine. External ear abnormalities with "crumpled ear" deformity are seen in the majority of patients. This is the first case to report imaging findings of the middle and inner ear in a patient with Beals.
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http://dx.doi.org/10.1016/j.ijporl.2018.11.009DOI Listing
February 2019

Preserve or sacrifice the stalk? Endocrinological outcomes, extent of resection, and recurrence rates following endoscopic endonasal resection of craniopharyngiomas.

J Neurosurg 2018 Nov 1:1-9. Epub 2018 Nov 1.

Departments of1Neurological Surgery.

OBJECTIVEGross-total resection (GTR) of craniopharyngiomas (CPs) is potentially curative and is often the goal of surgery, but endocrinopathy generally results if the stalk is sacrificed. In some cases, GTR can be attempted while still preserving the stalk; however, stalk manipulation or devascularization may cause endocrinopathy and this strategy risks leaving behind small tumor remnants that can recur.METHODSA retrospective review of a prospective cohort of patients who underwent initial resection of CP using the endoscopic endonasal approach over a period of 12 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital, was performed. Postresection integrity of the stalk was retrospectively assessed using operative notes, videos, and postoperative MRI. Tumors were classified based on location into type I (sellar), type II (sellar-suprasellar), and type III (purely suprasellar). Pre- and postoperative endocrine function, tumor location, body mass index, rate of GTR, radiation therapy, and complications were reviewed.RESULTSA total of 54 patients who had undergone endoscopic endonasal procedures for first-time resection of CP were identified. The stalk was preserved in 33 (61%) and sacrificed in 21 (39%) patients. GTR was achieved in 24 patients (73%) with stalk preservation and 21 patients (100%) with stalk sacrifice (p = 0.007). Stalk-preservation surgery achieved GTR and maintained completely normal pituitary function in only 4 (12%) of 33 patients. Permanent postoperative diabetes insipidus was present in 16 patients (49%) with stalk preservation and in 20 patients (95%) following stalk sacrifice (p = 0.002). In the stalk-preservation group, rates of progression and radiation were higher with intentional subtotal resection or near-total resection compared to GTR (67% vs 0%, p < 0.001, and 100% vs 12.5%, p < 0.001, respectively). However, for the subgroup of patients in whom GTR was achieved, stalk preservation did not lead to significantly higher rates of recurrence (12.5%) compared with those in whom it was sacrificed (5%, p = 0.61), and stalk preservation prevented anterior pituitary insufficiency in 33% and diabetes insipidus in 50%.CONCLUSIONSWhile the decision to preserve the stalk reduces the rate of postoperative endocrinopathy by roughly 50%, nevertheless significant dysfunction of the anterior and posterior pituitary often ensues. The decision to preserve the stalk does not guarantee preserved endocrine function and comes with a higher risk of progression and need for adjuvant therapy. Nevertheless, to reduce postoperative endocrinopathy attempts should be made to preserve the stalk if GTR can be achieved.
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http://dx.doi.org/10.3171/2018.6.JNS18901DOI Listing
November 2018

Influence of an intratumoral cyst on drug distribution by convection-enhanced delivery: case report.

J Neurosurg Pediatr 2017 Sep 7;20(3):256-260. Epub 2017 Jul 7.

Department of Neurological Surgery, NewYork-Presbyterian Hospital, Weill Cornell Medicine.

Convection-enhanced delivery (CED) uses positive pressure to induce convective flow of molecules and maximize drug distribution. Concerns have been raised about the effect of cystic structures on uniform drug distribution with CED. The authors describe the case of a patient with a diffuse intrinsic pontine glioma (DIPG) with a large cyst and examine its effect on drug distribution after CED with a radiolabeled antibody. The patient was treated according to protocol with CED of I-8H9 to the pons for nonprogressive DIPG after radiation therapy as part of a Phase I trial (clinical trial registration no. NCT01502917, clinicaltrials.gov). Care was taken to avoid the cystic cavity in the planned catheter track and target point. Co-infusion with Gd-DTPA was performed to assess drug distribution. Infusate distribution was examined by MRI immediately following infusion and analyzed using iPlan Flow software. Analysis of postinfusion MR images demonstrated convective distribution around the catheter tip and an elongated configuration of drug distribution, consistent with the superoinferior corticospinal fiber orientation in the brainstem. This indicates that the catheter was functioning and a pressure gradient was established. No infusate entry into the cystic region could be identified on T2-weighted FLAIR or T1-weighted images. The effects of ependymal and pial surfaces on drug delivery using CED in brainstem tumors remain controversial. Drug distribution is a critical component of effective application of CED to neurosurgical lesions. This case suggests that cyst cavities may not always behave as fluid "sinks" for drug distribution. The authors observed that infusate was not lost into the cyst cavity, suggesting that lesions with cystic components can be treated by CED without significant alterations to target and infusion planning.
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http://dx.doi.org/10.3171/2017.5.PEDS1774DOI Listing
September 2017

Calvarial Plasmacytoma Mimicking Meningioma as the Initial Presentation of Multiple Myeloma.

Cureus 2017 Mar 29;9(3):e1126. Epub 2017 Mar 29.

Department of Neurological Surgery, Weill Cornell Medical College.

Plasmacytoma of the calvarium is a well-described feature of multiple myeloma and in some cases has been reported as a solitary lesion. However, when associated with multiple myeloma these are typically identified after the initial diagnosis is made. This case is unusual in that the diagnosis of plasmacytoma was first suspected in a patient thought to have a meningioma on the day of surgery, when a magnetic resonance imaging (MRI) demonstrated spontaneous involution of the mass. Recognition of evolving changes in a calvarial or dural-based lesion should prompt the practitioner to consider alternative diagnoses other than meningioma prior to proceeding with surgical resection.
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http://dx.doi.org/10.7759/cureus.1126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409815PMC
March 2017

Image Guidance for Placement of Ommaya Reservoirs: Comparison of Fluoroscopy and Frameless Stereotactic Navigation in 145 Patients.

World Neurosurg 2016 Sep 10;93:154-8. Epub 2016 Jun 10.

Department of Neurological Surgery, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York, USA; Weill Cornell Medical College, New York, New York, USA; Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Objective: Ommaya reservoirs are used for administration of intrathecal chemotherapy and cerebrospinal fluid sampling. Ventricular catheter placement for these purposes requires a high degree of accuracy. Various options exist to optimize catheter placement. We analyze a cohort of patients receiving catheters using 2 different technologies.

Methods: Retrospective chart review was performed on patients undergoing Ommaya reservoir placement between 2011 and 2014. Most procedures were assisted by either frameless stereotactic neuronavigation or fluoroscopic guidance with pneumoencephalogram. Catheter accuracy, revision rates, perioperative complications, and operative time were measured. Preoperative similarities and differences in diagnosis, demographics, and ventricular size were also recorded to avoid a biased assessment of our results.

Results: One-hundred and forty-five patients were included, 57 using fluoroscopic guidance and 88 using frameless stereotaxy. Common diagnoses in both groups were lymphoma and leptomeningeal disease. Qualitative measures of catheter placement accuracy showed no significant difference between the 2 groups. Proximity to the foramen of Monro favored fluoroscopy by a small margin (8.6 mm vs. 10.2 mm, P = 0.03). Overall revision rates were not significantly different between the groups (3.5% vs. 4.5%, P = 1.00). Early surgical complications occurred in 6.8% of the frameless stereotaxy group and 1.8% of the fluoroscopy group (P = 0.25).

Conclusions: Ommaya reservoirs can be placed accurately using different methods. Although there are slight differences between fluoroscopy and frameless stereotaxy in quantitative accuracy and procedure time, there is no significant advantage of 1 method over the other when evaluating revision or complication rates. Technique familiarity and surgeon preference may dictate the preferred procedure.
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http://dx.doi.org/10.1016/j.wneu.2016.04.090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523660PMC
September 2016

Meningioma after radiotherapy for malignancy.

J Clin Neurosci 2016 Aug 8;30:93-97. Epub 2016 Apr 8.

Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Neurological Surgery, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA.

Complications of radiation exposure have gained importance with increasing cancer survivorship. Secondary malignancies have been associated with cranial radiation exposure. We present our experience with intracranial radiation-induced meningioma (RIM) and discuss the implications of its presentation and natural history for patient management. Patients diagnosed with meningioma who had received radiation therapy between 1960 and 2014 were identified. Records were retrospectively reviewed for details of radiation exposure, previous malignancies, meningioma subtypes, multiplicity and pathologic descriptions, treatment and follow-up. Thirty patients were diagnosed with RIM. Initial malignancies included acute lymphocytic leukemia (33.3%), medulloblastoma (26.7%) and glioma (16.7%) at a mean age of 8.1years (range 0.04-33years). The mean radiation dose was 34Gy (range 16-60Gy) and latency time to meningioma was 26years (range 8-51years). Twenty-one patients (70%) underwent surgery. Of these, 57.1% of tumors were World Health Organization (WHO) grade I while 42.9% were WHO II (atypical). The mean MIB-1 labeling index for patients with WHO I tumors was 5.44%, with 33.3% exhibiting at least 5% staining. Mean follow-up after meningioma diagnosis was 5.8years. Mortality was zero during the follow-up period. Meningioma is an important long-term complication of therapeutic radiation. While more aggressive pathology occurs more frequently in RIM than in sporadic meningioma, it remains unclear whether this translates into an effect on survival. Further study should be aimed at delineating the risks and benefits of routine surveillance for the development of secondary neoplasms after radiation therapy.
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http://dx.doi.org/10.1016/j.jocn.2016.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407008PMC
August 2016

Gene therapy blockade of dorsal striatal p11 improves motor function and dyskinesia in parkinsonian mice.

Proc Natl Acad Sci U S A 2016 Feb 19;113(5):1423-8. Epub 2016 Jan 19.

Laboratory of Molecular Neurosurgery, Department of Neurological Surgery, Weill Cornell Medical College, New York, NY 10065;

Complications of dopamine replacement for Parkinson's disease (PD) can limit therapeutic options, leading to interest in identifying novel pathways that can be exploited to improve treatment. p11 (S100A10) is a cellular scaffold protein that binds to and potentiates the activity of various ion channels and neurotransmitter receptors. We have previously reported that p11 can influence ventral striatal function in models of depression and drug addiction, and thus we hypothesized that dorsal striatal p11 might mediate motor function and drug responses in parkinsonian mice. To focally inhibit p11 expression in the dorsal striatum, we injected an adeno-associated virus (AAV) vector producing a short hairpin RNA (AAV.sh.p11). This intervention reduced the impairment in motor function on forced tasks, such as rotarod and treadmill tests, caused by substantia nigra lesioning in mice. Measures of spontaneous movement and gait in an open-field test declined as expected in control lesioned mice, whereas AAV.sh.p11 mice remained at or near normal baseline. Mice with unilateral lesions were then challenged with l-dopa (levodopa) and various dopamine receptor agonists, and resulting rotational behaviors were significantly reduced after ipsilateral inhibition of dorsal striatal p11 expression. Finally, p11 knockdown in the dorsal striatum dramatically reduced l-dopa-induced abnormal involuntary movements compared with control mice. These data indicate that focal inhibition of p11 action in the dorsal striatum could be a promising PD therapeutic target to improve motor function while reducing l-dopa-induced dyskinesias.
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http://dx.doi.org/10.1073/pnas.1524387113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747714PMC
February 2016

Postoperative imaging for detection of recurrent arteriovenous malformations in children.

J Neurosurg Pediatr 2016 Feb 30;17(2):134-140. Epub 2015 Oct 30.

Department of Neurological Surgery, NewYork-Presbyterian Hospital, Weill Cornell Medical Center; and.

OBJECT The optimal method for detecting recurrent arteriovenous malformations (AVMs) in children is unknown. An inherent preference exists for MR angiography (MRA) surveillance rather than arteriography. The validity of this strategy is uncertain. METHODS A retrospective chart review was performed on pediatric patients treated for cerebral AVMs at a single institution from 1998 to 2012. Patients with complete obliteration of the AVM nidus after treatment and more than 12 months of follow-up were included in the analysis. Data collection focused on recurrence rates, associated risk factors, and surveillance methods. RESULTS A total of 45 patients with a mean age of 11.7 years (range 0.5-18 years) were treated for AVMs via surgical, endovascular, radiosurgical, or combined approaches. Total AVM obliteration on posttreatment digital subtraction angiography (DSA) was confirmed in 27 patients, of whom the 20 with more than 12 months of follow-up were included in subsequent analysis. The mean follow-up duration in this cohort was 5.75 years (median 5.53 years, range 1.11-10.64 years). Recurrence occurred in 3 of 20 patients (15%). Two recurrences were detected by surveillance DSA and 1 at the time of rehemorrhage. No recurrences were detected by MRA. Median time to recurrence was 33.6 months (range 19-71 months). Two patients (10%) underwent follow-up DSA, 5 (25%) had DSA and MRI/MRA, 9 (45%) had MRI/MRA only, 1 (5%) had CT angiography only, and 3 (15%) had no imaging within the first 3 years of follow-up. After 5 years posttreatment, 2 patients (10%) were followed with MRI/MRA only, 2 (10%) with DSA only, and 10 (50%) with continued DSA and MRI/MRA. CONCLUSIONS AVM recurrence in children occurred at a median of 33.6 months, when MRA was more commonly used for surveillance, but failed to detect any recurrences. A recurrence rate of 15% may be an underestimate given the reliance on surveillance MRA over angiography. A new surveillance strategy is proposed, taking into account exposure to diagnostic radiation and the potential for catastrophic rehemorrhage.
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http://dx.doi.org/10.3171/2015.6.PEDS14708DOI Listing
February 2016

Perimesencephalic hemorrhage with negative angiography: case illustration.

J Neurosurg 2016 Jan 29;124(1):43-4. Epub 2015 May 29.

Department of Neurological Surgery, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York.

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http://dx.doi.org/10.3171/2014.12.JNS142513DOI Listing
January 2016

Behaviour of metalloids and metals from highly polluted soil samples when mobilized by water--evaluation of static versus dynamic leaching.

Environ Pollut 2012 Jun 8;165:59-66. Epub 2012 Mar 8.

Department of Analytical Chemistry, UFZ - Helmholtz Centre for Environmental Research, Permoserstrasse 15, 04318 Leipzig, Germany.

The mobilization behaviour of metalloids and metals when leached by water from highly polluted soil/sediment samples was studied using static and dynamic approaches employing batch methodology and rotating coiled columns (RCC), respectively. Increasing the solution-to-solid ratios during batch leaching resulted in different enhanced mobilization rates, which are element-specific and matrix-specific. When dynamic leaching is employed with continuous replacement of the eluent, a higher portion is mobilized than when using batch elution with an identical solid-to-water ratio. Using RCC the time-resolved leaching of the elements was monitored to demonstrate the leaching patterns. For the majority of elements a significant decrease could be shown in the mobilized portion of the elements with ongoing leaching process. The data were discussed targeted at solid liquid partitioning coefficients of the metal(loid)s. The capabilities in application of K(d) values was demonstrated for dynamic leaching which is relevant for environmental processes.
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http://dx.doi.org/10.1016/j.envpol.2012.02.006DOI Listing
June 2012

Pineal region tumors: simultaneous endoscopic third ventriculostomy and tumor biopsy.

World Neurosurg 2013 Feb 10;79(2 Suppl):S18.e9-13. Epub 2012 Feb 10.

Department of Neurological Surgery, Weill Cornell Medical College and Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Objective: Advances in neuroendoscopy have accommodated the development of intraventricular techniques that enhance the management of multiple disease processes. Tumors of the pineal region are amenable to endoscopic management in that they are accessible through the third ventricle and commonly cause hydrocephalus that can be alleviated by endoscopic third ventriculostomy (ETV). We describe the indications for and procedure of simultaneous ETV and biopsy of pineal region tumors, as well as the clinical features favoring different approaches to this procedure.

Methods: The current literature on endoscopic management of pineal region tumors and the senior author's clinic experience with current techniques are reviewed.

Results: Simultaneous tumor biopsy with ETV following initial evaluation with tumor markers and imaging can be accomplished using a single or dual entry approach. The choice of approach is dependent on multiple clinical factors including massa intermedia size, goals of surgery, degree of hydrocephalus, and the relationship between the tumor and massa intermedia.

Conclusions: Simultaneous ETV and tumor biopsy is a valuable technique that can be used to manage hydrocephalus and establish diagnosis in patients with newly diagnosed pineal region tumors, potentially avoiding traditional craniotomy and ventriculoperitoneal shunt placement. It is favored as an early step in the management of patients with marker-negative tumors.
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http://dx.doi.org/10.1016/j.wneu.2012.02.020DOI Listing
February 2013

Adeno-associated viral gene delivery in neurodegenerative disease.

Methods Mol Biol 2011 ;793:443-55

Laboratory of Molecular Neurosurgery, Department of Neurological Surgery, Weill Cornell Medical College, New York, NY, USA.

The advent of viral gene therapy technology has contributed greatly to the study of a variety of medical conditions, and there is increasing promise for clinical translation of gene therapy into human treatments. Adeno-associated viral (AAV) vectors provide one of the more promising approaches to gene delivery, and have been used extensively over the last 20 years. Derived from nonpathogenic parvoviruses, these vectors allow for stable and robust expression of desired transgenes in vitro and in vivo. AAV vectors efficiently and stably transduce neurons, with some strains targeting neurons exclusively in the brain. Thus, AAV vectors are particularly useful for neurodegenerative diseases, which have led to numerous preclinical studies and several human trials of gene therapy in patients with Parkinson's disease, Alzheimer's disease, and pediatric neurogenetic disorders. Here, we describe an efficient and reliable method for the production and purification of AAV serotype 2 vectors for both in vitro and in vivo applications.
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http://dx.doi.org/10.1007/978-1-61779-328-8_29DOI Listing
December 2011

Pineal region tumors: an optimal approach for simultaneous endoscopic third ventriculostomy and biopsy.

Neurosurg Focus 2011 Apr;30(4):E3

Department of Neurological Surgery, Weill Cornell Medical College, New York, New York, USA.

Object: Simultaneous endoscopic third ventriculostomy (ETV) and tumor biopsy is a widely accepted therapeutic and diagnostic procedure for patients with noncommunicating hydrocephalus secondary to a pineal region tumor. Multiple approaches have been advocated, including the use of a steerable fiberoptic or rigid lens endoscope via 1 or 2 trajectories. However, the optimal approach has not been established based on the individual anatomical characteristics of the patient.

Methods: A retrospective review of patients undergoing simultaneous ETV and tumor biopsy was undertaken. Preoperative MR images were examined to measure the width of the anterior third ventricle and maximal diameters of the tumor, Monro foramen (right), and massa intermedia. The distances between the tumor and massa intermedia, tumor and anterior commissure, midbrain and massa intermedia, and the dorsum sella and anterior commissure were also recorded. Single and dual trajectory approaches were compared using paired t-tests for each parameter.

Results: Over an 8-year interval, 15 patients underwent simultaneous ETV and tumor management. These patients ranged from 6 to 71 years of age (mean 36.7 years); 5 were younger than 18 years of age. Seven were treated using a dual trajectory approach, and 8 were treated using a single trajectory approach. All cases were completed without complications or the need for an additional CSF diversionary procedure within 6 months. The diagnostic yield at biopsy was 86.7%. There were no statistically significant differences between the single and dual trajectory groups for the measured parameters. However, the dual trajectory group demonstrated a larger anterior third ventricular diameter (1.43 vs 1.21 cm, p = 0.29). The single trajectory group trended toward a smaller tumor-anterior commissure interval (2.23 vs 2.51 cm, p = 0.24) and a larger dorsum sella-anterior commissure distance (1.67 vs 1.49 cm, p = 0.28).

Conclusions: These data confirm the safety and diagnostic efficacy of simultaneous ETV and biopsy for tumors of the pineal region. Although no statistically significant differences were seen in the authors' recorded measurements, several trends suggest a role for a tailored approach to selecting a single or dual trajectory approach when using a rigid endoscope.
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http://dx.doi.org/10.3171/2011.2.FOCUS10301DOI Listing
April 2011