Early Versus Delayed Fractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma.

BACKGROUND: Fractionated stereotactic radiotherapy (FSRT) is a common modality used to treat pituitary adenomas with good control rates. It is not known whether FSRT should be performed early or delayed until progression occurs. We compared FSRT in treating nonfunctional pituitary adenomas (NFPA) as an adjuvant (ADJ) or on-progression (PRG) therapy. METHODS: A retrospective review of patients who underwent FSRT for an NFPA between January 2004 and December 2022 at a single institution was performed. We compared endocrinologic, ophthalmologic, and radiographic outcomes in FSRT delivered as ADJ and PRG treatment. RESULTS: Seventy-five patients were analyzed, with a median follow-up of 53 months. FSRT was administered to 35 and 40 patients as ADJ and PRG, with a median time to treatment of 5.5 and 40 months, respectively. The tumor control rate was 94.3% for ADJ and 95.0% for PRG. Treatment resulted in 4 (11.4%) versus 7 (17.5%) new endocrinopathies and 2 (5.7%) versus 1 (2.5%) new visual deficits for ADJ versus PRG. A survival analysis of time to new endocrinopathy showed no difference between the 2 cohorts. The median time from surgery to new endocrinopathy was significantly different between ADJ and PRG, at 15.5 and 102.0 months, respectively. CONCLUSIONS: FSRT is effective in treating NFPA for residual and progressive tumors, with excellent tumor control rates and a low risk of developing new endocrinopathies and visual deficits. Delaying treatment delayed the development of new endocrinopathies, suggesting that observation with FSRT on tumor progression may delay the onset of hypopituitarism and maintain similar effectiveness in tumor control.

Predictive Clinical and Surgical Factors Associated with Recurrent Apoplexy in Pituitary Adenomas.

Introduction Pituitary apoplexy is an uncommon clinical condition that can require urgent surgical intervention, but the factors resulting in recurrent apoplexy remain unclear. The purpose of this study is to determine the risks of a recurrent apoplexy and better understand the goals of surgical treatment. Methods A retrospective chart review was performed for all consecutive patients diagnosed and surgically treated for pituitary apoplexy from 2004 to 2021. Univariate analysis was performed to identify risk factors associated with recurrent apoplexy. Results A total of 115 patients were diagnosed with pituitary apoplexy with 11 patients showing recurrent apoplexy. This occurred at a rate of 2.2 cases per 100 patient-years of follow-up. There were no major differences in demographic factors, such as hypertension or anticoagulation use. There were no differences in tumor locations, cavernous sinus invasion, or tumor volumes (6.84 ± 4.61 vs. 9.15 ± 8.45 cm, p = 0.5). Patients with recurrent apoplexy were less likely to present with headache (27.3%) or ophthalmoplegia (9.1%). Recurrent apoplexy was associated with prior radiation (0.0 vs. 27.3%, p = 0.0001) and prior subtotal resection (10.6 vs. 90.9%, p = 0.0001) compared with first time apoplexy. The mean time to recurrent apoplexy was 48.3 ± 76.9 months and no differences in overall follow-up were seen in this group. Conclusion Recurrent pituitary apoplexy represents a rare event with limited understanding of pathophysiology. Prior STR and radiation treatment are associated with an increased risk. The relatively long time from the first apoplectic event to a recurrence suggests long-term patient follow-up is necessary.

Cranial floor fracture: A growing orbital roof fracture with encephalocele - Case Report.

Orbital roof fractures are among the rarest of craniofacial fractures. The mechanism of injury is typically a high-impact blunt force vector directly to the orbit or forehead. Most patients are males between 20 and 40 years old, involved in motor vehicle accidents. Although most orbital roof fractures are managed conservatively, there is a significant risk of ophthalmologic and neurologic complications. Detailed craniofacial examination and high-resolution CT imaging is necessary for diagnosis. A multidisciplinary team approach is required for these challenging fractures.

Quantitative determination of the optimal temporoparietal fascia flap necessary to repair skull-base defects.

BACKGROUND: The ability to reconstruct large cranial base defects has greatly improved with the development of pedicled vascularized flaps. The temporoparietal fascia flap (TPFF) is a viable alternative to the Hadad-Bassagasteguy nasoseptal flap for large ventral skull-base defects. This study aims to characterize the size of the TPFF necessary for optimal ventral skull-base reconstruction. METHODS: Eleven formaldehyde-fixed cadaveric heads were used to harvest TPFF of varying heights on each side (total = 22). TPFF was passed through the pterygomaxillary fissure (PMF) to the ventral skull base to assess its coverage. For a subgroup of 12 sides, the TPFF was trimmed to determine the minimum height necessary for coverage. RESULTS: The TPFF height was (mean ± standard deviation [SD]) 14.72 ± 1.02 cm (range, 12.5 to 16.5 cm) and width was 8.43 ± 1.05 cm (range, 6 to 10.5 cm). The distance from the TPFF pedicle through the PMF was 5.8 ± 0.5 cm (range, 5 to 6.5 cm). All TPFF flaps provided complete ipsilateral coverage of clival defects, and all but 1 covered the entire clivus. All TPFF flaps, when rotated anteriorly, provided coverage up to the cribriform plate. The minimum TPFF height necessary for complete coverage of cribriform defects and ventral defects up to the planum sphenoidale was 12 cm. TPFF height for specimens with and without complete ventral skull-base coverage was significantly different (p < 0.0001). CONCLUSION: The TPFF is a versatile alternative to the nasoseptal flap and a height of at least 12 cm can provide enough coverage for all ventral skull base defects.

Endoscopic Transnasal Transclival Approach to a Pontine Cavernoma with Associated Developmental Venous Anomaly.

BACKGROUND: Brainstem cavernous malformations represent around 8%-22% of all intracranial cavernous malformations but exhibit a higher annual incidence of hemorrhage (2%-3%) compared with other cavernous angiomas and tend to be more symptomatic given their proximity to critical nuclei and fiber tracts. Recently, endoscopic endonasal techniques have been used for the removal of ventral skull base lesions, with significant improvement in operative morbidity and mortality compared with open approaches. Here we demonstrate the utility and feasibility of the endoscopic transclival approach for ventrally located pontine cavernomas in carefully selected patients. CASE DESCRIPTION: Consent was provided by the patient before the writing of this report. Institutional review board approval was not necessary because there was no other patient data accessed. A 21-year-old man presented to the emergency department with right-sided hemiparesis. Magnetic resonance imaging demonstrated evidence of hemorrhage from a ventrally located pontine cavernoma. Given the ventral location of the lesion and the desire for early control of an associated developmental venous anomaly (DVA), an endoscopic endonasal transclival approach was chosen. Gross total resection was achieved, and the patient did well postoperatively with no new neurologic deficits or cerebrospinal fluid leak. He is currently routinely followed and is neurologically well. CONCLUSIONS: This approach provided direct visualization of the lesion and the associated DVA allowing for a gross total resection without injury to the DVA. The transclival approach may be considered as an alternative to open lateral and dorsolateral neurosurgical approaches for ventral brainstem cavernomas in carefully selected patients.

Creating a Culture of Collaboration: A Brief History of Academic Neurosurgery in Washington, DC.

Clinical neurosurgery has been practiced in the US capital for just over 100 years. As former residents and fellows of Drs. Harvey Cushing and Walter Dandy moved to the region, hospitals at Georgetown and George Washington Universities became early adopters of this new surgical discipline. Later academic neurosurgery programs were established at the National Institutes of Health, Walter Reed Medical Center, and Children's National Medical Center. Neurosurgical pioneers at these institutions developed new technologies and diagnostic procedures which continue to inform our current practice. In addition, continued collaboration between the multiple training sites in Washington, DC has uniquely enriched our residents' training experience.

Extent of Resection, Visual, and Endocrinologic Outcomes for Endoscopic Endonasal Surgery for Recurrent Pituitary Adenomas.

OBJECTIVE: To assess outcomes after endoscopic endonasal surgery for recurrent or residual pituitary adenomas. METHODS: We retrospectively analyzed 61 patients from 2009 to 2016 who underwent endoscopic endonasal surgery for recurrent or residual pituitary adenomas after previous microscopic or endoscopic transsphenoidal operation. RESULTS: The previous surgical approach was endoscopic endonasal in 55.7% and microscopic in 44.2% of patients. The mean preoperative maximal tumor diameter was 2.3 cm. Tumor commonly invaded the suprasellar cistern (63.9%). Gross total resection (GTR) was achieved in 31 patients (51.7%). GTR rate was 68.4% and 21.7% for Knosp grade 0-2 and grade 3-4 tumors, respectively (P < 0.001). GTR was 73.1% and 35.3% for patients with previous microscopic and endoscopic transsphenoidal surgery, respectively (P = 0.002). On multivariate analysis, smaller tumor size (odds ratio [OR], 1.1 per cm; P = 0.007), Knosp grade 0-2 (OR, 9.7; P = 0.002), and previous microscopic approach (OR, 12.7; P = 0.007) were independent predictors of GTR. Preoperative visual deficit outcome was improved in 32.5%, unchanged in 62.5%, and worse in 5.0%. New postoperative endocrinopathies included adrenal insufficiency (6.5%), hypothyroidism (8.1%), hypogonadism (6.5%), and diabetes insipidus (4.9%). Complications included postoperative cerebrospinal fluid leak (4.9%), meningitis (1.6%), medical complications (4.9%), and postoperative hematoma requiring re-exploration (3.2%). CONCLUSIONS: The endoscopic endonasal approach provides a safe and effective option for recurrent pituitary adenomas. Smaller tumor size, absence of cavernous sinus invasion, and previous microscopic approach were independent predictors of GTR. This finding might suggest that inadequate exposure or limited viewing angle may adversely affect extent of resection in primary microscopic surgeries.

Comparison of posterior fossa volumes and clinical outcomes after decompression of Chiari malformation Type I.

OBJECTIVE Previous studies have indicated an association of Chiari malformation Type I (CM-I) and a small posterior fossa. Most of these studies have been limited by 2D quantitative methods, and more recent studies utilizing 3D methodologies are time-intensive with manual segmentation. The authors sought to develop a more automated tool to calculate the 3D posterior fossa volume, and correlate its changes after decompression with surgical outcomes. METHODS A semiautomated segmentation program was developed, and used to compare the pre- and postoperative volumes of the posterior cranial fossa (PCF) and the CSF spaces (cisterna magna, prepontine cistern, and fourth ventricle) in a cohort of pediatric patients with CM-I. Volume changes were correlated with postoperative symptomatic improvements in headache, syrinx, tonsillar descent, cervicomedullary kinking, and overall surgical success. RESULTS Forty-two pediatric patients were included in this study. The mean percentage increase in PCF volume was significantly greater in patients who showed clinical improvement versus no improvement in headache (5.89% vs 1.54%, p < 0.05) and tonsillar descent (6.52% vs 2.57%, p < 0.05). Overall clinical success was associated with a larger postoperative PCF volume increase (p < 0.05). These clinical improvements were also significantly associated with a larger increase in the volume of the cisterna magna (p < 0.05). The increase in the caudal portion of the posterior fossa volume was also larger in patients who showed improvement in syrinx (6.63% vs 2.58%, p < 0.05) and cervicomedullary kinking (9.24% vs 3.79%, p < 0.05). CONCLUSIONS A greater increase in the postoperative PCF volume, and specifically an increase in the cisterna magna volume, was associated with a greater likelihood of clinical improvements in headache and tonsillar descent in patients with CM-I. Larger increases in the caudal portion of the posterior fossa volume were also associated with a greater likelihood of improvement in syrinx and cervicomedullary kinking.

High-grade glioma with anterior skull base erosion and intranasal extension: case report.

The authors describe the case of a large WHO Grade III anaplastic oligoastrocytoma extending through the anterior skull base and into the right nasal cavity and sinuses. Glial neoplasms are typically confined to the intracranial compartment within the brain parenchyma and rarely extend into the nasal cavity without prior surgical or radiation therapy. This 42-year-old woman presented with progressive headaches and sinus congestion. MR imaging findings revealed a large intracranial lesion with intranasal extension. Endoscopic nasal biopsy revealed pathology consistent with an infiltrating glioma. The patient subsequently underwent a combined transcranial/endonasal endoscopic approach for resection of this lesion. Pathological diagnosis revealed a WHO Grade III oligoastrocytoma. This report reviews the mechanisms of extradural glioma extension. To the authors' knowledge, it is the second report of a high-grade glioma exhibiting nasal extension without prior surgical or radiation treatment.

A Cost Analysis of Regional Versus General Anesthesia for Carotid Endarterectomy.

BACKGROUND: Medical care in the United States has evolved into a more cost-conscious value-based health care system that necessitates a comparison of costs when there are alternative interventions considered to be acceptable in the treatment of a disease. This study compares the cost differences between regional anesthesia (RA) and general anesthesia (GA) for carotid endarterectomy (CEA). METHODS: Data from 346 consecutive patients who underwent CEA between January 2012 and September 2014 were retrospectively reviewed for the type of anesthesia used, outcomes data, and cost variables. Overall hospital day costs were compared between RA and GA. Medians and interquartile ranges were compared using Wilcoxon-Mann-Whitney test. A P < 0.05 was considered statistically significant using 2-sided tests. RESULTS: Median overall costs for GA were significantly higher than median costs for RA (medians [with interquartile ranges], $10,140 [$7,158-$12,658] versus $7,122 [$5,072-$8,511], P < 0.001). Median total operative time for GA was significantly longer than median time for RA (168 [144-188] versus 134 [115-147] min, P < 0.001). Median in-hospital length of stay (LOS) for GA was significantly longer compared with RA (2.0 vs 1.2 days, P < 0.001). Patients who received GA were also more likely to be admitted to the intensive care unit. CONCLUSIONS: Decreased cost, operating room expenses, postoperative resources, and overall LOS were observed for individuals who underwent RA for CEA as compared with GA. In summary, RA is more cost-effective and should be the optimal choice when clinically appropriate.

Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma.

Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often affect the PI3K pathway. Our findings are consistent with early tumour spread outside the brainstem including the cerebrum. The spatial and temporal homogeneity of main driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships.

Differential Effects of Cold Atmospheric Plasma in the Treatment of Malignant Glioma.

OBJECTIVE: Cold atmospheric plasma (CAP) has recently been shown to selectively target cancer cells with minimal effects on normal cells. We systematically assessed the effects of CAP in the treatment of glioblastoma. METHODS: Three glioma cell lines, normal astrocytes, and endothelial cell lines were treated with CAP. The effects of CAP were then characterized for viability, cytotoxicity/apoptosis, and cell cycle effects. Statistical significance was determined with student's t-test. RESULTS: CAP treatment decreases viability of glioma cells in a dose dependent manner, with the ID50 between 90-120 seconds for all glioma cell lines. Treatment with CAP for more than 120 seconds resulted in viability less than 35% at 24-hours posttreatment, with a steady decline to less than 20% at 72-hours. In contrast, the effect of CAP on the viability of NHA and HUVEC was minimal, and importantly not significant at 90 to 120 seconds, with up to 85% of the cells remained viable at 72-hours post-treatment. CAP treatment produces both cytotoxic and apoptotic effects with some variability between cell lines. CAP treatment resulted in a G2/M-phase cell cycle pause in all three cell lines. CONCLUSIONS: This preliminary study determined a multi-focal effect of CAP on glioma cells in vitro, which was not observed in the non-tumor cell lines. The decreased viability depended on the treatment duration and cell line, but overall was explained by the induction of cytotoxicity, apoptosis, and G2/M pause. Future studies will aim at further characterization with more complex pre-clinical models.

Use of cold atmospheric plasma in the treatment of cancer.

Cold atmospheric plasma (CAP) is an emerging modality for the treatment of solid tumors. In-vitro experiments have demonstrated that with increasing doses of plasma, tumor cells assays display decreased cell viability. CAP is theorized to induce tumor cells into apoptosis via multiple pathways including reactive oxygen and nitrogen species as well as cell cycle disruption. Studies have shown CAP treatment can decrease mouse model glioblastoma multiforme tumor volume by 56%, increase life span by 60%, and maintain up to 85% viability of normal cells. Emerging evidence suggests that CAP is a viable in-vivo treatment for a number of tumors, including glioblastoma, as it appears to selectively induce tumor cell death while noncancerous cells remain viable.

Acute management of military-related injury.

Since the dawn of armed conflict head trauma has remained one of the most challenging afflictions for surgeons and medical personnel to treat. Interventions for head trauma from antiquity through the American Civil War were met with dismal outcomes. In the 20th century, despite greater lethality of weapons, progressive advances in management led to improved outcomes for head injured patients. A triage system consisting of appropriate levels of care from the front lines, through combat support hospitals to reconstructive and rehabilitative hospitals, has also contributed to the improved outcomes of head injured patients. This chapter examines the progressive improvement in management strategies during major conflicts, the mechanisms causing head trauma during conflict, and the current medical and surgical therapies recommended in the care of head-injured patients during armed conflict.

Intracranial injectable tumor model: technical advancements.

Background and Objectives Few simulation models are available that provide neurosurgical trainees with the challenge of distorted skull base anatomy despite increasing importance in the acquisition of safe microsurgical and endoscopic techniques. We have previously reported a unique training model for skull base neurosurgery where a polymer is injected into a cadaveric head where it solidifies to mimic a skull base tumor for resection. This model, however, required injection of the polymer under direct surgical vision via a complicated alternative approach to that being studied, prohibiting its uptake in many neurosurgical laboratories. Conclusion We report our updated skull base tumor model that is contrast-enhanced and may be easily and reliably injected under fluoroscopic guidance. We have identified a map of burr holes and injection corridors available to place tumor at various intracranial sites. Additionally, the updated tumor model allows for the creation of mass effect, and we detail the variation of polymer preparation to mimic different tumor properties. These advancements will increase the practicality of the tumor model and ideally influence neurosurgical standards of training.

Spindle cell hemangioendothelioma of the sacrum: case report.

Spindle cell hemangioendothelioma is a rare benign vascular tumor that is not known to involve the sacrum. The authors describe the case of a 31-year-old woman presenting with low-back and radicular pain without weakness or bowel or bladder dysfunction. Admission CT and MRI studies revealed a large S1-3 lytic sacral lesion. The patient initially underwent a nondiagnostic percutaneous biopsy. She subsequently underwent an open biopsy, during which the lesion was found to be highly vascular. Histological investigation revealed a vasoformative lesion consistent with spindle cell hemangioendothelioma. Preoperative embolization followed by resection via intralesional currettage resulted in resolution of symptoms up to 9 months postintervention. Despite the authors' recommendation, the patient became pregnant at that time and requested no additional follow-up imaging. The authors present the first reported case of a spindle cell hemangioendothelioma of the sacrum and review the current literature.

Unilateral coronal craniosynostosis and Down syndrome.

There is no known correlation between Down syndrome and craniosynostosis. The authors report 2 infants with trisomy 21 and right unilateral coronal craniosynostosis. Both patients were clinically asymptomatic but displayed characteristic craniofacial features associated with each disorder. One patient underwent a bilateral fronto-orbital advancement and the other underwent an endoscopically assisted strip craniectomy with postoperative helmet therapy. Both patients demonstrated good cosmesis at follow-up.

Association of cerebellopontine angle atypical teratoid/rhabdoid tumors with acute facial nerve palsy in infants.

Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant CNS tumors found almost exclusively in childhood. Although essentially universally fatal when incompletely resected, prompt diagnosis followed by early chemoradiation can improve outcomes. An AT/RT can occur extraaxially at the cerebellopontine angle (CPA) and cause acute cranial nerve deficits as the presenting sign. The authors report a series of 3 children who presented with isolated acute facial nerve palsies and in whom subsequent diagnosis of a CPA AT/RT was made. The authors propose that in young children whose presenting symptom is an acute facial nerve palsy with a CPA tumor, AT/RT should be highly suspected.

Sorafenib tosylate as a radiosensitizer in malignant astrocytoma.

Progress in research on the molecular aspects of glioblastoma has yet to provide a medical therapy that significantly improves prognosis. Glioblastoma invariably progress through current treatment regimens with radiotherapy as a key component. Activation of several signaling pathways is thought to be associated with this resistance to radiotherapy. Ras activity is exceptionally high in glioblastoma and may regulate sensitivity to radiotherapy. Raf-1, a downstream effector of Ras, demonstrates a high amount of activity in glioblastoma. Therefore, Raf-1 inhibition should be considered as a mechanism to increase the effectiveness of radiotherapy in treatment regimen. In vitro analysis was performed with a novel Raf-1 kinase inhibitor (BAY 54-9085) in culture with the glioblastoma cell line U1242. The cell line was treated in serum-containing media and analyzed for the effect of the BAY 54-9085 alone and BAY 54-9085 combined with radiation on cell death. BAY 54-9085 displayed a cytocidal effect on glioblastoma cells following a 3 day incubation with the drug in serum-containing media. A dose of 2.5 µM displayed moderate cell death which significantly increased with a dose of 5.0 µM. In addition, glioblastoma cells treated with both the BAY 54-9085 and gamma radiation displayed a significant increase in cell death (85.5%) as compared to either BAY 54-9085 (73.1%) or radiation (34.4%) alone. Radiation therapy is a key component of treatment for glioblastoma. A novel Raf-1 inhibitor displayed in vitro evidence of synergistically increasing cell death of glioblastoma cells in combination with radiation.

Successful endoscopic repair of persistent cerebrospinal fluid leak following attempted transcranial repair.

Endoscopic techniques have become the preferred approach to address cerebrospinal fluid (CSF) leaks in the skull base, as they offer a minimally invasive method to directly visualize and repair the defect. The alternative technique of open craniotomy can still be considered for cases refractory to endoscopic repair; however, few studies have investigated the potential benefits of endoscopic repair for cases of persistent leaks after attempted transcranial repair. We report two such cases of successful long-term endoscopic repair of a persistent CSF leak, and demonstrate that endoscopic repair is a viable option to salvage an unsuccessful intracranial repair.