Fourth ventricular subarachnoid stent for Chiari malformation type I-associated persistent syringomyelia.

OBJECTIVE: Syringomyelia (syrinx) associated with Chiari malformation type I (CM-I) is commonly managed with posterior fossa decompression, which can lead to resolution in most cases. A persistent syrinx postdecompression is therefore uncommon and challenging to address. In the setting of radiographically adequate decompression with persistent syrinx, the authors prefer placing fourth ventricular subarachnoid stents that span the craniocervical junction particularly when intraoperative observation reveals arachnoid plane scarring. The objective of this study was to evaluate the safety and efficacy of a fourth ventricle stent for CM-I-associated persistent syringomyelia, assess dynamic changes in syrinx dimensions, and report stent-reduction durability, clinical outcomes, and procedure-associated complications. METHODS: The authors performed a single-institution, retrospective review of patients who underwent fourth ventricular subarachnoid stent placement for persistent CM-I-associated syringomyelia following a prior posterior fossa decompression. The authors' institutional Chiari database contains 600 cases with 149 decompressions for CM-I-associated syringomyelia, of which 13 met criteria for inclusion. Data on patient demographics, clinical presentation and outcomes, and MRI findings were collected. The maximal syrinx diameter was estimated by calculating the area of an elliptical cross-section in the largest axial plane from preoperative, immediately postoperative, and late postoperative T2-weighted MR images. RESULTS: All 13 patients experienced a significant decrease in mean syrinx area from the preoperative to the late postoperative MRI (mean syrinx diameter 114.1 ± 81.8 mm2 vs 24.5 ± 23.8 mm2, p < 0.001). The mean time until late postoperative MRI was 19.7 months (range 2.0-70.7 months). The syrinx area reduced on average by 75.0% ± 23.9% at the time of the last postoperative scan. Syrinx resolution was variable, with 4 patients (30.8%) achieving near-complete resolution (> 90%, grade III reduction), 7 patients (50%) having 50%-90% reduction (grade II), and 2 patients (14.3%) having < 50% decrease (grade I). One patient experienced catheter migration into the left brachium pontis with an associated cyst at the tip of the catheter that decreased in size on follow-up imaging. CONCLUSIONS: Placement of fourth ventricular subarachnoid stents spanning the craniocervical junction in patients with persistent CM-I-associated syringomyelia after posterior fossa decompression is a safe therapeutic option and significantly reduced the mean syrinx area, with a greater reductive effect seen over longer follow-up periods.

Quantifying intraventricular drug delivery utilizing programmable ventriculoperitoneal shunts as the intraventricular access device.

PURPOSE: Programmable ventriculoperitoneal shunts (pVP shunts) are increasingly utilized for intraventricular chemotherapy, radioimmunotherapy, and/or cellular therapy. Shunt adjustments allow optimization of drug concentrations in the thecal space with minimization in the peritoneum. This report assesses the success of the pVP shunt as an access device for intraventricular therapies. Quantifying intrathecal drug delivery using scintigraphy by pVP shunt model has not been previously reported. METHODS: We performed a single-institution, retrospective analysis on patients with CNS tumors and pVP shunts from 2003 to 2020, noting shunt model. pVP flow was evaluated for consideration of compartmental radioimmunotherapy (cRIT) using In-111-DTPA scintigraphy. Scintigraphy studies at 2-4 h and at 24 h quantified ventricular-thecal and peritoneal drug activity. RESULTS: Twenty-two CSF flow studies were administered to 15 patients (N = 15) with diagnoses including medulloblastoma, metastatic neuroblastoma, pineoblastoma, and choroid plexus carcinoma. Six different types of pVP models were noted. 100% of the studies demonstrated ventriculo-thecal drug activity. 27% (6 of 22) of the studies had no peritoneal uptake visible by imaging. 73% (16 of 22) of the studies had minimal relative peritoneal uptake (< 12%). 27% (6 of 22) of the studies demonstrated moderate relative peritoneal uptake (12-37%). No studies demonstrated peritoneal uptake above 37%. CONCLUSIONS: All patients had successful drug delivery of In-111-DTPA to the ventriculo-thecal space. 73% of the patients had minimal relative (< 12%) peritoneal drug uptake. Though efficacy varies by shunt model, low numbers preclude conclusions regarding model superiority. CSF flow scintigraphy studies assesses drug distribution of In-111-DTPA, informing CSF flow for delivery of intraventricular therapies.

Pediatric pituitary adenomas are more aggressive, more likely to be hormone producing and are more difficult to cure than adult pituitary adenomas: case series and systematic literature review.

PURPOSE: Pediatric pituitary adenomas (pPAs) are uncommon. Thus, their presentation and outcomes after treatment are less well-understood than those of pituitary adenomas in adulthood (aPAs). METHODS: A retrospective chart review was conducted for all patients who underwent endoscopic endonasal transsphenoidal surgery (EETS) for pPA at NewYork-Presbyterian Hospital/Weill Cornell Medicine (NYP/WCM) from 2005-2020. Eleven patients were identified, and information pertaining to age, sex, adenoma characteristics, procedural details, and outcomes was reviewed. A systematic review of the literature was also performed to compare outcomes of EETS versus microscopic endonasal transsphenoidal surgery (METS) for pPA. RESULTS: From 2005-2020, 11 patients underwent EETS for pPA at NYP/WCM. Mean age at operation was 14.9 ± 2.7 years, and 5 patients (45.5%) were male. 10 adenomas (90.9%) were hormone-producing. Of the functional adenomas, 8 (80.0%) were PRL-secreting and 2 (20.0%) were GH-secreting. Maximum adenoma diameter (MAD) ranged from 1.2-5.1 cm, with a median of 1.55 cm. Cavernous sinus invasion (CSI) occurred in 2 patients with macroprolactinoma. Gross total resection (GTR) was achieved in 10 (90.9%). Biochemical remission occurred in 5/10 (50.0%). Post-operative complications were documented in 8 cases (72.7%) and included diabetes insipidus, hypopituitarism, sinusitis, weight gain, cerebrospinal fluid leak, meningitis, and hydrocephalus. Systematic literature review of 105 microscopic and 175 endoscopic cases revealed high frequency of hormone-producing tumors (83.6%) and similar rates of GTR (82.4% vs 85.1%) and biochemical cure (75.8% vs 64.3%). CONCLUSIONS: pPAs are more likely to be hormone producing and may be more aggressive and difficult to cure than aPAs. EETS is an effective treatment, although complication rates may be higher than in adult populations.

Myofascial Flap Closure Decreases Complications in Complex Surgery of the Craniocervical Junction in Ehlers-Danlos Patients.

INTRODUCTION: Patients with Ehlers-Danlos syndrome (EDS) are at elevated risk for soft tissue complications when undergoing decompression with or without fusion of the craniocervical junction. We have previously shown that muscle flap closure can decrease reoperative rates. This study investigated whether myofascial flap closure improved clinical outcomes after simple or complex surgery of the craniocervical junction in EDS patients specifically. METHODS: We performed a retrospective chart review of EDS patients who had undergone surgery for Chiari malformation at the Weill Cornell Medical Center between 2013 and 2020. Postoperative complications were recorded, including infection, wound dehiscence, seroma, hematoma, hardware removal, cerebrospinal fluid (CSF) leak, reoperation, and pseudomeningocele. Patients were stratified by type of closure and type of surgery. Fisher exact test was used for statistical comparison. RESULTS: Between 2013 and 2020, 62 EDS patients who had surgery of the cervicocranial junction were reviewed. Of these, 31 patients had complex surgery with myofascial flap closure and 22 had simple surgery with traditional closure. The mean age at the time of surgery was 21.3 years. There were no significant differences in wound complications or reoperation rates between the simple surgery and complex surgery groups. In addition, there were no significant differences in complications between complex surgery with flap closure and simple surgery with traditional closure. Our CSF cutaneous fistula rate was 0%, considerably lower than rates reported in the literature, and, in one case, a patient developed a postoperative pseudomeningocele secondary to a dural leak, but the myofascial flap closure prevented its progression. CONCLUSIONS: Patients with EDS undergoing surgery of the cervicocranial junction may benefit from myofascial flap closure. Flap closure reduced complications after complex surgery of the craniocervical junction to the level of simple surgery. Our CSF leak rate was exceptionally low and only one patient experienced pseudomeningocele. Myofascial flaps are safe to perform in the EDS cohort and prevented CSF cutaneous fistula formation.

A critical analysis of surgery for occult tethered cord syndrome.

INTRODUCTION: Tethered cord syndrome (TCS) is an amalgamation of neurological, urological, orthopedic, and dermatologic signs and symptoms with radiographic evidence of a thickened filum and low-lying conus. Surgical sectioning of the filum and disconnection of any tethering entities such as dermal sinus tracts or lipomas has been shown to improve outcomes. The manifestation of TCS symptoms in the absence of a low-lying conus has been referred to as occult tethered cord syndrome (OTCS) and is much less well reviewed in the literature. To date, there has only been one randomized controlled trial examining the effect of intervention in OTCS; therefore, contemporary data is often elicited from limited cohorts. OBJECTIVE: To perform a comprehensive literature review of management in OTCS and evaluate treatment response rates to sectioning of the filum terminale. RESULTS: Seventeen papers met inclusion criteria for our review. Sample sizes ranged from 8 to 60 children, and results were mixed, often dependent on study design, definition of typical OTCS symptoms, and follow-up intervals. Symptomatic improvement was observed in > 50% of patients for all but one study; however, the recurrence rates were highly variable. CONCLUSION: The data regarding the efficacy of surgical treatment in OTCS is mixed and merits more rigorous scientific examination with strict and clear parameters regarding symptomatic operationalization and follow-up time points to monitor for TCS recurrence.

Increases in female academic productivity and female mentorship highlight sustained progress in previously identified neurosurgical gender disparities.

OBJECTIVE: A meta-analysis was performed to understand disparities in the representation of female authorship within the neurosurgical literature and implications for career advancement of women in neurosurgery. METHODS: Author names for articles published in 16 of the top neurosurgical journals from 2002 to 2019 were obtained from MEDLINE. The gender of each author was determined using automated prediction methods. Publication trends were compared over time and across subdisciplines. Female authorship was also compared to the proportionate composition of women in the field over time. RESULTS: The metadata obtained from 16 major neurosurgical journals yielded 66,546 research articles. Gender was successfully determined for 96% (127,809/133,578) of first and senior authors, while the remainder (3.9%) were unable to be determined through prediction methods. Across all years, 13.3% (8826) of articles had female first authorship and 9.1% (6073) had female senior authorship. Female first authorship increased significantly over time from 5.8% in 2002 to 17.2% in 2019 (p < 0.001). Female senior authorship also increased significantly over time, from 5.5% in 2002 to 12.0% in 2019 (p < 0.001). The journals with the highest proportions of female first authors and senior authors were the Journal of Neurosurgery: Pediatrics (33.5%) and the Asian Journal of Neurosurgery (23.8%), respectively. Operative Neurosurgery had the lowest fraction of female first (12.4%) and senior (4.7%) authors. There was a significant difference between the year-by-year proportion of female neurosurgical trainees and the year-by-year proportion of female neurosurgical first (p < 0.001) and senior (p < 0.001) authors. Articles were also more likely to have a female first author if the senior author of the article was female (OR 2.69, CI 2.52-2.86; p < 0.001). From 1944 to 2019, the Journal of Neurosurgery showed a steady increase in female first and senior authorship, with a plateau beginning in the 1990s. CONCLUSIONS: Large meta-analysis techniques have the potential to effectively leverage large amounts of bibliometric data to quantify the representation of female authorship in the neurosurgical literature. The proportion of female authors in major neurosurgical journals has steadily increased. However, the rate of increase in female senior authorship has lagged behind the rate of increase in first authorship, indicating a disparity in academic advancement in women in neurosurgery.

Revision Chiari Surgery in Young Children: Predictors and Outcomes.

INTRODUCTION: Children aged 0-6 years with Chiari malformation (CM) often present with atypical symptoms and require revision surgery more often than older children. We studied characteristics and outcomes of CM patients in this age-group who underwent one or more revision surgeries to assess how often revision surgery is necessary and successful in this age-group. METHODS: We retrospectively reviewed patients who were diagnosed with CM 1 or CM 1.5 and surgically treated with posterior fossa decompression (PFD) with or without duraplasty before their 7th birthday. Basic demographics, preoperative presentation, operative details, and postoperative outcomes were analyzed. RESULTS: Forty patients (mean age 3.2 ± 1.7 years, 35% female) were reviewed. The most common presenting symptoms were headache, dysphagia, and respiratory problems. Eight patients required one or more revision surgeries 11.6 ± 7.6 months on average after their initial surgery. Comparing the revision and no revision groups, dysautonomia was significantly more common prior to initial surgery in the children requiring revision (37.5 vs. 3.1%, p = 0.02). The revision group also trended toward more dysphagia (75.0 vs. 46.9%, p = 0.24) and respiratory problems (75.0 vs. 40.6%, p = 0.12). The most frequent reasons for reoperation were symptom recurrence (6/8), residual posterior fossa compression (3/8), significant scar tissue formation (2/8), ventral brainstem compression (1/8), and suspected craniocervical instability (1/8). Of the 8 children undergoing reoperation, surgery achieved symptom resolution or improvement in 5, while 3 had unchanged symptoms. Two patients underwent a third surgery, after which 1 showed improvement and the other did not. This last patient showed short-term improvement after a fourth surgery but had symptom recurrence 12 months later. DISCUSSION/CONCLUSION: Oropharyngeal and respiratory problems are particularly common in children aged 0-6 years with CM. Presentation with dysautonomia or other signs of brainstem compression will often predict an additional surgery will be needed after an initial PFD. Symptom recurrence is the most frequent reason for reoperation, and revision surgeries lead to improved clinical outcomes in the majority but not all of these young patients. Surgery in very young children is successful, but reoperation should be integrated into an up-front discussion algorithm particularly in children with severe symptoms.

Myofascial Flap Closure in Treatment for Patients With Craniocervical Instability and Ehlers-Danlos Syndrome.

INTRODUCTION: The benefits of decompression and fusion for patients with craniocervical instability are well described. However, complications such as wound breakdown and need for unplanned reoperation frequently occur. Recent studies have shown advantages of myofascial flap closure for various spinal procedures. This study investigated whether closure with myofascial flaps after surgery for craniocervical instability decreases complications with further subgroup analysis of patients with Ehlers-Danlos syndrome (EDS). METHODS: A retrospective review of patients presenting to Weill Cornell Medical Center from 2010 to 2017 for craniocervical surgery was performed. All patients who underwent craniocervical surgery, regardless of plastic surgical involvement, were included in the study. Data including patient demographics, comorbidities, EDS diagnosis, surgical history, complications, and follow-up information were collected and analyzed. RESULTS: Data from 57 patients were analyzed. Eighteen patients (31.6%) had craniocervical surgery without myofascial flap closure, whereas 39 (68.4%) had surgery with flap closure. In the nonflap group, 9 patients required unplanned reoperation (50%). In the flap group, there were 5 patients requiring unplanned reoperation (15%). For reoperation, the Fisher exact test 2-tailed P value is 0.0096. Of those 57 patients, 24 had EDS: 5 (20.8%) had no flap closure, whereas 19 (79.2%) had flap closure. In the no-flap group, 3 patients required unplanned reoperation (60%). In the flap group, 5 patients required unplanned reoperation (21%). For reoperation, the Fisher exact test 2-tailed P value is 0.1265. CONCLUSIONS: Patients undergoing surgery for craniocervical instability may benefit from myofascial flap closure even if they have EDS. Mobilizing well-vascularized tissue can decrease rates of reoperation.

Submuscular Placement of Baclofen Infusion Pumps: Case Series and Technique.

BACKGROUND: Baclofen pumps provide treatment of symptoms of spasticity for disease processes such as cerebral palsy and traumatic brain injury. These devices provide continuous infusion or periodic dosing of intrathecal baclofen (ITB). Traditionally, these pumps have been placed subcutaneously. Subcutaneous device placement has been associated with infection and extrusion. Baclofen pumps are large and range from 8 to 10 cm in diameter and 4 to 8 cm in width. Patients requiring device placement typically have a paucity of subcutaneous tissue. Cachexia coupled with the size and bulk of these devices leads to increased protusion and friction. Submuscular placement provides a well-vascularized pocket that directs the device inward eliminating protrusion and decreasing the potential for soft tissue breakdown. METHODS: A retrospective chart review of ITB pump placement in a submuscular plane by a single plastic surgeon at a major academic center in conjunction with a neurosurgeon was performed. Inclusion criteria were cases of primary placement or replacement of ITB pumps and spasticity requiring ITB. Major complications included infection, extrusion, and reoperation. RESULTS: Five patients during a 5-month period were treated with submuscular placement of ITB pumps. Average age of patients included was 18.4 years. Average preoperative body mass index was 18.8 kg/m, with values ranging from 15.8 to 20.1 kg/m. Medical histories of patients included diagnoses of cerebral palsy and traumatic brain injury causing spasticity. The most frequently cited reason for plastic surgical consultation preoperatively was cachexia. Two patients had previous baclofen pumps placed subcutaneously. Average follow-up was 6 months and ranged from 3 to 13 months. There were no major complications. One patient had a small seroma that spontaneously resolved. No patient had wound healing problems, and there were no extrusions of implanted devices or reoperations. CONCLUSION: Submuscular placement of baclofen pumps provides a well-vascularized and stable environment for device placement that minimizes the dangers of pump extrusion and infection. Patients who require treatment with ITB commonly have severe cachexia, which makes subcutaneous device placement high risk. Submuscular placement should be performed in all patients with body mass index less than 20 kg/m.

Instrumented arthrodesis for non-traumatic craniocervical instability in very young children.

PURPOSE: Occipitocervical instrumentation is infrequently required for stabilization of the axial and subaxial cervical spine in very young children. However, when it is necessary, unique surgical considerations arise in children when compared with similar procedures in adults. METHODS: The authors reviewed literature describing fusion of the occipitocervical junction (OCJ) in toddlers and share their experience with eight cases of young children (age less than or equal to 4 years) receiving occiput to axial or subaxial spine instrumentation and fixation. Diagnoses and indications included severe or secondary Chiari malformation, skeletal dysplastic syndromes, Klippel-Feil syndrome, Pierre Robin syndrome, Gordon syndrome, hemivertebra and atlantal occipitalization, basilar impression, and iatrogenic causes. RESULTS: All patients underwent occipital bone to cervical spine instrumentation and fixation at different levels. Constructs extended from the occiput to C2 and T1 utilizing various permutations of titanium rods, autologous rib autografts, Mersilene sutures, and combinations of autografts with bone matrix materials. All patients were placed in rigid cervical bracing or halo fixation postoperatively. No postoperative neurological deficits or intraoperative vascular injuries occurred. CONCLUSION: Instrumented arthrodesis can be a treatment option in very young children to address the non-traumatic craniocervical instability while reducing the need for prolonged external halo vest immobilization. Factors affecting fusion are addressed with respect to preoperative, intraoperative, and postoperative decision-making that may be unique to the toddler population.

Endonasal surgery for suprasellar germ cell tumors: two cases and review of the literature.

Germ cell tumors are rare malignant tumors frequently located in the suprasellar region. Definitive treatment is chemotherapy and radiation. However, in some circumstances, surgery is indicated for biopsy or resection. There are limited reports of the role of the endonasal endoscopic approach (EEA) in the management of this tumor. We present two cases in which EEA was utilized for successful management of germ cell tumor. The most challenging aspect of germ cell tumor management for the treating physician is knowing the proper indications for surgery. In this paper, we highlight two specific instances, namely diagnosis and tumor refractory to chemoradiation. Given the suprasellar location, EEA is an ideal approach.

A phase II study of radioimmunotherapy with intraventricular 131 I-3F8 for medulloblastoma.

BACKGROUND: High-risk and recurrent medulloblastoma (MB) is associated with significant mortality. The murine monoclonal antibody 3F8 targets the cell-surface disialoganglioside GD2 on MB. We tested the efficacy, toxicity, and dosimetry of compartmental radioimmunotherapy (cRIT) with intraventricular 131 I-labeled 3F8 in patients with MB on a phase II clinical trial. METHODS: Patients with histopathologically confirmed high-risk or recurrent MB were eligible for cRIT. After determining adequate cerebrospinal fluid (CSF) flow, patients received 2 mCi (where Ci is Curie) 124 I-3F8 or 131 I-3F8 with nuclear imaging for dosimetry, followed by up to four therapeutic (10 mCi/dose) 131 I-3F8 injections. Dosimetry estimates were based on serial CSF and blood samplings over 48 hr plus region-of-interest analyses on serial imaging scans. Disease evaluation included pre- and posttherapy brain/spine magnetic resonance imaging approximately every 3 months for the first year after treatment, and every 6-12 months thereafter. RESULTS: Forty-three patients received a total of 167 injections; 42 patients were evaluable for outcome. No treatment-related deaths occurred. Toxicities related to drug administration included acute bradycardia with somnolence, headache, fatigue, and CSF pleocytosis consistent with chemical meningitis and dystonic reaction. Total CSF absorbed dose was 1,453 cGy (where Gy is Gray; 350.0-2,784). Median overall survival from first dose of cRIT was 24.9 months (95% confidence interval [CI]:16.3-55.8). Patients treated in radiographic and cytologic remission were at a lower risk of death compared to patients with radiographically measurable disease (hazard ratio: 0.40, 95% CI: 0.18-0.88, P = 0.024). CONCLUSIONS: cRIT with 131 I-3F8 is safe, has favorable dosimetry to CSF, and when added to salvage therapy using conventional modalities, may have clinical utility in maintaining remission in high-risk or recurrent MB.

Synchronous complex Chiari malformation and cleft palate-a case-based review.

BACKGROUND: The association between mid-facial clefts and Chiari malformation in the medical literature has been restricted to patients with syndromic craniofacial abnormalities. A common shared developmental pathway including causative factors for facial clefts and "complex" Chiari malformations, both midline skull base pathologies, seems logical but has not been reported. The coincident presentation of these findings in a single patient, and our subsequent discovery of other patients harboring these mutual findings prompted further investigation. CASE ILLUSTRATION: We describe the case of a patient born with a cleft palate which was repaired during his first year of life, subsequently presenting as a teenager to our hospital with a severe and symptomatic complex Chiari malformation. We discuss his treatment strategy, suboccipital decompression with occipitocervical fusion and endoscopic anterior decompression surgeries, as well as his favorable radiological and clinical outcome, demonstrated at long-interval follow-up. Furthermore, we review his two pathologies, cleft palate and Chiari malformation, and posit a common embryological linkage. CONCLUSIONS: The embryologic interaction between the paraxial mesoderm and ectoderm may explain the co-occurrence of cleft palate and complex Chiari malformation in a single patient. Complete radiological, clinical, and genetic evaluation and counseling is advised in this situation and raises the question of whether the presence of a cleft palate independently increases the risk for other skull base developmental abnormalities.

Rapid autopsy of a patient with recurrent anaplastic ependymoma.

ABSTRACTObjective:Our aim was to outline a procedure for obtaining a rapid autopsy in order to collect high-quality postmortem tissue for genomic analysis. METHODS: This report details a bi-institutional collaborative effort to coordinate a rapid autopsy for a pediatric patient who had died at home. We discuss the scientific rationale for offering a rapid autopsy to caregivers of pediatric patients as well as parental perspectives on broaching the subject of autopsy. We then review the logistics and coordination involved with planning a rapid autopsy and the sequence of events needed to maximize tissue quality. RESULTS: We report the successful coordination of a rapid autopsy for a patient who died in a hospice setting at her out-of-state home. The time interval from death to the start of the rapid autopsy procedure was 4.5 hours, despite the logistical considerations demanded by the location of the patient. Tumor aliquots and nonneoplastic tissues were successfully snap frozen for downstream genomic studies. SIGNIFICANCE OF RESULTS: Physicians should consider trialing a rapid autopsy program at their institution that could be offered to caregivers of pediatric patients. This case report offers a framework to help clinicians develop their own rapid autopsy programs as well as guidelines to help streamline this process for appropriate candidates going forward.

Glioblastoma spheroids produce infiltrative gliomas in the rat brainstem.

PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is universally fatal without proven therapy other than radiation therapy for palliation. Representative animal models will play an essential role in the preclinical stage of future therapy development. To address the shortage of representative models, we created a novel infiltrative brainstem glioma model in rats based on glioblastoma spheroids. METHODS: Cells dissociated from glioblastoma spheroids grown from surgical specimens were implanted into the brainstem of NIH nude rats. Animals were serially assessed clinically and radiographically with magnetic resonance imaging (MRI). Tumors were further characterized using histology, immunohistochemistry, and cytogenetics. RESULTS: Tumor generation was successful in all animals receiving glioblastoma spheroid cells. The rats survived 17-25 weeks before severe symptoms developed. The tumors showed as diffuse hyperintense lesions on T2-weighted images. Histologically, they demonstrated cellular heterogeneity, and infiltrative and invasive features, with cells engorging vascular structures. The tumors were shown to comprise immature human origin glial tumor cells, with human epidermal growth factor receptor (EGFR) gene amplification and gain. CONCLUSIONS: This study showed that cells from glioblastoma spheroids produced infiltrative gliomas in rat brainstem. The rat brainstem gliomas are radiographically and histologically accurate compared to DIPG. These tumors develop over several months that would allow sequential clinical and radiographic assessments of therapeutic interventions. This study demonstrated in principle the feasibility of developing patient-specific animal models based on putative cancer stem cells from biopsy or resection samples.

Clinical Genomics: Challenges and Opportunities.

Next-generation sequencing (NGS) approaches are highly applicable to clinical studies. We review recent advances in sequencing technologies, as well as their benefits and tradeoffs, to provide an overview of clinical genomics from study design to computational analysis. Sequencing technologies enable genomic, transcriptomic, and epigenomic evaluations. Studies that use a combination of whole genome, exome, mRNA, and bisulfite sequencing are now feasible due to decreasing sequencing costs. Single-molecule sequencing increases read length, with the MinIONTM nanopore sequencer, which offers a uniquely portable option at a lower cost. Many of the published comparisons we review here address the challenges associated with different sequencing methods. Overall, NGS techniques, coupled with continually improving analysis algorithms, are useful for clinical studies in many realms, including cancer, chronic illness, and neurobiology. We, and others in the field, anticipate the clinical use of NGS approaches will continue to grow, especially as we shift into an era of precision medicine.

Gliomatosis cerebri: A consensus summary report from the First International Gliomatosis cerebri Group Meeting, March 26-27, 2015, Paris, France.

Gliomatosis cerebri (GC) is a universally fatal extensive and diffuse infiltration of brain parenchyma by a glial tumor. Many aspects of this phenomenon remain unknown. The First International Gliomatosis cerebri Group Meeting had the following goals: refine the clinical and radiologic diagnostic criteria for GC, suggest appropriate diagnostic procedures, standardize tissue manipulation for histologic and molecular characterization, and prioritize relevant preclinical projects. Also, general treatment recommendations were outlined for the pediatric population. Importantly, this meeting was the starting point for meaningful collaborative international research projects. This review is a consensus summary of discussions shared and conclusions derived from this meeting.

The rhinopalatine line as a reliable predictor of the inferior extent of endonasal odontoidectomies.

OBJECT: The endoscopic endonasal approach (EEA) provides a minimally invasive corridor through which the cervicomedullary junction can be decompressed with reduced morbidity rates compared to those with the classic transoral approaches. The limit of the EEA is its inferior extent, and preoperative estimation of its reach is vital for determining its suitability. The aim of this study was to evaluate the actual inferior limit of the EEA in a surgical series of patients and develop an accurate and reliable predictor that can be used in planning endonasal odontoidectomies. METHODS: The actual inferior extent of surgery was determined in a series of 6 patients with adequate preoperative and postoperative imaging who underwent endoscopie endonasal odontoidectomy. The medians of the differences between several previously described predictive lines, namely the nasopalatine line (NPL) and nasoaxial line (NAxL), were compared with the actual surgical limit and the hard-palate line by using nonparametric statistics. A novel line, called the rhinopalatine line (RPL), was established and corresponded best with the actual limit of the surgery. RESULTS: There were 4 adult and 2 pediatric patients included in this study. The NPL overestimated the inferior extent of the surgery by an average (± SD) of 21.9 ± 8.1 mm (range 14.7-32.5 mm). The NAxL and RPL overestimated the inferior limit of surgery by averages of 6.9 ± 3.8 mm (range 3.7-13.3 mm) and 1.7 ± 3.7 mm (range -2.8 to 8.3 mm), respectively. The medians of the differences between the NPL and NAxL and the actual surgery were statistically different (both p = 0.0313). In contrast, there was no statistically significant difference between the RPL and the inferior limit of surgery (p = 0.4375). CONCLUSIONS: The RPL predicted the inferior limit of the EEA to the craniovertebral junction more accurately than previously described lines. The use of the RPL may help surgeons in choosing suitable candidates for the EEA and in selecting those for whom surgery through the oropharynx or the facial bones is the better approach.

Age-specific cerebral perfusion pressure thresholds and survival in children and adolescents with severe traumatic brain injury*.

OBJECTIVES: Evidence-based traumatic brain injury guidelines support cerebral perfusion pressure thresholds for adults at a class 2 level, but evidence is lacking in younger patients. The purpose of this study is to identify the impact of age-specific cerebral perfusion pressure thresholds on short-term survival among patients with severe traumatic brain injury. DESIGN: Institutional review board-approved, prospective, observational cohort study. SETTING: Level I or II trauma centers in New York State. PATIENTS: Data on all patients with a postresuscitation Glasgow Coma Score less than 9 were added in the Brain Trauma Foundation prospective New York State TBI-trac database. MEASUREMENTS AND MAIN RESULTS: We calculated the survival rates and relative risks of mortality for patients with severe traumatic brain injury based on predefined age-specific cerebral perfusion pressure thresholds. A higher threshold and a lower threshold were defined for each age group: 60 and 50 mm Hg for 12 years old or older, 50 and 35 mm Hg for 6-11 years, and 40 and 30 mm Hg for 0-5 years. Patients were stratified into age groups of 0-11, 12-17, and 18 years old or older. Three exclusive groups of CPP-L (events below low cerebral perfusion pressure threshold), CPP-B (events between high and low cerebral perfusion pressure thresholds), and CPP-H (events above high cerebral perfusion pressure threshold) were defined. As an internal control, we evaluated the associations between cerebral perfusion pressure events and events of hypotension and elevated intracranial pressure. Survival was significantly higher in 0-11 and 18 years old or older age groups for patients with CPP-H events compared with those with CPP-L events. There was a significant decrease in survival with prolonged exposure to CPP-B events for the 0-11 and 18 years old and older age groups when compared with the patients with CPP-H events (p = 0.0001 and p = 0.042, respectively). There was also a significant decrease in survival with prolonged exposure to CPP-L events in all age groups compared with the patients with CPP-H events (p< 0.0001 for 0- to 11-yr olds, p = 0.0240 for 12- to 17-yr olds, and p < 0.0001 for 18-yr old and older age groups). The 12- to 17-year olds had a significantly higher likelihood of survival compared with adults with prolonged exposure to CPP-L events (< 50 mm Hg). CPP-L events were significantly related to systemic hypotension for the 12- to 17-year-old group (p = 0.004) and the 18-year-old and older group (p < 0.0001). CPP-B events were significantly related to systemic hypotension in the 0- to 11-year-old group (p = 0.014). CPP-B and CPP-L events were significantly related to elevated intracranial pressure in all age groups. CONCLUSIONS: Our data provide new evidence that cerebral perfusion pressure targets should be age specific. Furthermore, cerebral perfusion pressure goals above 50 or 60 mm Hg in adults, above 50 mm Hg in 6- to 17-year olds, and above 40 mm Hg in 0- to 5-year olds seem to be appropriate targets for treatment-based studies. Systemic hypotension had an inconsistent relationship to events of low cerebral perfusion pressure, whereas elevated intracranial pressure was significantly related to all low cerebral perfusion pressure events across all age groups. This may impart a clinically important difference in care, highlighting the necessity of controlling intracranial pressure at all times, while targeting systolic blood pressure in specific instances.

An aesthetic approach to the anterior cranial fossa: the endoscopic transadnexal transorbital roof method.

BACKGROUND: This case report describes a transadnexal transorbital roof approach to the anterior cranial fossa to treat an epidural abscess in a patient who had previously undergone extensive craniofacial reconstruction secondary to fibrous dysplasia. A standard frontal craniotomy or even a supraciliary craniotomy would have been burdensome due to the positioning of the porous polyethylene implant as well as extensive scar tissue and adhesions from prior surgical procedures. METHODS: We performed a retrospective review of the case of a 15-year-old male with an epidural abscess treated at a university hospital. RESULTS: The patient tolerated the procedure well with no postoperative complications. Surgical operative time was approximately 1.5 h with minimal blood loss and the patient was discharged on postoperative day 2. Six weeks after antibiotic therapy (intravenous ampicillin/sulbactam, 2,000 mg q.i.d. for 6 days total), an MRI showed complete resolution of the epidural abscess. At that time the patient had no visual changes, extraocular muscle dysfunction, headaches, periorbital cellulitis, or further seizures and is on no antiepileptic therapy. CONCLUSION: Minimally invasive approaches to treat complex problems in certain circumstances can yield excellent results and limit morbidity encountered by more extensive procedures. In the future, more formal studies with a larger subset of patients will help determine what role these approaches will ultimately have. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .