The role of induction chemotherapy for orbital invasion in sinonasal malignancies: A systematic review.

BACKGROUND: Sinonasal malignancies (SNMs) frequently present with orbital invasion. Orbital exenteration (OE) can lead to significant morbidity. Induction chemotherapy (IC) is a promising treatment alternative that may allow for orbit preserving (OP) treatments without compromising patient survival. This systematic review was conducted to synthesize the published data on SNM patients with orbital invasion who underwent IC, including tumor response, orbital outcomes, and survival. METHODS: The study protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Databases Embase, Cochrane, Medline, and Scopus, from inception to July 17, 2023, were searched. RESULTS: Nineteen studies were included, encompassing 305 SNM patients with orbital invasion treated with IC. Fourteen studies reported an overall IC response rate (positive response defined as complete or partial tumor volume reduction) of 77.2%. Among included studies, OE rates after IC ranged from 0 to 40%. Three studies reported a high rate of posttreatment functional orbital preservation (89.8-96.0%). Five studies specifically reported that 62.5% (60 out of 96) of patients were downgraded from planned OE to OP treatment following IC. Three studies reported a significant overall survival (OS) improvement in IC responders versus IC nonresponders. Following IC, 5-year OS ranged from 44.2 to 55.5%. Patients with olfactory neuroblastoma demonstrated the highest IC response rate and lowest OE rate (100 and 0%, respectively) versus those with sinonasal undifferentiated carcinomas (68.4 and 0%) or squamous cell carcinomas (76.7 and 16%). CONCLUSIONS: For select patients, IC may allow for OP in locally advanced SNMs with orbital involvement.

The utility of inflammatory biomarkers in predicting overall survival and recurrence in skull base chordoma.

OBJECTIVE: Numerous studies have investigated the impact of inflammatory factors in cancer, yet few attempts have been made to investigate these markers in skull base chordoma (SBC). Inflammatory values including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) can serve as prognostic markers in various cancers. This study aimed to determine whether these inflammatory factors influence overall survival (OS) or progression-free survival (PFS) in patients with primary SBC. METHODS: The electronic medical records of patients with primary SBC who underwent resection from 2001 to 2020 were retrospectively reviewed for the associations of sex, age at diagnosis, preoperative steroid use, tumor volume, extent of resection, adjuvant radiation after surgery, tumor metastasis, Ki-67 index, percent homozygous deletion of 9p23 and percent 1p36 loss, and potential prognostic inflammatory markers of NLR, PLR, LMR, SII, and SIRI with the primary outcome measures of OS and PFS. Maximum log-rank statistical tests were used to determine inflammatory marker thresholds for grouping prior to Kaplan-Meier and Cox proportional hazards analysis for OS and PFS of the elucidated groups. RESULTS: The cohort included 115 primary SBC patients. The mean ± SD tumor volume was 23.0 ± 28.0 cm3, 73% of patients received gross-total resection, 40% received postoperative radiation, 25% had local recurrence, and 6% had subsequent metastatic disease (mean follow-up 47.2 months). Univariable Cox analysis revealed that NLR (p < 0.01), PLR (p = 0.04), LMR (p = 0.04), SII (p < 0.01), and SIRI (p < 0.01) were independently associated with PFS. Additionally, NLR (p = 0.05) and SII (p = 0.03) were significant in multivariable Cox analysis of PFS. However, both univariable and multivariable Cox analysis revealed no correlations with OS. CONCLUSIONS: The routine assessment of inflammatory biomarkers such as NLR and SIRI could have prognostic value in postresection SBC patients.

Immunotherapy in the Management of Sinonasal Mucosal Melanoma: A Systematic Review.

OBJECTIVE: The aim of this work is to comprehensively review and synthesize the literature related to sinonasal mucosal melanoma (SNMM) treatment with immunotherapy, including potentially targetable genetic mutations, survival outcomes, and adverse events. DATA SOURCES: Embase, Cochrane, Scopus, and Web of Science. REVIEW METHODS: The study protocol was designed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Databases were searched from inception through May 23, 2023. RESULTS: A total of 42 studies met inclusion criteria. Twenty-four of the included studies reported genetic mutations for a combined 787 patients with SNMM. 8.1% (95% confidence interval, CI: 7.6-8.6), 18.9% (95% CI: 18.1-19.8), and 8.5% (95% CI: 8.1-9.0) of reported patients were positive for BRAF, NRAS, and KIT mutations, respectively. The presence of brisk tumor-infiltrating lymphocytes was associated with improved recurrence-free survival and overall survival (OS). Six studies reported a combined 5-year OS after adjuvant immunotherapy treatment of 42.6% (95% CI: 39.4-45.8). Thirteen studies encompassing 117 patients reported adjuvant or salvage immune checkpoint inhibitor (ICI) immunotherapy response rates: 40.2% (95% CI: 36.8-43.6) had a positive response (tumor volume reduction or resolution). Eleven studies reported direct comparisons between SNMM patients treated with or without immunotherapy; the majority (7/11) reported survival benefit for their entire cohort or select subgroups of SNMM patients. With the transition to modern ICIs, there is a stronger trend toward survival improvement with adjuvant ICI. Tumors with Ki67 <40% may respond better to ICI's. CONCLUSION: ICI therapy can be an effective in select SNMM patients, especially those with advanced/metastatic disease.

Multicenter Registry of Adenomas of the Pituitary and Related Disorders: Initial Description of Cushing Disease Cohort, Surgical Outcomes, and Surgeon Characteristics.

BACKGROUND AND OBJECTIVES: To address the lack of a multicenter pituitary surgery research consortium in the United States, we established the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). The goals of RAPID are to examine surgical outcomes, improve patient care, disseminate best practices, and facilitate multicenter surgery research at scale. Our initial focus is Cushing disease (CD). This study aims to describe the current RAPID patient cohort, explore surgical outcomes, and lay the foundation for future studies addressing the limitations of previous studies. METHODS: Prospectively and retrospectively obtained data from participating sites were aggregated using a cloud-based registry and analyzed retrospectively. Standard preoperative variables and outcome measures included length of stay, unplanned readmission, and remission. RESULTS: By July 2023, 528 patients with CD had been treated by 26 neurosurgeons with varying levels of experience at 9 academic pituitary centers. No surgeon treated more than 81 of 528 (15.3%) patients. The mean ± SD patient age was 43.8 ± 13.9 years, and most patients were female (82.2%, 433/527). The mean tumor diameter was 0.8 ± 2.7 cm. Most patients (76.6%, 354/462) had no prior treatment. The most common pathology was corticotroph tumor (76.8%, 381/496). The mean length of stay was 3.8 ± 2.5 days. The most common discharge destination was home (97.2%, 513/528). Two patients (0.4%, 2/528) died perioperatively. A total of 57 patients (11.0%, 57/519) required an unplanned hospital readmission within 90 days of surgery. The median actuarial disease-free survival after index surgery was 8.5 years. CONCLUSION: This study examined an evolving multicenter collaboration on patient outcomes after surgery for CD. Our results provide novel insights on surgical outcomes not possible in prior single-center studies or with national administrative data sets. This collaboration will power future studies to better advance the standard of care for patients with CD.

A novel classification and management scheme for craniocervical junction disorders with ventral neural element compression.

OBJECTIVE: Craniocervical junction (CCJ) pathologies with ventral neural element compression are poorly understood, and appropriate management requires accurate understanding, description, and a more uniform nomenclature. The aim of this study was to evaluate patients to identify anatomical clusters and better classify CCJ disorders with ventral compression and guide treatment. METHODS: A retrospective review of adult and pediatric patients with ventral CCJ compression from 2008 to 2022 at a single center was performed. The incidence of anatomical abnormalities and compressive etiologies was assessed. Surgical approach, radiographic data, and outcomes were recorded. Association rules analysis (ARA) was used to assess variable clustering. RESULTS: Among 51 patients, the main causes of compression were either purely bony (retroflexed dens [n = 18]; basilar invagination [BI; n = 13]) or soft tissue (degenerative pannus [n = 16]; inflammatory pannus [n = 2]). The primary cluster in ARA was a retroflexed dens, platybasia, and Chiari malformation (CM), and the secondary cluster was BI, C1-2 subluxation, and reducibility. These, along with degenerative pannus, formed the three major classes. In assessing the optimal treatment strategy, reducibility was evaluated. Of the BI cases, 12 of the 13 patients had anterolisthesis of C1 that was potentially reducible, compared with 2 of the 18 patients with a retroflexed dens (both with concomitant BI), and no pannus cases. The mean C1-2 facet angle was significantly higher in BI at 32.4°, compared with -2.3° in retroflexed dens and 8.1° in degenerative pannus (p < 0.05). Endonasal decompression with posterior fixation was performed in 48 (94.0%) of the 51 patients, whereas posterior reduction/fixation alone was performed in 3 patients (6.0%). Of 16 reducible cases, open posterior reduction alone was successful in 3 (60.0%) of 5 cases, with all successes containing isolated BI. Reduction was not attempted if vertebral anatomy was unfavorable (n = 9) or the C1 lateral mass was absent (n = 5). The mean follow-up was 28 months. Symptoms improved in 88.9% of patients and were stable in the remaining 11.1%. Tracheostomy and percutaneous G-tube placement occurred in 7.8% and 11.8% of patients, respectively. Reoperation for an endonasal CSF leak repair or posterior cervical wound revision both occurred in 3.9% of patients. CONCLUSIONS: In classifying, one cluster caused decreased posterior fossa volume due to an anatomical triad of retroflexed dens, platybasia, and CM. The second cluster caused pannus formation due to degenerative hypertrophy. For both, endonasal decompression with posterior fixation was ideal. The third group contained C1 anterolisthesis characterized by a steep C1-2 facet angle causing reducible BI. Posterior reduction/fixation is the first-line treatment when anatomically feasible or endonasal decompression with in situ posterior fixation when anatomical constraints exist.

Trigeminal neuralgia pain outcomes following microsurgical resection versus stereotactic radiosurgery for petroclival meningiomas: a systematic review and meta-analysis.

OBJECTIVE: Petroclival meningiomas (PCMs) are challenging lesions to treat because of their deep location and proximity to critical neurovascular structures. Patients with these lesions commonly present because of local mass effect. A symptom that proves challenging to definitively manage is trigeminal neuralgia (TN), which occurs in approximately 5% of PCM cases. To date, there is no consensus on whether microsurgical resection or stereotactic radiosurgery (SRS) leads to better outcomes in the treatment of TN secondary to PCM. In this systematic review and meta-analysis, the authors aimed to evaluate the available literature on the efficacy of microsurgical resection versus SRS for controlling TN secondary to PCM. METHODS: The Embase, MEDLINE, Scopus, and Cochrane databases were queried from database inception to May 17, 2022, using the search terms "(petroclival AND meningioma) AND (trigeminal AND neuralgia)." Study inclusion criteria were as follows: 1) reports on patients aged ≥ 18 years and diagnosed with TN secondary to PCM, 2) cases treated with microsurgical resection or SRS, 3) cases with at least one posttreatment follow-up report of TN pain, 4) cases with at least one outcome of tumor control, and 5) publications describing randomized controlled trials, comparative or single-arm observational studies, case reports, or case series. Exclusion criteria were 1) literature reviews, technical notes, conference abstracts, or autopsy reports; 2) publications that did not clearly differentiate data on patients with PCMs from data on patients with different tumors or with meningiomas in different locations (other intracranial or spinal meningiomas); 3) publications that contained insufficient data on treatments and outcomes; and 4) publications not written in the English language. References of eligible studies were screened to retrieve additional relevant studies. Data on pain and tumor outcomes were compared between the microsurgical resection and SRS treatment groups. The DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction was used to pool estimates from the included studies. RESULTS: Two comparative observational studies and 6 single-arm observational studies describing outcomes after primary intervention were included in the analyses (138 patients). Fifty-seven patients underwent microsurgical resection and 81 underwent SRS for the management of TN secondary to PCM. By the last follow-up (mean 71 months, range 24-149 months), the resection group had significantly higher rates of pain resolution than the SRS group (82%, 95% CI 50%-100% vs 31%, 95% CI 18%-45%, respectively; p = 0.004). There was also a significantly longer median time to tumor recurrence following resection (43.75 vs 16.7 months, p < 0.01). The resection group showed lower rates of pain persistence (0%, 95% CI 0%-6% vs 25%, 95% CI 13%-39%, p = 0.001) and pain exacerbation (0% vs 12%, 95% CI 3%-23%, p = 0.001). The most common postintervention Barrow Neurological Institute pain score in the surgical group was I (66.7%) compared with III (27.2%) in the SRS group. Surgical reintervention was less frequently required following primary resection (1.8%, 95% CI 0%-37% vs 19%, 95% CI 1%-48%, p < 0.01). CONCLUSIONS: Microsurgical resection is associated with higher rates of TN pain resolution and lower rates of pain persistence and exacerbation than SRS in the treatment of PCM. SRS with further TN management is a viable alternative in patients who are not good candidates for microsurgical resection.

A Prospective, Multicenter, Observational Study of Surgical vs Nonsurgical Management for Pituitary Apoplexy.

CONTEXT: Pituitary apoplexy (PA) has been traditionally considered a neurosurgical emergency, yet retrospective single-institution studies suggest similar outcomes among patients managed medically. OBJECTIVE: We established a multicenter, international prospective registry to compare presentation and outcomes in PA patients treated with surgery or medical management alone. METHODS: A centralized database captured demographics, comorbidities, clinical presentation, visual findings, hormonal status, and imaging features at admission. Treatment was determined independently by each site. Key outcomes included visual, oculomotor, and hormonal recovery, complications, and hospital length of stay. Outcomes were also compared based on time from symptom onset to surgery, and from admission or transfer to the treating center. Statistical testing compared treatment groups based on 2-sided hypotheses and P less than .05. RESULTS: A total of 100 consecutive PA patients from 12 hospitals were enrolled, and 97 (67 surgical and 30 medical) were evaluable. Demographics, clinical features, presenting symptoms, hormonal deficits, and imaging findings were similar between groups. Severe temporal visual field deficit was more common in surgical patients. At 3 and 6 months, hormonal, visual, and oculomotor outcomes were similar. Stratifying based on severity of visual fields demonstrated no difference in any outcome at 3 months. Timing of surgery did not affect outcomes. CONCLUSION: We found that medical and surgical management of PA yield similar 3-month outcomes. Although patients undergoing surgery had more severe visual field deficits, we could not clearly demonstrate that surgery led to better outcomes. Even without surgery, apoplectic tumor volumes regress substantially within 2 to 3 months, indicating that surgery is not always needed to reduce mass effect.

The role of surgical management for prolactin-secreting tumors in the era of dopaminergic agonists: An international multicenter report.

OBJECTIVE: First-line prolactin-secreting tumor (PST) management typically involves treatment with dopamine agonists and the role of surgery remains to be further explored. We examined the international experience of 12 neurosurgical centers to assess the patient characteristics, safety profile, and effectiveness of surgery for PST management. METHODS: Patients surgically treated for PST from January 2017 through December 2020 were evaluated for surgical characteristics, outcomes, and safety. RESULTS: Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PST were macroadenomas. Minor complications were seen in 39.3% of patients and major complications were in 4.4%. The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. At 3-6 months, local control on imaging was achieved in 94.8% of cases and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. On multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly protective against early endocrinological cure. Knosp classification was highly predictive of residual tumor or PST recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). There was noted institutional variation in clinical factors and outcomes. CONCLUSION: Our results evaluate a modern, multicenter, global series of PST. These data can serve as a benchmark to compare with DA therapy and other surgical series. Further study and longer term outcomes could provide insight into how patients benefit from surgical treatment.

Endoscopic Endonasal Far-Medial Approach: 2-Dimensional Operative Video.

INDICATIONS CORRIDOR AND LIMITS OF EXPOSURE: Endoscopic endonasal far-medial approach provides an effective and safe corridor to access the parasagittal structures of the lower clivus such as the medial jugular tubercle (JT) and occipital condyle (OC) for lesions that displace neurovascular structures laterally. ANATOMIC ESSENTIALS NEED FOR PREOPERATIVE PLANNING AND ASSESSMENT: Parapharyngeal internal carotid arteries (ICAs) run posterolateral to the eustachian tubes and lateral to the OC. The supracondylar groove is a superficial landmark for the hypoglossal canal, which divides the lateral extension of clivus into the JT and OC. ESSENTIAL STEPS OF THE PROCEDURE: Typically, approach starts with opening of the sphenoid sinus to localize the paraclival ICA. An "inverted U" rhinopharyngeal (RP) flap exposing the supracondylar groove and lower clivus. Doppler and navigation can confirm the course of the ICA. Drilling is started in the midline in the lower clivus and extended laterally to expose the hypoglossal canal, JT, and OC. PITFALLS/AVOIDANCE OF COMPLICATIONS: Neurovascular injuries can be avoided by using intraoperative Doppler and nerve stimulator. Multilayer reconstruction with vascularized nasoseptal (NSF) and RP flaps minimize postoperative cerebrospinal fluid leak. VARIANTS AND INDICATIONS FOR THEIR USE: The contralateral transmaxillary approach provides an increased angle of access behind foramen lacerum and the petrous ICA.The endoscopic endonasal far-medial approach can be used for a variety of pathologies, including petroclival or JT meningiomas, chordomas and chondrosarcomas, and hypoglossal schwannomas, inferiorly extending cholesterol granulomas and even rare, ventral posterior inferior cerebellar artery aneurysms.The patients consented to the procedure.

Incidence of postoperative hyponatremia after endoscopic endonasal pituitary transposition for skull base pathologies.

PURPOSE: Pituitary transposition is a novel surgical approach to access the retroinfundibular space and interpeduncular cistern. Few studies have evaluated post-surgical outcomes, including incidence of hyponatremia, following pituitary transposition. METHODS: This is a retrospective study including 72 patients who underwent endoscopic endonasal surgery involving pituitary transposition for non-pituitary derived tumors over a decade at the University of Pittsburgh Medical Center. Anterior pituitary deficiencies and replacement therapy, tumor pathology and pre-operative serum sodium (Na) were recorded. Na was assessed at postoperative day 1, 3, 5, 7, and 10. Anatomical/surgical parameters included sellar height, sellar access angle to approach the tumor, and cranial extension of the tumor above the sellar floor (B) compared to the height of the gland (A) (B/A). T-test (normally distributed variables) and Wilcoxon rank-sum test (not-normally distributed) were applied for mean comparison. Logistic regression analyzed correlations between anatomical/surgical parameters and postoperative hyponatremia. RESULTS: 55.6% of patients developed post-operative transient hyponatremia. Two patients (5%) developed severe hyponatremia (sodium level < 120 mmol/L). Eleven (15.3%) patients required desmopressin replacement immediately post-operatively, and 2 other patients needed desmopressin after discharge and after sodium nadir developed. Hyponatremia was inversely associated with sellar access angle (p = 0.02) and the tumor cranial extension above the sellar floor showing a trend towards significance (p = 0.09). CONCLUSION: More than half of patients who had pituitary transposition developed transient hyponatremia. Hyponatremia was more common in those with narrower sellar access angle and smaller cranial extension of the tumor above the sellar floor. Anatomical/surgical parameters may allow risk-stratification for post-operative hyponatremia following pituitary transposition.

Anteromedial Petrous (Gardner's) Triangle: Surgical Anatomy and Relevance for Endoscopic Endonasal Approach to the Petrous Apex and Petroclival Region.

BACKGROUND AND OBJECTIVES: Triangular corridors have been used as reliable surgical entry points for open transcranial approaches to the petrous apex (PA) and petroclival region (PCR). The endoscopic endonasal approaches have grown rapidly in the last decade, and the indications have advanced. The knowledge of accurate and reliable anatomic landmarks through endoscopic endonasal route is essential and remain to be established. The purpose of this study was to describe the feasibility and surgical exposure of the anteromedial petrous (Gardner's) triangle as a novel corridor to the PA and PCR. METHODS: Five anatomic specimens were dissected. The PA and PCR were accessed through endoscopic endonasal approaches and contralateral transmaxillary approach. The limits of the anteromedial petrous (Gardner's) triangle were identified and dissected and associated measurements performed. RESULTS: The dissection was divided into 6 steps. The limits of the anteromedial petrous (Gardner's) triangle were identified and defined by the paraclival internal carotid artery anterolaterally, the abducens nerve posteromedially, and the petroclival synchondrosis inferiorly. Three lines were established following the limits of the triangle. The mean distance of the anterolateral limit was 10.03 mm (SD = 0.94), of the posteromedial limit was 20.06 mm (SD = 2.90), and of the inferior limit was 17.99 mm (SD = 2.99). The mean area was 87.56 mm 2 (SD = 20.06). The 3 anatomic landmarks with a critical role to safely define the triangle were the pterygosphenoidal fissure, the petrosal process of the sphenoid bone, and the petroclival synchondrosis. CONCLUSION: The anteromedial (Gardner's) triangle is a well-defined bone corridor which provides access to the entire petrous bone and petroclival junction through endoscopic endonasal route. Regardless of the anatomic variations or tumor location, the landmarks of the abducens nerve, paraclival internal carotid artery, and petroclival synchondrosis are key for understanding lateral access to tumors extending from the clivus.

Endoscopic endonasal repair of encephaloceles of the lateral sphenoid sinus: multiinstitution confirmation of a new classification.

OBJECTIVE: Encephaloceles of the lateral sphenoid sinus are rare. Originally believed to be due to defects in a patent lateral craniopharyngeal canal (Sternberg canal), they are now thought to originate more commonly from idiopathic intracranial hypertension, not unlike encephaloceles elsewhere in the skull base. A new classification of these encephaloceles was recently introduced, which divided them in relation to the foramen rotundum. Whether this classification can be applied to a larger cohort from multiple institutions and whether it might be useful in predicting outcome is unknown. Thus, the authors' goal was to divide a multiinstitutional cohort of patients with lateral sphenoid encephaloceles into four subtypes to determine their incidence and any correlation with surgical outcome. METHODS: A multicenter retrospective review of prospectively acquired databases was carried out across three institutions. Cases were categorized into one of four subtypes (type I, Sternberg canal; type II, medial to rotundum; type III, lateral to rotundum; and type IV, both medial and lateral with rotundum enlargement). Demographic and outcome metrics were collected. Kaplan-Meyer curves were used to determine the rate of recurrence after surgical repair. RESULTS: A total of 49 patients (71% female) were included. The average BMI was 32.8. All encephaloceles fell within the classification scheme. Type III was the most common (71.4%), followed by type IV (16.3%), type II (10.2%), and type I (2%). Cases were repaired endonasally, via a transpterygoidal approach. Lumbar drains were placed in 78% of cases. A variety of materials was used for closure, with a nasoseptal flap used in 65%. After a mean follow-up of 47 months, there were 4 (8%) CSF leak recurrences, all in patients with type III or type IV leaks and all within 1 year of the first repair. Two leaks were fixed with ventriculoperitoneal shunt and reoperation, 1 with ventriculoperitoneal shunt only, and 1 with a lumbar drain only. Of 45 patients in whom detailed information was available, there were 12 (26.7%) with postoperative dry eye or facial numbness, with facial numbness occurring in type III or type IV defects only. CONCLUSIONS: Endoscopic endonasal repair of lateral sphenoid wing encephaloceles is highly successful, but repair may lead to dry eye or facial numbness. True Sternberg (type I) leaks were uncommon. Failures and facial numbness occurred only in patients with type III and type IV leaks.

Electromyographic predictors of abducens nerve palsy after endoscopic skull base surgery.

OBJECTIVE: Recovery of abducens nerve palsy (ANP) after endoscopic endonasal skull base surgery (ESBS) has been shown to be potentially predicted by postoperative ophthalmological examination. Triggered electromyography (t-EMG) and free-run electromyography (f-EMG) activity provide an intraoperative assessment of abducens nerve function, but associations with long-term ANP outcomes have not been explored. The objective of this study was to describe intraoperative abducens EMG characteristics and determine whether these electrophysiological profiles are associated with immediately postoperative and long-term ANP outcomes after ESBS. METHODS: The authors conducted a 5-year (2011-2016) retrospective case-control study of patients who underwent ESBS in whom the abducens nerve was stimulated (t-EMG). Electrophysiological metrics were compared between patients with a new postoperative ANP (cases) and those without ANP (controls). Pathologies included chordoma, pituitary adenoma, meningioma, cholesterol granuloma, and chondrosarcoma. Electrophysiological data included the presence of abnormal f-EMG activity, t-EMG stimulation voltage, stimulation threshold, evoked compound muscle action potential (CMAP) amplitude, onset latency, peak latency, and CMAP duration at various stages of the dissection. Controls were selected such that pathologies were similarly distributed between cases and controls. RESULTS: Fifty-six patients were included, 26 with new postoperative ANP and 30 controls without ANP. Abnormal f-EMG activity (28.0% vs 3.3%, p = 0.02) and lack of response to stimulation (27% vs 0%, p = 0.006) were more frequent in patients with immediately postoperative ANP than in controls. Patients with immediately postoperative ANP also had a lower median CMAP amplitude (35.0 vs 71.2 µV, p = 0.02) and longer onset latency (5.2 vs 2.8 msec, p = 0.04). Comparing patients with transient versus persistent ANP on follow-up, those with persistent ANP tended to have a lower CMAP amplitude (12.8 vs 57 µV, p = 0.07) and higher likelihood of not responding to stimulation at the end of the case (45.5% vs 7.1%, p = 0.06). Abnormal f-EMG was not associated with long-term ANP outcomes. CONCLUSIONS: The presence of f-EMG activity, lack of CMAP response to stimulation, decreased CMAP amplitude, and increased CMAP onset latency were associated with immediately postoperative ANP. Long-term ANP outcomes may be associated with t-EMG parameters, including whether the nerve is able to be stimulated once identified and CMAP amplitude. Future prospective studies may be designed to standardize abducens nerve electrophysiological monitoring protocols to further refine operative and prognostic utility.

Chordoma: A Comprehensive Systematic Review of Clinical Trials.

This systematic review aims to characterize ongoing clinical trials and therapeutic treatment options for chordoma, a rare notochordal remnant tumor that primarily affects the cranial base, mobile spine, and sacrum. While radical surgical resection remains the cornerstone for chordoma management, unique technical challenges posed by its proximity to critical neurovascular structures confer a tendency towards disease recurrence which often requires additional treatment modalities. In an attempt to better understand the current treatment landscape, a systematic review was designed to identify clinical trials directed at chordoma. A total of 108 chordoma trials were identified from four clinical trial databases; fifty-one trials were included in the final analysis, of which only 14 were designated as completed (27.5%). Aggregate data suggests most chordoma interventions are repurposed from other neoplasms that share common molecular pathways, with a recent emphasis on combination therapeutics within and across drug classes. Naturally, the publication and dissemination of clinical trial results remain a concern (n = 4, 28.6%), highlighting the need for enhanced reporting and transparency measures. Active clinical trial efforts are quite promising, with a renewed focus on novel biotherapeutic targets and deciphering the natural history, as well as survivorship of this complex disease.

Crooke Cell Adenoma Confers Poorer Endocrinological Outcomes Compared with Corticotroph Adenoma: Results of a Multicenter, International Analysis.

BACKGROUND: Crooke cell adenomas (CCAs) are a rare, aggressive subset of secretory pituitary corticotroph adenomas (sCTAs) found in 5%-10% of patients with Cushing disease. Multiple studies support worse outcomes in CCAs but are limited by small sample size and single-institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers. METHODS: Patients surgically treated for pituitary adenoma from January 2017 through December 2020 were included. RESULTS: Among 2826 patients from 12 international centers, 20 patients with CCA and 480 patients with sCTA were identified. No difference in baseline demographics, tumor characteristics, or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection was higher in CCA patients (100% vs. 83%, P = 0.05). Among patients with gross total resection according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, P < 0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, P < 0.01). This was the case despite CCA having better local control rates (100% vs. 96%, P < 0.01) and fewer patients with remnant on magnetic resonance imaging (0% vs. 7.2%, P < 0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients. CONCLUSIONS: This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced postsurgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches.

Trigeminal Schwannoma: A Retrospective Analysis of Endoscopic Endonasal Management, Treatment Outcomes, and Neuropathic Sequelae.

Introduction Trigeminal schwannomas (TS) are rare skull base tumors that have been associated with significant neuropathic sequalae for patients. The authors aim to evaluate the clinical features, treatment outcomes, and neuropathic sequelae following endoscopic endonasal approach (EEA) for TS. Methods The study involves a retrospective review of patients who underwent EEA for resection of TS at a single academic institution between 2004 and 2020. Radiographic and clinical data were recorded and analyzed. Results A total of 16 patients were abstracted, with a mean age at the time of surgery of 44 years with a slight female (1.83:1) predominance. Primary preoperative symptomatology included facial pain/neuralgia ( n = 5, 31.3%), facial hypoesthesia ( n = 4, 25.0%), and headache ( n = 4, 25.0%). Following TS resection, patients were found to have facial hypoesthesia ( n = 11, 68.8%), neuropathic keratopathy ( n = 4, 25.0%), and mastication musculature atrophy ( n = 3, 18.8%). Patients with preoperative facial pain/neuralgia ( n = 5, 31.3%) were significantly more likely to try adjunctive pain therapies ( p = 0.018) as well as seek pain consultation ( p = 0.018). Patients with preoperative migraines ( n = 2, 12.5%) were significantly more likely to trial adjunctive pain therapies ( p = 0.025) and undergo evaluation with pain specialists ( p = 0.025). Finally, patients with preoperative pharmacologic agent utilization were significantly more likely to trial adjunctive pain therapies ( p = 0.036) and pursue pain consultation ( p = 0.036). Conclusion Some degree of trigeminal dysfunction may be more common than previously reported following EEA for TS resection. Factors that appear to play a role in the development of trigeminal dysfunction include pre-existing pain syndromes such as facial pain/neuralgia or headache and preoperative medication utilization.

Defining benchmark outcomes for transsphenoidal surgery of pituitary adenomas: a multicenter analysis.

IMPORTANCE: Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available. OBJECTIVE: We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas. DESIGN: A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed. SETTING: Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinology-specific values, and neurology-specific values. RESULTS: Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%. CONCLUSIONS: This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context.

Malignant Brain and Spinal Tumors Originating from Bone or Cartilage.

Malignant bone tumors affecting the brain and spine are a rare and exceedingly difficult-to-treat group of diseases. Most commonly consisting of chordoma and chondrosarcoma, these tumors also include giant-cell tumors and osteosarcomas. This chapter will cover the background, epidemiology, genetics, molecular biology, histopathology, radiographic features, clinical manifestations, therapeutic approaches, and clinical management of each entity.

International Tuberculum Sellae Meningioma Study: Preoperative Grading Scale to Predict Outcomes and Propensity-Matched Outcomes by Endonasal Versus Transcranial Approach.

BACKGROUND AND OBJECTIVES: Tuberculum sellae meningiomas are resected via an expanded endonasal (EEA) or transcranial approach (TCA). Which approach provides superior outcomes is debated. The Magill-McDermott (M-M) grading scale evaluating tumor size, optic canal invasion, and arterial involvement remains to be validated for outcome prediction. The objective of this study was to validate the M-M scale for predicting visual outcome, extent of resection (EOR), and recurrence, and to use propensity matching by M-M scale to determine whether visual outcome, EOR, or recurrence differ between EEA and TCA. METHODS: Forty-site retrospective study of 947 patients undergoing tuberculum sellae meningiomas resection. Standard statistical methods and propensity matching were used. RESULTS: The M-M scale predicted visual worsening (odds ratio [OR]/point: 1.22, 95% CI: 1.02-1.46, P = .0271) and gross total resection (GTR) (OR/point: 0.71, 95% CI: 0.62-0.81, P < .0001), but not recurrence ( P = .4695). The scale was simplified and validated in an independent cohort for predicting visual worsening (OR/point: 2.34, 95% CI: 1.33-4.14, P = .0032) and GTR (OR/point: 0.73, 95% CI: 0.57-0.93, P = .0127), but not recurrence ( P = .2572). In propensity-matched samples, there was no difference in visual worsening ( P = .8757) or recurrence ( P = .5678) between TCA and EEA, but GTR was more likely with TCA (OR: 1.49, 95% CI: 1.02-2.18, P = .0409). Matched patients with preoperative visual deficits who had an EEA were more likely to have visual improvement than those undergoing TCA (72.9% vs 58.4%, P = .0010) with equal rates of visual worsening (EEA 8.0% vs TCA 8.6%, P = .8018). CONCLUSION: The refined M-M scale predicts visual worsening and EOR preoperatively. Preoperative visual deficits are more likely to improve after EEA; however, individual tumor features must be considered during nuanced approach selection by experienced neurosurgeons.