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Endocrine function and gland volume after endoscopic transsphenoidal surgery for nonfunctional pituitary macroadenomas

Maya Harary, Aislyn C. DiRisio, Hassan Y. Dawood, John Kim, Nayan Lamba, Charles H. Cho, Timothy R. Smith, Hasan A. Zaidi, and Edward R. Laws Jr.

OBJECTIVE

Loss of pituitary function due to nonfunctional pituitary adenoma (NFPA) may be due to compression of the pituitary gland. It has been proposed that the size of the gland and relative perioperative gland expansion may relate to recovery of pituitary function, but the extent of this is unclear. This study aims to assess temporal changes in hormonal function after transsphenoidal resection of NFPA and the relationship between gland reexpansion and endocrine recovery.

METHODS

Patients who underwent endoscopic transsphenoidal surgery by a single surgeon for resection of a nonfunctional macroadenoma were selected for inclusion. Patients with prior pituitary surgery or radiosurgery were excluded. Patient characteristics and endocrine function were extracted by chart review. Volumetric segmentation of the pre- and postoperative (≥ 6 months) pituitary gland was performed using preoperative and long-term postoperative MR images. The relationship between endocrine function over time and clinical attributes, including gland volume, were examined.

RESULTS

One hundred sixty eligible patients were identified, of whom 47.5% were female; 56.9% of patients had anterior pituitary hormone deficits preoperatively. The median tumor diameter and gland volume preoperatively were 22.5 mm (interquartile range [IQR] 18.0–28.8 mm) and 0.18 cm3 (IQR 0.13–0.28 cm3), respectively. In 55% of patients, endocrine function normalized or improved in their affected axes by median last clinical follow-up of 24.4 months (IQR 3.2–51.2 months). Older age, male sex, and larger tumor size were associated with likelihood of endocrine recovery. Median time to recovery of any axis was 12.2 months (IQR 2.5–23.9 months); hypothyroidism was the slowest axis to recover. Although the gland significantly reexpanded from preoperatively (0.18 cm3, IQR 0.13–0.28 cm3) to postoperatively (0.33 cm3, IQR 0.23–0.48 cm3; p < 0.001), there was no consistent association with improved endocrine function.

CONCLUSIONS

Recovery of endocrine function can occur several months and even years after surgery, with more than 50% of patients showing improved or normalized function. Tumor size, and not gland volume, was associated with preserved or recovered endocrine function.

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Examining barriers to care: a retrospective cohort analysis investigating the relationship between hospital volume and outcomes in pediatric patients with cerebral arteriovenous malformations

Michael G. Brandel, Hernan Gonzalez, David D. Gonda, Michael L. Levy, Edward R. Smith, Sandi K. Lam, William T. Couldwell, Jeffrey Steinberg, and Vijay M. Ravindra

OBJECTIVE

Comprehensive data on treatment patterns of pediatric cerebral arteriovenous malformations (AVMs) are lacking. The authors’ aim was to examine national trends, assess the effect of hospital volume on outcomes, and identify variables associated with treatment at high-volume centers.

METHODS

Pediatric AVM admissions (for ruptured and unruptured lesions) occurring in the US in 2016 and 2019 were identified using the Kids’ Inpatient Database. Demographics, treatment methods, costs, and outcomes were recorded. The effect of hospital AVM volume on outcomes and factors associated with treatment at higher-volume hospitals were analyzed.

RESULTS

Among 2752 AVM admissions identified, 730 (26.5%) patients underwent craniotomy, endovascular treatment, or a combination. High-volume (vs low-volume) centers saw lower proportions of Black (8.7% vs 12.9%, p < 0.001) and lowest-income quartile (20.7% vs 27.9%, p < 0.001) patients, but were more likely to provide endovascular intervention (19.5%) than low-volume institutions (13.7%) (p = 0.001). Patients treated at high-volume hospitals had insignificantly lower numbers of complications (mean 2.66 vs 4.17, p = 0.105) but significantly lower odds of nonroutine discharge (OR 0.18 [95% CI 0.06–0.53], p = 0.009) and death (OR 0.13 [95% CI 0.02–0.75], p = 0.023). Admissions at high-volume hospitals cost more than at low-volume hospitals, regardless of whether intervention was performed ($64,811 vs $48,677, p = 0.001) or not ($64,137 vs $33,779, p < 0.001). Multivariable analysis demonstrated that Hispanic children, patients who received AVM treatment, and those in higher-income quartiles had higher odds of treatment at high-volume hospitals.

CONCLUSIONS

In this largest study of US pediatric cerebral AVM admissions to date, higher hospital volume correlated with several better outcomes, particularly when patients underwent intervention. Multivariable analysis demonstrated that higher income and Hispanic race were associated with treatment at high-volume centers, where endovascular care is more common. The findings highlight the fact that ensuring access to appropriate treatment of patients of all races and socioeconomic classes must be a focus.

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Focal selective dorsal rhizotomy and concurrent deformity correction: a combined approach

Nisha Gadgil, Aloysia L. Schwabe, Edward Wright, Amy Barbuto, Eric L. Dugan, Sruthi P. Thomas, Jeffrey S. Shilt, Dorothy Beauvais, Yushane Shih, Brian G. Smith, David F. Bauer, and Daniel J. Curry

OBJECTIVE

Selective dorsal rhizotomy (SDR) is a neurosurgical procedure to reduce spasticity in children with cerebral palsy and spastic diplegia. The authors developed a procedure called focal SDR for children with spasticity predominantly in the L5 or S1 motor distribution, which can be combined with orthopedic correction of fixed soft-tissue or bony deformity. The authors describe in detail the technique of minimally invasive focal SDR and propose selection criteria.

METHODS

The authors conducted a retrospective study of patients who underwent focal SDR at their institution and underwent baseline and 1-year postoperative 3D gait analysis. Modified Ashworth scale (MAS) and Gait Deviation Index (GDI) scores were the primary outcome measures.

RESULTS

Ten patients met the study criteria, all with an underlying diagnosis of cerebral palsy. All underwent focal SDR at the unilateral or bilateral S1 level, and 4 additionally underwent focal SDR at the L5 level unilaterally or bilaterally. All but 1 patient underwent concurrent orthopedic surgery. The improvement in spasticity of the plantar flexors, as measured by the MAS score, was 2.2 (p < 0.001). In the patients who underwent L5 focal SDR, there was an improvement in the hamstring MAS score of 1.4 (p = 0.004). The mean improvement in the GDI score following focal SDR was 11 (range −6 to 29, p < 0.001).

CONCLUSIONS

Focally impairing spasticity in the gastrocsoleus complex and/or hamstrings muscle group in the setting of less functionally impactful proximal tone is extremely common in cerebral palsy. The novel technique of focal SDR, combined with orthopedic intervention, improves spasticity scores and overall gait mechanics. Further investigation is warranted to define the ideal candidacy and outcomes.

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Human genetics and molecular mechanisms of vein of Galen malformation

Daniel Duran, Philipp Karschnia, Jonathan R. Gaillard, Jason K. Karimy, Mark W. Youngblood, Michael L. DiLuna, Charles C. Matouk, Beverly Aagaard-Kienitz, Edward R. Smith, Darren B. Orbach, Georges Rodesch, Alejandro Berenstein, Murat Gunel, and Kristopher T. Kahle

Vein of Galen malformations (VOGMs) are rare developmental cerebrovascular lesions characterized by fistulas between the choroidal circulation and the median prosencephalic vein. Although the treatment of VOGMs has greatly benefited from advances in endovascular therapy, including technical innovation in interventional neuroradiology, many patients are recalcitrant to procedural intervention or lack accessibility to specialized care centers, highlighting the need for improved screening, diagnostics, and therapeutics. A fundamental obstacle to identifying novel targets is the limited understanding of VOGM molecular pathophysiology, including its human genetics, and the lack of an adequate VOGM animal model. Herein, the known human mutations associated with VOGMs are reviewed to provide a framework for future gene discovery. Gene mutations have been identified in 2 Mendelian syndromes of which VOGM is an infrequent but associated phenotype: capillary malformation–arteriovenous malformation syndrome (RASA1) and hereditary hemorrhagic telangiectasia (ENG and ACVRL1). However, these mutations probably represent only a small fraction of all VOGM cases. Traditional genetic approaches have been limited in their ability to identify additional causative genes for VOGM because kindreds are rare, limited in patient number, and/or seem to have sporadic inheritance patterns, attributable in part to incomplete penetrance and phenotypic variability. The authors hypothesize that the apparent sporadic occurrence of VOGM may frequently be attributable to de novo mutation or incomplete penetrance of rare transmitted variants. Collaboration among treating physicians, patients’ families, and investigators using next-generation sequencing could lead to the discovery of novel genes for VOGM. This could improve the understanding of normal vascular biology, elucidate the pathogenesis of VOGM and possibly other more common arteriovenous malformation subtypes, and pave the way for advances in the diagnosis and treatment of patients with VOGM.

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Translabyrinthine resection of NF2 associated vestibular schwannoma with cochlear implant insertion

Cathal John Hannan, Priya Sharma, Matthew Edward Smith, Laurence Johann Glancz, Martin O’Driscoll, Andrew Thomas King, Charlotte Hammerbeck-Ward, Dafydd Gareth Evans, Scott Alexander Rutherford, Simon Kinsella Lloyd, Simon Richard Mackenzie Freeman, and Omar Nathan Pathmanaban

The authors present the case of a 24-year-old female with neurofibromatosis type 2. Growth of the left vestibular schwannoma and progressive hearing loss prompted the decision to proceed to translabyrinthine resection with cochlear nerve preservation and cochlear implant insertion. Complete resection with preservation of the facial and cochlear nerves was achieved. The patient had grade 1 facial function and was discharged on postoperative day 4 following suturing of a minor CSF leak. This case highlights the feasibility of cochlear nerve preservation and cochlear implant insertion in appropriately selected patients, offering a combination of effective tumor control and hearing rehabilitation.

The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID21122

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Spindle cell oncocytoma of the pituitary gland

Alexandra M. Giantini Larsen, David J. Cote, Hasan A. Zaidi, Wenya Linda Bi, Paul J. Schmitt, J. Bryan Iorgulescu, Michael B. Miller, Timothy R. Smith, M. Beatriz Lopes, John A. Jane Jr., and Edward R. Laws Jr.

OBJECTIVE

The authors report the diagnosis, management, and outcomes of 6 cases of spindle cell oncocytoma (SCO) in an effort to guide clinical diagnosis and management of these uncommon lesions.

METHODS

This study is a retrospective review of cases involving adult patients who underwent resection of pituitary lesions at the authors’ institutions between January 2000 and October 2017. The authors identified patients with histopathological confirmation of SCO and collected clinical data, including preoperative, perioperative, and postoperative management, complications, and outcomes.

RESULTS

Six patients with SCO were identified. Clinical findings at initial presentation included visual disturbances, dizziness, and headache. All patients underwent resection. Four resections were initially performed by the transsphenoidal approach, and 2 resections were performed by craniotomy at an outside institution with subsequent transsphenoidal reoperations. Neither necrosis nor increased mitotic activity was seen in the tumor samples. All samples stained positive for S100 protein and thyroid transcription factor 1 and negative for glial fibrillary acidic protein and pituitary hormones. Five of the samples stained positive for epithelial membrane antigen. The average MIB-1 index was 8.3% (range 2–17). Postoperatively, 3 of the 6 patients received further treatment for progression of residual tumor or for recurrence, 2 have stable residual tumor, and 1 has had no recurrence after gross-total resection. Two patients developed postoperative complications of transient sixth cranial nerve palsy and diplopia. There were no other complications.

CONCLUSIONS

SCO poses both a diagnostic and therapeutic challenge. These tumors are often initially misdiagnosed as nonfunctional pituitary adenomas because of their sellar location and nonspecific symptomatology. Postoperatively, SCO must also be distinguished from other neoplasms of the posterior pituitary gland through histopathological examination. Resection of SCO can be challenging, given its highly vascular and adherent nature. Long-term follow-up is critical, as the tumor is associated with higher recurrence and progression rates compared to other benign neoplasms of the sella.

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Defensive medicine in neurosurgery: the Canadian experience

Timothy R. Smith, M. Maher Hulou, Sandra C. Yan, David J. Cote, Brian V. Nahed, Maya A. Babu, Sunit Das, William B. Gormley, James T. Rutka, Edward R. Laws Jr., and Robert F. Heary

OBJECT

Recent studies have examined the impact of perceived medicolegal risk and compared how this perception impacts defensive practices within the US. To date, there have been no published data on the practice of defensive medicine among neurosurgeons in Canada.

METHODS

An online survey containing 44 questions was sent to 170 Canadian neurosurgeons and used to measure Canadian neurosurgeons’ perception of liability risk and their practice of defensive medicine. The survey included questions on the following domains: surgeon demographics, patient characteristics, type of physician practice, surgeon liability profile, policy coverage, defensive behaviors, and perception of the liability environment. Survey responses were analyzed and summarized using counts and percentages.

RESULTS

A total of 75 neurosurgeons completed the survey, achieving an overall response rate of 44.1%. Over one-third (36.5%) of Canadian neurosurgeons paid less than $5000 for insurance annually. The majority (87%) of Canadian neurosurgeons felt confident with their insurance coverage, and 60% reported that they rarely felt the need to practice defensive medicine. The majority of the respondents reported that the perceived medicolegal risk environment has no bearing on their preferred practice location. Only 1 in 5 respondent Canadian neurosurgeons (21.8%) reported viewing patients as a potential lawsuit. Only 4.9% of respondents would have selected a different career based on current medicolegal risk factors, and only 4.1% view the cost of annual malpractice insurance as a major burden.

CONCLUSIONS

Canadian neurosurgeons perceive their medicolegal risk environment as more favorable and their patients as less likely to sue than their counterparts in the US do. Overall, Canadian neurosurgeons engage in fewer defensive medical behaviors than previously reported in the US.

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Multiinstitutional validation of the University of California at San Francisco Low-Grade Glioma Prognostic Scoring System

Clinical article

Edward F. Chang, Aaron Clark, Randy L. Jensen, Mark Bernstein, Abhijit Guha, Giorgio Carrabba, Debabrata Mukhopadhyay, Won Kim, Linda M. Liau, Susan M. Chang, Justin S. Smith, Mitchel S. Berger, and Michael W. McDermott

Object

Medical and surgical management of low-grade gliomas (LGGs) is complicated by a highly variable clinical course. The authors recently developed a preoperative scoring system to prognosticate outcomes of progression and survival in a cohort of patients treated at a single institution (University of California, San Francisco [UCSF]). The objective of this study was to validate the scoring system in a large patient group drawn from multiple external institutions.

Methods

Clinical data from 3 outside institutions (University of Utah, Toronto Western Hospital, and University of California, Los Angeles) were collected for 256 patients (external validation set). Patients were assigned a prognostic score based upon the sum of points assigned to the presence of each of the 4 following factors: 1) location of tumor in presumed eloquent cortex, 2) Karnofsky Performance Scale (KPS) Score ≤ 80, 3) age > 50 years, and 4) maximum diameter > 4 cm. A chi-square analysis was used to analyze categorical differences between the institutions; Cox proportional hazard modeling was used to confirm that the individual factors were associated with shorter overall survival (OS) and progression-free survival (PFS); and Kaplan–Meier curves estimated OS and PFS for the score groups. Differences between score groups were analyzed by the log-rank test.

Results

The median OS duration was 120 months, and there was no significant difference in survival between the institutions. Cox proportional hazard modeling confirmed that the 4 components of the UCSF Low-Grade Glioma Scoring System were associated with lower OS in the external validation set; presumed eloquent location (hazard ratio [HR] 2.04, 95% CI 1.28–2.56), KPS score ≤ 80 (HR 5.88, 95% CI 2.44–13.7), age > 50 years (HR 1.82, 95% CI 1.02–3.23), and maximum tumor diameter > 4 cm (HR 2.63, 95% CI 1.58–4.35). The stratification of patients based on scores generated groups (0–4) with statistically different OS and PFS estimates (p < 0.0001, log-rank test). Lastly, the UCSF patient group (construction set) was combined with the external validation set (total of 537 patients) and analyzed for OS and PFS. For all patients, the 5-year survival probability was 0.79; the 5-year cumulative OS probabilities stratified by score group were: score of 0, 0.98; score of 1, 0.90; score of 2, 0.81; score of 3, 0.53; and score of 4, 0.46.

Conclusions

The UCSF scoring system accurately predicted OS and PFS in an external large, multiinstitutional population of patients with LGGs. The strengths of this system include ease of use and ability to be applied preoperatively, with the eventual goal of aiding in the design of individualized treatment plans for patients with LGG at diagnosis.

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Influence of catastrophizing, anxiety, and depression on in-hospital opioid consumption, pain, and quality of recovery after adult spine surgery

Lauren K. Dunn, Marcel E. Durieux, Lucas G. Fernández, Siny Tsang, Emily E. Smith-Straesser, Hasan F. Jhaveri, Shauna P. Spanos, Matthew R. Thames, Christopher D. Spencer, Aaron Lloyd, Russell Stuart, Fan Ye, Jacob P. Bray, Edward C. Nemergut, and Bhiken I. Naik

OBJECTIVE

Perception of perioperative pain is influenced by various psychological factors. The aim of this study was to determine the impact of catastrophizing, anxiety, and depression on in-hospital opioid consumption, pain scores, and quality of recovery in adults who underwent spine surgery.

METHODS

Patients undergoing spine surgery were enrolled in this study, and the preoperatively completed questionnaires included the verbal rating scale (VRS), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), and Oswestry Disability Index (ODI). Quality of recovery was assessed using the 40-item Quality of Recovery questionnaire (QoR40). Opioid consumption and pain scores according to the VRS were recorded daily until discharge.

RESULTS

One hundred thirty-nine patients were recruited for the study, and 101 completed the QoR40 assessment postoperatively. Patients with higher catastrophizing scores were more likely to have higher maximum pain scores postoperatively (estimate: 0.03, SE: 0.01, p = 0.02), without increased opioid use (estimate: 0.44, SE: 0.27, p = 0.11). Preoperative anxiety (estimate: 1.18, SE: 0.65, p = 0.07) and depression scores (estimate: 1.06, SE: 0.71, p = 0.14) did not correlate with increased postoperative opioid use; however, patients with higher preoperative depression scores had lower quality of recovery after surgery (estimate: −1.9, SE: 0.56, p < 0.001).

CONCLUSIONS

Catastrophizing, anxiety, and depression play important roles in modulating postoperative pain. Preoperative evaluation of these factors, utilizing a validated tool, helps to identify patients at risk. This might allow for earlier psychological intervention that could reduce pain severity and improve the quality of recovery.

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A national stratification of the global macroeconomic burden of central nervous system cancer

Jakob V. E. Gerstl, Alexander G. Yearley, John L. Kilgallon, Philipp Lassarén, Faith C. Robertson, Vendela Herdell, Andy Y. Wang, David J. Segar, Joshua D. Bernstock, Edward R. Laws, Kavitha Ranganathan, and Timothy R. Smith

OBJECTIVE

Country-by-country estimates of the macroeconomic disease burden of central nervous system (CNS) cancers are important when determining the allocation of resources related to neuro-oncology. Accordingly, in this study the authors investigated macroeconomic losses related to CNS cancer in 173 countries and identified pertinent epidemiological trends.

METHODS

Data for CNS cancer incidence, mortality, and disability-adjusted life years (DALYs) were collected from the Global Burden of Disease 2019 database. Gross domestic product data were combined with DALY data to estimate economic losses using a value of lost welfare approach.

RESULTS

The mortality-to-incidence ratio of CNS cancer in 2019 was 0.60 in high-income regions compared to 0.82 in Sub-Saharan Africa and 0.87 in Central Europe, Eastern Europe, and Central Asia. Welfare losses varied across both high- and low-income countries. Welfare losses attributable to CNS cancer in Japan represented 0.07% of the gross domestic product compared to 0.23% in Germany. In low- and middle-income countries, Iraq reported welfare losses of 0.20% compared to 0.04% in Angola. Globally, the DALY rate in 2019 was the same for CNS cancer as for prostate cancer at 112 per 100,000 person-years, despite a 75% lower incidence rate, equating to CNS cancer welfare losses of 182 billion US dollars.

CONCLUSIONS

Macroeconomic losses vary across high- and low-income settings and appear to be region specific. These differences may be explained by differences in regional access to screening and diagnosis, population-level genetic predispositions, and environmental risk factors. Mortality-to-incidence ratios are higher in low- and middle-income countries than in high-income countries, highlighting possible gaps in treatment access. Quantification of macroeconomic losses related to CNS cancer can help to justify the spending of finite resources to improve outcomes for neuro-oncological patients globally.