Clinical Implications of Pituitary Adenomas Exhibiting Dual Transcription Factor Staining: A Case Series of 27 Patients.

OBJECTIVE: According to the 2017 World Health Organization classification of neuro-endocrine tumors, pituitary adenomas (PAs) are classified according to immunoexpression of the pituitary-specific transcription factors (TFs). A small subset of PAs exhibit multiple TF staining on immunohistochemistry and we present a series of 27 pathologically-confirmed cases of dual TF staining PAs (dsTF-PAs), and report clinically relevant implications. METHODS: A retrospective chart review of a multi-institutional database of patients with PAs surgically resected between 2008-2021 was performed. PAs expressing immunopositivity 2+ TFs. Patient demographics, neuro-imaging characteristics, histopathologic findings, and clinical data were collected. RESULTS: Twenty-seven patients had pathologically verified dsTF-PAs, of whom 17 were female (63%), with ages ranging from 20-84 years. Twenty-three (85.2%) patients harbored functional PAs, with acromegaly being the most common functional subtype (86.4%). The most common combination of TFs within a single tumor was PIT-1/SF-1 (85.2%). Six PAs exhibited Knosp cavernous sinus invasion grades of 3 or 4 and the Ki-67 labeling index was ≥3% in 6 patients (24.0%) and all stained for PIT-1/SF-1. Hormonal remission was achieved in 78% of functional dsTF-PAs. No PAs showed evidence of recurrence or progression over the mean follow-up period of 28.5 months. CONCLUSIONS: PAs exhibiting dsTF-PAs represent a small but clinically relevant diagnostic subset of PAs according to the 2021 World Health Organization criteria, as a majority are GH-producing. Precise classification using TF staining plays a key role in understanding the biology of these tumors. Favorable outcomes can be achieved in this subset of PAs with evolving TF classification.

Tumor characteristics guiding selection of channel-based versus open microscopic approaches for resection of atrial intraventricular meningiomas: patient series.

BACKGROUND: Atrial intraventricular meningiomas (AIMs) are relatively rare and typically deep-seated tumors that can mandate resection. Compared with transsulcal or transcortical open microscopic approaches, port- or channel-based exoscopic approaches have facilitated a less invasive alternative of tumor access and resection. The authors present a case series of seven patients with AIMs who underwent open microscopic versus channel-based exoscopic resection by a senior neurosurgeon at their institution between 2012 and 2022 to understand patient and tumor features that lent themselves to selection of a particular approach. OBSERVATIONS: In the patients harboring three AIMs selected for channel-based resection, the average AIM diameter (2.9 vs 5.2 cm) was smaller, the AIMs were deeper from the cortical surface (2.5 vs 1.1 cm), and the patients had a shorter average postoperative length of stay (3.3 vs 5.8 days) compared with the four patients who underwent open resection. Gross-total resection was achieved in all cases. Complications for both groups included transient homonymous hemianopsia and aphasia. No recurrences were identified over the follow-up period. LESSONS: The authors demonstrate that channel-based exoscopic resection is safe and effective for AIMs 3 cm in diameter and over 2 cm deep. This may help guide neurosurgeons in future approach selection based on tumor features, including size/volume, location, and depth from cortical surface.

A cross-sectional study to test equivalence of low- versus intermediate-flip angle dynamic susceptibility contrast MRI measures of relative cerebral blood volume in patients with high-grade gliomas at 1.5 Tesla field strength.

Introduction: 1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle ("low-FA") with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle ("intermediate-FA") and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) patients. Methods: This was a single-institution cross-sectional study of patients who had undergone 1.5T MRI for HGG. DSC-MRI consisted of gradient-echo echo-planar imaging (GRE-EPI) with a low-FA without preload (30°/P-); this then subsequently served as a preload for the standard intermediate-FA acquisition (60°/P+). Both normalized (nrCBV) and standardized relative cerebral blood volumes (srCBV) were calculated using model-based leakage correction (C+) with IBNeuro™ software. Whole-enhancing lesion mean and median nrCBV and srCBV from the low- and intermediate-FA methods were compared using the Pearson's, Spearman's and intraclass correlation coefficients (ICC). Results: Twenty-three HGG patients composing a total of 31 scans were analyzed. The Pearson and Spearman correlations and ICCs between the 30°/P-/C+ and 60°/P+/C+ acquisitions demonstrated high correlations for both mean and median nrCBV and srCBV. Conclusion: Our study provides preliminary evidence that for HGG patients at 1.5T MRI, a low FA, no preload DSC-MRI acquisition can be an appealing alternative to the reference standard higher FA acquisition that utilizes a preload.

Endoscopic endonasal approach for MRI-Negative Cushing's microadenoma.

A 54-year-old male with a history of diabetes mellitus type 2 for 12 years and hypertension was seen in the clinic due to poorly controlled diabetes. Inferior petrosal sinus sampling (IPSS) confirmed Cushing's disease with primary adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma on the right. However, 3T and subsequent 7T MRI showed no visible tumor. An endoscopic transsphenoidal approach was selected to explore the pituitary gland and resect the presumed microadenoma. Tumor was identified in the lateral recess along the right medial cavernous sinus wall and gross-total resection (GTR) was performed. The normal pituitary gland was preserved, and the patient went into remission. The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2324.

Validation of Myc-Associated Protein X (MAX) regulation in growth hormone secreting and nonfunctional pituitary adenoma.

INTRODUCTION: Many patients with growth hormone-secreting pituitary adenoma (GHPA) fail to achieve biochemical remission, warranting investigation into epigenetic and molecular signatures associated with tumorigenesis and hormonal secretion. Prior work exploring the DNA methylome showed Myc-Associated Protein X (MAX), a transcription factor involved in cell cycle regulation, was differentially methylated between GHPA and nonfunctional pituitary adenoma (NFPA). We aimed to validate the differential DNA methylation and related MAX protein expression profiles between NFPA and GHPA. METHODS: DNA methylation levels were measured in 52 surgically resected tumors (37 NFPA, 15 GHPA) at ~100,000 known MAX binding sites derived using ChIP-seq analysis from ENCODE. Findings were correlated with MAX protein expression using a constructed tissue microarray (TMA). Gene ontology analysis was performed to explore downstream genetic and signaling pathways regulated by MAX. RESULTS: GHPA had more hypomethylation events across all known MAX binding sites. Of binding sites defined using ChIP-seq analysis, 1,551 sites had significantly different methylation patterns between the two cohorts; 432 occurred near promoter regions potentially regulated by MAX, including promoters of TNF and MMP9. Gene ontology analysis suggested enrichment in genes involved in oxygen response, immune system regulation, and cell proliferation. Thirteen MAX binding sites were within coding regions of genes. GHPA demonstrated significantly increased expression of MAX protein compared to NFPA. CONCLUSION: GHPA have significantly different DNA methylation and downstream protein expression levels of MAX compared to NFPA. These differences may influence mechanisms involved with cellular proliferation, tumor invasion and hormonal secretion.

Association of Relative Cerebral Blood Volume from Dynamic Susceptibility Contrast-Enhanced Perfusion MR with HER2 Status in Breast Cancer Brain Metastases.

RATIONALE AND OBJECTIVES: With the development of HER2-directed therapies, identifying non-invasive imaging biomarkers of HER2 expression in breast cancer brain metastases has become increasingly important. The purpose of this study was to investigate whether relative cerebral blood volume (rCBV) from dynamic susceptibility contrast-enhanced (DSC) perfusion MR could help identify the HER2 status of breast cancer brain metastases. MATERIALS AND METHODS: With IRB approval for this HIPAA-compliant cross-sectional study and a waiver of informed consent, we queried our institution's electronic medical record to derive a cohort of 14 histologically proven breast cancer brain metastases with preoperative DSC perfusion MR and HER2 analyses of the resected/biopsied brain specimens from 2011-2021. The rCBV of the lesions was measured and compared using Mann-Whitney tests. Receiver operating characteristic analyses were performed to evaluate the performance of rCBV in identifying HER2 status. RESULTS: The study cohort was comprised of 14 women with a mean age of 56 years (range: 32-81 years) with a total of 14 distinct lesions. The rCBV of HER2-positive breast cancer brain metastases was significantly greater than the rCBV of HER2-negative lesions (8.02 vs 3.97, U=48.00, p=0.001). rCBV differentiated HER2-positive lesions from HER2-negative lesions with an area under the curve of 0.98 (standard error=0.032, p<0.001). The accuracy-maximizing rCBV threshold (4.8) was associated with an accuracy of 93% (13/14), a sensitivity of 100% (7/7), and a specificity of 86% (6/7). CONCLUSION: rCBV may assist in identifying the HER2 status of breast cancer brain metastases, if validated in a large prospective trial.

MR multitasking-based dynamic imaging for cerebrovascular evaluation (MT-DICE): Simultaneous quantification of permeability and leakage-insensitive perfusion by dynamic T 1 / T 2 * mapping.

PURPOSE: To develop an MR multitasking-based dynamic imaging for cerebrovascular evaluation (MT-DICE) technique for simultaneous quantification of permeability and leakage-insensitive perfusion with a single-dose contrast injection. METHODS: MT-DICE builds on a saturation-recovery prepared multi-echo fast low-angle shot sequence. The k-space is randomly sampled for 7.6 min, with single-dose contrast agent injected 1.5 min into the scan. MR multitasking is used to model the data into six dimensions, including three spatial dimensions for whole-brain coverage, a saturation-recovery time dimension, and a TE dimension for dynamic T 1 $$ {\mathrm{T}}_1 $$ and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ quantification, respectively, and a contrast dynamics dimension for capturing contrast kinetics. The derived pixel-wise T 1 / T 2 * $$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ time series are converted into contrast concentration-time curves for calculation of kinetic metrics. The technique was assessed for its agreement with reference methods in T 1 $$ {\mathrm{T}}_1 $$ and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ measurements in eight healthy subjects and, in three of them, inter-session repeatability of permeability and leakage-insensitive perfusion parameters. Its feasibility was also demonstrated in four patients with brain tumors. RESULTS: MT-DICE T 1 / T 2 * $$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ values of normal gray matter and white matter were in excellent agreement with reference values (intraclass correlation coefficients = 0.860/0.962 for gray matter and 0.925/0.975 for white matter ). Both permeability and perfusion parameters demonstrated good to excellent intersession agreement with the lowest intraclass correlation coefficients at 0.694. Contrast kinetic parameters in all healthy subjects and patients were within the literature range. CONCLUSION: Based on dynamic T 1 / T 2 * $$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ mapping, MT-DICE allows for simultaneous quantification of permeability and leakage-insensitive perfusion metrics with a single-dose contrast injection.

Ultra-high field 7 T MRI localizes regional brain volume recovery following corticotroph adenoma resection and hormonal remission in Cushing's disease: A case series.

Background: Cushing's disease (CD) is defined by glucocorticoid excess secondary to the increased section of corticotropin by a pituitary adenoma. Magnetic resonance imaging (MRI) studies performed at 1.5 or 3 Tesla (T) have demonstrated correlations between regional changes in brain structure and the progression of CD. In this report, we examine the changes in brain volume following corticotroph pituitary adenoma resection using ultra-high field 7 T MRI to increase the accuracy of our volumetric analyses. Methods: Thirteen patients were referred to the endocrinology clinic at our institution from 2017 to 2020 with symptoms of cortisol excess and were diagnosed with ACTH-dependent endogenous Cushing syndrome. Five patients had follow-up 7 T imaging at varying time points after a transsphenoidal resection. Results: Symmetrized percent change in regional volumes demonstrated a postoperative increase in cortical volume that was relatively larger than that of cerebral white matter or subcortical gray matter (percent changes = 0.0172%, 0.0052%, and 0.0120%, respectively). In the left cerebral hemisphere, the medial orbitofrontal, lateral orbitofrontal, and pars opercularis cortical regions experienced the most robust postoperative percent increases (percent changes = 0.0166%, 0.0122%, and 0.0068%, respectively). In the right cerebral hemisphere, the largest percent increases were observed in the pars triangularis, rostral portion of the middle frontal gyrus, and superior frontal gyrus (percent changes = 0.0156%, 0.0120%, and 0.0158%). Conclusion: Cerebral volume recovery following pituitary adenoma resection is driven by changes in cortical thickness predominantly in the frontal lobe, while subcortical white and gray matter volumes increase more modestly.

Association between socioeconomic status and presenting characteristics and extent of disease in patients with surgically resected nonfunctioning pituitary adenoma.

OBJECTIVE: The aim of this study was to evaluate the association between zip code-level socioeconomic status (SES) and presenting characteristics and short-term clinical outcomes in patients with nonfunctioning pituitary adenoma (NFPA). METHODS: A retrospective review of prospectively collected data from the University of Southern California Pituitary Center was conducted to identify all patients undergoing surgery for pituitary adenoma (PA) from 2000 to 2021 and included all patients with NFPA with recorded zip codes at the time of surgery. A normalized socioeconomic metric by zip code was then constructed using data from the American Community Survey estimates, which was categorized into tertiles. Multiple imputation was used for missing data, and multivariable linear and logistic regression models were constructed to estimate mean differences and multivariable-adjusted odds ratios for the association between zip code-level SES and presenting characteristics and outcomes. RESULTS: A total of 637 patients were included in the overall analysis. Compared with patients in the lowest SES tertile, those in the highest tertile were more likely to be treated at a private (rather than safety net) hospital, and were less likely to present with headache, vision loss, and apoplexy. After multivariable adjustment for age, sex, and prior surgery, SES in the highest compared with lowest tertile was inversely associated with tumor size at diagnosis (-4.9 mm, 95% CI -7.2 to -2.6 mm, p < 0.001) and was positively associated with incidental diagnosis (multivariable-adjusted OR 1.72, 95% CI 1.02-2.91). Adjustment for hospital (private vs safety net) attenuated the observed associations, but disparities by SES remained statistically significant for tumor size. Despite substantial differences at presentation, there were no significant differences in length of stay or odds of an uncomplicated procedure by zip code-level SES. Patients from lower-SES zip codes were more likely to require postoperative steroid replacement and less likely to achieve gross-total resection. CONCLUSIONS: In this series, lower zip code-level SES was associated with more severe disease at the time of diagnosis for NFPA patients, including larger tumor size and lower rates of incidental diagnosis. Despite these differences at presentation, no significant differences were observed in short-term postoperative complications, although patients with higher zip code-level SES had higher rates of gross-total resection.

Growth hormone secreting pituitary adenomas show distinct extrasellar extension patterns compared to nonfunctional pituitary adenomas.

PURPOSE: Patterns of extension of pituitary adenomas (PA) may vary according to PA subtype. Understanding extrasellar extension patterns in growth hormone PAs (GHPA) vis-a-vis nonfunctional PAs (NFPAs) may provide insights into the biology of GHPA and future treatment avenues. METHODS: Preoperative MR imaging (MRI) in 179 consecutive patients treated surgically for NFPA (n = 139) and GHPA (n = 40) were analyzed to determine patterns of extrasellar growth. Extension was divided into two principal directions: cranio-caudal (measured by infrasellar/suprasellar extension), and lateral cavernous sinus invasion (CSI) determined by Knosp grading score of 3-4. Suprasellar extension was defined as tumor extension superior to the tuberculum sellae- dorsum sellae line, and inferior extension as invasion through the sellar floor into the sphenoid sinus or clivus. Categorical analysis was performed using Fisher's exact test. RESULTS: GHPAs were overall more likely to remain purely intrasellar compared to NFPA (50% vs 26%, p < 0.001). GHPAs, however, were 7 times more likely to exhibit isolated infrasellar extension compared to NFPA (20% vs 2.8%, p = 0.001). Conversely, NFPAs were twice as likely to exhibit isolated suprasellar extension compared to GHPA (60% vs 28%, p < 0.001), as well as combined suprasellar/infrasellar extension (25% vs 3%, p = 0.011). There were no overall differences in CSI between the two subgroups. DISCUSSION: GHPA and NFPA demonstrate distinct extrasellar extension patterns on MRI. GHPAs show proclivity for inferior extension with bony invasion, whereas NFPAs are more likely to exhibit suprasellar extension through the diaphragmatic aperture. These distinctions may have implications into the biology and future treatment of PAs.

5-Aminolevulinic acid-enhanced fluorescence-guided treatment of high-grade glioma using angled endoscopic blue light visualization: technical case series with preliminary follow-up.

OBJECTIVE: 5-Aminolevulinic acid (5-ALA)-enhanced fluorescence-guided resection of high-grade glioma (HGG) using microscopic blue light visualization offers the ability to improve extent of resection (EOR); however, few descriptions of HGG resection performed using endoscopic blue light visualization are currently available. In this report, the authors sought to describe their surgical experience and patient outcomes of 5-ALA-enhanced fluorescence-guided resection of HGG using primary or adjunctive endoscopic blue light visualization. METHODS: The authors performed a retrospective review of prospectively collected data from 30 consecutive patients who underwent 5-ALA-enhanced fluorescence-guided biopsy or resection of newly diagnosed HGG was performed. Patient demographic data, tumor characteristics, surgical technique, EOR, tumor fluorescence patterns, and progression-free survival were recorded. RESULTS: In total, 30 newly diagnosed HGG patients were included for analysis. The endoscope was utilized for direct 5-ALA-guided port-based biopsy (n = 9), microscopic to endoscopic (M2E; n = 18) resection, or exoscopic to endoscopic (E2E; n = 3) resection. All endoscopic biopsies of fluorescent tissue were diagnostic. 5-ALA-enhanced tumor fluorescence was visible in all glioblastoma cases, but only in 50% of anaplastic astrocytoma cases and no anaplastic oligodendroglioma cases. Gross-total resection (GTR) was achieved in 10 patients in whom complete resection was considered safe, with 11 patients undergoing subtotal resection. In all cases, endoscopic fluorescence was more avid than microscopic fluorescence. The endoscope offered the ability to diagnose and resect additional tumor not visualized by the microscope in 83.3% (n = 10/12) of glioblastoma cases, driven by angled lenses and increased fluorescence facilitated by light source delivery within the cavity. Mean volumetric EOR was 90.7% in all resection patients and 98.8% in patients undergoing planned GTR. No complications were attributable to 5-ALA or blue light endoscopy. CONCLUSIONS: The blue light endoscope is a viable primary or adjunctive visualization platform for optimization of 5-ALA-enhanced HGG fluorescence. Implementation of the blue light endoscope to guide resection of HGG glioma is feasible and ergonomically favorable, with a potential advantage of enabling increased detection of tumor fluorescence in deep surgical cavities compared to the microscope.

Treatment strategies for giant pituitary adenomas in the era of endoscopic transsphenoidal surgery: a multicenter series.

OBJECTIVE: Given the anatomical complexity and frequently invasive growth of giant pituitary adenomas (GPAs), individually tailored approaches are required. The aim of this study was to assess the treatment strategies and outcomes in a large multicenter series of GPAs in the era of endoscopic transsphenoidal surgery (ETS). METHODS: This was a retrospective case-control series of 64 patients with GPAs treated at two tertiary care centers by surgeons with experience in ETS. GPAs were defined by a maximum diameter of ≥ 4 cm and a volume of ≥ 10 cm3 on preoperative isovoxel contrast-enhanced MRI. RESULTS: The primary operation was ETS in all cases. Overall gross-total resection rates were 64% in round GPAs, 46% in dumbbell-shaped GPAs, and 8% in multilobular GPAs (p < 0.001). Postoperative outcomes were further stratified into two groups based on extent of resection: group A (gross-total resection or partial resection with intracavernous remnant; 21/64, 33%) and group B (partial resection with intracranial remnant; 43/64, 67%). Growth patterns of GPAs were mostly round (11/14, 79%) in group A and multilobular (33/37, 89%) in group B. In group A, no patients required a second operation, and 2/21 (9%) were treated with adjuvant radiosurgery. In group B, early transcranial reoperation was required in 6/43 (14%) cases due to hemorrhagic transformation of remnants. For the remaining group B patients with remnants, 5/43 (12%) underwent transcranial surgery and 12/43 (28%) underwent delayed second ETS. There were no deaths in this series. Severe complications included stroke (6%), meningitis (6%), hydrocephalus requiring shunting (6%), and loss or distinct worsening of vision (3%). At follow-up (mean 3 years, range 0.5-16 years), stable disease was achieved in 91% of cases. CONCLUSIONS: ETS as a primary treatment modality to relieve mass effect in GPAs and extent of resection are dependent on GPA morphology. The pattern of residual pituitary adenoma guides further treatment strategies, including early transcranial reoperation, delayed endoscopic transsphenoidal/transcranial reoperation, and adjuvant radiosurgery.

Voxelwise Prediction of Recurrent High-Grade Glioma via Proximity Estimation-Coupled Multidimensional Support Vector Machine.

PURPOSE: To provide early and localized glioblastoma (GBM) recurrence prediction, we introduce a novel postsurgery multiparametric magnetic resonance-based support vector machine (SVM) method coupling with stem cell niche (SCN) proximity estimation. METHODS AND MATERIALS: This study used postsurgery magnetic resonance imaging (MRI) scans from 50 patients with recurrent GBM, obtained approximately 2 months before clinically diagnosed recurrence. The main prediction pipeline consisted of a proximity-based estimator to identify regions with high risk of recurrence (HRRs) and an SVM classifier to provide voxelwise prediction in HRRs. The HRRs were estimated using the weighted sum of inverse distances to 2 possible origins of recurrence-the SCN and the tumor cavity. Subsequently, multiparametric voxels (from T1, T1 contrast-enhanced, fluid-attenuated inversion recovery, T2, and apparent diffusion coefficient) within the HRR were grouped into recurrent (warped from the clinical diagnosis) and nonrecurrent subregions and fed into the proximity estimation-coupled SVM classifier (SVMPE). The cohort was randomly divided into 40% and 60% for training and testing, respectively. The trained SVMPE was then extrapolated to an earlier time point for earlier recurrence prediction. As an exploratory analysis, the SVMPE predictive cluster sizes and the image intensities from the 5 magnetic resonance sequences were compared across time to assess the progressive subclinical traces. RESULTS: On 2-month prerecurrence MRI scans from 30 test cohort patients, the SVMPE classifier achieved a recall of 0.80, a precision of 0.69, an F1-score of 0.73, and a mean boundary distance of 7.49 mm. Exploratory analysis at early time points showed spatially consistent but significantly smaller subclinical clusters and significantly increased T1 contrast-enhanced and apparent diffusion coefficient values over time. CONCLUSIONS: We demonstrated a novel voxelwise early prediction method, SVMPE, for GBM recurrence based on clinical follow-up MR scans. The SVMPE is promising in localizing subclinical traces of recurrence 2 months ahead of clinical diagnosis and may be used to guide more effective personalized early salvage therapy.

Silent corticotroph pituitary adenomas: clinical characteristics, long-term outcomes, and management of disease recurrence.

OBJECTIVE: Silent corticotroph adenomas (SCAs) are a distinct subtype of nonfunctioning pituitary adenomas (NFAs) that demonstrate positive immunohistochemistry for adrenocorticotropic hormone (ACTH) without causing Cushing's disease. SCAs are hypothesized to exhibit more aggressive behavior than standard NFAs. The authors analyzed their institution's surgical experience with SCAs in an effort to characterize rates of invasion, postoperative clinical outcomes, and patterns of disease recurrence and progression. The secondary objectives were to define the best treatment strategies in the event of tumor recurrence and progression. METHODS: A retrospective analysis of patients treated at the authors' institution identified 100 patients with SCAs and 841 patients with NFAs of other subtypes who were treated surgically from 2000 to 2019. Patient demographics, tumor characteristics, surgical and neuroimaging data, rates of endocrinopathy, and neurological outcomes were recorded. Cohorts of patients with SCAs and patients with standard NFAs were compared with regard to these characteristics and outcomes. RESULTS: The SCA cohort presented with cranial neuropathy (13% vs 5.7%, p = 0.0051) and headache (53% vs 42.3%, p = 0.042) compared to the NFA cohort, despite similar rates of apoplexy. The SCA cohort included a higher proportion of women (SCA 60% vs NFA 45.8%, p = 0.0071) and younger age at presentation (SCA 50.5 ± 13.3 vs NFA 54.6 ± 14.9 years of age, p = 0.0082). Reoperations were comparable between the cohorts (SCA 16% vs NFA 15.7%, p = 0.98). Preoperative pituitary function was comparable between the cohorts with the exception of higher rates of preoperative panhypopituitarism in NFA patients (2% vs 6.1%, respectively; p = 0.0033). The mean tumor diameter in SCA patients was 24 ± 10.8 mm compared to 26 ± 11.3 mm in NFA patients (p = 0.05). Rates of cavernous sinus invasion were higher in the SCA group (56% vs 49.7%), although this result did not reach statistical significance. There were no significant differences in extent of resection, intraoperative CSF leak rates, endocrine or neurological outcomes, or postoperative complications. Ki-67 rates were significantly increased in the SCA cohort (2.88 ± 2.79) compared to the NFA cohort (1.94 ± 1.99) (p = 0.015). Although no differences in overall rates of progression or recurrence were noted, SCAs had a significantly lower progression-free survival (24.5 vs 51.1 months, p = 0.0011). Among the SCA cohort, progression was noted despite the use of adjuvant radiosurgery in 33% (n = 4/12) of treated tumors. Adequate tumor control was not achieved in half (n = 6) of the SCA progression cohort despite radiosurgery or multiple resections. CONCLUSIONS: In this study, to the authors' knowledge the largest surgical series to assess outcomes in SCAs to date, the findings suggest that SCAs are more biologically aggressive tumors than standard NFAs. The progression-free survival duration of patients with SCAs is only about half that of patients with other NFAs. Therefore, close neuroimaging and clinical follow-up are warranted in patients with SCAs, and residual disease should be considered for early postoperative adjuvant radiosurgery, particularly in younger patients.

Bilateral arachnoid cyst-associated subdural fluid collections in an infant following TBI.

INTRODUCTION: arachnoid cyst-associated subdural fluid collections have been documented in children and adults following traumatic brain injury (TBI). However, this phenomenon has not been previously demonstrated in infants less than 12 months of age. We present a case of an infant with bilateral arachnoid cyst-associated subdural fluid collections identified after TBI. CASE PRESENTATION: a 9-month-old female infant with profound macrocephaly presented to medical care with altered mental status following a witnessed fall down steps while unsecured in a stroller. Neuroimaging revealed bilateral subdural fluid collections, in addition to a hyperdense subdural hematoma, that raised concern for abusive head trauma (AHT) among the pediatric inpatient team and the hospital's Suspected Child Abuse and Neglect (SCAN) Team was consulted. After excluding occult abusive injuries as well as testing for underlying medical conditions, the infant's bilateral subdural fluid collections were attributed to rupture of a pre-existing left middle cranial fossa arachnoid cyst with evidence of prior macrocephaly. CONCLUSION: In infants and toddlers, the identification of subdural fluid collections on neuroimaging warrants inclusion of AHT in the differential diagnosis. However, in infants with a history of congenital macrocephaly, and an otherwise negative AHT workup, an accidental mechanism for the formation of subdural collections should be considered, especially when co-occurring with an arachnoid cyst.

Safety and Effectiveness of the Direct Endoscopic Endonasal Approach for Primary Sellar Pathology: A Contemporary Case Series of More Than 400 Patients.

BACKGROUND: The direct endoscopic endonasal approach (EEA) has become the primary technique used for resection of sellar pathology, meriting investigation into the risk factors for complications and predictors of postoperative outcomes after direct EEA. METHODS: We retrospectively analyzed the patient and tumor characteristics from 404 patients who had undergone direct EEA for sellar pathology at the USC Pituitary Center from September 2011 to December 2019. RESULTS: Of the 404 pathologic entities included, 349 (86%) were pituitary adenomas (PAs), 29 (7%) were Rathke cleft cysts, and 26 (6%) were other sellar lesions. The mean lesion diameter was 2.3 cm, with 34 microadenomas (10%) and 315 macroadenomas (90%). Cavernous sinus invasion was present in 39% of the PAs. No patient died. The surgical complications included internal carotid artery injury without neurological sequelae (0.2%), vision loss (0.7%), meningitis (0.7%), cerebrospinal fluid leak (4%), epistaxis (4%), sinusitis (1%), transient cranial nerve paresis (0.5%), and postoperative abscess (0.25%). New hypopituitarism developed in 3%. Gross total resection was achieved in 208 PA cases (58%). Clinical improvement of headaches and visual deficits were reported for 67% and 76% of cases, respectively. Hormonal remission was achieved in 82% of patients with functional PAs. The median hospital stay was 2 days, with 34 patients (8%) readmitted within 30 days and 10 (3%) undergoing early reoperation. Disease recurrence or progression developed in 10% and was less likely in the case of gross total resection and apoplexy. CONCLUSION: In the present, large, consecutive, mostly single-surgeon series, the patients experienced clinical improvement in most preoperative symptoms and had low rates of perioperative morbidity. We have demonstrated that direct EEA can be efficiently, safely, and successfully performed by a neurosurgical team.

Repeatability of tumor perfusion kinetics from dynamic contrast-enhanced MRI in glioblastoma.

BACKGROUND: Dynamic contrast-enhanced MRI (DCE-MRI) parameters have been shown to be biomarkers for treatment response in glioblastoma (GBM). However, variations in analysis and measurement methodology complicate determination of biological changes measured via DCE. The aim of this study is to quantify DCE-MRI variations attributable to analysis methodology and image quality in GBM patients. METHODS: The Extended Tofts model (eTM) and Leaky Tracer Kinetic Model (LTKM), with manually and automatically segmented vascular input functions (VIFs), were used to calculate perfusion kinetic parameters from 29 GBM patients with double-baseline DCE-MRI data. DCE-MRI images were acquired 2-5 days apart with no change in treatment. Repeatability of kinetic parameters was quantified with Bland-Altman and percent repeatability coefficient (%RC) analysis. RESULTS: The perfusion parameter with the least RC was the plasma volume fraction (v p ), with a %RC of 53%. The extra-cellular extra-vascular volume fraction (v e ) %RC was 82% and 81%, for extended Tofts-Kety Model (eTM) and LTKM respectively. The %RC of the volume transfer rate constant (K trans ) was 72% for the eTM, and 82% for the LTKM, respectively. Using an automatic VIF resulted in smaller %RCs for all model parameters, as compared to manual VIF. CONCLUSIONS: As much as 72% change in K trans (eTM, autoVIF) can be attributable to non-biological changes in the 2-5 days between double-baseline imaging. Poor K trans repeatability may result from inferior temporal resolution and short image acquisition time. This variation suggests DCE-MRI repeatability studies should be performed institutionally, using an automatic VIF method and following quantitative imaging biomarkers alliance guidelines.

Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly.

OBJECTIVE: Acromegaly is a disease of acral enlargement and elevated serum levels of insulin-like growth factor-1 (IGF-1) and growth hormone (GH), usually caused by a pituitary adenoma. A lack of consensus on factors that reliably predict outcomes in acromegalic patients following endoscopic endonasal transsphenoidal surgery (EETS) warrants additional investigation. METHODS: The authors identified 52 patients with acromegaly who underwent an endoscopic endonasal approach (EEA) for resection of a GH-secreting pituitary adenoma. Preoperative and postoperative tumor and endocrinological characteristics such as tumor size, invasiveness, and GH/IGF-1 levels were evaluated as potential indicators of postoperative hormonal remission. Endocrinological remission was defined as postoperative IGF-1 levels at or below the age- and sex-normalized values. RESULTS: The 52 patients had a mean age of 50.7 ± 13.4 years and a mean follow-up duration of 24.4 ± 19.1 months. Ten patients (19%) had microadenomas and 42 (81%) had macroadenomas. Five patients (9.6%) had giant adenomas. Forty-four tumors (85%) had extrasellar extension, with 40 (77%) exhibiting infrasellar invasion, 18 (35%) extending above the sella, and 7 (13%) invading the cavernous sinuses. Thirty-six patients (69%) underwent gross-total resection (GTR; mean maximal tumor diameter 1.47 cm), and 16 (31%) underwent subtotal resection (STR; mean maximal tumor diameter 2.74 cm). Invasive tumors were significantly larger, and Knosp scores were negatively correlated with GTR. Thirty-eight patients (73%) achieved hormonal remission after EEA resection alone, which increased to 87% with adjunctive medical therapy. Ninety percent of patients with microadenomas and 86% of patients with macroadenomas achieved hormonal remission. Preoperative IGF-1 and postoperative day 1 (POD1) GH levels were inversely correlated with hormonal remission. Postoperative CSF leakage occurred in 2 patients (4%), and none experienced vision loss, death, or injury to internal carotid arteries or cranial nerves. CONCLUSIONS: Endoscopic transsphenoidal resection of GH-secreting pituitary adenomas is a safe and highly effective treatment for achieving hormonal remission and tumor control in up to 87% of patients with acromegaly when combined with postoperative medical therapy. Patients with lower preoperative IGF-1 and POD1 GH levels, with less invasive pituitary adenomas, and who undergo GTR are more likely to achieve postoperative biochemical remission.

Development and clinical validation of a grading system for pituitary adenoma consistency.

OBJECTIVE: Pituitary adenoma (PA) consistency, or texture, is an important intraoperative characteristic that may dictate operative dissection techniques and/or instruments used for tumor removal during endoscopic endonasal approaches (EEAs). The impact of PA consistency on surgical outcomes has yet to be elucidated. METHODS: The authors developed an objective 5-point grading scale for PA consistency based on intraoperative characteristics, including ease of tumor debulking, manipulation, and instrument selection, ranging from cystic/hemorrhagic tumors (grade 1) to calcified tumors (grade 5). The proposed grading system was prospectively assessed in 306 consecutive patients who underwent an EEA for PAs, and who were subsequently analyzed for associations with surgical outcomes, including extent of resection (EOR) and complication profiles. RESULTS: Institutional database review identified 306 patients who underwent intraoperative assessment of PA consistency, of which 96% were macroadenomas, 70% had suprasellar extension, and 44% had cavernous sinus invasion (CSI). There were 214 (69.9%) nonfunctional PAs and 92 functional PAs (31.1%). Distribution of scores included 15 grade 1 tumors (4.9%), 112 grade 2 tumors (36.6%), 125 grade 3 tumors (40.8%), 52 grade 4 tumors (17%), and 2 grade 5 tumors (0.7%). Compared to grade 1/2 and grade 3 PAs, grade 4/5 PAs were significantly larger (22.5 vs 26.6 vs 27.4 mm, p < 0.01), more likely to exhibit CSI (39% vs 42% vs 59%, p < 0.05), and trended toward nonfunctionality (67% vs 68% vs 82%, p = 0.086). Although there was no association between PA consistency and preoperative headaches or visual dysfunction, grade 4/5 PAs trended toward preoperative (p = 0.058) and postoperative panhypopituitarism (p = 0.066). Patients with preoperative visual dysfunction experienced greater improvement if they had a grade 1/2 PA (p < 0.05). Intraoperative CSF leaks were noted in 32% of cases and were more common with higher-consistency-grade tumors (p = 0.048), although this difference did not translate to postoperative CSF leaks. Gross-total resection (%) was more likely with lower PA consistency score as follows: grade 1/2 (60%), grade 3 (50%), grade 4/5 (44%; p = 0.045). Extracapsular techniques were almost exclusively performed in grade 4/5 PAs. Assignment of scores showed low variance and high reproducibility, with an intraclass correlation coefficient of 0.905 (95% CI 0.815-0.958), indicating excellent interrater reliability. CONCLUSIONS: These findings demonstrate clinical validity of the proposed intraoperative grading scale with respect to PA subtype, neuroimaging features, EOR, and endocrine complications. Future studies will assess the relation of PA consistency to preoperative MRI findings to accurately predict consistency, thereby allowing the surgeon to tailor the exposure and prepare for varying resection strategies.

Ultra-high field magnetic resonance imaging for localization of corticotropin-secreting pituitary adenomas.

Cushing's disease manifests as symptoms of glucocorticoid excess secondary to the increased secretion of corticotropin by a corticotroph adenoma in the pituitary gland. Unfortunately, magnetic resonance imaging (MRI) performed at conventional clinical field strengths of 1.5 or 3 Tesla has limited sensitivity for the detection of these pituitary tumors, and radiologic uncertainty often necessitates more invasive workup to confirm diagnosis and guide resection. It has been postulated that higher static magnetic field strengths may increase the adenoma detection rate and thus the utility of MRI for this clinical application. In this report, we describe our initial experience using ultra-high field 7 Tesla (7 T) MRI in patients with suspected Cushing's disease and negative or equivocal imaging at conventional field strengths. We performed contrast-enhanced 7 T pituitary MRI in 10 patients with up to three different T1-weighted sequences and correlated the imaging abnormalities identified with results of histologic evaluation in patients who subsequently underwent resection. We found that 7 T MRI enabled the identification of previously undetected areas of focal pituitary hypoenhancement in 9 patients (90%), of which 7 corresponded histologically to corticotroph adenomas. These early findings suggest an important adjunctive role for ultra-high field MR imaging in the noninvasive clinical workup of suspected Cushing's disease.