Elevated EMMPRIN Serum Levels Indicate Plaque Vulnerability in Patients With Asymptomatic High Grade Carotid Stenosis.

OBJECTIVE: Carotid atherosclerosis is an important cause of cerebral ischaemic stroke. Sonographic plaque characteristics are inappropriate for exact prediction of possible future ischaemic events. Additional markers are needed to predict the clinical outcome in high grade carotid stenosis. This study aimed to test extracellular matrix metalloproteinase inducer (EMMPRIN), due to its involvement in plaque formation and destabilisation, as a potential marker of high risk vulnerable plaques. METHODS: EMMPRIN was analysed in pre-operative serum samples from patients with symptomatic and asymptomatic carotid artery stenosis by a specific ELISA. Pre-operative duplex sonography classified the atherosclerotic plaque due to echogenicity. Histopathological analysis of vulnerable and non-vulnerable plaques was based on the American Heart Association (AHA) classification. RESULTS: The study included 265 patients undergoing carotid endarterectomy: 90 (m:f, 69:21) patients with symptomatic and 175 (m:f, 118:57) with asymptomatic disease. Analysis of circulating EMMPRIN revealed significantly higher levels in patients with echolucent plaques (4 480; IQR 3 745, 6 144 pg/mL) compared with echogenic plaques (4 159; IQR 3 418, 5 402 pg/mL; p = .025). Asymptomatic patients with vulnerable plaques had significantly higher levels of EMMPRIN (4 875; IQR 3 850, 7 016 pg/mL) compared with non-vulnerable plaques (4 109; IQR 3 433, 5 402 pg/mL; p < .001). In logistic regression analysis, duplex sonography combined with age, gender, and clinical risk factors predicted vulnerable plaques in asymptomatic patients with an AUC of 0.71 (95% CI 0.61 - 0.80). EMMPRIN significantly improved the AUC in asymptomatic patients (AUC 0.79; 95% CI 0.71 - 0.87; p = .014). CONCLUSION: Patients with high risk plaques according to ultrasound and histopathological characteristics demonstrated increased serum EMMPRIN levels. EMMPRIN on top of clinical risk factors, including age, gender, and duplex sonography may be used for pre-operative risk stratification in asymptomatic patients.

Neural network modeling for prediction of recurrence, progression, and hormonal non-remission in patients following resection of functional pituitary adenomas.

PURPOSE: Functional pituitary adenomas (FPAs) cause severe neuro-endocrinopathies including Cushing's disease (CD) and acromegaly. While many are effectively cured following FPA resection, some encounter disease recurrence/progression or hormonal non-remission requiring adjuvant treatment. Identification of risk factors for suboptimal postoperative outcomes may guide initiation of adjuvant multimodal therapies. METHODS: Patients undergoing endonasal transsphenoidal resection for CD, acromegaly, and mammosomatotroph adenomas between 1992 and 2019 were identified. Good outcomes were defined as hormonal remission without imaging/biochemical evidence of disease recurrence/progression, while suboptimal outcomes were defined as hormonal non-remission or MRI evidence of recurrence/progression despite adjuvant treatment. Multivariate regression modeling and multilayered neural networks (NN) were implemented. The training sets randomly sampled 60% of all FPA patients, and validation/testing sets were 20% samples each. RESULTS: 348 patients with mean age of 41.7 years were identified. Eighty-one patients (23.3%) reported suboptimal outcomes. Variables predictive of suboptimal outcomes included: Requirement for additional surgery in patients who previously had surgery and continue to have functionally active tumor (p = 0.0069; OR = 1.51, 95%CI 1.12-2.04), Preoperative visual deficit not improved after surgery (p = 0.0033; OR = 1.12, 95%CI 1.04-1.20), Transient diabetes insipidus (p = 0.013; OR = 1.27, 95%CI 1.05-1.52), Higher MIB-1/Ki-67 labeling index (p = 0.038; OR = 1.08, 95%CI 1.01-1.15), and preoperative low cortisol axis (p = 0.040; OR = 2.72, 95%CI 1.06-7.01). The NN had overall accuracy of 87.1%, sensitivity of 89.5%, specificity of 76.9%, positive predictive value of 94.4%, and negative predictive value of 62.5%. NNs for all FPAs were more robust than for CD or acromegaly/mammosomatotroph alone. CONCLUSION: We demonstrate capability of predicting suboptimal postoperative outcomes with high accuracy. NNs may aid in stratifying patients for risk of suboptimal outcomes, thereby guiding implementation of adjuvant treatment in high-risk patients.

Optimizing MR imaging for intraoperative image guidance in sellar pathologies.

PURPOSE: With the advancement of extended endonasal approaches, the ability to surgically reach parasellar tumor extensions increase. The aim of the study was to propose an optimized imaging protocol for surgical guidance in the cavernous sinus (CS) for proper visualization structures at risk. METHODS: Prospective case control analysis of 20 consecutive pituitary adenoma patients scheduled for endoscopic transnasal surgery. Assessment of the capability of three different MRI sequences (MPRAGE, VIBE, CISS) by 4 investigators to correctly visualize sellar and parasellar structures. Invasiveness and position of the normal pituitary gland were compared with the intraoperative findings. RESULTS: The consensus between the 4 examiners to achieve the same results for all modalities was 40% for MPRAGE, 70% for VIBE and 60% for CISS sequences (p = 0.155). A consensus of Knosp Grade per patient was 80% for MPRAGE, 100% for VIBE and 90% for CISS (overall kappa 0.60). A higher Knosp Grade was found in MPRAGE sequences compared to the other sequences. Intraoperative status of invasiveness was correctly identified in 12/20 (60%) with MPRAGE, 19/20 (95%) with VIBE and 11/20 (55%) with CISS sequences. The position of the normal pituitary gland was most frequent evaluable in 15/20 (75%) and correctly identified in 12/15 (80%) cases. CONCLUSION: Our data showed that VIBE sequences obtain the highest degree of consensus with intraoperative findings of invasiveness and position of the normal pituitary gland. VIBE sequences, due to their high spatial resolution and at the same time fast image acquisition could provide improved imaging for neuronavigation.

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.

Challenging the osseous component of sphenoorbital meningiomas.

BACKGROUND: Intraosseous growth is a unique feature of sphenoorbital meningiomas (SOM). Its close relation to neurovascular structures limits complete surgical resection and possibly contributes to the high recurrence rate. OBJECTIVE: To evaluate the growth behavior of intraosseous remnants and develop a protocol for precise intraoperative visualization of intraosseous SOM. METHODS: We included 31 patients operated for SOM from 2004 to 2017. The growth velocity of the intraosseous tumor component was volumetrically calculated in 20 cases. To improve accuracy of image guidance, we implemented a specialized bone surface-based registration algorithm. For intraoperative bone visualization, we included CT in multimodality continuous image guidance in 23 patients. The extent of resection (EOR) was compared with a standard MR-only navigation group (n = 8). RESULTS: In 11/20 cases (55%), a progressive regrowth of the intraosseous SOM remnant was noted during a mean follow-up of 52 months (range 20-132 months). We observed a mean increase of 6.2 cm3 (range 0.2-23.7 cm3) per patient and side during the follow-up period. Bone surface-based registration was significantly more accurate than skin surface-based registration (mean 0.7 ± 0.4 mm and 1.9 ± 0.7 mm, p < 0.001). The EOR of the intraosseous component was significantly higher using CT + MRI navigation compared with controls (96% vs. 81%, p = 0.044). CONCLUSION: Quantitative assessment of the biological behavior of intraosseous remnants revealed a continuous slow growth rate independent of the soft tumor component of more than half of SOM. According to our data, application of a multimodal image guidance provided high accuracy and significantly increased the resection rate of the intraosseous component of SOM.

Line Scan Raman Microspectroscopy for Label-Free Diagnosis of Human Pituitary Biopsies.

Pituitary adenomas are neoplasia of the anterior pituitary gland and can be subdivided into hormone-producing tumors (lactotroph, corticotroph, gonadotroph, somatotroph, thyreotroph or plurihormonal) and hormone-inactive tumors (silent or null cell adenomas) based on their hormonal status. We therefore developed a line scan Raman microspectroscopy (LSRM) system to detect, discriminate and hyperspectrally visualize pituitary gland from pituitary adenomas based on molecular differences. By applying principal component analysis followed by a k-nearest neighbor algorithm, specific hormone states were identified and a clear discrimination between pituitary gland and various adenoma subtypes was achieved. The classifier yielded an accuracy of 95% for gland tissue and 84-99% for adenoma subtypes. With an overall accuracy of 92%, our LSRM system has proven its potential to differentiate pituitary gland from pituitary adenomas. LSRM images based on the presence of specific Raman bands were created, and such images provided additional insight into the spatial distribution of particular molecular compounds. Pathological states could be molecularly differentiated and characterized with texture analysis evaluating Grey Level Cooccurrence Matrices for each LSRM image, as well as correlation coefficients between LSRM images.

MGMT assessment in pituitary adenomas: comparison of different immunohistochemistry fixation chemicals.

PURPOSE: Despite the established role of O6-methyl-guanine-DNA methyltransferase (MGMT) as a marker for temozolomide response, consensus of the most reliable method to assess MGMT expression in pituitary adenomas is still missing. Currently, immunohistochemistry (IHC) assessment of formaldehyde fixed tissue samples is most widely used in a semiquantitative description. As formaldehyde fails to completely preserve nucleic acids, RCL2, an alcohol-based formaldehyde-free fixative, has been proposed as a more reliable alternative in terms of cell stability. Furthermore, as the current method of IHC is semiquantitative and observer-dependent, pyrosequencing, an objective tool to evaluate the methylation status of the MGMT promoter, has emerged as a reliable and accurate alternative. The aim of this study was to validate the current IHC method for assessment of MGMT protein expression in pituitary adenomas. METHODS: The tissue samples of 8 macroadenomas with positive IHC MGMT expression (> 50%) were investigated: first, we compared the time dependent stability of MGMT protein expression after pituitary adenoma removal between formaldehyde vs. RCL2. Then, we compared positive IHC MGMT expression with methylated promoter status using pyrosequencing. RESULTS: In the first 12 h after adenoma removal, tissue samples remained MGMT positive in significantly more samples when fixated with formaldehyde than with RCL2, respectively (96 vs. 81%, p = 0.025). CONCLUSION: Our data confirm that the current method using formaldehyde tissue fixation and IHC reveals stable and reliable results of MGMT assessment in pituitary adenomas.

MGMT and MSH6 immunoexpression for functioning pituitary macroadenomas.

PURPOSE: Knowledge of biological behavior is crucial for clinical management of functioning pituitary macroadenomas. For recurrent cases unresponsive to standard treatment, temozolomide (TMZ) has been used as a therapeutic alternative. MGMT (O6-methyl-guanine-DNA methyltransferase) and MSH6 (mutS homolog 6) immunoexpression have been linked to the response to TMZ treatment and MGMT immunoexpression has been additionally linked to early recurrence of non-functioning pituitary adenomas. The aim of this study was to assess the prognostic value of MGMT and MSH6 immunoexpression for aggressive functioning pituitary adenomas. METHODS: The study cohort comprised a single center series of 76 patients who underwent an operation for functioning pituitary macroadenoma. We retrospectively compared 38 patients with postoperative persistent or recurrent disease with another set of 38 patients who were in endocrine remission. RESULTS: Low-to-moderate MGMT immunoexpression (<50%) was significantly more frequent in the group with persistent/recurrent disease than in cases of endocrine remission (66 vs. 21%, p < 0.001). Furthermore, adenomas with low-to-moderate MGMT immunoexpression were significantly more often recurrent (76 vs. 30%, p < 0.001) and invasive (64 vs. 28%, p = 0.002). CONCLUSION: In our series, low-to-moderate MGMT immunoexpression was the only marker that significantly correlated with surgical invasiveness and recurrence in functioning pituitary macroadenomas. Therefore, in the future, MGMT status may be considered an additional marker for understanding the biological behavior of pituitary adenomas.

Multi-Dynamic-Multi-Echo-based MRI for the Pre-Surgical Determination of Sellar Tumor Consistency: a Quantitative Approach for Predicting Lesion Resectability.

PURPOSE: Pre-surgical information about tumor consistency could facilitate neurosurgical planning. This study used multi-dynamic-multi-echo (MDME)-based relaxometry for the quantitative determination of pituitary tumor consistency, with the aim of predicting lesion resectability. METHODS: Seventy-two patients with suspected pituitary adenomas, who underwent preoperative 3 T MRI between January 2020 and January 2022, were included in this prospective study. Lesion-specific T1-/T2-relaxation times (T1R/T2R) and proton density (PD) metrics were determined. During surgery, data about tumor resectability were collected. A Receiver Operating Characteristic (ROC) curve analysis was performed to investigate the diagnostic performance (sensitivity/specificity) for discriminating between easy- and hard-to-remove by aspiration (eRAsp and hRAsp) lesions. A Mann-Whitney-U-test was done for group comparison. RESULTS: A total of 65 participants (mean age, 54 years ± 15, 33 women) were enrolled in the quantitative analysis. Twenty-four lesions were classified as hRAsp, while 41 lesions were assessed as eRAsp. There were significant differences in T1R (hRAsp: 1221.0 ms ± 211.9; eRAsp: 1500.2 ms ±â€¯496.4; p = 0.003) and T2R (hRAsp: 88.8 ms ± 14.5; eRAsp: 137.2 ms ± 166.6; p = 0.03) between both groups. The ROC analysis revealed an area under the curve of 0.72 (95% CI: 0.60-0.85) at p = 0.003 for T1R (cutoff value: 1248 ms; sensitivity/specificity: 78%/58%) and 0.66 (95% CI: 0.53-0.79) at p = 0.03 for T2R (cutoff value: 110 ms; sensitivity/specificity: 39%/96%). CONCLUSION: MDME-based relaxometry enables a non-invasive, pre-surgical characterization of lesion consistency and, therefore, provides a modality with which to predict tumor resectability.

Does High-Definition 3-Dimensional Imaging Improve Orientation During Endoscopic Transsphenoidal Surgery? A Prospective Trial.

BACKGROUND: Endoscopy has evolved as the standard visualization tool for endonasal transsphenoidal resection of sellar lesions. The most widely used 2-dimensional (2D) endoscopes harbor the problem of limited depth perception. Therefore, 3-dimensional (3D) endoscopes have been developed to enable depth perception through a stereoscopic view. OBJECTIVE: To evaluate the impact of high-definition (HD) 2D vs 3D HD endoscopes on spatial orientation within the sphenoid sinus. METHODS: In this prospective single-center study, 21 patients have been investigated (2021-2022). Eleven standardized anatomic landmarks, which were preoperatively defined on neuronavigation imaging, were intraoperatively targeted with a navigation probe using either 2D HD or 3D HD endoscopes for visualization. RESULTS: Overall, 3D HD endoscopes provided a statistically significant higher accuracy of identification of sphenoid sinus landmarks (median deviation: 5.2 mm vs 4.2 mm, P < .001). In detail: tuberculum sellae (3.0 mm vs 4.3 mm, P = .047), most anterior point of sella (3.3 mm vs 4.8 mm, P = .049), and clivus indentation (3.8 mm vs 5.3 mm, P = .035). Anatomic variations such as a complex sphenoid sinus configuration had no influence on identifying sphenoid sinus landmarks. CONCLUSION: According to our data, stereoscopic 3D HD endoscopy enhances intraoperative orientation by improved depth perception within the sphenoid sinus. This may add to the safety of endoscopic skull base procedures, especially in extended approaches and cases with distorted anatomy.

Bilateral inferior petrosal sinus sampling with human CRH stimulation in ACTH-dependent Cushing's syndrome: results from a retrospective multicenter study.

OBJECTIVE: Bilateral inferior petrosal sinus sampling (BIPSS) is regarded as gold standard to differentiate between Cushing´s disease (CD) and ectopic Cushing's syndrome (ECS). However, published data e.g. on the diagnostic value of additional prolactin analysis is controversial. Thus, we evaluated the diagnostic performance of BIPSS with and without prolactin in a multicenter study. DESIGN AND METHODS: Retrospective study in 5 European reference centers. Patients with overt adrenocorticotropin (ACTH)-dependent Cushing's syndrome at the time of BIPSS with human corticotropin-releasing hormone stimulation were eligible. Cut-offs for the inferior petrosal sinus (IPS) to peripheral (P) ACTH ratio and the normalized ACTH:prolactin IPS:P ratio were calculated via receiver operator characteristics analyses (reference: CD). RESULTS: 156 patients with BIPSS were identified. Of these, 120 patients (92 (77%) females; 106 (88%) CD, 14 (12%) ECS) had either histopathologically confirmed tumors or biochemical remission and/or adrenal insufficiency after surgery; only this subgroup was analyzed by ROC analysis. The optimal cut-offs for the ACTH IPS:P ratio were ≥1.9 at baseline (sensitivity 82.1% (95%CI 73.2-88.6), specificity 85.7% (95%CI 56.2-97.5), AUC 0.86) and ≥2.1 at 5 minutes post-CRH (sensitivity 91.3% (95%CI 83.6-95.7), specificity 92.9%(95%CI 64.1-99.6), AUC 0.96). A subgroup underwent additional prolactin analysis. An optimal cut-off of ≥1.4 was calculated for the normalized ACTH:prolactin IPS:P ratio (sensitivity 96.0% (95%CI 77.7-99.9), specificity 100% (95%CI 56.1-100), AUC 0.99). CONCLUSION: Our study confirms the high accuracy of BIPSS in the differential diagnosis of ACTH-dependent Cushing's syndrome and suggests that the simultaneous measurement of prolactin might further improve the diagnostic performance of this test.

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.

A Patient-Specific Reference Tracker for Noninvasive Electromagnetic Navigation of Endoscopic Skull Base Surgery.

BACKGROUND: Owing to the possibility of nonrigid head fixation, electromagnetic navigation (EM) is a mainstay for endoscopic skull base surgery. The currently available dynamic reference trackers (RTs) are invasive or inaccurate. OBJECTIVE: To investigate the feasibility and stability of this innovative oral tracker (OT), which is adhesive to the hard palate in comparison with a commercially available skin adhesive tracker (ST). METHODS: A prospective series of 31 patients with intrasellar lesions who underwent surgery between 2019 and 2021 using a pure endoscopic transsphenoidal approach were evaluated. A patient-specific palatal mold was designed from preoperative computed tomography data. The OT was cast using a biocompatible algin with an integrated EM tracker assembly. In comparison with a skull-mounted RT, which served as a gold standard, the deviations of OT vs those of the ST with the RT were continuously assessed. RESULTS: The OT showed significantly lower deviations from the RT than the ST during the surgical steps: start of endoscopic surgery (OT vs ST: 0.62 mm, IQR 0.36-0.89 vs 1.65 mm, IQR 1.35-2.32, P < .001), drilling phase (OT vs ST: 0.81 mm, IQR 0.51-1.32 vs 1.89 mm, IQR 1.6-2.74, P < .001), and end of endoscopic surgery (OT vs ST: 1.1 mm, IQR 0.68-1.64 vs 1.9 mm, IQR 1.6-2.72, P < .001). CONCLUSION: The OT showed significantly higher intraoperative stability than the ST. Therefore, this noninvasive and patient-specific tool could be used to achieve accurate EM guidance during endoscopic skull base surgeries.

Diagnostic criteria of small sellar lesions with hyperprolactinemia: Prolactinoma or else.

Objective: To evaluate the combined predictive value of MRI criteria with the prolactin-volume-ratio (PVR) to differentiate prolactinoma from non-prolactinoma, in small sellar lesions with hyperprolactinemia. Methods: Retrospective analysis of 55 patients with sellar lesions of ≤15 mm diameter on MRI and hyperprolactinemia of ≤150 ng/mL, surgically treated between 2003 and 2020 at the Medical University of Vienna, with a conclusive histopathological report. Serum prolactin levels, extent of pituitary stalk deviation, size and volume of the lesion were assessed. The PVR was calculated by dividing the preoperative prolactin level by tumor volume. Results: Our study population consisted of 39 patients (71%) with a prolactin-producing pituitary adenoma (group A), while 16 patients (29%) had another type of sellar lesion (group B). Patients in group A were significantly younger (p=0.012), had significantly higher prolactin levels at diagnosis (p<0.001) as well as smaller tumor volume (p=0.036) and lower degree of pituitary stalk deviation (p=0.009). The median PVR was significantly higher in group A (243 ng/mL per cm3) than in group B (83 ng/mL per cm3; p=0.002). Furthermore, the regression operating characteristics analysis revealed a PVR >100 ng/mL per cm3 to be predictive for distinguishing prolactin-producing lesions from other small sellar lesions. Conclusion: In patients with small sellar lesions, Prolactin-Volume-Ratios >100 represents a possible predictive marker for the diagnosis of prolactin-producing pituitary adenomas.

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.

Demographic-Dependent Risk of Developing Severe Novel Psychiatric Disorders after Concussion.

Current guidelines for patients experiencing a concussion or mild traumatic brain injury (mTBI) often focus on conservative care and observation. However, mTBI may increase the risk of severe novel psychiatric disorders (NPDs) within 180 days, and long-term management of mTBI should include psychiatric evaluation in patient populations. Retrospective cohort analysis was conducted using 8 years of the Nationwide Readmission Database. All individuals who were admitted for concussion and were readmitted within 180 days were queried. This cohort was then subdivided based on age, sex, and whether they experienced loss of consciousness (LOC) to control for demographic-dependent confounding. A binary decision tree provided recommendations for patients who may be at risk of developing severe NPDs. Analysis included 12,080 patients who experienced concussion. Males and females with LOC had higher rates of depression in all age quartiles within 180 days (p < 0.05). Young females with LOC had increased rates of suicidal ideation (p < 0.01), and those >25 years of age had increased rates of anxiety (p < 0.005). Adult males with LOC had increased rates of suicidal ideation (p < 0.002) and males >75 years of age had increased rates of anxiety at readmission (p < 0.05). Males without LOC had increased rates of depression (p < 0.005), with men in the second quartile also at higher risk of developing anxiety (p < 0.05). Females without LOC showed the fewest number of NPDs at readmission. Concussion may be associated with increased rates of NPDs in the first 6 months following discharge. We use these data to develop recommendations for psychiatric screening of patients with mTBI.

Development of a miniaturized robotic guidance device for stereotactic neurosurgery.

OBJECTIVE: Consistently high accuracy and a straightforward use of stereotactic guidance systems are crucial for precise stereotactic targeting and a short procedural duration. Although robotic guidance systems are widely used, currently available systems do not fully meet the requirements for a stereotactic guidance system that combines the advantages of frameless surgery and robotic technology. The authors developed and optimized a small-scale yet highly accurate guidance system that can be seamlessly integrated into an existing operating room (OR) setup due to its design. The aim of this clinical study is to outline the development of this miniature robotic guidance system and present the authors' clinical experience. METHODS: After extensive preclinical testing of the robotic stereotactic guidance system, adaptations were implemented for robot fixation, software usability, navigation integration, and end-effector application. Development of the robotic system was then advanced in a clinical series of 150 patients between 2013 and 2019, including 111 needle biopsies, 13 catheter placements, and 26 stereoelectroencephalography (SEEG) electrode placements. During the clinical trial, constant modifications were implemented to meet the setup requirements, technical specifications, and workflow for each indication. For each application, specific setup, workflow, and median procedural accuracy were evaluated. RESULTS: Application of the miniature robotic system was feasible in 149 of 150 cases. The setup in each procedure was successfully implemented without adding significant OR time. The workflow was seamlessly integrated into the preexisting procedure. In the course of the study, procedural accuracy was improved. For the biopsy procedure, the real target error (RTE) was reduced from a mean of 1.8 ± 1.03 mm to 1.6 ± 0.82 mm at entry (p = 0.05), and from 1.7 ± 1.12 mm to 1.6 ± 0.72 mm at target (p = 0.04). For the SEEG procedures, the RTE was reduced from a mean of 1.43 ± 0.78 mm in the first half of the procedures to 1.12 ± 0.52 mm (p = 0.002) at entry in the second half, and from 1.82 ± 1.13 mm to 1.57 ± 0.98 mm (p = 0.069) at target, respectively. No healing complications or infections were observed in any case. CONCLUSIONS: The miniature robotic guidance device was able to prove its versatility and seamless integration into preexisting workflow by successful application in 149 stereotactic procedures. According to these data, the robot could significantly improve accuracy without adding time expenditure.

Prevalence Rate of Coexisting Rathke Cleft Cysts and Pineal Cysts: A Multicenter Cross-Sectional Study.

BACKGROUND: Rathke cleft cysts (RCCs) are benign sellar lesions originating from remnants of primitive ectoderm. They have not been previously linked to other cystic lesions, such as pineal cysts (PCs). Our objective was to perform a multicenter cross-sectional neuroimaging study to examine prevalence rates of coexisting RCC and PC. METHODS: We retrospectively queried prospectively maintained, institutional review board-approved, databases from the authors' centers. All patients undergoing transsphenoidal surgery for RCC between the years of 2011 and 2020 were included for analysis. Preoperative magnetic resonance imaging was reviewed to identify the coexistence of a PC. Patient demographics and neuroimaging characteristics were recorded. A control cohort comprised of 100 age- and sex-matched patients with nonfunctional pituitary adenoma (NFPA) who also underwent surgical intervention was utilized. RESULTS: Eighty-four patients with RCC were identified for analysis. A coexistent PC was identified in 40.5% (n = 34) of patients with RCC compared with 14.3% (n = 12) in the NFPA cohort (P < 0.001). There was no significant difference in PC size between patients with RCC and PA (8 vs. 8.8 mm, respectively; P = 0.77). Although the majority (85.7%; n = 72) of the RCC cohort were female patients, there was no sex predominance with respect to coexisting PC in either the RCC or PA cohort. CONCLUSIONS: This is the first study to report an increased prevalence of coexisting PC and RCC, possibly because of an embryologic link or other propensity for intracranial cyst formation. Additional studies in more generalizable populations can further explore the relation between RCC and PC, or other cyst formation.